Toxnet

The following information was generated from the
Hazardous Substances Data Bank (HSDB),

a database of the National Library of Medicine's TOXNET system
(http://toxnet.nlm.nih.gov) on November 28, 2018.
Query: Records containing the term 100986 85 4
1 - HSDB
NAME: Levofloxacin
HSN: 8028
RN: 100986-85-4
OVERVIEW:
HUMAN TOXICITY EXCERPTS:

/HUMAN EXPOSURE STUDIES/ Twenty-six patients who were diagnosed as having
community-acquired pneumonia were enrolled in the study. Intravenous
levofloxacin, 500 mg daily, was given, and 12-lead ECG measurements were
obtained before the infusion, at 30 and 60 minutes during infusion, and 10
minutes after its cessation. Resting late potentials were recorded before
and after infusion. Twelve female and 14 male patients were participated
the study. Mean age was 51.3 +/- 22.3 years. Levofloxacin infusion
increased the heart rate (HR) and prolonged the corrected QT (QTc)
intervals significantly (baseline HR: 84.6 +/- 18.8 vs. HR at 60 minutes:
88.6 +/- 18, P = 0.02; baseline QTc: 413.5 +/- 36.9 milliseconds vs. QTc
at 60 minutes: 426.1 +/- 34.7, P = 0,006). There was no significant
difference between the late potential values obtained before and after
infusion. None of our patients experienced severe arrhythmia that required
stopping the treatment. A single dose of IV levofloxacin prolongs the QTc
interval without significant change in late potentials. Monitoring ECG
during levofloxacin infusion might be necessary in patients who have a
condition that could affect the QTc interval.[Basyigit I et al; Am J Ther
12 (5): 407-10 (2005)] **PEER REVIEWED** <a
href="http://www.ncbi.nlm.nih.gov/pubmed/16148425?dopt=Abstract"
target=new>PubMed Abstract
/CASE REPORTS/ ... A 73-year-old white man, with a medical history of

non-small-cell lung cancer and idiopathic myelofibrosis with myeloid
metaplasia, was prescribed levofloxacin because of a lower urinary tract
infection. Three days later, he presented with palpable purpura and
erythematous skin lesions over the lower limbs and trunk, with a markedly
reduced urinary output. Serum creatinine and urea nitrogen were 6.4 and
190 mg/dL, respectively. Levofloxacin was discontinued, and prednisone,
furosemide, and intravenous fluids were given. The patient fully recovered
over the ensuing 4 weeks. Nephrotoxicity associated with levofloxacin is
uncommon. Allergic interstitial nephritis or vasculitis is believed to be
the underlying pathologic process. Definitive diagnosis requires
performance of renal biopsy, although this is not always feasible. In this
case, a return of renal function to normal, with the disappearance of
purpura following the discontinuation of levofloxacin and corticosteroid
treatment, supports the presumptive diagnosis of a hypersensitivity
reaction to levofloxacin.[Famularo G, De Simone C; Ann Pharmacother 36
(9): 1380-2 (2002)] **PEER REVIEWED** <a
/CASE REPORTS/ A 72-year-old female dialysis patient with
insulin-dependent diabetes mellitus who was under long-term medication
with oral prednisolone due to chronic obstructive pulmonary disease was
given levofloxacin for one week to treat an acute bronchitis (one 500 mg
dose on the first day, 125 mg/day orally from second day onwards). One day
after the end of levofloxacin treatment, the patient complained about a
constant dragging pain above the right heel that receded under local
application of diclofenac ointment and inactivity of the right foot.
Twelve days after ending administration of levofloxacin, strong pains in
the right calf were suddenly felt during normal walking, and active
plantar flexion was lost. Palpation showed the right calf to be soft; a
distinct gap was found in the middle third of the Achilles tendon. The
Thompson test was positive, and the patient was unable to stand on her
right toes. Ultrasonography showed a discontinuity of the right Achilles
tendon. A spontaneous Achilles tendon rupture after taking fluoroquinolone
was diagnosed. Conservative treatment was applied due to the reduced
general condition. Initial treatment involved a below-knee plaster cast in
equinus position; the cast was replaced on the fourth day by a pneumatic
walker, which was also worn during mobilisation by physiotherapy. A
typical feature of fluoroquinolone-induced tendinopathy (FIT) is a
considerable latency period in some cases between the commencement of
treatment with a fluoroquinolone and the onset of FIT symptoms. In
addition to fluoroquinolone intake, there are three other predisposing
risk factors for tendinopathy: age over 60 years, long-term treatment with
systemic glucocorticoids, and chronic kidney disease. The patient showed a
combination of all the aforementioned risk factors. In patients with these
risk factors, especially among people with a combination of said risk
factors - which is frequently the case with nephrologic and dialysis
patients, especially -, fluoroquinolones should be administered only after
critical evaluation and with a dosage that is adapted to renal
function.[Maurin N; Dtsch Med Wochenschr 133 (6): 241-4 (2008)] **PEER
REVIEWED** <a
/CASE REPORTS/ ... A 49-year-old woman with a history of asthma was

admitted for a presumed asthma exacerbation related to an infectious
process. She was given levofloxacin and standard management for an acute
exacerbation. On two occasions the patient's respiratory distress
worsened, requiring intubation. The second reaction occurred immediately
after levofloxacin administration and was accompanied by a marked
cutaneous reaction. Levofloxacin was discontinued, and supportive care was
provided. No further symptoms occurred. The patient later was found to
have been started on levofloxacin before admission for a suspected upper
respiratory infection.[Smythe MA et al; Pharmacotherapy 20 (12): 1520-3
(2000)] **PEER REVIEWED** <a
/CASE REPORTS/ A 78-year-old woman with many medical problems, including

chronic obstructive pulmonary disease, was treated with parenteral
levofloxacin for community-acquired pneumonia. She was discharged with
oral levofloxacin to complete an additional 3 days of treatment as an
outpatient. Two days after completing this regimen, the patient developed
a rash with blistering. The rash progressed to toxic epidermal necrolysis
in 7 days, and she was transferred to a burn treatment center. She was
treated with fluid resuscitation, wound dressing, and antibiotics. Her
condition improved, and she was discharged after 22 days. To our
knowledge, this case is the first published report of levofloxacin-induced
toxic epidermal necrolysis.[Digwood-Lettieri S et al; Pharmacotherapy 22
(6): 789-93 (2002)] **PEER REVIEWED** <a
/CASE REPORTS/ An elderly, non-diabetic patient with renal impairment

presented with a possible duodenal perforation. After successful surgery,
the patient developed recurrent hypoglycemic episodes in the
post-operative period after use of levofloxacin. Delay in recognition of
the cause of hypoglycemia led to irreversible brain damage and death. The
calculated Naranjo adverse drug reaction probability scale criteria
suggest the possibility that these episodes were related to levofloxacin.
The mechanism of hypoglycemia with levofloxacin relates to the potential
inhibition of the K(ATP) channel on the pancreatic beta cell by the
drug.[Singh M et al; Langenbecks Arch Surg 393 (2): 235-8 (2008)] **PEER
REVIEWED** <a
/CASE REPORTS/ ... A 20-year-old man without any history of disease or

medication presented with community-acquired pneumonia. Levofloxacin was
administered and 3 days later, he complained of pain in the left Achilles
tendon and revealed redness and swelling in the area. On suspecting
Achilles tendinitis, levofloxacin treatment was discontinued, and the
tendinitis subsequently improved.[Durey A et al; Yonsei Med J 51 (3):
454-6 (2010)] **PEER REVIEWED** <a
target=new>PubMed Abstract Full text: <a
href='https://www.ncbi.nlm.nih.gov/pmc/?term=PMC2852805'
target=new>PMC2852805
/CASE REPORTS/ ... A case of a 60-year-old male patient who was treated
with oral levofloxacin /is described/. The patient sustained a total
subcutaneous rupture of the left Achilles tendon which was not diagnosed
for at least 5 months. Surgical treatment was successful.[Luthje P et al;
Arch Orthop Trauma Surg 125 (2): 124-6 (2005)] **PEER REVIEWED** <a
/CASE REPORTS/ ... A seventy-eight-year-old male patient who developed

severe thrombocytopenia with hemoptysis after taking levofloxacin for 4
days due to infected bronchiectasis /is reported/. His platelet count was
gradually recovered to normal value after the discontinuation of
levofloxacin. Levofloxacin can cause severe thrombocytopenia. Specific
antibody to platelet surface glycoproteins caused by levofloxacin should
be further studied to confirm the association.[Polprasert C, Prayongratana
K; J Med Assoc Thai 92 (Suppl 3): S69-71 (2009)] **PEER REVIEWED** <a
/CASE REPORTS/ ... A 79-year-old white man received levofloxacin for

presumed pneumonia, developed acute renal failure in the setting of
dehydration, and began having ankle pain on the 12th day of admission.
Levofloxacin was discontinued, and magnetic resonance imaging revealed a
6-cm partial tear and degenerative changes. The Naranjo probability scale
indicates a possible association between levofloxacin and tendon rupture
because the event occurred in the setting of known risk factors such as
steroid use, renal failure, older age, and male gender. Levofloxacin, like
other fluoroquinolones, may cause Achilles tendon rupture, and this may be
particularly likely with known risk factors.[Mathis AS et al; Ann
Pharmacother 37 (7-8): 1014-7 (2003)] **PEER REVIEWED** <a
/CASE REPORTS/ ... To report 2 cases of seizures following admin of

levofoxacin & ciprofloxacin. ... A 75-yr-old white woman admitted to
the hospital was prescribed levofloxacin for ischemic toes. After
receiving 3 doses of oral levofloxacin, the patient experienced a seizure.
One month later, the patient was rechallenged with ciprofloxacin &
again experienced a seizure. The patient was hypomagnesemic & had
elevated serum creatinine at the time of both seizures, & was
hyponatremic during the second seizure. A 74-yr-old white woman admitted
to the hospital was prescribed levofloxacin for bacterial pneumonia. After
5 doses, the patient experienced a seizure. The woman had no electrolyte
imbalances at the time of the seizure & no history of a seizure
disorder. ... Quinolone antibiotics vary in their ability to induce
seizures, with trovafloxacin having the greatest potential &
levofloxacin possibly having the least potential. Neither patient had a
history of a previous seizure disorder. Electrolyte imbalances are common
with previous reports of fluoroquinolone-induced seizures. ... Although
levofloxacin monotherapy has not been implicated in inducing seizures, it
appears to be the causative agent in the second case. In the first case,
the quinolones may have been a necessary, but not sufficient, cause in a
patient with electrolyte abnormalities. Risk factors for
fluoroquinolone-induced seizures may Include seizure history, electrolyte
imbalances,dose unadjusted for renal insufficiency, & concomitant
treatment with agents that lower the seizure threshold.[Kushner JM,
Peckman HJ, Snyder CR; Ann Pharmacother 35 (10): 1194-1198 (2001)] **PEER
REVIEWED** <a
/CASE REPORTS/ ... An 87-year-old white woman was admitted to the hospital
following a transient episode of unresponsiveness that had been
accompanied by flailing of her limbs. Approximately 4 hours earlier, she
had developed a pruritic rash on her trunk and limbs, and 3 hours before
this had taken a first dose of levofloxacin. The fluoroquinolone had been
prescribed for treatment of an upper respiratory tract infection. She had
developed a skin rash approximately 3 years earlier following
ciprofloxacin prescribed for a urinary tract infection. On admission, the
patient had a normal neurologic examination. She was mildly hypomagnesemic
(serum magnesium 1.7 mg/dL), with no other electrolyte imbalances present.
Skin biopsy confirmed toxic epidermal necrolysis. The lesions progressed
to involve 30% of the body surface area and were managed with polymyxin B
and gramicidin cream. Levofloxacin was discontinued on admission, and no
anticonvulsants were prescribed. The woman remained seizure-free at
discharge one week later.[Christie MJ et al; Ann Pharmacother 39 (5):
953-5 (2005)] **PEER REVIEWED** <a
/CASE REPORTS/A 67-year-old man with minor alcoholism and a past-history

of gastrectomy and cholecystectomy was given 300 mg/day of oral
levofloxacin and fulfenamic acid for an upper respiratory infection. On
the 4th day, he reported gradual exacerbation of hand tremor which
resembled chorea-like involuntary movement and gait disturbance. He also
experienced visual hallucinations. On the 7th day, he suffered generalized
convulsions and was admitted. Serum concentration of levofloxacin at this
time (3 hours after last administration of a 100 mg tablet of
levofloxacin) was 3.6 ugs/mL. Cessation of the agents promoted complete
recovery of these neurological adverse effects within a week. Another
85-year-old man with chronic bronchitis and slight renal impairment
received long term administration of 200 mg/day of levofloxacin. On the
68th day of administration, gradual exacerbation of gait disturbance,
dysarthria and chorea-like involuntary movement occurred. On the day of
admission, 76 days after the start of administration, the serum level of
levofloxacin was 2.55 micrograms/ml and that of spinal fluid was 1.12
ug/mL (3 hours after the last administration of a 100 mg tablet of
levofloxacin). Cessation of the agents promoted complete recovery of these
neurological adverse effects within the next two weeks. Both patients had
no apparent neurological disorders except age-related brain atrophy.
Age-related renal and brain impairment might have contributed to the
neurological adverse effects of levofloxacin.[Yasuda H et al; Nihon Ronen
Igakkai Zasshi 36 (3): 213-7 (1999)] **PEER REVIEWED** <a
/SURVEILLANCE/ ... Subjects with fluoroquinolone hepatotoxicity enrolled

in the Drug-Induced Liver Injury Network from September 2004 to January
2010 /were identified/. Demographic, clinical, and laboratory data were
analyzed by descriptive statistical methods. Of the 679 registrants in the
Drug-Induced Liver Injury Network prospective study, 12 had
fluoroquinolone hepatotoxicity (6 ciprofloxacin, 4 moxifloxacin, 1
levofloxacin, and 1 gatifloxacin). Seven were women; median age was 57
years (range, 23-80 years), and median time from fluoroquinolone start to
symptoms was only 4 days (range, 1-39 days). Nine patients developed
symptoms on medication; 3 did so 2, 8, and 32 days after stopping the
medication. Cases were equally distributed among hepatocellular injury
(predominantly increased levels of alanine aminotransferase), cholestatic
injury (predominantly increased levels of alkaline phosphatase), and both.
Seven patients had immunoallergic features. Patients with mixed
hepatocellular and cholestatic injury had mild disease without jaundice;
all recovered. In contrast, 2 of 4 patients with hepatocellular injury and
jaundice died, 1 of acute liver failure. One patient with cholestatic
injury developed vanishing bile duct syndrome and required liver
transplantation; another had a persistently increased serum level of
alkaline phosphatase. Fluoroquinolone liver injury is rapid in onset and
often has immunoallergic features, indicating a hypersensitivity reaction.
The pattern of injury can be hepatocellular, cholestatic, or mixed; mixed
cases are the least severe. Acute and chronic liver failure can
occur.[Orman ES et al; Clin Gastroenterol Hepatol 9 (6): 517-523 (2011)]
**PEER REVIEWED** <a
target=new>PubMed Abstract Full text: <a
href='https://www.ncbi.nlm.nih.gov/pmc/?term=PMC3718017'
target=new>PMC3718017
/SURVEILLANCE/ The aim of this retrospective study was to evaluate

postmarketing adverse event reports submitted to the US FDA and case
reports published in the scientific literature for a potential association
between fluoroquinolone exposure and acute exacerbations of myasthenia
gravis. On 1 March 2011, /the investigators/ searched the FDA Adverse
Event Reporting System (AERS) database to retrieve all reports of
myasthenia gravis exacerbation as a serious adverse event in patients
treated with fluoroquinolones.... /The investigators/ identified a total
of 37 unique cases describing myasthenia gravis exacerbation following
fluoroquinolone systemic exposure. /The investigators/ retrieved AERS
reports for 27 non-ventilated patients administered the following
fluoroquinolones: levofloxacin (n=9), moxifloxacin (n=6), ciprofloxacin
(n=6), ofloxacin (n=2), gatifloxacin (n=2), norfloxacin (n=1) and
trovafloxacin (n=1). Additionally, /the investigators/ retrieved ten case
reports published in the literature involving non-ventilated patients
administered ciprofloxacin (n=4), levofloxacin (n=2) and ofloxacin,
norfloxacin, pefloxacin and prulifloxacin (1 patient each). Myasthenia
gravis exacerbations developed a median of 1 day following fluoroquinolone
exposure. The 37 cases describe dyspnoea (n=19; 51%), myasthenic crisis
requiring ventilatory support (n=11; 30%) and death (n=2; 5%). Additional
exacerbation-related adverse events were generalized muscle weakness
(n=20; 54%), dysphagia (n=9; 24%), diplopia (n=6; 16%) and ptosis (n=6;
16%). Six patients (16%) experienced a positive rechallenge, with
recurrent myasthenia gravis exacerbation after fluoroquinolone
reintroduction. Fluoroquinolone exposure may result in potentially
life-threatening myasthenia gravis exacerbations in patients with
underlying disease. Healthcare professionals should be aware of this
serious drug-disease association and carefully weigh the benefit-risks of
fluoroquinolones when treating infections in non-ventilated myasthenic
patients.[Jones SC et al; Drug Saf 34 (10): 839-47 (2011)] **PEER
REVIEWED** <a
/OTHER TOXICITY INFORMATION/ New fluoroquinolones &

fluoronaphthyridones continue to provide the mainstay of antibiotic
development, despite recent events associated with unexpected or
uncharacteristically severe adverse drug reactions. These have included
hepatotoxicity caused by trovafloxacin (suspended), cardiotoxicity
associated with grepafloxacin, & phototoxicity caused by clinafloxacin
(both withdrawn). Prolongation of the QT interval appears to be an
emergent class effect, the implications of which are not yet fully
understood. However, the second-generation agents ciprofloxacin &,
latterly, levofloxacin have excellent safety profiles & provide
standard optimal choices for therapy of a wide range of gram-negative
pathogens. They are also useful for many respiratory infections, though
the use of ciprofloxacin in pneumococcal pneumonia has been questioned
& continued use of levofloxacin may act as a selection pressure for
emergence of quinolone-resistant Streptococcus pneumoniae. Active
conservation measures may be required to protect the class from this
problem because alternatives, should high-level penicillin-resistance
continue to spread, are few. The new 8-methoxy quinolones (moxifloxacin
& gatifloxacin) are more highly potent against both
penicillin-susceptible & multidrug-resistant S. pneumoniae, while
retaining activity against enterobacteria. Clinical Phase III development
has shown them to produce very satisfactory clinical & bacteriologic
responses in respiratory infections & to be remarkably free of
clinically significant adverse effects. Postmarketing surveillance of
moxifloxacin in Germany has revealed no additional concerns. These agents
are now licensed in many countries, including the United States, & add
a further, broad-based respiratory dimension to the future of the
class.[Ball P; Semin Respir Infect 16 (3): 215-224 (2001)] **PEER
REVIEWED** <a
DRUG WARNINGS:
/BOXED WARNING/ WARNING: Fluoroquinolones, including Levaquin, are
associated with an increased risk of tendinitis and tendon rupture in all
ages. This risk is further increased in older patients usually over 60
years of age, in patients taking corticosteroid drugs, and in patients
with kidney, heart or lung transplants.[US Natl Inst Health; DailyMed.
Current Medication Information for LEVAQUIN (levofloxacin) tablet, film
coated for oral use; LEVAQUIN (levofloxacin) solution for oral use;
LEVAQUIN (levofloxacin) injection, solution, concentrate for intravenous
use; LEVAQUIN (levofloxacin) injection, solution for intravenous use
(October 2011). Available from, as of March 7, 2012:
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a1f01e8e-97e9-11de-
b91d-553856d89593]
**QC REVIEWED**
/BOXED WARNING/ WARNING: Fluoroquinolones, including Levaquin may

exacerbate muscle weakness in persons with myasthenia gravis. Avoid
Levaquin in patients with a known history of myasthenia gravis[US Natl
Inst Health; DailyMed. Current Medication Information for LEVAQUIN
(levofloxacin) tablet, film coated for oral use; LEVAQUIN (levofloxacin)
solution for oral use; LEVAQUIN (levofloxacin) injection, solution,
concentrate for intravenous use; LEVAQUIN (levofloxacin) injection,
solution for intravenous use (October 2011). Available from, as of March
7, 2012:
b91d-553856d89593]
**QC REVIEWED**
Other serious and sometimes fatal events, some due to hypersensitivity,

and some due to uncertain etiology, have been reported rarely in patients
receiving therapy with fluoroquinolones, including Levaquin. These events
may be severe and generally occur following the administration of multiple
doses. Clinical manifestations may include one or more of the following:
fever, rash, or severe dermatologic reactions (e.g., toxic epidermal
necrolysis, Stevens-Johnson Syndrome); vasculitis; arthralgia; myalgia;
serum sickness; allergic pneumonitis; interstitial nephritis; acute renal
insufficiency or failure; hepatitis; jaundice; acute hepatic necrosis or
failure; anemia, including hemolytic and aplastic; thrombocytopenia,
including thrombotic thrombocytopenic purpura; leukopenia;
agranulocytosis; pancytopenia; and/or other hematologic abnormalities. The
drug should be discontinued immediately at the first appearance of skin
rash, jaundice, or any other sign of hypersensitivity and supportive
measures instituted.[US Natl Inst Health; DailyMed. Current Medication
Information for LEVAQUIN (levofloxacin) tablet, film coated for oral use;
LEVAQUIN (levofloxacin) solution for oral use; LEVAQUIN (levofloxacin)
injection, solution, concentrate for intravenous use; LEVAQUIN
(levofloxacin) injection, solution for intravenous use (October 2011).
Available from, as of March 7, 2012:
http://dailymed.nlm.nih.gov/dailymed/search.cfm?startswith=levofloxacin]
**PEER REVIEWED**
Post-marketing reports of severe hepatotoxicity (including acute hepatitis

and fatal events) have been received for patients treated with Levaquin No
evidence of serious drug-associated hepatotoxicity was detected in
clinical trials of over 7,000 patients. Severe hepatotoxicity generally
occurred within 14 days of initiation of therapy and most cases occurred
within 6 days. Most cases of severe hepatotoxicity were not associated
with hypersensitivity. The majority of fatal hepatotoxicity reports
occurred in patients 65 years of age or older and most were not associated
with hypersensitivity. Levaquin should be discontinued immediately if the
patient develops signs and symptoms of hepatitis.[US Natl Inst Health;
DailyMed. Current Medication Information for LEVAQUIN (levofloxacin)
tablet, film coated for oral use; LEVAQUIN (levofloxacin) solution for
oral use; LEVAQUIN (levofloxacin) injection, solution, concentrate for
intravenous use; LEVAQUIN (levofloxacin) injection, solution for
intravenous use (October 2011). Available from, as of March 7, 2012:
**PEER REVIEWED**
Levofloxacin is indicated in pediatric patients for inhalational anthrax

(post-exposure). The risk-benefit assessment indicates that administration
of levofloxacin to pediatric patients is appropriate. The safety of
levofloxacin in pediatric patients treated for more than 14 days has not
been studied.[US Natl Inst Health; DailyMed. Current Medication
**PEER REVIEWED**
Serious and occasionally fatal hypersensitivity and/or anaphylactic

reactions reported in patients receiving fluoroquinolones, including
levofloxacin. These reactions may occur with first dose. Some
hypersensitivity reactions have been accompanied by cardiovascular
collapse, hypotension or shock, seizures, loss of consciousness, tingling,
angioedema (e.g., edema or swelling of the tongue, larynx, throat, or
face), airway obstruction (e.g., bronchospasm, shortness of breath, acute
respiratory distress), urticaria, pruritus, and other severe skin
reactions. In addition, other possible severe and potentially fatal
reactions (may be hypersensitivity reactions or of unknown etiology) have
been reported most frequently after multiple doses. These include fever,
rash or other severe dermatologic reactions (e.g., toxic epidermal
necrolysis, Stevens-Johnson syndrome), vasculitis, arthralgia, myalgia,
serum sickness, allergic pneumonitis, interstitial nephritis, acute renal
insufficiency or failure, hepatitis, jaundice, acute hepatic necrosis or
failure, anemia (including hemolytic and aplastic), thrombocytopenia
(including thrombotic thrombocytopenic purpura), leukopenia,
agranulocytosis, pancytopenia and/or other hematologic effects.
Discontinue levofloxacin at first appearance of rash, jaundice, or any
other sign of hypersensitivity. Institute appropriate therapy as indicated
(e.g., epinephrine, corticosteroids, and maintenance of an adequate airway
and oxygen).[American Society of Health-System Pharmacists 2011; Drug
Information 2011. Bethesda, MD. 2011, p. 390] **PEER REVIEWED**
Seizures, toxic psychoses, and increased intracranial pressure and CNS

stimulation, which may lead to tremor, restlessness, anxiety,
lightheadedness, confusion, hallucinations, paranoia, depression,
nightmares, insomnia, and, rarely, suicidal thoughts or acts, have been
reported with fluoroquinolones, including levofloxacin. Such nervous
system effects may occur following the first dose of the drug. Use with
caution in patients with known or suspected CNS disorders (e.g., severe
cerebral arteriosclerosis, epilepsy) or other risk factors that predispose
to seizures or lower the seizure threshold (e.g., certain drugs, renal
impairment). If nervous system effects occur, discontinue levofloxacin and
institute appropriate measures.[American Society of Health-System
Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011, p. 390]
**PEER REVIEWED**
Fluoroquinolones, including levofloxacin, are associated with an increased
risk of tendinitis and tendon rupture in all age groups. This risk is
further increased in older adults (usually those over 60 years of age),
individuals receiving concomitant corticosteroids, and kidney, heart, or
lung transplant recipients. Other factors that may independently increase
risk of tendon rupture include strenuous physical activity, renal failure,
and previous tendon disorders such as rheumatoid arthritis. Tendinitis and
tendon rupture have been reported in patients receiving fluoroquinolones
who did not have any of these risk factors. Fluoroquinolone-associated
tendinitis and tendon rupture most frequently involve the Achilles tendon
and may require surgical repair. Tendinitis and tendon rupture in the
rotator cuff (shoulder), hand, biceps, thumb, and other tendon sites also
reported. Tendon rupture can occur during or following fluoroquinolone
therapy and has been reported up to several months after completion of
therapy. Advise patients to rest and refrain from exercise and contact a
clinician at the first sign of tendinitis or tendon rupture (e.g., pain,
swelling, or inflammation of a tendon or weakness or inability to use a
joint). Discontinue levofloxacin if pain, swelling, inflammation, or
rupture of a tendon occurs.[American Society of Health-System Pharmacists
2011; Drug Information 2011. Bethesda, MD. 2011, p. 390] **PEER REVIEWED**
Severe hepatotoxicity, including acute hepatitis, has occurred and

sometimes resulted in death. Most cases of severe hepatotoxicity occurred
within 6-14 days of initiation of levofloxacin therapy and were not
associated with hypersensitivity reactions. The majority of fatal cases of
hepatotoxicity were in geriatric patients 65 years of age or older.
Levofloxacin should be discontinued in any patient who experiences loss of
appetite, nausea, vomiting, fever, weakness, tiredness, right upper
quadrant tenderness, itching, yellowing of the skin or eyes, light colored
bowel movements, or dark colored urine.[American Society of Health-System
**PEER REVIEWED**
Moderate to severe photosensitivity/phototoxicity reactions reported

rarely with fluoroquinolones, including levofloxacin. Phototoxicity may
manifest as exaggerated sunburn reactions (e.g., burning, erythrema,
exudation, vesicles, blistering, edema) on areas exposed to sun or
artificial ultraviolet (UV) light (usually the face, neck, extensor
surfaces of forearms, dorsa of hands). Relative potential of the various
fluoroquinolones to cause photosensitivity/phototoxicity is unclear.
Factors that contribute to susceptibility to this adverse effect during
fluoroquinolone therapy include patient's skin pigmentation, frequency and
duration of exposure to sun and UV light, use of protective clothing and
sunscreen, concomitant use of other drugs, and dosage and duration of
fluoroquinolone therapy. As with other fluoroquinolones, patients should
be advised to avoid unnecessary or excessive exposure to sunlight or
artificial UV light (e.g., tanning beds, UVA/UVB treatment). If patient
needs to be outdoors, they should wear loose-fitting clothing that
protects skin from sun exposure and use other sun protection measures
(sunscreen).[American Society of Health-System Pharmacists 2011; Drug
When prescribing a fluoroquinolone, consider potential benefits and risks

to the individual patient. Most patients tolerate the drugs, but serious
adverse reactions (e.g., CNS effects, QT prolongation, C.
difficile-associated diarrhea and colitis, damage to liver, kidneys, or
bone marrow, alterations in glucose homeostatis) may occur rarely. To
reduce development of drug-resistant bacteria and maintain effectiveness
of levofloxacin and other antibacterials, use only for treatment or
prevention of infections proven or strongly suspected to be caused by
susceptible bacteria. When selecting or modifying anti-infective therapy,
use results of culture and in vitro susceptibility testing. In the absence
of such data, consider local epidemiology and susceptibility patterns when
selecting anti-infectives for empiric therapy.[American Society of
Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011,
p. 390] **PEER REVIEWED**
Hypoglycemia or hyperglycemia reported with fluoroquinolones, including

levofloxacin. Blood glucose disturbances usually have occurred in patients
with diabetes receiving insulin or oral hypoglycemic agents. Carefully
monitor blood glucose concentrations in diabetic patients. Discontinue
levofloxacin and initiate appropriate therapy immediately if hypoglycemic
reaction occurs.[American Society of Health-System Pharmacists 2011; Drug
An increased incidence of musculoskeletal disorders (arthralgia,

arthritis, tendinopathy, gait abnormality) has been reported in pediatric
patients receiving levofloxacin. Use in pediatric patients only for
prevention of inhalational anthrax (postexposure) in those 6 months of age
or older. Fluoroquinolones, including levofloxacin, cause arthropathy and
osteochondrosis in immature animals of various species. Persistent lesions
in cartilage reported in levofloxacin studies in immature dogs; similar
erosions in weight-bearing joints and other signs of arthropathy have been
reported with other fluoroquinolones. The relevance of these adverse
effects in immature animals to use in humans is unknown.[American Society
of Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD.
2011, p. 390] **PEER REVIEWED**
Prolonged QT interval leading to ventricular arrhythmias, including

torsades de pointes, reported with some fluoroquinolones, including
levofloxacin. Avoid use of levofloxacin in patients with a history of
prolonged QT interval, in those with uncorrected electrolyte disorders
(e.g., hypokalemia), and in those receiving class IA (e.g., quinidine,
procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic
agents.1 Risk may be increased in geriatric patients.[American Society of
Possible emergence and overgrowth of nonsusceptible bacteria or fungi.

Institute appropriate therapy if superinfection occurs. Treatment with
anti-infectives alters normal colon flora and may permit overgrowth of
Clostridium difficile. C. difficile-associated diarrhea and colitis (CDAD;
also known as antibiotic-associated diarrhea and colitis or
pseudomembranous colitis) has been reported with nearly all
anti-infectives, including levofloxacin, and may range in severity from
mild diarrhea to fatal colitis. Outbreaks of severe CDAD caused by
fluoroquinolone-resistant C. difficile have been reported with increasing
frequency over the last several years. Hypertoxin-producing strains of C.
difficile are associated with increased morbidity and mortality since they
may be refractory to anti-infectives and colectomy may be required.
Consider CDAD if diarrhea develops during or after therapy and manage
accordingly. Careful medical history is necessary since CDAD has been
reported to occur as late as 2 months or longer after anti-infective
therapy is discontinued. If CDAD is suspected or confirmed, levofloxacin
may need to be discontinued. Some mild cases of CDAD may respond to
discontinuance alone. Manage moderate to severe cases with fluid,
electrolyte, and protein supplementation, appropriate anti-infective
therapy active against C. difficile (e.g., oral metronidazole or
vancomycin), and surgical evaluation when clinically indicated.[American
Society of Health-System Pharmacists 2011; Drug Information 2011.
Bethesda, MD. 2011, p. 390] **PEER REVIEWED**
Sensory or sensorimotor axonal polyneuropathy affecting small and/or large

axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness
reported with fluoroquinolones, including levofloxacin. To prevent
development of an irreversible condition, discontinue levofloxacin if
symptoms of neuropathy (e.g., pain, burning, tingling, numbness, weakness)
or other alterations of sensation (e.g., light touch, pain, temperature,
position sense, vibratory sensation) occur.[American Society of
Although very useful agents, fluoroquinolones are associated with a number

of adverse events, some with considerable clinical significance.
Prolongation of the QT interval, for example, is an adverse effect
associated with the use of fluoroquinolones. Fluoroquinolones prolong the
QT interval by blocking voltage-gated potassium channels, especially the
rapid component of the delayed rectifier potassium current I(Kr),
expressed by HERG (the human ether-a-go-go-related gene). According to the
available case reports and clinical studies, moxifloxacin carries the
greatest risk of QT prolongation from all available quinolones in clinical
practice and it should be used with caution in patients with predisposing
factors for Torsades de pointes (TdP). Although gemifloxacin,
levofloxacin, and ofloxacin are associated with a lower risk of QT
prolongation compared with moxifloxacin, they should also be used with
caution in patients at risk for QT prolongation. Ciprofloxacin appears to
be associated with the lowest risk for QT prolongation and the lowest TdP
rate. The overall risk of TdP is small with the use of fluoroquinolones.
Clinicians can minimize that risk by avoiding prescriptions of multiple
medications associated with QT-interval prolongation, especially in
high-risk patients.[Briasoulis A et al; Cardiology 120 (2): 103-10 (2011)]
The fluoroquinolones ciprofloxacin, levofloxacin, moxifloxacin and

gemifloxacin are widely used for the treatment of various types of
bacterial infections. Overall, these antibacterial agents can be
considered safe and well tolerated drugs. Comparative studies have
evaluated the use of quinolones in elderly and younger populations.
Although age per se does not seem to decrease their tolerability, specific
adverse effects of the quinolones must be considered when they are chosen
for antibacterial treatment. Renal function declines consistently with age
and doses of renally excreted quinolones (e.g. ofloxacin, levofloxacin,
gatifloxacin) need to be adjusted if a clinically relevant reduction of
creatinine clearance is identified. Reactions of the gastrointestinal
tract, such as nausea, dyspepsia, vomiting or diarrhoea, are among the
most often registered adverse drug reactions during therapy with
fluoroquinolones. Treatment with a quinolone causes diarrhoea less
frequently than treatment with other classes of antimicrobials.
Conflicting data have been published with respect to the incidence of
Clostridium difficile-associated diarrhoea in quinolone-treated patients.
Hypersensitivity reactions, often manifested on the skin, occur less
commonly during therapy with quinolones than, for example, during therapy
with beta-lactam antibacterials. Adverse reactions of the CNS are of
particular concern in the elderly population. Given the CNS excitatory
effects of quinolones, elderly patients should be monitored carefully for
such symptoms. It is likely that many signs of possible adverse reactions,
such as confusion, weakness, loss of appetite, tremor or depression, are
often mistakenly attributed to old age and remain unreported. Quinolones
should be used with caution in patients with known or suspected CNS
disorders that predispose to seizures (e.g. severe cerebral
arteriosclerosis or epilepsy). Quinolones can cause QT interval
prolongation. They should be avoided in patients with known prolongation
of the QT interval, patients with uncorrected hypokalaemia or
hypomagnesaemia and patients receiving class IA (e.g. quinidine,
procainamide) or class III (e.g. amiodarone, sotalol) antiarrhythmic
agents. Tendinitis and tendon ruptures are recognized as quinolone-induced
adverse effects that can occur during treatment or as late as several
months after treatment. Chronic renal diseases, concomitant use of
corticosteroids and age > 60 years are known risk factors for
quinolone-induced tendopathies. Overall, the specific adverse-effect
profile of quinolones must be considered when they are chosen for
treatment of bacterial infections. Because of physiological changes in
renal function and when certain co-morbidities are present, some special
considerations are necessary when elderly patients are treated with these
drugs.[Stahlmann R, Lode H; Drugs Aging 27 (3): 193-209 (2010)] **PEER
REVIEWED** <a
With levofloxacin 0.5% ophthalmic solution transient decrease in vision,

transient ocular burning, ocular pain or discomfort, foreign body
sensation, headache, fever, pharyngitis, and photophobia occur in 1-3% of
patients. Allergic reactions, lid edema, ocular dryness, and ocular
itching occur in less than 1% of patients receiving levofloxacin 0.5%
ophthalmic solution.[American Society of Health-System Pharmacists 2011;
Drug Information 2011. Bethesda, MD. 2011] **PEER REVIEWED**
POPULATIONS AT SPECIAL RISK:

Levaquin should be avoided in patients with known prolongation of the QT
interval, patients with uncorrected hypokalemia ... .[US Natl Inst Health;
**PEER REVIEWED**
Avoid Levaquin in patients with a known history of myasthenia gravis.[US

Natl Inst Health; DailyMed. Current Medication Information for LEVAQUIN
7, 2012:
**PEER REVIEWED**
Healthcare professionals should be aware of this serious drug-disease

association and carefully weigh the benefit-risks of fluoroquinolones when
treating infections in non-ventilated myasthenic patients.[Jones SC et al;
Drug Saf 34 (10): 839-47 (2011)] **PEER REVIEWED** <a
Fluoroquinolones, including Levaquin, are associated with an increased
risk of tendinitis and tendon rupture in all ages. This risk is further
increased in older patients usually over 60 years of age, in patients
taking corticosteroid drugs, and in patients with kidney, heart or lung
transplants.[US Natl Inst Health; DailyMed. Current Medication Information
for LEVAQUIN (levofloxacin) tablet, film coated for oral use; LEVAQUIN
(levofloxacin) solution for oral use; LEVAQUIN (levofloxacin) injection,
solution, concentrate for intravenous use; LEVAQUIN (levofloxacin)
injection, solution for intravenous use (October 2011). Available from, as
of March 7, 2012:
**PEER REVIEWED**

**PEER REVIEWED**
PROBABLE ROUTES OF HUMAN EXPOSURE:

Occupational exposure to levofloxacin may occur through inhalation and
dermal contact with this compound at workplaces where levofloxacin is
produced or used. Monitoring data indicate that the general population may
be exposed to levofloxacin via dermal contact with contaminated water.
Exposure to levofloxacin among the general population will occur to those
administered the drug. (SRC) **PEER REVIEWED**
EMERGENCY MEDICAL TREATMENT:
EMT COPYRIGHT DISCLAIMER:

The information contained in the Truven Health Analytics Inc. products is
intended as an educational aid only. All treatments or procedures are intended
to serve as an information resource for physicians or other competent healthcare
professionals performing the consultation or evaluation of patients and must be
interpreted in view of all attendant circumstances, indications and
contraindications.
The use of the Truven Health Analytics Inc. products is at
your sole risk. These products are provided "as is" and "as available" for use,
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Analytics Inc. makes no representation or warranty as to the accuracy,
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products. All implied warranties of merchantability and fitness for a particular
purpose or use are hereby excluded. Truven Health Analytics Inc. does not assume
any responsibility or risk for your use of the Truven Health Analytics Inc.
products.<p>The following Overview, *** FLUOROQUINOLONES ***, is relevant for
this HSDB record chemical.
LIFE SUPPORT:
o This overview assumes that basic life support measures
have been instituted.
CLINICAL EFFECTS:
0.2.1 SUMMARY OF EXPOSURE
0.2.1.1 ACUTE EXPOSURE
A) USES: Fluoroquinolones are bacteriocidal broad spectrum
antibiotics.
B) PHARMACOLOGY: Fluoroquinolones inhibit bacterial
topoisomerase IV and DNA gyrase enzymes required for
DNA replication, transcription, repair and
recombination.
C) EPIDEMIOLOGY: Overdose is rare.
D) WITH THERAPEUTIC USE
1) Adverse effects from therapeutic doses have included
minor to moderate gastrointestinal effects, headache,
drowsiness, and insomnia following fluoroquinolone
use.
2) Rare adverse effects include rhabdomyolysis,
tendonitis, tendon rupture, delirium, altered mental
status, QT prolongation and ventricular dysrhythmias.
3) Both hyperglycemia and hypoglycemia have been reported
in diabetic patients receiving an oral hypoglycemic
agent or insulin. Fatal hypoglycemia was reported in
an elderly man with type 2 diabetes mellitus
(receiving an oral sulfonylurea) following the
administration of levofloxacin.
4) Elevated liver enzymes and hepatic dysfunction have
been reported with some fluoroquinolones. Therapeutic
use of trovafloxacin has resulted in rare cases of
fatal liver failure.
5) WITHDRAWAL FROM MARKET: Grepafloxacin was withdrawn
from the worldwide market in October, 1999 after
reports of cardiovascular toxicity; QT prolongation
had been associated with its use. Gatifloxacin was
voluntarily withdrawn from the market in May 2006 due
to reports of severe hypo- and hyperglycemic events.
6) QT prolongation has been reported following the use of
several fluoroquinolones.
7) Fatal toxic epidermal necrolysis was reported in an
adult following a dose of trovafloxacin.
E) WITH POISONING/EXPOSURE
1) OVERDOSE has caused dizziness, drowsiness,
disorientation, slurred speech, nausea, vomiting, and
tremors.
0.2.5 CARDIOVASCULAR
A) WITH THERAPEUTIC USE
1) QT prolongation and polymorphic ventricular
tachycardia have been reported with therapeutic use.
0.2.7 NEUROLOGIC
A) Headache, dizziness, and drowsiness have all been
reported when used therapeutically and in overdose.
B) At therapeutic doses seizures, hallucinations, and
sleep disturbances have been reported.
0.2.8 GASTROINTESTINAL
1) Abdominal pain, nausea, vomiting, and diarrhea have
been reported after therapeutic use of these agents.
B) WITH POISONING/EXPOSURE
1) Abdominal pain, nausea, vomiting, and diarrhea have
been reported after overdose.
0.2.9 HEPATIC
1) Elevated liver enzymes and liver dysfunction have been
reported following therapeutic use of
fluoroquinolones. Rare, but severe liver injury has
been reported with trovafloxacin at therapeutic
levels.
0.2.13 HEMATOLOGIC
1) Hematologic toxicity has been reported infrequently
with therapeutic use of fluoroquinolones.
0.2.14 DERMATOLOGIC
1) Photosensitivity reactions have been reported with
ciprofloxacin, fleroxacin, and enoxacin;
photoonycholysis has been reported with perfloxacin
and ofloxacin. Epidermal necrolysis has occurred
following the use of trovafloxacin.
0.2.15 MUSCULOSKELETAL
1) Joint or cartilage tenderness or swelling may be seen.
2) Tendinopathy (a rare effect) appears to be a class
related adverse effect of fluoroquinolone therapy.
0.2.19 IMMUNOLOGIC
1) Hypersensitivity reactions including anaphylaxis and
vasculitis have been associated with fluoroquinolone
use.
0.2.20 REPRODUCTIVE HAZARDS
A) Fluoroquinolones are classified as FDA pregnancy
category C. There are no adequate human studies
available, and most animal studies have shown no
evidence of teratogenicity or maternal toxicity.
Levofloxacin and moxifloxacin crossed the placental
barrier in one human study. Azoospermia, testicular
damage with impaired spermatogenesis, and testicular
atrophy were noted in fluoroquinolone studies in
experimental laboratory animals. For besifloxacin
(administered orally), maternal toxicity (ie, reduced
body weight gain and food consumption), maternal
mortality, increased post-implantation loss, decreased
fetal body weights, decreased fetal ossification,
significantly reduced pup weights, and reduced neonatal
survival rate were seen compared with controls.
Ciprofloxacin otic suspension does not show substantial
systemic exposure or risk to the mother or fetus.
0.2.21 CARCINOGENICITY
0.2.21.3 ANIMAL OVERVIEW
A) Studies in mice and rats showed no indication of a
carcinogenic effect from ciprofloxacin
0.2.22 GENOTOXICITY
A) FINAFLOXACIN
1) Finafloxacin was shown to be genotoxic and clastogenic
in vitro, with and without metabolic activation, and in
vivo. Finafloxacin was positive only in the TA102
strain in the bacterial reverse mutation assay. It was
also positive in the mouse lymphoma cell forward
mutation assay, in mutagenicity assays with V79 Chinese
hamster lung cells, and a micronucleus test in V79
cells. Finafloxacin was also clastogenic in mouse
micronucleus tests (Prod Info XTORO otic suspension
0.3% , 2014).
0.2.23 OTHER
A) Drug interactions involving theophylline, caffeine,
cimetidine, and antacids have been reported with these
agents.
LABORATORY:
A) No specific tests are available to determine the toxicity
of these agents.
B) Although not expected, the urine may be monitored for
hematuria and crystalluria.
C) Monitor hepatic and renal function in symptomatic
patients.
TREATMENT OVERVIEW:
0.4.2 ORAL EXPOSURE
A) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240
mL water/30 g charcoal). Usual dose: 25 to 100 g in
adults/adolescents, 25 to 50 g in children (1 to 12
years), and 1 g/kg in infants less than 1 year old.
B) All other treatment is supportive.
C) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT:
5 to 10 mg IV initially; repeat every 5 to 20 minutes as
needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes;
up to a maximum of 10 mg/dose. May repeat dose every 5
to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg
IV initially; repeat every 5 to 10 minutes as needed, if
seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to
5 minutes, up to a maximum of 4 mg/dose; may repeat in 5
to 15 minutes as needed, if seizures continue).
1) Consider phenobarbital or propofol if seizures recur
after diazepam 30 mg (adults) or 10 mg (children
greater than 5 years).
2) Monitor for hypotension, dysrhythmias, respiratory
depression, and need for endotracheal intubation.
Evaluate for hypoglycemia, electrolyte disturbances,
and hypoxia.
RANGE OF TOXICITY:
A) TOXICITY: A specific toxic dose has not been established.
CIPROFLOXACIN: A 15-year-old girl developed acute renal
failure with distal nephron apoptosis following an
ingestion of 7.5 to 10 g (15 to 20 tablets) of
ciprofloxacin and 100 mg of trazodone; 3 months later,
laboratory studies were normal with no permanent sequelae
reported. However, another teenager only reported mild
symptoms (ie, nausea, vomiting, epigastric pain, and
tremors) after intentionally ingesting 12 g of
ciprofloxacin.
B) THERAPEUTIC DOSE: Dosing varies by agent and indication.
Refer to Dosing and Administration section.
ANTIDOTE AND EMERGENCY TREATMENT:
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been
carried out. If patient is not breathing, start artificial respiration,
preferably with a demand valve resuscitator, bag-valve-mask device, or
pocket mask, as trained. Perform CPR if necessary. Immediately flush
contaminated eyes with gently flowing water. Do not induce vomiting. If
vomiting occurs, lean patient forward or place on the left side (head-down
position, if possible) to maintain an open airway and prevent aspiration.
Keep patient quiet and maintain normal body temperature. Obtain medical
attention. /Poisons A and B/[Currance, P.L. Clements, B., Bronstein, A.C.
(Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition,
Elsevier Mosby, St. Louis, MO 2005, p. 160] **PEER REVIEWED**
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or

nasopharyngeal airway, if needed). Suction if necessary. Watch for signs
of respiratory insufficiency and assist ventilations if needed. Administer
oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary
edema and treat if necessary ... . Monitor for shock and treat if
necessary ... . Anticipate seizures and treat if necessary ... . For eye
contamination, flush eyes immediately with water. Irrigate each eye
continuously with 0.9% saline (NS) during transport ... . Do not use
emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of
water for dilution if the patient can swallow, has a strong gag reflex,
and does not drool ... . Cover skin burns with dry sterile dressings after
decontamination ... . /Poisons A and B/[Currance, P.L. Clements, B.,
Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure.
3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160] **PEER REVIEWED**
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation

for airway control in the patient who is unconscious, has severe pulmonary
edema, or is in severe respiratory distress. Positive-pressure ventilation
techniques with a bag valve mask device may be beneficial. Consider drug
therapy for pulmonary edema ... . Consider administering a beta agonist
such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and
treat arrhythmias as necessary ... . Start IV administration of D5W /SRP:
"To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated
Ringer's if signs of hypovolemia are present. For hypotension with signs
of hypovolemia, administer fluid cautiously. Watch for signs of fluid
overload ... . Treat seizures with diazepam or lorazepam ... . Use
proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and
B/[Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For
Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO
2005, p. 160-1] **PEER REVIEWED**
Emergency and supportive measures: Maintain an open airway and assist

ventilation if necessary. Treat coma, seizures, hypotension, anaphylaxis,
and hemolysis if they occur. replace fluid losses resulting from
gastroenteritis with IV crystalloids. ... /Antibacterial agents/[OLSON,
K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New
York, NY 2012, p. 90] **PEER REVIEWED**
Decontamination: Administer activated charcoal orally if conditions are

appropriate. Gastric lavage is not necessary after small to moderate
ingestions if activated charcoal can be given promptly. /Antibacterial
agents/[OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition.
McGraw-Hill, New York, NY 2012, p. 90] **PEER REVIEWED**
Enhanced elimination: Most antibiotics are excreted unchanged in the

urine, so maintenance of adequate urine flow is important. The role of
forced diuresis is unclear. Hemodialysis is not usually indicated, except
perhaps in patients with renal dysfunction and a high level of a toxic
agent. ... /Antibacterial agents/[OLSON, K.R. (Ed). Poisoning and Drug
Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 91] **PEER
REVIEWED**
In the event of an acute overdosage, the stomach should be emptied. The

patient should be observed and appropriate hydration maintained.
Levofloxacin is not efficiently removed by hemodialysis or peritoneal
dialysis.[US Natl Inst Health; DailyMed. Current Medication Information
for LEVAQUIN (levofloxacin) tablet, film coated for oral use; LEVAQUIN
(levofloxacin) solution for oral use; LEVAQUIN (levofloxacin) injection,
solution, concentrate for intravenous use; LEVAQUIN (levofloxacin)
injection, solution for intravenous use (October 2011). Available from, as
of March 7, 2012:
**PEER REVIEWED**
NON-HUMAN TOXICITY EXCERPTS:

/LABORATORY ANIMALS: Acute Exposure/ Mice, rats, dogs and monkeys
exhibited the following clinical signs after receiving a single high dose
of Levaquin: ataxia, ptosis, decreased locomotor activity, dyspnea,
prostration, tremors, and convulsions. Doses in excess of 1500 mg/kg
orally and 250 mg/kg IV produced significant mortality in rodents.[US Natl
7, 2012:
**PEER REVIEWED**
/LABORATORY ANIMALS: Acute Exposure/ The phototoxic potential of

levofloxacin (DR-3355) was evaluated in mice and compared with that for
enoxacin. Levofloxacin showed no changes in ear swelling at 200 mg/kg, but
caused ear swelling at 800 mg/kg. Enoxacin caused severe phototoxicity in
a dose dependent manner from 50 mg/kg. These data suggest that
levofloxacin has minor phototoxic potential, but is approximately 4-fold
less toxic than enoxacin in these experimental conditions.[Wagai N et al;
Arzneim. Forsch 42 (3 Suppl): 404-5 (1992)] **PEER REVIEWED**
/LABORATORY ANIMALS: Acute Exposure/ ... Rats received an intravenous

injection of levofloxacin and their arterial blood was sampled
periodically. The serum glucose concentration decreased after an injection
of 100 mg/kg of levofloxacin, while it increased at levofloxacin 300
mg/kg. The serum immunoreactive insulin concentration increased as the
dose of levofloxacin increased. The serum epinephrine concentration was
rapidly elevated by levofloxacin at 300 mg/kg. The serum histamine
concentration increased after injections of levofloxacin, 200 and 300
mg/kg. Diphenhydramine (1 mg/kg) antagonized the hyperglycemia induced by
300 mg/kg of levofloxacin. In an in vitro study, the release of
epinephrine from the adrenal medulla in the presence of levofloxacin was
determined. Levofloxacin (300 ug/mL) did not affect epinephrine release
from the adrenal medulla. Levofloxacin can induce hypoglycemia and
hyperglycemia in rats. Levofloxacin can promote histamine release, leading
to an increased serum epinephrine concentration and
hyperglycemia.[Ishiwata Y et al; Eur J Pharmacol 551 (1-3): 168-74 (2006)]
/LABORATORY ANIMALS: Acute Exposure/ Sixteen albino rabbits were used in

this study, and divided four groups. Levofloxacin in doses of 50, 100, 250
and 500 ug was injected into the midvitreous of rabbit's left eyes. The
other eye served as a control and received normal saline solution.
Indirect ophthalmoscopy, electroretinography (ERG) and light microscopy
were used for retinal toxicity of levofloxacin. ERGs were recorded before
injection and at 1(st) day, 1(st), 2(nd) and 4(th) weeks. At the end of
follow-up period, the rabbits were killed and the eyes were enucleated for
histologic evaluation. Intravitreal injections of 50, 100, 250 and 500 ug
levofloxacin did not cause any deterioration of the a-wave, b-wave or
oscillatory potentials of ERG throughout the follow-up period of 4 weeks.
No evidence of retinal toxicity was observed by indirect ophthalmoscopy
and light microscopy in any case. In therapeutic doses of 500 ug or less,
intravitreal levofloxacin does not have retinal toxicity in rabbit eyes
and this dose was well above the MIC(90) values of ocular pathogens that
cause endophthalmitis. If future studies in other species confirm our
findings, intravitreal levofloxacin may be a potentially important drug in
the treatment and prevention of clinical bacterial endophthalmitis.[Gurler
B et al; Curr Eye Res 24 (4): 253-62 (2002)] **PEER REVIEWED** <a
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The oral toxicity

of levofloxacin was investigated in rats and monkeys over a 26-wk period.
Rats receiving higher doses of the drug exhibited an increased number of
larger fecal pellets, salivation, lower neutrophil counts, enlargement of
the cecum, and prominent goblet cells in the cecal mucosa. Monkeys showed
no adverse effects.[Kato M et al; Arzneim. Forsch 42 (3 Suppl): 367-73,
(1992)] **PEER REVIEWED**
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The

reproductive toxicity of oral levofloxacin was investigated in rats and
rabbits. No adverse effects on fertility or teratogenicity were noted at
any dose in rats during early pregnancy. The drug elicited no evidence of
teratogenicity when administered during the fetal organogenesis period to
pregnant rats at doses of up to 810 mg/kg or to pregnant rabbits at doses
of up to 50 mg/kg. Rat fetuses in the 810 mg/kg group exhibited decreased
body weight and retardation of ossification, and showed increases in
mortality and skeletal variations.[Watanabe T et al; Arzneim. Forsch 42 (3
Suppl): 374-7 (1992)] **PEER REVIEWED**
/GENOTOXICITY/ The mutagenic effects of levofloxacin in lacZ transgenic

mice (Muta Mouse) have been investigated. Male Muta-Mouse mice were
administered levofloxacin i.p. at a dose of 300 or 600 mg/kg. The higher
dose corresponded to half the LD50 of the compound in ddY strain mice. The
mutant frequencies in the bone marrow, liver (day 10 only), testis and
sperm were examined by the positive selection method for lacZ mutations on
days 1 and 10 after treatment. Levofloxacin did not induce any
statistically significant increase in mutant frequency in any of the
examined tissues at either dose level or at either sampling time. The
mutant frequency increases over the spontaneous values in the bone marrow,
liver, testis and sperm were 1.0- to 1.2-fold, 0.9-fold, 0.5- to 1.0-fold
and 0.9- to 1.3-fold respectively. N-Ethyl-N-nitrosourea (100 mg/kg as a
positive control), on the other hand, induced significant increases in
mutant frequencies in both somatic cells (bone marrow and liver) and germ
cells (testis and sperm) on day 10 after treatment. The mutagenic potency
for ENU was bone marrow > > liver approximately testis approximately
sperm (50.1-fold, 3.4-fold, 2.9-fold and 2.3-fold respectively over the
spontaneous values). Levofloxacin was not mutagenic in the lacZ transgenic
mice under the present experimental conditions.[Itoh S et al; Mutagenesis
13 (1): 51-5 (1998)] **PEER REVIEWED**
ECOTOXICITY VALUES:
EC50; Species: Microcystis aeruginosa (Blue-Green Algae); Conditions:
freshwater, static, 20 deg C; Concentration: 7.9 ug/L for 5 days (95%
confidence interval: 6.4-9.4 ug/L); Effect: population, decreased
chlorophyll A concentration /100% purity formulation/[Robinson AA et al;
Environ Toxicol Chem 24 (2): 423-30 (2005) as cited in the ECOTOX
database. Available from, as of March 12, 2012:
http://cfpub.epa.gov/ecotox/] **PEER REVIEWED**
EC50; Species: Pseudokirchneriella subcapitata (Green Algae); Conditions:

freshwater, static, 20 deg C; Concentration: 7400 ug/L for 3 days (95%
confidence interval: 6400-8400 ug/L); Effect: population, decreased
chlorophyll A concentration /100% purity formulation/[Robinson AA et al;
Environ Toxicol Chem 24 (2): 423-30 (2005) as cited in the ECOTOX
database. Available from, as of March 12, 2012:
http://cfpub.epa.gov/ecotox/] **PEER REVIEWED**
EC50; Species: Lemna minor (Duckweed); Conditions: freshwater, renewal, 20

deg C; Concentration: 51 ug/L for 7 days (95% confidence interval: 8.6-94
ug/L); Effect: population, decreased abundance (counted number of fronds)
/100% purity formulation/[Robinson AA et al; Environ Toxicol Chem 24 (2):
423-30 (2005) as cited in the ECOTOX database. Available from, as of March
12, 2012: http://cfpub.epa.gov/ecotox/] **PEER REVIEWED**
METABOLISM/ METABOLITES:
Levofloxacin is stereochemically stable in plasma and urine and does not
invert metabolically to its enantiomer, D-ofloxacin. Levofloxacin
undergoes limited metabolism in humans and is primarily excreted as
unchanged drug in the urine. Following oral administration, approximately
87% of an administered dose was recovered as unchanged drug in urine
within 48 hours, whereas less than 4% of the dose was recovered in feces
in 72 hours. Less than 5% of an administered dose was recovered in the
urine as the desmethyl and N-oxide metabolites, the only metabolites
identified in humans. These metabolites have little relevant
pharmacological activity.[US Natl Inst Health; DailyMed. Current
Medication Information for LEVAQUIN (levofloxacin) tablet, film coated for
oral use; LEVAQUIN (levofloxacin) solution for oral use; LEVAQUIN
(levofloxacin) injection, solution, concentrate for intravenous use;
LEVAQUIN (levofloxacin) injection, solution for intravenous use (October
2011). Available from, as of March 7, 2012:
**PEER REVIEWED**
ABSORPTION, DISTRIBUTION & EXCRETION:

The mean volume of distribution of levofloxacin generally ranges from 74
to 112 L after single and multiple 500 mg or 750 mg doses, indicating
widespread distribution into body tissues. Levofloxacin reaches its peak
levels in skin tissues and in blister fluid of healthy subjects at
approximately 3 hours after dosing. The skin tissue biopsy to plasma AUC
ratio is approximately 2 and the blister fluid to plasma AUC ratio is
approximately 1 following multiple once-daily oral administration of 750
mg and 500 mg doses of levaquin, respectively, to healthy subjects.
Levofloxacin also penetrates well into lung tissues. Lung tissue
concentrations were generally 2- to 5-fold higher than plasma
concentrations and ranged from approximately 2.4 to 11.3 ug/g over a
24-hour period after a single 500 mg oral dose.[US Natl Inst Health;
**PEER REVIEWED**
Levofloxacin pharmacokinetics are linear and predictable after single and

multiple oral or IV dosing regimens. Steady-state conditions are reached
within 48 hours following a 500 mg or 750 mg once-daily dosage regimen.
The mean + or - SD peak and trough plasma concentrations attained
following multiple once-daily oral dosage regimens were approximately 5.7
+ or - 1.4 and 0.5 + or - 0.2 ug/mL after the 500 mg doses, and 8.6+ or -
1.9 and 1.1 + or - 0.4 ug/mL after the 750 mg doses, respectively. The
mean + or - SD peak and trough plasma concentrations attained following
multiple once-daily IV regimens were approximately 6.4 + or - 0.8 and 0.6
+ or - 0.2 ug/mL after the 500 mg doses, and 12.1+ or - 4.1 and 1.3 + or -
0.71 ug/mL after the 750 mg doses, respectively. Oral administration of a
500 mg dose of levaquin with food prolongs the time to peak concentration
by approximately 1 hour and decreases the peak concentration by
approximately 14% following tablet and approximately 25% following oral
solution administration. Therefore, levaquin tablets can be administered
without regard to food. It is recommended that levaquin oral solution be
taken 1 hour before or 2 hours after eating.[US Natl Inst Health;
**PEER REVIEWED**
Levofloxacin is rapidly and essentially completely absorbed after oral

administration. Peak plasma concentrations are usually attained one to two
hours after oral dosing. The absolute bioavailability of levofloxacin from
a 500 mg tablet and a 750 mg tablet of Levaquin are both approximately
99%, demonstrating complete oral absorption of levofloxacin. Following a
single intravenous dose of Levaquin to healthy volunteers, the mean + or -
SD peak plasma concentration attained was 6.2 + or - 1.0 ug/mL after a
500 mg dose infused over 60 minutes and 11.5+ or - 4.0 ug/mL after a 750
mg dose infused over 90 minutes.[US Natl Inst Health; DailyMed. Current
**PEER REVIEWED**
Levofloxacin is excreted largely as unchanged drug in the urine. The mean

terminal plasma elimination half-life of levofloxacin ranges from
approximately 6 to 8 hours following single or multiple doses of
levofloxacin given orally or intravenously. The mean apparent total body
clearance and renal clearance range from approximately 144 to 226 mL/min
and 96 to 142 mL/min, respectively. Renal clearance in excess of the
glomerular filtration rate suggests that tubular secretion of levofloxacin
occurs in addition to its glomerular filtration. Concomitant
administration of either cimetidine or probenecid results in approximately
24% and 35% reduction in the levofloxacin renal clearance, respectively,
indicating that secretion of levofloxacin occurs in the renal proximal
tubule. No levofloxacin crystals were found in any of the urine samples
freshly collected from subjects receiving levaquin.[US Natl Inst Health;
**PEER REVIEWED**
The pharmacokinetics of oral levofloxacin and its penetration into

inflammatory fluid were studied in 6 healthy male subjects (ages 18-45 yr)
who received 500 mg drug every 12 hr for 5 doses or 500 mg every 24 hr for
3 doses in an open crossover design. Mean peak plasma levels of 9.3 and
6.6 ug/mL were attained 1.1 and 1.2 hr after the 12 hr and 24 hr regimens,
respectively. Mean peak inflammatory fluid levels of 6.8 and 4.3 mcg/ml
were attained at 2.3 and 3.7 hr, respectively. Average steady state levels
were 5 and 2.2 ug/mL in plasma and 4.7 and 2.3 ug/mL in inflammatory
fluid, respectively. Mean terminal elimination half-lives in plasma were
7.9 and 8 hr for the 2 regimens, respectively, and the same values were
seen for inflammatory fluid. Overall penetration into inflammatory fluid
was 88-101% with the 12 hr regimen and 83-112% with the 24 hr regimen.
Mean urinary recoveries were 87 and 86% over the interval of the 12 hr and
24 hr regimens, respectively.[Child J et al; Chemother 39 (Dec): 2749-51
After single oral administration of (14)C-levofloxacin at a dose of 20 mg

kg(-1) under non-fasting conditions, the absorption, distribution and
excretion of radioactivity were studied in albino and pigmented rats. Good
penetration of radioactivity into tissues was indicated by higher
concentrations in most tissues compared with serum and there were no
quantitative differences in the distribution of radioactivity between
albino and pigmented rats except for melanin-containing tissues such as
the uveal tract of eyes and hair follicles. There was selective and strong
binding of drug-related radioactivity to these tissues in pigmented rats.
The uveal tract concentrations reached the maximum value (C(max)) of 26.33
+/- 0.75 ug eq. g(-1) at 24 hr after dosing and declined slowly with a
terminal half-life of 468.1 hr (19.5 days). The uveal tract concentration
at 12 weeks was 0.73+/- 0.12 ug eq. g(-1), which is c. 1/36 of C(max). The
AUC(0- infinity ) for the uveal tract was 12.58 mg h(-1) g(-1). The uveal
tracts separated from one eye of each rat were extracted with 0.067 M
phosphate buffer (pH 7.4) and 1M HCl/EtOH (30:70), successively. In
pigmented rats, approximately 85-48% of radioactivity bound to the uveal
tract was released from the tissue by the washing procedures. Most of the
eluted radioactivity was released with 1M HCl/EtOH (30:70), indicating
that the binding to melanin is reversible, and hydrophobic and
electrostatic interactions play an important role in the binding of
levofloxacin and/or its metabolites with melanin-containing ocular
tissues. Only unchanged drug was detected in the extracts of the uveal
tracts. The concentrations and half-life of radioactivity in the uveal
tract after dosing of (14)C-levofloxacin were found to be much lower and
shorter than those after dosing of (14)C-chloroquine. It is unlikely that
levofloxacin causes toxicity because of its much lower affinity to
melanin-containing ocular tissues and shorter duration of therapy compared
to chloroquine.[Tanaka M et al; J Pharm Pharmacol 56 (4): 463-9 (2004)]
BIOLOGICAL HALF-LIFE:
The mean terminal plasma elimination half-life of levofloxacin ranges from
approximately 6 to 8 hours following single or multiple doses of
levofloxacin given orally or intravenously.[US Natl Inst Health; DailyMed.
**PEER REVIEWED**
The pharmacokinetics of oral levofloxacin and its penetration into

inflammatory fluid were studied in 6 healthy male subjects (ages 18-45 yr)
who received 500 mg drug every 12 hr for 5 doses or 500 mg every 24 hr for
3 doses in an open crossover design. ... Mean terminal elimination
half-lives in plasma were 7.9 and 8 hr for the 2 regimens, respectively,
and the same values were seen for inflammatory fluid. ...[Child J et al;
Chemother 39 (Dec): 2749-51 (1995)] **PEER REVIEWED**
After single oral administration of (14)C-levofloxacin at a dose of 20 mg

kg(-1) under non-fasting conditions, the absorption, distribution and
excretion of radioactivity were studied in albino and pigmented rats. ...
The uveal tract concentrations reached the maximum value (C(max)) of 26.33
+/- 0.75 ug eq. g(-1) at 24 hr after dosing and declined slowly with a
terminal half-life of 468.1 hr (19.5 days).[Tanaka M et al; J Pharm
Pharmacol 56 (4): 463-9 (2004)] **PEER REVIEWED** <a
MECHANISM OF ACTION:
Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone
antimicrobial agent. The antibacterial activity of ofloxacin resides
primarily in the L-isomer. The mechanism of action of levofloxacin and
other fluoroquinolone antimicrobials involves inhibition of bacterial
topoisomerase IV and DNA gyrase (both of which are type II
topoisomerases), enzymes required for DNA replication, transcription,
repair and recombination.[US Natl Inst Health; DailyMed. Current
**PEER REVIEWED**
Fluoroquinolones prolong the QT interval by blocking voltage-gated

potassium channels, especially the rapid component of the delayed
rectifier potassium current I(Kr), expressed by HERG (the human
ether-a-go-go-related gene). According to the available case reports and
clinical studies, moxifloxacin carries the greatest risk of QT
prolongation from all available quinolones in clinical practice and it
should be used with caution in patients with predisposing factors for
Torsades de pointes (TdP).[Briasoulis A et al; Cardiology 120 (2): 103-10
INTERACTIONS:
Warfarin: Potential pharmacologic interaction (increased prothrombin
time). Monitor prothrombin time or other suitable coagulation tests and
monitor for bleeding.[American Society of Health-System Pharmacists 2011;
Drug Information 2011. Bethesda, MD. 2011, p. 391] **PEER REVIEWED**
Theophylline: Pharmacokinetic interaction unlikely. However,

pharmacokinetic interaction (increased theophylline half-life and
increased risk of theophylline-related adverse effects) occurs with some
other quinolones. Closely monitor serum theophylline concentrations and
adjust theophylline dosage accordingly; consider that adverse theophylline
effects (e.g., seizures) may occur with or without elevated theophylline
concentrations.[American Society of Health-System Pharmacists 2011; Drug
Sucralfate: Potential pharmacokinetic interaction (decreased levofloxacin

absorption); no pharmacokinetic interaction if given 2 hours apart.
Administer levofloxacin at least 2 hours before or 2 hours after
sucralfate.[American Society of Health-System Pharmacists 2011; Drug
Probenecid: Potential pharmacokinetic interaction (increased levofloxacin

AUC and half-life). Not considered clinically important; dosage
adjustments are not required.[American Society of Health-System
**PEER REVIEWED**
Nonsteroidal Anti-Iinflammatory Agents (NSAIAs): Potential pharmacologic

interaction (possible increased risk of CNS stimulation and seizures).
Animal studies suggest risk may be less than that associated with some
other fluoroquinolones and that risk varies depending on the specific
Nonsteroidal anti-inflammatory agents.[American Society of Health-System
**PEER REVIEWED**
Iron , Multivitamins, and Mineral Supplements: Potential pharmacokinetic

interaction (decreased levofloxacin absorption). Administer levofloxacin
at least 2 hours before or 2 hours after ferrous sulfate or dietary
supplements containing zinc, calcium, magnesium, or iron.[American Society
Didanosine: Potential pharmacokinetic interaction (decreased levofloxacin

absorption). Administer levofloxacin at least 2 hours before or 2 hours
after buffered didanosine (pediatric oral solution admixed with
antacid).[American Society of Health-System Pharmacists 2011; Drug
Cyclosporine and Tacrolimus: Possible pharmacokinetic interactions with

cyclosporine or tacrolimus (increased AUC of the immunosuppressive agent).
Manufacturer of levofloxacin states that dosage adjustments are not
required; some clinicians suggest that plasma concentrations of the
immunosuppressive agent be monitored if used concomitantly with
levofloxacin.[American Society of Health-System Pharmacists 2011; Drug
Corticosteroids: Concomitant use of corticosteroids increases the risk of
severe tendon disorders (e.g., tendinitis, tendon rupture), especially in
geriatric patients older than 60 years of age.[American Society of
Cimetidine: Potential pharmacokinetic interaction (slightly increased

levofloxacin AUC and half-life). Not considered clinically important;
levofloxacin dosage adjustments are not recommended.[American Society of
Antidiabetic Agents: Potential pharmacodynamic interaction (altered blood

glucose concentrations and symptomatic hyperglycemia or hypoglycemia) in
diabetic patients receiving concomitant levofloxacin and antidiabetic
therapy (e.g., insulin, glyburide). Careful monitoring of blood glucose
concentrations recommended; discontinue levofloxacin if a hypoglycemic
Antidepressants: Potential pharmacologic interaction with fluoxetine or

imipramine (additive effect on QT interval prolongation).[American Society
Antiarrhythmic Agents: Potential pharmacologic interaction (additive

effect on QT interval prolongation). Levofloxacin should be avoided in
those receiving class IA (e.g., quinidine, procainamide) or class III
(e.g., amiodarone, sotalol) antiarrhythmic agents. Pharmacokinetic
interaction with procainamide (increased half-life and decreased clearance
of procainamide).[American Society of Health-System Pharmacists 2011; Drug
Antacids: Potential pharmacokinetic interaction (decreased levofloxacin

after antacids containing magnesium or aluminum.[American Society of
Drugs That Prolong QT Interval: Potential pharmacologic interaction

(additive effects on QT interval prolongation). Avoid concomitant use with
class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone,
sotalol) antiarrhythmic agents.[American Society of Health-System
**PEER REVIEWED**
All fluoroquinolones interact with multivalent cation-containing products

& bioavailability is reduced by 50% when co-administered with iron
cmpds (ciprofloxacin & moxifloxacin are more affected than
levofloxacin or gemifloxacin). The interaction between theophylline &
fluoroquinolones is most marked with enoxacin, pefloxacin, &
ciprofloxacin, with no such interaction reported for levofloxacin.[Lode H;
Chemotherapy 47 Suppl 3: 24-31 (2001)] **PEER REVIEWED**
THERAPEUTIC USES:
Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Nucleic Acid
Synthesis Inhibitors[National Library of Medicine's Medical Subject
Headings online file (MeSH, 2012)] **PEER REVIEWED**
Levofloxacin is used for the treatment of acute bacterial sinusitis caused
by susceptible Streptococcus pneumoniae, Haemophilus influenzae, or
Moraxella catarrhalis. /Included in US product label/[American Society of
Levofloxacin is used for the treatment of community-acquired pneumonia

caused by susceptible S. aureus (oxacillin-susceptible strains), S.
pneumoniae (including penicillin-resistant strains (penicillin MIC of 2
ug/mL or greater)), H. influenzae, H. parainfluenzae, Klebsiella
pneumoniae, Legionella pneumophila, M. catarrhalis, Chlamydophila
pneumoniae (formerly Chlamydia pneumoniae), or Mycoplasma pneumoniae.
/Included in US product label/[American Society of Health-System
**PEER REVIEWED**
Levofloxacin is used for the treatment of mild to moderate complicated

urinary tract infections caused by susceptible E. faecalis, Enterobacter
cloacae, E. coli, K. pneumoniae, P. mirabilis, or Ps. aeruginosa and acute
pyelonephritis caused by susceptible E. coli, including cases with
concurrent bacteremia. /Included in US product label/[American Society of
Levofloxacin is used for the treatment of mild to moderate uncomplicated

urinary tract infections caused by susceptible E. coli, K. pneumoniae, or
S. saprophyticus. /Included in US product label/[American Society of
Levofloxacin is used for the treatment of mild to moderate uncomplicated

skin and skin structure infections caused by susceptible S. aureus
(oxacillin-susceptible strains) or S. pyogenes (group A beta-hemolytic
streptococci) and for the treatment of complicated skin and skin structure
infections caused by susceptible S. aureus (oxacillin-susceptible
strains), Enterococcus faecalis, S. pyogenes, or Proteus mirabilis.
**PEER REVIEWED**
Levofloxacin is used for the treatment of nosocomial pneumonia caused by

susceptible S. aureus (oxacillin-susceptible strains), S. pneumoniae, H.
influenzae, Escherichia coli, K. pneumoniae, Ps. aeruginosa, or Serratia
marcescens. /Included in US product label/[American Society of
Levofloxacin is used for the treatment of acute bacterial exacerbations of

chronic bronchitis caused by susceptible Staphylococcus aureus
(oxacillin-susceptible (methicillin-susceptible) strains), S. pneumoniae,
H. influenzae, H. parainfluenzae, or M. catarrhalis. /Included in US
product label/[American Society of Health-System Pharmacists 2011; Drug
Levofloxacin is used for inhalational anthrax (postexposure) to reduce the

incidence or progression of disease following exposure to aerosolized
Bacillus anthracis.1 Although the efficacy of levofloxacin for
postexposure prophylaxis to prevent inhalational anthrax has not been
evaluated in human clinical trials, the drug is labeled by the US Food and
Drug Administration (FDA) for this indication based on a surrogate end
point derived from a primate model of inhalational anthrax that predicts
clinical benefit based on plasma levofloxacin concentrations achievable in
humans with recommended oral or IV dosages. The US Centers for Disease
Control and Prevention (CDC), US Working Group on Civilian Biodefense, and
US Army Medical Research Institute of Infectious Diseases (USAMRIID)
recommend ciprofloxacin or doxycycline as the initial drug of choice for
postexposure prophylaxis following exposure to aerosolized anthrax spores
that occurs in the context of biologic warfare or bioterrorism. Some
experts suggest that other fluoroquinolones (e.g., levofloxacin,
moxifloxacin, ofloxacin) can be considered alternatives for postexposure
prophylaxis when oral ciprofloxacin and oral doxycycline are unavailable.
**PEER REVIEWED**
Levofloxacin is used for the treatment of chronic prostatitis caused by

susceptible E. coli, E. faecalis, or S. epidermidis (oxacillin-susceptible
strains). /Included in US product label/[American Society of Health-System
**PEER REVIEWED**
Oral levofloxacin is used for short-term treatment of travelers' diarrhea

or for the prevention of travelers' diarrhea in adults traveling for
relatively short periods of time to high-risk areas. /NOT included in US
Fluoroquinolones (e.g., ciprofloxacin, levofloxacin, ofloxacin) have been

suggested as alternative agents for the treatment of plague caused by
Yersinia pestis and also have been recommended for postexposure
prophylaxis following a high risk exposure to Y. pestis, including
exposure in the context of biologic warfare or bioterrorism. /NOT included
in US product label/[American Society of Health-System Pharmacists 2011;
Levofloxacin is recommended as an alternative for the treatment of acute

pelvic inflammatory disease (PID), but should not be used if
quinolone-resistant N. gonorrhoeae may be involved or if in vitro
susceptibility cannot be tested. /NOT included in US product
label/[American Society of Health-System Pharmacists 2011; Drug
The CDC recommends oral levofloxacin as an alternative agent for the

treatment of nongonococcal urethritis. /NOT included in US product
label/[American Society of Health-System Pharmacists 2011; Drug
Fluoroquinolones, including levofloxacin, have been used in multiple-drug

regimens for the treatment of active tuberculosis, usually in patients
with infections caused by Mycobacterium tuberculosis resistant to
first-line agents and in patients intolerant of some first-line agents.
/NOT included in US product label/[American Society of Health-System
**PEER REVIEWED**
Levofloxacin has been used in a limited of patients for the treatment of

meningitis caused by susceptible organisms (e.g., Rhodococcus equi)64 and
has been suggested as a possible alternative for use in conjunction with
other anti-infectives for the treatment of meningitis caused by
susceptible bacteria. /NOT included in US product label/[American Society
Levofloxacin is used for the treatment of epididymitis most likely caused

by sexually transmitted enteric bacteria (e.g., E. coli) or when culture
or nucleic acid amplification tests are negative for N. gonorrhoeae. /NOT
included in US product label/[American Society of Health-System
**PEER REVIEWED**
Levofloxacin has been used in the treatment of disseminated gonococcal

infections caused by susceptible N. gonorrhoeae. /NOT included in US
Levofloxacin has been used for the treatment of uncomplicated gonorrhea

caused by susceptible Neisseria gonorrhoeae. Although fluoroquinolones
(ciprofloxacin, levofloxacin, ofloxacin) were previously considered drugs
of choice for the treatment of uncomplicated gonorrhea, the CDC currently
states that fluoroquinolones should not be used for the treatment of
gonorrhea or any associated infections that may involve N. gonorrhoeae
(e.g., pelvic inflammatory disease (PID), epididymitis). /NOT included in
US product label/[American Society of Health-System Pharmacists 2011; Drug
Levofloxacin is used as an alternative for treatment of native or

prosthetic valve endocarditis caused by fastidious gram-negative bacilli
known as the HACEK group (Actinobacillus actinomycetemcomitans,
Cardiobacterium hominis, Eikenella corrodens, Haemophilus aphrophilus, H.
influenzae, H. parainfluenzae, H. paraphrophilus, Kingella denitrificans,
K. kingae). /NOT included in US product label/[American Society of
Although levofloxacin has not been evaluated in clinical trials for the
treatment of chlamydial infections, levofloxacin is considered an
alternative agent for the treatment of urogenital infections caused by C.
trachomatis. /NOT included in US product label/[American Society of
Levofloxacin 0.5% ophthalmic solution is used for the treatment of

conjunctivitis caused by susceptible strains of Acinetobacter lwoffii,
Corynebacterium spp, Haemophilus influenzae, Serratia marcescens,
Staphylococcus aureus, S. epidermidis, groups C, F, and G streptococci,
viridans streptococci, or Streptococcus pneumoniae. /Included in US
Information 2011. Bethesda, MD. 2011] **PEER REVIEWED**
In an open-label, multicenter, noninferiority trial, children with

community-acquired pneumonia were randomized 3:1 to receive levofloxacin
or comparator antimicrobial therapy (0.5 to < 5 years:
amoxicillin/clavulanate or ceftriaxone; > or = 5 years: clarithromycin
or ceftriaxone with clarithromycin or erythromycin lactobinate) for 10
days. The primary outcome was cure rates at the test-of-cure visit (10-17
days after completing treatment) as determined by symptoms, physical
examination, and chest radiography. Seven hundred and thirty-eight
children were enrolled and 539 (405 levofloxacin-treated, 134
comparator-treated) were clinically evaluable at test-of-cure visit.
Clinical cure rates were 94.3% (382 of 405) in levofloxacin-treated and
94.0% (126 of 134) in comparator-treated children. Cure rates were also
similar for levofloxacin and comparator for each age group ( < 5 years,
92.2% versus 90.8%; > or =5 years, 96.5% versus 97.1%; respectively)
and for children categorized as being at higher risk for severe disease.
Mycoplasma pneumoniae was the most frequently identified cause of
pneumonia (230 children). Levofloxacin was as well tolerated as
comparators, with similar type and incidence of adverse events.
Levofloxacin was as well tolerated and effective as standard-of-care
antibiotics for the treatment of community-acquired pneumonia in infants
and children.[Bradley JS et al; Pediatr Infect Dis J 26 (10): 868-78
DRUG WARNINGS:
/BOXED WARNING/ WARNING: Fluoroquinolones, including Levaquin, are
associated with an increased risk of tendinitis and tendon rupture in all
ages. This risk is further increased in older patients usually over 60
years of age, in patients taking corticosteroid drugs, and in patients
with kidney, heart or lung transplants.[US Natl Inst Health; DailyMed.
b91d-553856d89593]
**QC REVIEWED**
/BOXED WARNING/ WARNING: Fluoroquinolones, including Levaquin may

exacerbate muscle weakness in persons with myasthenia gravis. Avoid
Levaquin in patients with a known history of myasthenia gravis[US Natl
7, 2012:
b91d-553856d89593]
**QC REVIEWED**
Other serious and sometimes fatal events, some due to hypersensitivity,

and some due to uncertain etiology, have been reported rarely in patients
receiving therapy with fluoroquinolones, including Levaquin. These events
may be severe and generally occur following the administration of multiple
doses. Clinical manifestations may include one or more of the following:
fever, rash, or severe dermatologic reactions (e.g., toxic epidermal
necrolysis, Stevens-Johnson Syndrome); vasculitis; arthralgia; myalgia;
serum sickness; allergic pneumonitis; interstitial nephritis; acute renal
insufficiency or failure; hepatitis; jaundice; acute hepatic necrosis or
failure; anemia, including hemolytic and aplastic; thrombocytopenia,
including thrombotic thrombocytopenic purpura; leukopenia;
agranulocytosis; pancytopenia; and/or other hematologic abnormalities. The
drug should be discontinued immediately at the first appearance of skin
rash, jaundice, or any other sign of hypersensitivity and supportive
measures instituted.[US Natl Inst Health; DailyMed. Current Medication
**PEER REVIEWED**
Post-marketing reports of severe hepatotoxicity (including acute hepatitis

and fatal events) have been received for patients treated with Levaquin No
evidence of serious drug-associated hepatotoxicity was detected in
clinical trials of over 7,000 patients. Severe hepatotoxicity generally
occurred within 14 days of initiation of therapy and most cases occurred
within 6 days. Most cases of severe hepatotoxicity were not associated
with hypersensitivity. The majority of fatal hepatotoxicity reports
occurred in patients 65 years of age or older and most were not associated
with hypersensitivity. Levaquin should be discontinued immediately if the
patient develops signs and symptoms of hepatitis.[US Natl Inst Health;
**PEER REVIEWED**
Levofloxacin is indicated in pediatric patients for inhalational anthrax

(post-exposure). The risk-benefit assessment indicates that administration
of levofloxacin to pediatric patients is appropriate. The safety of
levofloxacin in pediatric patients treated for more than 14 days has not
been studied.[US Natl Inst Health; DailyMed. Current Medication
**PEER REVIEWED**
Serious and occasionally fatal hypersensitivity and/or anaphylactic

reactions reported in patients receiving fluoroquinolones, including
levofloxacin. These reactions may occur with first dose. Some
hypersensitivity reactions have been accompanied by cardiovascular
collapse, hypotension or shock, seizures, loss of consciousness, tingling,
angioedema (e.g., edema or swelling of the tongue, larynx, throat, or
face), airway obstruction (e.g., bronchospasm, shortness of breath, acute
respiratory distress), urticaria, pruritus, and other severe skin
reactions. In addition, other possible severe and potentially fatal
reactions (may be hypersensitivity reactions or of unknown etiology) have
been reported most frequently after multiple doses. These include fever,
rash or other severe dermatologic reactions (e.g., toxic epidermal
necrolysis, Stevens-Johnson syndrome), vasculitis, arthralgia, myalgia,
serum sickness, allergic pneumonitis, interstitial nephritis, acute renal
insufficiency or failure, hepatitis, jaundice, acute hepatic necrosis or
failure, anemia (including hemolytic and aplastic), thrombocytopenia
(including thrombotic thrombocytopenic purpura), leukopenia,
agranulocytosis, pancytopenia and/or other hematologic effects.
Discontinue levofloxacin at first appearance of rash, jaundice, or any
other sign of hypersensitivity. Institute appropriate therapy as indicated
(e.g., epinephrine, corticosteroids, and maintenance of an adequate airway
and oxygen).[American Society of Health-System Pharmacists 2011; Drug
Seizures, toxic psychoses, and increased intracranial pressure and CNS

stimulation, which may lead to tremor, restlessness, anxiety,
lightheadedness, confusion, hallucinations, paranoia, depression,
nightmares, insomnia, and, rarely, suicidal thoughts or acts, have been
reported with fluoroquinolones, including levofloxacin. Such nervous
system effects may occur following the first dose of the drug. Use with
caution in patients with known or suspected CNS disorders (e.g., severe
cerebral arteriosclerosis, epilepsy) or other risk factors that predispose
to seizures or lower the seizure threshold (e.g., certain drugs, renal
impairment). If nervous system effects occur, discontinue levofloxacin and
institute appropriate measures.[American Society of Health-System
**PEER REVIEWED**
Fluoroquinolones, including levofloxacin, are associated with an increased

risk of tendinitis and tendon rupture in all age groups. This risk is
further increased in older adults (usually those over 60 years of age),
individuals receiving concomitant corticosteroids, and kidney, heart, or
lung transplant recipients. Other factors that may independently increase
risk of tendon rupture include strenuous physical activity, renal failure,
and previous tendon disorders such as rheumatoid arthritis. Tendinitis and
tendon rupture have been reported in patients receiving fluoroquinolones
who did not have any of these risk factors. Fluoroquinolone-associated
tendinitis and tendon rupture most frequently involve the Achilles tendon
and may require surgical repair. Tendinitis and tendon rupture in the
rotator cuff (shoulder), hand, biceps, thumb, and other tendon sites also
reported. Tendon rupture can occur during or following fluoroquinolone
therapy and has been reported up to several months after completion of
therapy. Advise patients to rest and refrain from exercise and contact a
clinician at the first sign of tendinitis or tendon rupture (e.g., pain,
swelling, or inflammation of a tendon or weakness or inability to use a
joint). Discontinue levofloxacin if pain, swelling, inflammation, or
rupture of a tendon occurs.[American Society of Health-System Pharmacists
2011; Drug Information 2011. Bethesda, MD. 2011, p. 390] **PEER REVIEWED**

**PEER REVIEWED**
Moderate to severe photosensitivity/phototoxicity reactions reported

rarely with fluoroquinolones, including levofloxacin. Phototoxicity may
manifest as exaggerated sunburn reactions (e.g., burning, erythrema,
exudation, vesicles, blistering, edema) on areas exposed to sun or
artificial ultraviolet (UV) light (usually the face, neck, extensor
surfaces of forearms, dorsa of hands). Relative potential of the various
fluoroquinolones to cause photosensitivity/phototoxicity is unclear.
Factors that contribute to susceptibility to this adverse effect during
fluoroquinolone therapy include patient's skin pigmentation, frequency and
duration of exposure to sun and UV light, use of protective clothing and
sunscreen, concomitant use of other drugs, and dosage and duration of
fluoroquinolone therapy. As with other fluoroquinolones, patients should
be advised to avoid unnecessary or excessive exposure to sunlight or
artificial UV light (e.g., tanning beds, UVA/UVB treatment). If patient
needs to be outdoors, they should wear loose-fitting clothing that
protects skin from sun exposure and use other sun protection measures
(sunscreen).[American Society of Health-System Pharmacists 2011; Drug
When prescribing a fluoroquinolone, consider potential benefits and risks

to the individual patient. Most patients tolerate the drugs, but serious
adverse reactions (e.g., CNS effects, QT prolongation, C.
difficile-associated diarrhea and colitis, damage to liver, kidneys, or
bone marrow, alterations in glucose homeostatis) may occur rarely. To
reduce development of drug-resistant bacteria and maintain effectiveness
of levofloxacin and other antibacterials, use only for treatment or
prevention of infections proven or strongly suspected to be caused by
susceptible bacteria. When selecting or modifying anti-infective therapy,
use results of culture and in vitro susceptibility testing. In the absence
of such data, consider local epidemiology and susceptibility patterns when
selecting anti-infectives for empiric therapy.[American Society of
Hypoglycemia or hyperglycemia reported with fluoroquinolones, including

levofloxacin. Blood glucose disturbances usually have occurred in patients
with diabetes receiving insulin or oral hypoglycemic agents. Carefully
monitor blood glucose concentrations in diabetic patients. Discontinue
levofloxacin and initiate appropriate therapy immediately if hypoglycemic
An increased incidence of musculoskeletal disorders (arthralgia,

arthritis, tendinopathy, gait abnormality) has been reported in pediatric
patients receiving levofloxacin. Use in pediatric patients only for
prevention of inhalational anthrax (postexposure) in those 6 months of age
or older. Fluoroquinolones, including levofloxacin, cause arthropathy and
osteochondrosis in immature animals of various species. Persistent lesions
in cartilage reported in levofloxacin studies in immature dogs; similar
erosions in weight-bearing joints and other signs of arthropathy have been
reported with other fluoroquinolones. The relevance of these adverse
effects in immature animals to use in humans is unknown.[American Society
Prolonged QT interval leading to ventricular arrhythmias, including

torsades de pointes, reported with some fluoroquinolones, including
levofloxacin. Avoid use of levofloxacin in patients with a history of
prolonged QT interval, in those with uncorrected electrolyte disorders
(e.g., hypokalemia), and in those receiving class IA (e.g., quinidine,
procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic
agents.1 Risk may be increased in geriatric patients.[American Society of
Possible emergence and overgrowth of nonsusceptible bacteria or fungi.
Institute appropriate therapy if superinfection occurs. Treatment with
anti-infectives alters normal colon flora and may permit overgrowth of
Clostridium difficile. C. difficile-associated diarrhea and colitis (CDAD;
also known as antibiotic-associated diarrhea and colitis or
pseudomembranous colitis) has been reported with nearly all
anti-infectives, including levofloxacin, and may range in severity from
mild diarrhea to fatal colitis. Outbreaks of severe CDAD caused by
fluoroquinolone-resistant C. difficile have been reported with increasing
frequency over the last several years. Hypertoxin-producing strains of C.
difficile are associated with increased morbidity and mortality since they
may be refractory to anti-infectives and colectomy may be required.
Consider CDAD if diarrhea develops during or after therapy and manage
accordingly. Careful medical history is necessary since CDAD has been
reported to occur as late as 2 months or longer after anti-infective
therapy is discontinued. If CDAD is suspected or confirmed, levofloxacin
may need to be discontinued. Some mild cases of CDAD may respond to
discontinuance alone. Manage moderate to severe cases with fluid,
electrolyte, and protein supplementation, appropriate anti-infective
therapy active against C. difficile (e.g., oral metronidazole or
vancomycin), and surgical evaluation when clinically indicated.[American
Society of Health-System Pharmacists 2011; Drug Information 2011.
Bethesda, MD. 2011, p. 390] **PEER REVIEWED**
Sensory or sensorimotor axonal polyneuropathy affecting small and/or large

axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness
reported with fluoroquinolones, including levofloxacin. To prevent
development of an irreversible condition, discontinue levofloxacin if
symptoms of neuropathy (e.g., pain, burning, tingling, numbness, weakness)
or other alterations of sensation (e.g., light touch, pain, temperature,
position sense, vibratory sensation) occur.[American Society of
Although very useful agents, fluoroquinolones are associated with a number

of adverse events, some with considerable clinical significance.
Prolongation of the QT interval, for example, is an adverse effect
associated with the use of fluoroquinolones. Fluoroquinolones prolong the
QT interval by blocking voltage-gated potassium channels, especially the
rapid component of the delayed rectifier potassium current I(Kr),
expressed by HERG (the human ether-a-go-go-related gene). According to the
available case reports and clinical studies, moxifloxacin carries the
greatest risk of QT prolongation from all available quinolones in clinical
practice and it should be used with caution in patients with predisposing
factors for Torsades de pointes (TdP). Although gemifloxacin,
levofloxacin, and ofloxacin are associated with a lower risk of QT
prolongation compared with moxifloxacin, they should also be used with
caution in patients at risk for QT prolongation. Ciprofloxacin appears to
be associated with the lowest risk for QT prolongation and the lowest TdP
rate. The overall risk of TdP is small with the use of fluoroquinolones.
Clinicians can minimize that risk by avoiding prescriptions of multiple
medications associated with QT-interval prolongation, especially in
high-risk patients.[Briasoulis A et al; Cardiology 120 (2): 103-10 (2011)]
The fluoroquinolones ciprofloxacin, levofloxacin, moxifloxacin and

gemifloxacin are widely used for the treatment of various types of
bacterial infections. Overall, these antibacterial agents can be
considered safe and well tolerated drugs. Comparative studies have
evaluated the use of quinolones in elderly and younger populations.
Although age per se does not seem to decrease their tolerability, specific
adverse effects of the quinolones must be considered when they are chosen
for antibacterial treatment. Renal function declines consistently with age
and doses of renally excreted quinolones (e.g. ofloxacin, levofloxacin,
gatifloxacin) need to be adjusted if a clinically relevant reduction of
creatinine clearance is identified. Reactions of the gastrointestinal
tract, such as nausea, dyspepsia, vomiting or diarrhoea, are among the
most often registered adverse drug reactions during therapy with
fluoroquinolones. Treatment with a quinolone causes diarrhoea less
frequently than treatment with other classes of antimicrobials.
Conflicting data have been published with respect to the incidence of
Clostridium difficile-associated diarrhoea in quinolone-treated patients.
Hypersensitivity reactions, often manifested on the skin, occur less
commonly during therapy with quinolones than, for example, during therapy
with beta-lactam antibacterials. Adverse reactions of the CNS are of
particular concern in the elderly population. Given the CNS excitatory
effects of quinolones, elderly patients should be monitored carefully for
such symptoms. It is likely that many signs of possible adverse reactions,
such as confusion, weakness, loss of appetite, tremor or depression, are
often mistakenly attributed to old age and remain unreported. Quinolones
should be used with caution in patients with known or suspected CNS
disorders that predispose to seizures (e.g. severe cerebral
arteriosclerosis or epilepsy). Quinolones can cause QT interval
prolongation. They should be avoided in patients with known prolongation
of the QT interval, patients with uncorrected hypokalaemia or
hypomagnesaemia and patients receiving class IA (e.g. quinidine,
procainamide) or class III (e.g. amiodarone, sotalol) antiarrhythmic
agents. Tendinitis and tendon ruptures are recognized as quinolone-induced
adverse effects that can occur during treatment or as late as several
months after treatment. Chronic renal diseases, concomitant use of
corticosteroids and age > 60 years are known risk factors for
quinolone-induced tendopathies. Overall, the specific adverse-effect
profile of quinolones must be considered when they are chosen for
treatment of bacterial infections. Because of physiological changes in
renal function and when certain co-morbidities are present, some special
considerations are necessary when elderly patients are treated with these
drugs.[Stahlmann R, Lode H; Drugs Aging 27 (3): 193-209 (2010)] **PEER
REVIEWED** <a
With levofloxacin 0.5% ophthalmic solution transient decrease in vision,

transient ocular burning, ocular pain or discomfort, foreign body
sensation, headache, fever, pharyngitis, and photophobia occur in 1-3% of
patients. Allergic reactions, lid edema, ocular dryness, and ocular
itching occur in less than 1% of patients receiving levofloxacin 0.5%
ophthalmic solution.[American Society of Health-System Pharmacists 2011;
Drug Information 2011. Bethesda, MD. 2011] **PEER REVIEWED**
INTERACTIONS:
Warfarin: Potential pharmacologic interaction (increased prothrombin
time). Monitor prothrombin time or other suitable coagulation tests and
monitor for bleeding.[American Society of Health-System Pharmacists 2011;
Theophylline: Pharmacokinetic interaction unlikely. However,

pharmacokinetic interaction (increased theophylline half-life and
increased risk of theophylline-related adverse effects) occurs with some
other quinolones. Closely monitor serum theophylline concentrations and
adjust theophylline dosage accordingly; consider that adverse theophylline
effects (e.g., seizures) may occur with or without elevated theophylline
concentrations.[American Society of Health-System Pharmacists 2011; Drug
Sucralfate: Potential pharmacokinetic interaction (decreased levofloxacin

absorption); no pharmacokinetic interaction if given 2 hours apart.
Administer levofloxacin at least 2 hours before or 2 hours after
sucralfate.[American Society of Health-System Pharmacists 2011; Drug
Probenecid: Potential pharmacokinetic interaction (increased levofloxacin

AUC and half-life). Not considered clinically important; dosage
adjustments are not required.[American Society of Health-System
**PEER REVIEWED**
Nonsteroidal Anti-Iinflammatory Agents (NSAIAs): Potential pharmacologic

interaction (possible increased risk of CNS stimulation and seizures).
Animal studies suggest risk may be less than that associated with some
other fluoroquinolones and that risk varies depending on the specific
Nonsteroidal anti-inflammatory agents.[American Society of Health-System
**PEER REVIEWED**
Iron , Multivitamins, and Mineral Supplements: Potential pharmacokinetic

interaction (decreased levofloxacin absorption). Administer levofloxacin
at least 2 hours before or 2 hours after ferrous sulfate or dietary
supplements containing zinc, calcium, magnesium, or iron.[American Society
Didanosine: Potential pharmacokinetic interaction (decreased levofloxacin

after buffered didanosine (pediatric oral solution admixed with
antacid).[American Society of Health-System Pharmacists 2011; Drug
Cyclosporine and Tacrolimus: Possible pharmacokinetic interactions with

cyclosporine or tacrolimus (increased AUC of the immunosuppressive agent).
Manufacturer of levofloxacin states that dosage adjustments are not
required; some clinicians suggest that plasma concentrations of the
immunosuppressive agent be monitored if used concomitantly with
levofloxacin.[American Society of Health-System Pharmacists 2011; Drug
Corticosteroids: Concomitant use of corticosteroids increases the risk of

severe tendon disorders (e.g., tendinitis, tendon rupture), especially in
geriatric patients older than 60 years of age.[American Society of
Cimetidine: Potential pharmacokinetic interaction (slightly increased

levofloxacin AUC and half-life). Not considered clinically important;
levofloxacin dosage adjustments are not recommended.[American Society of
Antidiabetic Agents: Potential pharmacodynamic interaction (altered blood

glucose concentrations and symptomatic hyperglycemia or hypoglycemia) in
diabetic patients receiving concomitant levofloxacin and antidiabetic
therapy (e.g., insulin, glyburide). Careful monitoring of blood glucose
concentrations recommended; discontinue levofloxacin if a hypoglycemic
Antidepressants: Potential pharmacologic interaction with fluoxetine or

imipramine (additive effect on QT interval prolongation).[American Society
Antiarrhythmic Agents: Potential pharmacologic interaction (additive

effect on QT interval prolongation). Levofloxacin should be avoided in
those receiving class IA (e.g., quinidine, procainamide) or class III
(e.g., amiodarone, sotalol) antiarrhythmic agents. Pharmacokinetic
interaction with procainamide (increased half-life and decreased clearance
of procainamide).[American Society of Health-System Pharmacists 2011; Drug
Antacids: Potential pharmacokinetic interaction (decreased levofloxacin

after antacids containing magnesium or aluminum.[American Society of
Drugs That Prolong QT Interval: Potential pharmacologic interaction

(additive effects on QT interval prolongation). Avoid concomitant use with
class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone,
sotalol) antiarrhythmic agents.[American Society of Health-System
**PEER REVIEWED**
All fluoroquinolones interact with multivalent cation-containing products

& bioavailability is reduced by 50% when co-administered with iron
cmpds (ciprofloxacin & moxifloxacin are more affected than
levofloxacin or gemifloxacin). The interaction between theophylline &
fluoroquinolones is most marked with enoxacin, pefloxacin, &
ciprofloxacin, with no such interaction reported for levofloxacin.[Lode H;
Chemotherapy 47 Suppl 3: 24-31 (2001)] **PEER REVIEWED**
ENVIRONMENTAL FATE/EXPOSURE SUMMARY:

Levofloxacin's production and use as an antibiotic may result in its
release to the environment through various waste streams. If released to
air, an estimated vapor pressure of 9.8X10-13 mm Hg at 25 deg C indicates
levofloxacin will exist solely in the particulate phase in the atmosphere.
Particulate-phase levofloxacin will be removed from the atmosphere by wet
or dry deposition. Levofloxacin in solution is susceptible to
photodegradation in natural light, exhibiting a mean half-life of 6.3
days, and therefore may be susceptible to direct photolysis by sunlight.
If released to soil, levofloxacin is expected to have no mobility based
upon a Koc of 44,143. The pKa1 of levofloxacin is 6.24 (carboxylic acid
moiety) and pKa2 = 8.74 for analogous ciprofloxacin for the nitrogen on
the piperazinyl ring; at pHs greater than 6.24, the acid will be primarily
dissociated and at pHs less than approximately 8.74, the nitrogen will be
primarily protonated; therefore, levofloxacin will have an ionic charge at
any environmental pH. Volatilization from moist soil is not expected
because the compound exists as an ion and ions do not volatilize. Using
the OECD closed bottle biodegradation study, 0% degradation over a 40-day
incubation period was observed for analogous ciprofloxacin, indicating
that biodegradation may not be an important environmental fate process for
levofloxacin in soil and water. If released into water, levofloxacin is
expected to adsorb to suspended solids and sediment based upon the Koc.
Levofloxacin will have an ionic charge at pH values of 5 to 9 and
therefore volatilization from water surfaces is not expected to be an
important fate process. An estimated BCF of 3 suggests the potential for
bioconcentration in aquatic organisms is low. Hydrolysis is not expected
to be an important environmental fate process since this compound lacks
functional groups that hydrolyze under environmental conditions (pH 5 to
9). Occupational exposure to levofloxacin may occur through inhalation and
PROBABLE ROUTES OF HUMAN EXPOSURE:

Occupational exposure to levofloxacin may occur through inhalation and
ARTIFICIAL POLLUTION SOURCES:

Levofloxacin's production and use as an antibiotic(1) may result in its
release to the environment through various waste streams(SRC).[(1)
Physicians' Desk Reference. 66th ed. Montvale, NJ: Medical Economics Co,
p. 1514 (2012)] **PEER REVIEWED**
ENVIRONMENTAL FATE:
TERRESTRIAL FATE: Based on a classification scheme(1), a Koc value of
44,143 for the sterioisomer,ofloxacin(2) indicates that levofloxacin is
expected to be immobile in soil(SRC). The pKa1 of levofloxacin is 6.24
(carboxylic acid moiety)(1) and pKa2 = 8.74 for analogous ciprofloxacin
for the nitrogen on the piperazinyl ring(3); at pHs greater than 6.24, the
acid will be primarily dissociated and at pHs less than approximately
8.74, the nitrogen will be primarily protonated(SRC); therefore,
levofloxacin will have an ionic charge at any environmental pH(SRC).
Volatilization from moist soil is not expected because the compound exists
as an ion and ions do not volatilize. Levofloxacin is not expected to
volatilize from dry soil surfaces(SRC) based upon an estimated vapor
pressure of 9.8X10-13 mm Hg at 25 deg C(SRC), determined from a fragment
constant method(4). Using the OECD closed bottle biodegradation study, 0%
degradation over a 40-day incubation period was observed for analogous
ciprofloxacin(5), indicating that biodegradation may not be an important
environmental fate process for levofloxacin in soil(SRC).[(1) Swann RL et
al; Res Rev 85: 17-28 (1983) (2) Nowara A et al; J Agric Food Chem 45:
1459-63 (1997) (3) Torniainen K et al; Int J Pharm 132: 53-61 (1996) (4)
Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB,
Blau GE, eds, Boca Raton, FL: CRC Press (1985) (5) Al-Ahmad A et al; Arch
Environ Contam Toxicol 37: 158-163 (1999)] **PEER REVIEWED**
AQUATIC FATE: Based on a classification scheme(1), a Koc value of

44,143(2) indicates that levofloxacin is expected to adsorb to suspended
solids and sediment(SRC). The pKa1 of levofloxacin is 6.24 (carboxylic
acid moiety)(1) and pKa2 = 8.74 for analogous ciprofloxacin for the
nitrogen on the piperazinyl ring(3); at pHs greater than 6.24, the acid
will be primarily dissociated and at pHs less than approximately 8.74, the
nitrogen will be primarily protonated(SRC); therefore, levofloxacin will
have an ionic charge at any environmental pH(SRC). Due to this ionic
state, volatilization from water surfaces is not expected to be an
important fate process(SRC). According to a classification scheme(4), an
estimated BCF of 3(SRC), from a log Kow of -0.39 for sterioisomer
ofloxacin(5) and a regression-derived equation(6), suggests the potential
for bioconcentration in aquatic organisms is low(SRC). Using the OECD
closed bottle biodegradation study, 0% degradation over a 40-day
incubation period was observed for analogous ciprofloxacin(7), indicating
that biodegradation may not be an important environmental fate process for
levofloxacin in water(SRC).[(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Nowara A et al; J Agric Food Chem 45: 1459-63 (1997) (3) Torniainen K
et al; Int J Pharm 132: 53-61 (1996) (4) Franke C et al; Chemosphere 29:
1501-14 (1994) (5) Hansch C et al; Exploring QSAR. Hydrophobic,
Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult.
ed., Washington, DC: Amer Chem Soc p. 156 (1995) (6)US EPA; Estimation
Program Interface (EPI) Suite. Ver. 4.1. Jan, 2010. Available from, as of
Feb 3, 2012: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm (7)
Al-Ahmad A et al; Arch Environ Contam Toxicol 37: 158-163 (1999)] **PEER
REVIEWED**
AQUATIC FATE: Using outdoor aquatic field microcosms, levofloxacin, at

concentrations of 1.00, 10.00, 100.00, and 300.00 ug/L exhibited
half-lives of 6.2, 6.5, 6.0, and 6.3 days, overall mean of 6.3 days, with
photodegradation being the main loss process. Photoproducts have been
identified as analogues altered at the N-methylpiperazine moiety and
reached a maximum by 2 hours after which their concentrations
decreased(1). Therefore levofloxacin may be susceptible to direct
photolysis by sunlight(SRC).[(1) Lam MW et al; Environ Toxicol Chem 23:
1431-1440 (2004)] **PEER REVIEWED**
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of

semivolatile organic compounds in the atmosphere(1), levofloxacin, which
has an estimated vapor pressure of 8.8X10-13 mm Hg at 25 deg C(SRC),
determined from a fragment constant method(2), is expected to exist solely
in the particulate phase in the ambient atmosphere. Particulate-phase
levofloxacin may be removed from the air by wet or dry deposition(SRC).
Levofloxacin in solution is susceptible to photodegradation in natural
light, exhibiting a mean half-life of 6.3 days(4), and therefore may be
susceptible to direct photolysis by sunlight(SRC).[(1) Bidleman TF;
Environ Sci Technol 22: 361-367 (1988) (2) Lyman WJ; p. 31 in
Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca
Raton, FL: CRC Press (1985) (3) Meylan WM, Howard PH; Chemosphere 26:
2293-99 (1993) (4) Lam MW et al; Environ Toxicol Chem 23: 1431-1440
ENVIRONMENTAL ABIOTIC DEGRADATION:

Levofloxacin is not expected to undergo hydrolysis in the environment due
to the lack of functional groups that hydrolyze under environmental
conditions(1). Using outdoor aquatic field microcosms, levofloxacin, at
concentrations of 1.00, 10.00, 100.00, and 300.00 ug/L exhibited
half-lives of 6.2, 6.5, 6.0, and 6.3 days, overall mean of 6.3 days, with
photodegradation being the main loss process. Photoproducts have been
identified as analogues altered at the N-methylpiperazine moiety and
reached a maximum by 2 hours after which their concentrations
decreased(2). Therefore levofloxacin may be susceptible to direct
photolysis by sunlight(SRC).[(1) Lyman WJ et al; Handbook of Chemical
Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5
(1990) (2) Lam MW et al; Environ Toxicol Chem 23: 1431-1440 (2004)] **PEER
REVIEWED**
ENVIRONMENTAL BIOCONCENTRATION:
An estimated BCF of 3 was calculated in fish for levofloxacin(SRC), using
a log Kow of -0.39 for ofloxacin, the stereoisomer(1) and a
regression-derived equation(2). According to a classification scheme(3),
this BCF suggests the potential for bioconcentration in aquatic organisms
is low(SRC).[(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic,
and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed.,
Washington, DC: Amer Chem Soc p. 156 (1995) (2) US EPA; Estimation Program
Interface (EPI) Suite. Ver. 4.1. Jan, 2010. Available from, as of Feb 3,
2012:m http://www.epa.gov/oppt/exposure/pubs/episuitedl.ht (3) Franke C et
al; Chemosphere 29: 1501-14 (1994)] **PEER REVIEWED**
SOIL ADSORPTION/MOBILITY:
Using a centric flurisol (Germany; 80.1% sand; 16.7% silt; 2.5% clay; pH
5.3), a measured Koc of 44,143 was reported for the steroisomer,
ofloxacin(1). According to a classification scheme(2), this Koc value
suggests that levofloxacin is expected to be immobile in soil. The pKa1 of
levofloxacin is 6.24 (carboxylic acid moiety)(1) and pKa2 = 8.74 for
analogous ciprofloxacin for the nitrogen on the piperazinyl ring(3); at
pHs greater than 6.24, the acid will be primarily dissociated and at pHs
less than 8.74, the nitrogen will be primarily protonated(SRC); therefore,
levofloxacin will have an ionic charge at any environmental pH(SRC).[(1)
Nowara A et al; J Agric Food Chem 45: 1459-63 (1997) (2) Swann RL et al;
Res Rev 85: 17-28 (1983) (3) Torniainen K et al; Int J Pharm 132: 53-61
VOLATILIZATION FROM WATER/SOIL:

The pKa1 of levofloxacin is 6.24 (carboxylic acid moiety)(1) and pKa2 =
8.74 for analogous ciprofloxacin for the nitrogen on the piperazinyl
ring(3); at pHs greater than 6.24, the acid will be primarily dissociated
and at pHs less than approximately 8.74, the nitrogen will be primarily
protonated(SRC); therefore, levofloxacin will have an ionic charge at any
environmental pH(SRC). Due to this ionic state, volatilization from water
and moist soil surfaces is not expected to be an important fate
process(SRC). Levofloxacin is not expected to volatilize from dry soil
surfaces(SRC) based upon an estimated vapor pressure of 9.8X10-13 mm
Hg(SRC), determined from a fragment constant method(3).[(1) Nowara A et
al; J Agric Food Chem 45: 1459-63 (1997) (2) Torniainen K et al; Int J
Pharm 132: 53-61 (1996) (3) Lyman WJ; p. 31 in Environmental Exposure From
Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)]
**PEER REVIEWED**
ENVIRONMENTAL WATER CONCENTRATIONS:

SURFACE WATER: Levofloxacin was detected in 6.3% of 120 water samples
collected seasonally from Upper Tennessee River from the confluence of the
Holston and French Broad Rivers to the beginning of the Tennessee River
Gorge between December 2006 and October 2007 at concentrations ranging
from 6.2 to 59.3 ng/L, average/median 11.9 ng/L(1).[(1) Conley JM et al;
Chemosphere 73: 1178-1187 (2008)] **PEER REVIEWED**
FDA REQUIREMENTS:
The Approved Drug Products with Therapeutic Equivalence Evaluations
identifies currently marketed prescription drug products, including
levofloxacin, approved on the basis of safety and effectiveness by FDA
under sections 505 of the Federal Food, Drug, and Cosmetic Act.[DHHS/FDA;
Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence
Evaluations. Available from, as of March 12, 2012:
http://www.fda.gov/cder/ob/] **PEER REVIEWED**
MOLECULAR FORMULA:
C18-H20-F-N3-O4[National Library of Medicine, SIS; ChemIDplus Lite Record
for Levofloxacin (100986-85-4). Available from, as of March 13, 2012:
http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp] **PEER REVIEWED**
COLOR/FORM:
Light yellowish -white to yellow-white crystal or crystalline
powder[Physicians' Desk Reference. 66th ed. Montvale, NJ: Medical
Economics Co, p. 1514 (2012)] **PEER REVIEWED**
Needles from ethanol + ethyl ether[O'Neil, M.J. (ed.). The Merck Index -
An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station,
NJ: Merck and Co., Inc., 2006., p. 1171] **PEER REVIEWED**
MELTING POINT:
225-227 deg C (decomposes)[O'Neil, M.J. (ed.). The Merck Index - An
Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ:
Merck and Co., Inc., 2006., p. 1171] **PEER REVIEWED**
DISSOCIATION CONSTANTS:
pKa1 = 6.24 (carboxylic acid moiety)[Nowara A et al; J Agric Food Chem 45:
1459-63 (1997)] **PEER REVIEWED**
OCTANOL/WATER PARTITION COEFFICIENT:

log Kow = -0.39[Hansch, C., Leo, A., D. Hoekman. Exploring QSAR -
Hydrophobic, Electronic, and Steric Constants. Washington, DC: American
Chemical Society., 1995., p. 156] **PEER REVIEWED**
SOLUBILITIES:
Freely soluble in glacial acetic acid, chloroform; sparingly soluble in
water[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals,
Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc.,
2006., p. 1171] **PEER REVIEWED**
SPECTRAL PROPERTIES:
Specific optical rotation: -76.9 deg at 23 deg C/D ( c = 0.385 in 05N
NaOH)[O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals,
Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc.,
2006., p. 1171] **PEER REVIEWED**
VAPOR PRESSURE:
9.8X10-13 mm Hg at 25 deg C (est)[US EPA; Estimation Program Interface
(EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Feb 3, 2012:
http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm] **PEER REVIEWED**
OTHER CHEMICAL/PHYSICAL PROPERTIES:

The molecule exists as a zwitterion at the pH conditions in the small
intestine.[Physicians' Desk Reference. 66th ed. Montvale, NJ: Medical
Economics Co, p. 1514 (2012)] **PEER REVIEWED**
FIRE POTENTIAL:
This material is assumed to be combustible.[United States Pharmacopeial
Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet:
Levofloxacin; Catalog Number: 1362103; (Revision Date: May 16, 2008)]
**PEER REVIEWED**
FIRE FIGHTING PROCEDURES:

Water spray, dry chemical, carbon dioxide, or foam as appropriate for
surrounding fire and materials.[United States Pharmacopeial Convention,
Inc (USP); MSDS Database Online; Material Safety Data Sheet: Levofloxacin;
Catalog Number: 1362103; (Revision Date: May 16, 2008)] **PEER REVIEWED**
TOXIC COMBUSTION PRODUCTS:

Emits toxic fumes under fire conditions.[United States Pharmacopeial
Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet:
Levofloxacin; Catalog Number: 1362103; (Revision Date: May 16, 2008)]
**PEER REVIEWED**
HAZARDOUS DECOMPOSITION:
When heated to decomposition material emits toxic fumes of /nitrogen
oxides and hydrogen fluoride/.[United States Pharmacopeial Convention, Inc
(USP); MSDS Database Online; Material Safety Data Sheet: Levofloxacin;
PROTECTIVE EQUIPMENT & CLOTHING:

Respiratory Protection: Use a NIOSH-approved respirator, if it is
determined to be necessary by an industrial hygiene survey involving air
monitoring. In the event that a respirator is not required, an approved
dust mask should be used. Gloves: Chemically compatible. Eye Protection:
Safety glasses or goggles. Protective Clothing: Protect exposed
skin.[United States Pharmacopeial Convention, Inc (USP); MSDS Database
Online; Material Safety Data Sheet: Levofloxacin; Catalog Number: 1362103;
(Revision Date: May 16, 2008)] **PEER REVIEWED**
PREVENTIVE MEASURES:
Engineering controls such as exhaust ventilation are recommended.[United
States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material
Safety Data Sheet: Levofloxacin; Catalog Number: 1362103; (Revision Date:
May 16, 2008)] **PEER REVIEWED**
As with all dry powders it is advisable to ground mechanical equipment in

contact with dry material to dissipate the potential buildup of static
electricity.[United States Pharmacopeial Convention, Inc (USP); MSDS
Database Online; Material Safety Data Sheet: Levofloxacin; Catalog Number:
1362103; (Revision Date: May 16, 2008)] **PEER REVIEWED**
As a general rule, when handling USP Reference Standards avoid all contact
and inhalation of dust, mists, and/or vapors associated with the material.
Wash thoroughly after handling.[United States Pharmacopeial Convention,
Inc (USP); MSDS Database Online; Material Safety Data Sheet: Levofloxacin;
SRP: Local exhaust ventilation should be applied wherever there is an

incidence of point source emissions or dispersion of regulated
contaminants in the work area. Ventilation control of the contaminant as
close to its point of generation is both the most economical and safest
method to minimize personnel exposure to airborne contaminants. Ensure
that the local ventilation moves the contaminant away from the worker.
**PEER REVIEWED**
STORAGE CONDITIONS:
Store in tight, light-resistant container as defined in the USP-NF. This
material should be handled and stored per label instructions to ensure
product integrity.[United States Pharmacopeial Convention, Inc (USP); MSDS
Database Online; Material Safety Data Sheet: Levofloxacin; Catalog Number:
1362103; (Revision Date: May 16, 2008)] **PEER REVIEWED**
CLEANUP METHODS:
Wear approved respiratory protection, chemically compatible gloves and
protective clothing. Wipe up spillage or collect spillage using a high
efficiency vacuum cleaner. Avoid breathing dust. Place spillage in
appropriately labelled container for disposal. Wash spill site.[United
States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material
Safety Data Sheet: Levofloxacin; Catalog Number: 1362103; (Revision Date:
May 16, 2008)] **PEER REVIEWED**
DISPOSAL METHODS:
SRP: Expired or waste pharmaceuticals shall carefully take into
consideration applicable DEA, EPA, and FDA regulations. It is not
appropriate to dispose by flushing the pharmaceutical down the toilet or
discarding to trash. If possible return the pharmaceutical to the
manufacturer for proper disposal being careful to properly label and
securely package the material. Alternatively, the waste pharmaceutical
shall be labeled, securely packaged and transported by a state licensed
medical waste contractor to dispose by burial in a licensed hazardous or
toxic waste landfill or incinerator. **PEER REVIEWED**
SRP: At the time of review, regulatory criteria for small quantity

disposal are subject to significant revision, however, household
quantities of waste pharmaceuticals may be managed as follows: Mix with
wet cat litter or coffee grounds, double bag in plastic, discard in trash.
**PEER REVIEWED**
USES:
MEDICATION **PEER REVIEWED**
MANUFACTURERS:
Janssen Pharmaceuticals, Inc., 1000 Toure 202 S, Raritan, NJ 08869-0602,
(908) 218-7325 /Formulator/[Physicians' Desk Reference. 66th ed. Montvale,
NJ: Medical Economics Co, p. 1514 (2012)] **PEER REVIEWED**
Janssen Pharmaceuticals, Inc., 1125 Trenton-Harbourton Road, Titusville,

NJ 08560-0200, (908) 218-7325 /Formulator/[Physicians' Desk Reference.
66th ed. Montvale, NJ: Medical Economics Co, p. 1514 (2012)] **PEER
REVIEWED**
Levofloxacin Manufacturers Company Address Aurobindo Pharma Limited

Unit-VII(SEZ), Mahboob Nagar, AP-509 302 India Dr. Reddy's Laboratories
Limited Bachepalli - 502 325, India Hikma Farmaceutica (Portugal), S.A.
Estrada do Rio da Mo, Mo. 8, 8A & 8B, Fervenca-2705-906, Terrugem SNT,
Portugal Hospira, Inc. Lake Forest, IL 60045 Janssen Ortho LLC Gurabo,
Puerto Rico 00778 Janssen Pharmaceutica N.V. Beerse, Belgium Lupin Limited
Goa 403 722, India Nexus Pharmaceuticals Inc. Vernon Hills, IL 60061
(India) Sagent Pharmaceuticals, Inc. Switzerland Santen Oy P.O. Box 33,
FIN-33721 Tampere, Finland Teva Pharmaceuticals Inc. Ltd. Jerusalem,
91010, Israel Torrent Pharmaceuticals Ltd. Indrad-382 721, Dist. Mehsana,
India Wockhardt Limited Mumbai, India [US Natl Inst Health; DailyMed.
Current Medical Information. Available from, as of Feb 2, 2011:
http://dailymed.nlm.nih.gov/dailymed/about.cfm] **PEER REVIEWED**
Levofloxacin Distributors Company Address Akorn, Inc. Lake Forest, IL

60045 American Health Packaging Columbus, OH 43217 Aurobindo Pharma USA,
Ltd. 2400 Route 130 North, Dayton, NH 08810 Bryant Ranch North Hollywood,
CA 91605 Cardinal Health Zanesville, OH 43701 Greenstone LLC Peapack, NJ
07977 Hi-Tech Pharmacal Co., Inc. Amityville, NY 11701 Lake Erie Medical
DBA Quality Care Products LLC Lupin Pharmaceuticals, Inc. Baltimore MD
21202 Major Pharmaceuticals 31778 Enterprise Dr., Livonia, MI 48150 Mylan
Pharmaceuticals Inc. Morgantown, WV 26505 Ortho-McNeil-Janssen
Pharmaceuticals, Inc. Raritan, NJ 08869 PACK Pharmaceuticals, LLC Buffalo
Grove, IL 60089 PD-Rx Pharmaceuticals, Inc. Oklahoma City, OK 73127
Physicians Total Care, Inc. Tulsa, OK 74146 Preferred Pharmaceuticals,
Inc. Anaheim, CA 92807 PriCara Raritan, NJ 08869 Rebel Distributors Corp.
Thousand Oaks, CA 91320 RedPharm Drug, Inc. Eden Prairie, MN 55344 Sagent
Pharmaceuticals Schaumburg, IL 60195 Sandoz Inc. Princeton, NJ 08540 Stat
Rx USA LLC Gainesville, GA 30501 Teva Pharmaceuticals USA Sellersville, PA
18960 Torrent Pharmaceuticals Limited 5380 Holiday Terrace, Suite 40,
Kalamazoo, MI 49009 UDL Laboratories, Inc. Rockford, IL 61103 Vistakon
Pharmaceuticals LLC Jacksonville, FL 32255 West-ward Pharmaceutical Corp.
Eatontown, NJ 07724 Wockhardt USA LLC 20 Waterview Blvd., Parsippany, NJ
07054 [US Natl Inst Health; DailyMed. Current Medical Information.
Available from, as of Feb 2, 2011:
http://dailymed.nlm.nih.gov/dailymed/about.cfm] **PEER REVIEWED**
GENERAL MANUFACTURING INFORMATION:

The more active levo isomer of ofloxacin (a racemic mixture of
D,L,-isomers) that has improved activity against gram-potitive pathogens
(in particular against S. pneumoniae) compared to ciprofloxacin.[Troy,
D.B. (Ed); Remmington The Science and Practice of Pharmacy. 21 st Edition.
Lippincott Williams & Williams, Philadelphia, PA 2005, p. 1657] **PEER
REVIEWED**
Prepared as the hemihydrate[O'Neil, M.J. (ed.). The Merck Index - An

Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ:
Merck and Co., Inc., 2006., p. 1171] **PEER REVIEWED**
The methyl group at the C-3 position in the oxazine ring results in the
formation of isoenantiomers; ofloxacin occurs as a racemic mixture of the
two isomers. The S-(-)isomer is 8-128 times as active against susceptible
gram-positive and gram-negative organisms as the R-(+)isomer and
approximately twice as active as racemic ofloxacin.[American Society of
FORMULATIONS/PREPARATIONS:
Levofloxacin PreparationsRoute of Administration Dosage Form Strength
Brand or Generic Name (Manufacturer) Oral Solution 125 mg/5 mL Levaquin
(Ortho-McNeil) Oral Tablets, film-coated 250 mg (of anhydrous
levofloxacin) Levaquin (Ortho-McNeil) Oral Tablets, film-coated 500 mg (of
anhydrous levofloxacin) Levaquin (Ortho-McNeil) Oral Tablets, film-coated
750 mg (of anhydrous levofloxacin) Levaquin (Ortho-McNeil) Parenteral For
injection, concentrate, for IV infustion equivalent ot levofloxacin 25
mg/mL (500 or 750 mg) Levaquin (Ortho-McNeil) [American Society of
Parenteral Injection, for IV infusion: equivalent to levofloxacin 5 mg/mL

(250, 500, or 750 mg) in 5% Dextrose; Levaquin in Dextrose Injection
Premix (in flexible containers) (Ortho-McNeil).[American Society of
Ophthalmic: Solution 0.5%, Quixin (Vistakon)[American Society of
Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011]
**PEER REVIEWED**
Tavanic (levofloxacin; 250 and 500 mg film-coated tablets and 5mg/mL

solution for infusion)[European Medicines Agency; Questions and Answers on
Tavanic (levofloxacin; 250 and 500 mg film-coated tablets and 5mg/ml
solution for infusion), EMA/332109/2012 EMEA/H/A-30/1262 (May 24, 2012).
Available from, as of August 29, 2012:
http://www.ema.europa.eu/ema/index.jsp?
curl=pages/home/Home_Page.jsp&mid=]
**PEER REVIEWED**
CLINICAL LABORATORY METHODS:

Penetration of levofloxacin and moxifloxacin into cancellous and cortical
bone was studied using high-performance liquid chromatography
(HPLC).[Metallidis S et al; J Chemother 19 (6): 682-7 (2007)] **PEER
REVIEWED** <a
A rapid and selective high performance liquid chromatography-tandem mass

spectrometry (HPLC-MS/MS) method for simultaneous determination of
isoniazid (INH), rifampicin (RFP) and levofloxacin (LVX) in mouse tissues
and plasma has been developed and validated, using gatifloxacin as the
internal standard (I.S.). ... The lower limits of quantification (LLOQs)
for INH, RFP and LVX in mouse tissues were 0.11, 0.12 and 0.13microg/g and
for those in mouse plasma were 18.1, 20.0 and 21.8ng/mL, respectively. The
limits of detection (LODs) for INH, RFP and LVX in mouse tissues were
0.04, 0.05 and 0.05microg/g and for those in mouse plasma were 5.5, 6.0
and 6.6ng/mL, respectively.[Fang PF et al; J Chromatogr B Analyt Technol
Biomed Life Sci 878 (24): 2286-91 (2010)] **PEER REVIEWED** <a
... Three fluoroquinolones, pazufloxacin, ciprofloxacin and levofloxacin,

were simultaneously determined in spiked human serum by high-performance
liquid chromatography (HPLC) method with fluorescence detection.
Chromatography was performed using a C8 column with an isocratic mobile
phase consisting of 1% triethylamine (pH 3.0)/acetonitrile (86/14, v/v).
Protein precipitation was conducted using perchloric acid and methanol.
The calibration curves for the three fluoroquinolones were linear over
concentrations ranging from 0.1 to 20.0 microg/mL. The within-day and
between-day coefficients of variation obtained from three fluoroquinolones
were less than 7%, and relative errors ranged from -1.6% to 9.3%. Mean
recoveries of pazufloxacin, ciprofloxacin, and levofloxacin from spiked
human serum were 97%, 88%, and 90%, respectively. The proposed method
proved to be simple and reliable for the determination of three
fluoroquinolones.[Watabe S et al; J Chromatogr B Analyt Technol Biomed
Life Sci 878 (19): 1555-61 (2010)] **PEER REVIEWED** <a
A novel, rapid and sensitive analytical method is described for

determination of ofloxacin and levofloxacin by enhanced chemiluminescence
(CL) with flow-injection sampling. The method is based on the CL reaction
of the Ce(IV)-Na2S2O4-ofloxacin/levofloxacin-H2SO2 system. ... The CL
intensity was correlated linearly (r = 0.9988) with the concentration of
ofloxacin (or levofloxacin) in the range of 1.0 x 10(-8) - 1.0 x 10(-7) g
mL(-1) and 1.0 x 10(-7) - 6.0 x 10(-6) g mL(-1). The detection limit (S/N
= 3) is 7 x 10(-9) g mL(-1). The relative standard derivation (RSD, n =
11) is 2.0% for ofloxacin at 4 x 10(-7) g mL(-1) and for levofloxacin at 6
x 10(-7) g mL(-1). This method has been successfully applied for the
determination of ofloxacin and levofloxacin in pharmaceutical preparations
and biological fluids with satisfactory results.[Sun H et al; Anal Sci 22
(8): 1145-9 (2006)] **PEER REVIEWED** <a
Liquid chromatography with a column-switching technique was developed for

simultaneous direct quantification of levofloxacin, gatifloxacin and
moxifloxacin in human serum. Serum samples were injected on a LiChroCART
4-4 pre-column (PC) filled with a LiChrospher 100 RP-18, 5 microm where
fluoroquinolones (FQs) were purified and concentrated. The FQs were
back-flushed from the PC and then separated on a Supelcosil ABZ+ Plus (150
mm x 4.6 mm i.d.) analytical column with a mobile phase containing 10 mM
phosphate buffer (pH 2.5), acetonitrile (88:12, v/v) and 2mM tetrabutyl
ammonium bromide. The effects of ion-pair reagents, buffer type, pH and
acetonitrile concentrations in the mobile phase on the separation of the
three FQs were investigated. Fluorescence detection provided sufficient
sensitivity to achieve a quantification limit of 125 ng/mL for
levofloxacin and moxifloxacin; 162.5 ng/mL for gatifloxacin with a 5
microL sample size.[Nguyen HA et al; J Chromatogr B Analyt Technol Biomed
Life Sci 810 (1): 77-83 (2004)] **PEER REVIEWED** <a
... A specific and sensitive high-performance liquid chromatographic

(HPLC) assay /was developed/ for the determination of levofloxacin in
human plasma, bronchoalveolar lavage and bone tissues. The sample
extraction was based on a fully automated liquid-solid extraction with an
OASIS cartridge. The method used ultraviolet detection set at a wavelength
of 299 nm and a separation with a Supelcosil ABZ+ column. The assay has
been found linear over the concentration range 0.25-25 microg/mL for
levofloxacin in plasma, 1-6 microg/mL in bronchoalveolar lavage and 0.5-10
microg/g for bone tissues and it provided good validation data for
accuracy and precision.[Djabarouti S et al; J Chromatogr B Analyt Technol
Biomed Life Sci 799 (1): 165-72 (2004)] **PEER REVIEWED** <a
ANALYTIC LABORATORY METHODS:

A highly sensitive spectrofluorimetric method was developed ... for the
analysis of three fluoroquinolones (FQ) antibacterials, namely
enrofloxacin (ENR), levofloxacin (LEV) and ofloxacin (OFL) in
pharmaceutical preparations through charge transfer (CT) complex formation
with 2,3,5,6-tetrachloro-p-benzoquinone (chloranil,CLA). At the optimum
reaction conditions, the FQ-CLA complexes showed excitation maxima ranging
from 359 to 363nm and emission maxima ranging from 442 to 488nm.
Rectilinear calibration graphs were obtained in the concentration range of
50-1000, 50-1000 and 25-500ngmL(-1) for ENR, LEV and OFL, respectively.
The detection limit was found to be 17ngmL(-1) for ENR, 17ngmL(-1) for
LEV, 8ngmL(-1) for OFL, respectively.[Ulu ST; Spectrochim Acta A Mol
Biomol Spectrosc 72 (5): 1038-42 (2009)] **PEER REVIEWED** <a
A simple and rapid HPLC method with UV detection was developed for the
separation of ciprofloxacin, levofloxacin and moxifloxacin. Chromatography
was carried out using a BDS Hypersil C18 (100 x 4.6 mm, 2.4 microm) HPLC
column and an isocratic mobile phase consisting of MeOH/25 mM phosphate
buffer 28/72 (v/v) at pH 3 and flow rate 1 ml.min-1 . The effect of mobile
phase variables such as methanol content, pH and buffer concentration on
the chromatographic behavior of the three fluoroquinolones was
investigated. The retention behavior on a sub 3 microm C18 column was also
compared with that on three different calixarene-bonded and on monolithic
stationary phases. The results indicate that some differences exist
between these three types of stationary phases, particularly in the effect
of buffer concentration on the retention mechanism of the three used FQs
on calixarene-bonded stationary phases.[Chamseddin C, Jira TH; Pharmazie
66 (4): 244-8 (2011)] **PEER REVIEWED** <a
A flow injection analysis (FIA) using UV detection, potentiometry and

conductometry for levofloxacin (LVF) are described in this study. The best
solvent system was found to consist of 0.2 M acetate buffer at pH 3 having
10% MeOH. A flow rate of 1 mL min(-1) was pumped and active material was
detected at 288 nm. The detection limit (LOD) and limit of quantification
(LOQ) for FIA were calculated to be 3 x 10(-7) M (S/N = 3) and 1 x 10(-7)
M (S/N = 10), respectively. In the analysis of tablets, the RSD values
were found to be 0.83, 0.98 and 0.99 for FIA, potentiometric and
conductometric methods, respectively.[Altiokka G et al; J Pharm Biomed
Anal 30 (3): 881-5 (2002)] **PEER REVIEWED** <a
RELATED HSDB RECORDS:

8030 [Ofloxacin] (isomer)
SYNONYMS:
2,3-Dihydro-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-
pyrido(1,2,3-de)-1,4-benzoxazine-6-carboxylic
acid[Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial
Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc.
Hoboken, NJ. 2004., p. 2773] **PEER REVIEWED**
FORMULATIONS/PREPARATIONS:
Levofloxacin PreparationsRoute of Administration Dosage Form Strength
Brand or Generic Name (Manufacturer) Oral Solution 125 mg/5 mL Levaquin
(Ortho-McNeil) Oral Tablets, film-coated 250 mg (of anhydrous
levofloxacin) Levaquin (Ortho-McNeil) Oral Tablets, film-coated 500 mg (of
anhydrous levofloxacin) Levaquin (Ortho-McNeil) Oral Tablets, film-coated
750 mg (of anhydrous levofloxacin) Levaquin (Ortho-McNeil) Parenteral For
injection, concentrate, for IV infustion equivalent ot levofloxacin 25
mg/mL (500 or 750 mg) Levaquin (Ortho-McNeil) [American Society of
Parenteral Injection, for IV infusion: equivalent to levofloxacin 5 mg/mL

(250, 500, or 750 mg) in 5% Dextrose; Levaquin in Dextrose Injection
Premix (in flexible containers) (Ortho-McNeil).[American Society of
Ophthalmic: Solution 0.5%, Quixin (Vistakon)[American Society of

Health-System Pharmacists 2011; Drug Information 2011. Bethesda, MD. 2011]
**PEER REVIEWED**
Tavanic (levofloxacin; 250 and 500 mg film-coated tablets and 5mg/mL

solution for infusion)[European Medicines Agency; Questions and Answers on
Tavanic (levofloxacin; 250 and 500 mg film-coated tablets and 5mg/ml
solution for infusion), EMA/332109/2012 EMEA/H/A-30/1262 (May 24, 2012).
Available from, as of August 29, 2012:
http://www.ema.europa.eu/ema/index.jsp?
curl=pages/home/Home_Page.jsp&mid=]
**PEER REVIEWED**
HAZARDOUS SUBSTANCES DATABANK NUMBER:

8028
LAST REVIEW DATE:

Reviewed by SRP on 5/17/2012

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The following information was generated from the

Hazardous Substances Data Bank (HSDB),

Query: Records containing the term 100986 85 4

HUMAN TOXICITY EXCERPTS:

/CASE REPORTS/ ... A 73-year-old white man, with a medical history of

/CASE REPORTS/ ... A 49-year-old woman with a history of asthma was

/CASE REPORTS/ A 78-year-old woman with many medical problems, including

/CASE REPORTS/ An elderly, non-diabetic patient with renal impairment

/CASE REPORTS/ ... A 20-year-old man without any history of disease or

/CASE REPORTS/ ... A seventy-eight-year-old male patient who developed

/CASE REPORTS/ ... A 79-year-old white man received levofloxacin for

/CASE REPORTS/ ... To report 2 cases of seizures following admin of

/CASE REPORTS/A 67-year-old man with minor alcoholism and a past-history

/SURVEILLANCE/ ... Subjects with fluoroquinolone hepatotoxicity enrolled

/SURVEILLANCE/ The aim of this retrospective study was to evaluate

/OTHER TOXICITY INFORMATION/ New fluoroquinolones &amp;

/BOXED WARNING/ WARNING: Fluoroquinolones, including Levaquin may

Other serious and sometimes fatal events, some due to hypersensitivity,

Post-marketing reports of severe hepatotoxicity (including acute hepatitis

Levofloxacin is indicated in pediatric patients for inhalational anthrax

Serious and occasionally fatal hypersensitivity and/or anaphylactic

Seizures, toxic psychoses, and increased intracranial pressure and CNS

Severe hepatotoxicity, including acute hepatitis, has occurred and

Moderate to severe photosensitivity/phototoxicity reactions reported

When prescribing a fluoroquinolone, consider potential benefits and risks

Hypoglycemia or hyperglycemia reported with fluoroquinolones, including

An increased incidence of musculoskeletal disorders (arthralgia,

Prolonged QT interval leading to ventricular arrhythmias, including

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.

Sensory or sensorimotor axonal polyneuropathy affecting small and/or large

Although very useful agents, fluoroquinolones are associated with a number

The fluoroquinolones ciprofloxacin, levofloxacin, moxifloxacin and

With levofloxacin 0.5% ophthalmic solution transient decrease in vision,

POPULATIONS AT SPECIAL RISK:

Avoid Levaquin in patients with a known history of myasthenia gravis.[US

Healthcare professionals should be aware of this serious drug-disease

Severe hepatotoxicity, including acute hepatitis, has occurred and

PROBABLE ROUTES OF HUMAN EXPOSURE:

EMERGENCY MEDICAL TREATMENT:

EMT COPYRIGHT DISCLAIMER:

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation

Emergency and supportive measures: Maintain an open airway and assist

Decontamination: Administer activated charcoal orally if conditions are

Enhanced elimination: Most antibiotics are excreted unchanged in the

In the event of an acute overdosage, the stomach should be emptied. The

NON-HUMAN TOXICITY EXCERPTS:

/LABORATORY ANIMALS: Acute Exposure/ The phototoxic potential of

/LABORATORY ANIMALS: Acute Exposure/ ... Rats received an intravenous

/LABORATORY ANIMALS: Acute Exposure/ Sixteen albino rabbits were used in

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The oral toxicity

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The

/GENOTOXICITY/ The mutagenic effects of levofloxacin in lacZ transgenic

EC50; Species: Pseudokirchneriella subcapitata (Green Algae); Conditions:

EC50; Species: Lemna minor (Duckweed); Conditions: freshwater, renewal, 20

ABSORPTION, DISTRIBUTION & EXCRETION:

Levofloxacin pharmacokinetics are linear and predictable after single and

Levofloxacin is rapidly and essentially completely absorbed after oral

Levofloxacin is excreted largely as unchanged drug in the urine. The mean

The pharmacokinetics of oral levofloxacin and its penetration into

After single oral administration of (14)C-levofloxacin at a dose of 20 mg

The pharmacokinetics of oral levofloxacin and its penetration into

After single oral administration of (14)C-levofloxacin at a dose of 20 mg

/OTHER TOXICITY INFORMATION/ New fluoroquinolones &