DRUG PROTOCOL OF GANCICLOVIR

GENERIC NAME: Ganciclovir

PRONOUNCIATION: gan·ci·clo·vir

DESCRIPTION:

An acyclovir analog that is a potent inhibitor of the Herpesvirus family including

cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated
cytomegalovirus infections.

THERAPEUTIC CLASSIFICATION:

Antiviral

 Guanosine Nucleoside Analog

 Viral DNA Polymerase Inhibitor

COMPOSITION / ACTIVE INGREDIENTS:

Ganciclovir Tablet is composed of the following active ingredients (salts)

Ganciclovir Sodium- 500mg

Ganciclovir - 500mg

TRADE NAMES:

 INDIA: cymevene, cytogan, ganguard, gatelevir, gavir, natclovir .

 INTERNATIONAL: valcyte, ziran,

CHEMISTRY:

STRUCTURE:

STRUCTURAL ACTIVITY RELATIONSHIP:

PHARMACOLOGICAL PROPERTIES:

a) PHARMACOKINETICS:
Absorption:
 less than7% is absorbed after oral administration .
Distribution:
 only 2% to 3% protein-based. It preferentially concentrates within CMV-
infected cells because of action of cellular kinases that convert it to ganciclovir
triphosphate.
Metabolism:
 most(over 90%) is excreted unchanged.
Excretion:
 Elimination half-life is about 3 hours in patients with normal renal function;it
can be as long as 30 hours in patient with severe renal failure. The primary
route of excretion is through the kidney by glomerular filtration and some
renal secretion.

b) MECHANISM OF ACTION:
 Ganciclovir is a synthetic analogue of 2′-deoxy-guanosine. It is
first phosphorylated to ganciclovir monophosphate by a viral kinase encoded
by the cytomegalovirus (CMV) gene UL97 during infection. Subsequently,
cellular kinases catalyze the formation of ganciclovir diphosphate and
ganciclovir triphosphate, which is present in 10-fold greater concentrations in
CMV or herpes simplex virus (HSV)-infected cells than uninfected cells.
 Ganciclovir triphosphate is a competitive inhibitor of deoxyguanosine
0triphosphate (dGTP) incorporation into DNA and preferentially inhibits viral
DNA polymerases more than cellular DNA polymerases. In addition,
ganciclovir triphosphate serves as a poor substrate for chain elongation,
thereby disrupting viral DNA synthesis by a second route.

INDICATIONS:

 Ganciclovir capsules are used to treat cytomegalovirus (CMV) retinitis (eye infection
that can cause blindness) in people whose immune system is not working normally.
 Ganciclovir capsules are used to treat CMV retinitis after the condition has been
controlled by intravenous (injected into a vein) ganciclovir.
 Ganciclovir is also used to prevent cytomegalovirus (CMV) disease in people who
have acquired immunodeficiency syndrome (AIDS) or who have received an organ
transplant and are at risk of CMV disease.
 Ganciclovir is in a class of medications called antivirals. It works by preventing the
spread of CMV disease or slowing the growth of CMV.

CONTRAINDICATIONS:
  Hypersensitivity to acyclovir, ganciclovir, or any component of the formulation
 Zidovudine: increased hematological toxicity
 Not to be used if ANC <500/cu.mm or Plts <25,000/cu.mm

PREGNANCY CATEGORY:

 A: Generally acceptable. Controlled studies in pregnant women show no evidence of

fetal risk.
 B: May be acceptable. Either animal studies show no risk but human studies not
available or animal studies showed minor risks and human studies done and showed
no risk.
 C: Use with caution if benefits outweigh risks. Animal studies show risk and human
studies not available or neither animal nor human studies done.
 D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive
evidence of human fetal risk.
 X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer
alternatives exist.

VARIOUS DOSAGE FORMS / FORMULATION:

 Capsule
250mg

500mg

 Powder for injection

500mg

 Oral solution

25mg/mL

100mg/mL

COMBINATION IF ANY WITH REASON:

 Imipramine 25mg, Diazepam 2mg.

 Diazepam 2.5 mg,Propranolol 20mg.

 Propanthelinebromide 15mg,diazepam 2.5mg,dihydroxy aluminiumamino acetate
100mg.
  Aluminiumhydroxide 300mg,magnesiumtrisilicate 200mg,diazepam
2mg,activateddimethylpolysiloxane20mg.
 Oxphenonium bromide5 mg, diazepam 2.5mg, magaldrate 400mg.

DOSAGE:

For oral dosage form (capsules):

 For treatment of CMV retinitis after you have received ganciclovir injection for at
least fourteen to twenty-one days:
 Adults and teenagers—1000 milligrams (mg) three times a day with food; or 500 mg
six times a day, every three hours with food, during waking hours.
 Children—Use and dose must be determined by your doctor.
 For prevention of CMV disease in transplant patients and patients with advanced HIV
infection:
 Adults and teenagers—1000 mg three times a day with food.
 Children—Use and dose must be determined by your doctor.

For injection dosage form:

 For treatment of : CMV retinitis

 Adults and teenagers—Dose is based on body weight and must be determined by your
doctor. At first, 5 mg per kilogram (2.3 mg per pound) of body weight is injected into
a vein every twelve hours for fourteen to twenty-one days. Then, 5 mg per kilogram
(2.3 mg per pound) of body weight is injected into a vein once a day for seven days of
the week; or 6 mg per kilogram (2.7 mg per pound) of body weight is injected into a
vein once a day for five days of the week.
 Children—Use and dose must be determined by your doctor.
 For prevention of CMV in transplant patients:
 Adults and teenagers—Dose is based on body weight and must be determined by your
doctor. At first, 5 mg per kilogram (2.3 mg per pound) of body weight is injected into
a vein every twelve hours for seven to fourteen days. Then the dose is reduced to 5
mg per kilogram (2.3 mg per pound) of body weight once a day for seven days of the
week; or 6 mg per kilogram (2.7 mg per pound) of body weight is injected into a vein
once a day for five days of the week.
 Children—Use and dose must be determined by your doctor.

ADMINISTRATION:

 Oral
 Rectal
 Intravenous
WARNINGS AND PRECAUTIONS:

a) PEDIATRIC PRECAUTIONS: Ganciclovir can cause serious side effects in any

patient. Therefore, it is especially important that you discuss with the child's doctor
the good that ganciclovir may do as well as the risks of using it.
b) GERIATRIC PRECAUTIONS: Many medicines have not been studied specifically
in older people. Therefore, it may not be known whether they work exactly the same
way they do in younger adults or if they cause different side effects or problems in
older people. There is no specific information comparing use of ganciclovir in the
elderly with use in other age groups.

PREGNANCY AND LACTATION:

Pregnancy
Placental transfer of ganciclovir has been shown to occur based on ex vivo experiments with
human placenta and in at least 1 case report in a pregnant woman; however, no adequate
human data are available to establish whether ganciclovir poses a risk to pregnancy outcomes
In animal studies, ganciclovir caused maternal and fetal toxicity and embryo-fetal mortality
in pregnant mice and rabbits as well as teratogenicity in rabbits at exposures 2 times the
exposure at the recommended human dose (RHD)
Disease-associated maternal and/or embryo-fetal risk

 Most maternal CMV infections are asymptomatic or they may be associated with a self-
limited mononucleosis-like syndrome; however, in immunocompromised patients, CMV
infections may be symptomatic and may result in significant maternal morbidity and
mortality
 CMV fetal transmission results from maternal viremia and transplacental infection
 Perinatal infection can also occur from exposure of the neonate to CMV shedding in the
genital tract ~10% of children with congenital CMV infection are symptomatic at birth
 Mortality in symptomatic infants is ~10% and ~50-90% of symptomatic surviving
newborns experience significant morbidity, including mental retardation, sensorineural
hearing loss, microcephaly, seizures, and other medical problems
 Risk of congenital CMV infection resulting from primary maternal CMV infection may
be higher and of greater severity than that resulting from maternal reactivation of CMV
infection
Contraception

 Test for pregnancy in females of reproductive potential before initiating treatment

 Females: Because of ganciclovir’s mutagenic and teratogenic potential, use effective
contraception during treatment and for at least 30 days following treatment
 Males: Because of ganciclovir’s mutagenic and teratogenic potential, use barrier
contraception during treatment and for at least 90 days following treatment
Lactation
No data are available regarding the presence of ganciclovir in human milk, the effects on the
breastfed infant, or the effects on milk production
Ganciclovir was present in milk in lactating rats following administration
Breastfeeding is not recommended during treatment owing to the potential for serious adverse
reactions in nursing infants
 c) ADVERSE DRUG REACTION / SIDE EFFECTS:

Blood and lymphatic disorders: Pancytopenia, bone marrow failure

Cardiac disorders: Arrhythmias
Ear and labyrinth disorders: Tinnitus, ear pain, deafness
Eye disorders: Visual impairment, vitreous disorders, eye pain, conjunctivitis, macular
edema
Gastrointestinal disorders: Abdominal pain, dyspepsia, flatulence, constipation, mouth
ulceration, dysphagia, abdominal distention, pancreatitis, gastrointestinal perforation,
eructation, dry mouth
General disorders and administration site conditions: Fatigue, injection site inflammation,
edema, pain, malaise, asthenia, chest pain, multiple organ failure
Blood Immune system disorders: Hypersensitivity Infections and infestations: Candida
infections including oral candidiasis, upper respiratory infection, influenza, urinary tract
infections, cellulitis
Investigations: Blood alkaline phosphatase increased, hepatic function abnormal, aspartate
aminotransferase increased, alanine aminotransferase increased, creatinine clearance
decreased
Metabolism and nutrition disorders: Weight decreased
Musculoskeletal and connective tissue disorders: Back pain, myalgia, arthralgia, muscle
spasms, leg cramps, myasthenia
Nervous system disorders: Headache, insomnia, dizziness, paresthesia, hypoaesthesia,
seizures, somnolence, dysgeusia (taste disturbance), tremor
Psychiatric disorders: Depression, confusional state, anxiety, agitation, psychotic disorder,
thinking abnormal, abnormal dreams
Renal and urinary disorders: Kidney failure, renal function abnormal, urinary frequency,
hematuria
Respiratory, thoracic and mediastinal disorders: Cough, dyspnea
Skin and subcutaneous tissues disorders: Dermatitis, alopecia, dry skin, urticaria, rash
Vascular disorders: Hypotension, hypertension, phlebitis, vasodialation.

ANTIDOTE / SPECIFIC TREATMENT IF ANY:

There is no antidote for ganciclovir overdose.
DRUG INTERACTION:

Some products that may interact with this drug include: didanosine, imipenem/cilastatin.

You may be taking other drugs that decrease bone marrow function and lower your number
of blood cells (such as cancer chemotherapy, trimethoprim/sulfamethoxazole, zidovudine) or other
drugs that may cause kidney problems (such as cyclosporine). Your doctor or pharmacist will
monitor you closely and adjust your medications to decrease your risk of serious side effects.

Ganciclovir is very similar to valganciclovir. Do not use medications containing valganciclovir

while using ganciclovir.
OTHER PRECAUTIONS:

This drug may make you dizzy or drowsy or make it harder for you to think clearly. Alcohol
or marijuana can worsen these effects. Do not drive, use machinery, or do anything that needs
alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are
using marijuana.

Wash your hands well to prevent the spread of infection. Avoid contact with people who have
infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if
you have been exposed to an infection or for more details.

Do not have immunizations/vaccinations without the consent of your doctor. Avoid contact with
people who have recently received live vaccines (such as flu vaccine inhaled through the nose).

To lower the chance of getting cut, bruised, or injured, use caution with sharp objects like razors
and nail cutters, and avoid activities such as contact sports.

Older adults may be at greater risk for kidney problems while using this drug.

Women who are pregnant or who may become pregnant should not handle this medication.

During pregnancy, this medication should be used only when clearly needed. It may harm an
unborn baby. Women of child-bearing age should have a pregnancy test before starting this
medication. To prevent pregnancy, men with female partners should always use effective
barrier protection (such as latex or polyurethane condoms) during all sexual activity during
treatment and for at least 90 days after stopping the medication. Women of child-bearing age
who are using ganciclovir should use reliable forms of birth control (such as birth control
pills and condoms) during treatment and for at least 30 days after stopping the medication.
Consult your doctor for more details.

It is unknown if this medication passes into breast milk. Because of the possible risk to
the infant, breast-feeding while using this drug is not recommended. Consult your doctor
before breast-feeding. If you have HIV, do not breast-feed because breast milk can
transmit HIV.

STORAGE CONDITIONS:

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F)

COST / PACK:

PATIENT COUNSELLING: