PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

Print Close Window

Handbook of Nonprescription Drugs > Chapter 12. Cough

Cough: Introduction

Cough is an important defensive respiratory reflex with potentially significant adverse physical and psychological consequences
and economic impact. Cough is the most common symptom for which patients seek medical care.1 Cough is also a common
reason for emergency department visits. In 2010, cough was the second most common reason for children younger than 15
years to visit emergency departments and the seventh most common reason for adults.2 Americans spend more than $4 billion
annually on nonprescription cough/cold and related medications, more than any other nonprescription sales category.3

Pathophysiology of Cough

Cough is initiated by stimulation of chemically and mechanically sensitive, vagally mediated sensory pathways in laryngeal,
esophageal, and tracheobronchial airway epithelium.4,5 The number of afferent nerves activated and the intensity of activation
may influence the cough threshold.6 Receptors in the larynx and proximal large airways are more sensitive to mechanical
stimulation, whereas laryngeal receptors are more sensitive to chemical stimulation.7 A complex medullary brainstem network
(cough control center) processes the sensory input and stimulates the motor efferents. Voluntary cough is controlled by the
cerebral cortex.8 Viruses promote cough by a different though not well-understood mechanism.9
A cough starts with a deep inspiration followed by closure of the glottis and forceful contraction of the chest wall, abdominal wall,
and diaphragmatic muscles against the closed glottis; pressure within the thoracic cavity may reach 300 mm Hg.4 When the
glottis opens, air is expelled with a velocity of about 11-15 m/s, propelling mucus, cellular debris, and foreign material out of the
respiratory system.10 Cough may occur in epochs (coughing fits).
Cough, classified as acute (duration of less than 3 weeks), subacute (duration of 3-8 weeks), or chronic (duration of more than 8
weeks), is a symptom of diverse infectious and noninfectious disorders (Table 12-1).11 In children, cough may also be a
symptom of aspiration caused by poor coordination of sucking and swallowing or esophageal motility disorders.12 Angiotensin-
converting enzyme inhibitors cause dry cough in approximately 20% of treated patients.13 Systemic and ophthalmic
beta-adrenergic blockers may cause cough in patients with obstructive airway diseases (e.g., asthma or chronic obstructive
pulmonary disease [COPD]).
TABLE 12-1 Etiology of Cough

Classification Etiology

Acute Viral URTI, pneumonia, acute left ventricular failure, asthma, foreign body aspiration

Subacute Postinfectious cough, bacterial sinusitis, asthma

Chronic UACS, asthma, GERD, COPD (chronic bronchitis), ACEIs, bronchogenic carcinoma, carcinomatosis,
sarcoidosis, left ventricular failure, aspiration secondary to pharyngeal dysfunction

Key: ACEI = Angiotensin-converting enzyme inhibitor; COPD = chronic obstructive pulmonary disease; GERD =
gastroesophageal reflux disease; UACS = upper airway cough syndrome; URTI = upper respiratory tract infection.

Source: Reference 11.

Clinical Presentation of Cough

Coughs are described as productive or nonproductive. A productive cough (a wet or chesty cough) expels secretions from the
lower respiratory tract that, if retained, could impair ventilation and the lungs ability to resist infection. Productive coughs may be
effective (secretions easily expelled) or ineffective (secretions present but difficult to expel). The appearance of the secretions is
not always a reliable diagnostic indicator, but secretions are typically clear with bronchitis and purulent with bacterial infection.
Anaerobic bacterial infections are associated with a distinct malodor. Nonproductive coughs (a dry or hacking cough), which
are associated with viral and atypical bacterial infections, gastroesophageal reflux disease (GERD), cardiac disease, and some
medications, serve no useful physiologic purpose.

1 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

Common complications of cough include exhaustion, insomnia, musculoskeletal pain, hoarseness, excessive perspiration, and
urinary incontinence. Less common complications include cardiac dysrhythmias, syncope, stroke, and rib fractures. Mechanical
irritation from coughing may cause sore throat. Cough may cause prolonged absence from work or school, withdrawal from
social activities, and fear that the cough is a symptom of a serious illness, such as cancer or tuberculosis.

Treatment of Cough

Treatment Goals

The primary goal of self-treatment of cough is to reduce the number and severity of cough episodes. The second goal is to
prevent complications. Cough treatment is symptomatic; the underlying disorder must be treated to stop the cough.

General Treatment Approach

Selection of a medication for self-care of cough depends on the nature and etiology of the cough. Figure 12-1 lists exclusions for
self-care. These exclusions are based on the presence of signs and symptoms of potentially serious medical conditions
associated with cough that require medical evaluation.14,15 Antitussives (cough suppressants) control or eliminate cough and
are the drugs of choice for nonproductive coughs. Antitussives should not be used to treat productive cough unless the potential
benefit outweighs the risk (e.g., significant nocturnal cough). Suppression of productive coughs may lead to retention of lower
respiratory tract secretions, increasing the risk of airway obstruction and secondary bacterial infection. Protussives
(expectorants) change the consistency of mucus and increase the volume of expectorated sputum and may provide some relief
for coughs that expel thick, tenacious secretions from the lungs with difficulty.

2 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

Self-care of cough. Key: CHF = Congestive heart failure; COPD = chronic obstructive pulmonary disease; UACS = upper airway cough
syndrome.
Cough medications are marketed in a variety of dosage forms (syrups, liquids, solutions, suspensions, tablets, capsules,
lozenges, oral granules, topical ointments and creams, topical patches, and vaporizer solutions). Generic formulations are
widely available. The Food and Drug Administration (FDA) allows various combinations of antitussives, protussives, analgesics,
decongestants, and antihistamines. However, combinations of antitussives and protussives are potentially counterproductive.

Nonpharmacologic Therapy

Nonpharmacologic therapy includes nonmedicated lozenges, humidification, interventions to promote nasal drainage, and
hydration. Nonmedicated lozenges may reduce cough by decreasing throat irritation. Humidifiers (ultrasonic, impeller, and
evaporative) increase the amount of moisture in inspired air, which may soothe irritated airways. However, high humidity may
increase environmental mold, dust mites, minerals, and microorganisms. Vaporizers (humidifiers with a medication well or cup
for volatile inhalants) produce a medicated vapor. Cool-mist humidifiers and vaporizers are preferred because fewer bacteria
grow at the cooler temperatures and there is less risk of scalding if they are tipped over. Humidifiers and vaporizers must be
cleaned daily and disinfected weekly. Babies and young children up to about 2 years of age cannot blow their noses; a rubber
bulb nasal syringe may be used to clear the nasal passages and reduce cough if postnasal drip causes cough. Propping infants
upright when they sleep and raising the head of the bed at night promotes drainage of nasal secretions. Less viscous and thus
easier-to-expel secretions are formed when a person is well hydrated. Cautious hydration is recommended for patients with
lower respiratory tract infections, heart failure, renal failure, or other conditions potentially exacerbated by overhydration.

Pharmacologic Therapy

Table 12-2 lists examples of antitussive and expectorant products.

TABLE 12-2 Selected Nonprescription Products for Cough

Primary Ingredients Trade Name

Single-Ingredient Products

Dextromethorphan DayQuil Cough, Delysm Adult 12 Hour Cough, Robitussin Long-Acting CoughGels,
Hold DM

Guaifenesin Mucinex, Robitussin Mucus + Chest Congestion

Menthol Vicks VapoDrops, Halls Ice Blue Drops

Combination Products

Dextromethorphan and guaifenesin Robitussin Cough + Chest Congestion DM, Mucinex-DM, DayQuil Mucus Control

Codeine and guaifenesin Guaiatussin AC, Cheratussin AC

Camphor, menthol, and eucalyptus Vicks VapoRub, Mentholatum for Kids

oil

Oral Antitussives

FDA-approved nonprescription oral antitussives include codeine (codeine, codeine phosphate, codeine sulfate),
dextromethorphan (dextromethorphan, dextromethorphan hydrobromide), diphenhydramine (diphenhydramine citrate,
diphenhydramine hydrochloride), and chlophedianol hydrochloride.16
Codeine
At antitussive dosages, codeine is a Schedule C-V narcotic available without a prescription in 30 states (9 of the 30 states limit
sales to products sold by a pharmacist in a pharmacy).17 Codeine-containing Schedule C-V products must contain one or more
noncodeine active ingredients and no more than 200 mg of codeine per 100 milliliters.18 Abuse of the combination of codeine
and promethazine hydrochloride, known by the street names of purple drank and lean, is a common problem.19
Codeine acts centrally on the medulla to increase the cough threshold. Codeine is methylmorphine; morphine may be the active
antitussive. Codeine is well absorbed orally with a 15- to 30-minute onset of action and a 4- to 6-hour duration of effect. The
elimination half-life is 2.5-3 hours. Ten percent of a codeine dose is demethylated in the liver to form morphine. Approximately
3%-16% of codeine is eliminated unchanged in the urine.

3 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

Codeine is indicated for the suppression of nonproductive cough caused by chemical or mechanical respiratory tract irritation.
Codeines efficacy and safety as an antitussive drug in children are not established; pediatric dosage guidelines are
extrapolated from the adult literature. Table 12-3 lists FDA-approved codeine dosages.16 Reduced doses are appropriate for
patients of advanced age and the debilitated. Codeine is available as oral solutions, liquids, suspensions, and syrups in
combination with other active ingredients, including guaifenesin, antihistamines, and decongestants. Alcohol-, dye-, gluten-, and
sucrose-free formulations are available.
Usual antitussive codeine dosages have low toxicity and little risk of addiction. The most common side effects associated with
antitussive codeine dosages are nausea, vomiting, sedation, dizziness, and constipation. The lethal dose of codeine in adults is
0.5-1 gram, with death from marked respiratory depression and cardiopulmonary collapse. Concomitant use of codeine and
central nervous system (CNS) depressants (e.g., barbiturates, sedatives, or alcohol) causes additive CNS depression. Codeine
is contraindicated in patients with known codeine hypersensitivity and during labor when a premature birth is anticipated.
Patients with impaired respiratory reserve (e.g., asthma or COPD) or preexisting respiratory depression, drug addicts, and
individuals who take other respiratory depressants or sedatives, including alcohol, should use codeine with caution.
Dextromethorphan
Considered approximately equipotent with codeine, dextromethorphan is a nonopioid with no analgesic, sedative, respiratory
depressant, or addictive properties at usual antitussive doses. Dextromethorphan, the methylated dextrorotatory analogue of
levorphanol (a codeine analogue), acts centrally in the medulla to increase the cough threshold. It is well absorbed orally with a
15- to 30-minute onset of action and a 3- to 6-hour duration of effect. Dextromethorphan exhibits polymorphic metabolism, with
a usual elimination half-life of 1.2-2.2 hours. However, the half-life may be as long as 45 hours in people with a poor metabolism
phenotype.
Dextromethorphan is indicated for the suppression of nonproductive cough caused by chemical or mechanical respiratory tract
irritation. The efficacy and safety of dextromethorphan as an antitussive drug in children have not been established.20Table 12-3
lists FDA-approved dextromethorphan dosages.16 Dextromethorphan is marketed in the form of syrups, liquids, solutions,
extended-release oral suspensions, liquid-filled gelcaps, tablets, capsules, powders, and lozenges. Alcohol-, sucrose-, gluten-,
and dye-free formulations are available.
TABLE 12-3 Dosage Guidelines for Nonprescription Oral Antitussives and Expectorants

Dosage (maximum daily dosage)

Drug Adults/Children 12 Years Children 6 to <12 Years Children 2 to <6 Yearsa

Chlophedianolb,c 25 mg every 6-8 hours (100 mg) 12.5 mg every 6-8 hours 12.5 mg every 6-8 hours (50
(50 mg) mg)

Codeineb-d 10-20 mg every 4-6 hours 5-10 mg every 4-6 hours 1 mg/kg/day in 4 equal divided
(120 mg) (60 mg) dosages or by average body
weight

Dextromethorphan 10-20 mg every 4 hours or 30 mg 5-10 mg every 4 hours or 2.5-5 mg every 4 hours or 7.5
hydrobromideb every 6-8 hours (120 mg) 15 mg every 6-8 hours mg every 6-8 hours (30 mg)
(60 mg)

Diphenhydramine 38 mg every 4 hours (228 mg) 19 mg every 4 hours (114 9.5 mg every 4 hours (57 mg)
citrateb,c mg)

Diphenhydramine HClb,c 25 mg every 4 hours (150 mg) 12.5 mg every 4 hours (75 6.25 mg every 4 hours (37.5 mg)
mg)

Guaifenesinb 200-400 mg every 4 hours (2.4 g) 100-200 mg every 4 hours 50-100 mg every 4 hours (600
(1.2 g) mg)

a The Consumer Health Care Products Association announced in October 2008 that manufacturers were voluntarily updating
cough and cold product labels to state do not use in children under 4 years of age.41 FDA announced that it would not object
to the more restrictive labeling.42 These actions have not changed the official monograph for cold, cough, allergy,
bronchodilator, and antiasthmatic drug products.16

b Not recommended for use in children younger than 2 years; no FDA-approved dosing recommendations.

4 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

cFDA recommends that the labels on nonprescription products not provide dosage information for children younger than 6
years.

d Codeine may be dosed by average body weight: 2 years of age (average body weight of 12 kg) = 3 mg every 4-6 hours
(maximum in 24 hours: 12 mg); 3 years of age (average body weight of 14 kg) = 3.5 mg every 4-6 hours (maximum in 24 hours:
14 mg); 4 years of age (average body weight of 16 kg) = 4 mg every 4-6 hours (maximum in 24 hours: 16 mg); 5 years of age
(average body weight of 18 kg) = 4.5 mg every 4-6 hours (maximum in 24 hours: 18 mg). A dispensing device such as a
dropper calibrated for age or weight should be dispensed along with the product when it is intended for use in children 2 to <6
years of age to prevent possible overdose from an improperly measured dose.

Source: Reference 16.

Dextromethorphan has a wide margin of safety. Side effects with usual doses are uncommon but may include drowsiness,
nausea or vomiting, stomach discomfort, or constipation. Dextromethorphan overdoses cause confusion, excitation,
nervousness, irritability, restlessness, drowsiness, as well as severe nausea and vomiting; respiratory depression may occur
with very high doses. Additive CNS depression occurs with alcohol, antihistamines, and psychotropic medications. The
combination of monoamine oxidase inhibitors (MAOIs) and dextromethorphan may cause serotonergic syndrome (e.g.,
increased blood pressure, hyperpyrexia, arrhythmias, and myoclonus). Dextromethorphan should not be taken for at least 14
days after the MAOI is discontinued. Patients who have known hypersensitivity to dextromethorphan or who have a prior history
of dextromethorphan dependence should not take it. Dextromethorphan is abused for its phencyclidine-like euphoric effect
(robo-tripping)21,22; abuse may be associated with psychosis and mania. Dextromethorphan abuse is especially common
among male adolescents.23 In 2010, at the request of the Drug Enforcement Administration, FDAs Drug Safety and Risk
Management Advisory Committee considered, but voted against, recommending that dextromethorphan be scheduled in the
Controlled Substances Act.24
Diphenhydramine
Diphenhydramine, a nonselective (first-generation) antihistamine with significant sedating and anticholinergic properties, acts
centrally in the medulla to increase the cough threshold. Second-generation antihistamines (e.g., loratadine and fexofenadine)
lack antitussive activity. Diphenhydramine is well absorbed following oral administration, with a bioavailability of 40%-70%, an
onset of action of about 15 minutes, and a duration of action of about 4-6 hours. The volume of distribution is 3.3-4.5 L/kg.
Diphenhydramine is hepatically metabolized to N-dealkylated urine and acidic metabolites with a clearance of 0.4-0.7 L/kg per
hour. Less than 4% is excreted unchanged in the urine.
Diphenhydramine is indicated for the suppression of nonproductive cough caused by chemical or mechanical respiratory tract
irritation. Table 12-3 lists FDA-approved diphenhydramine dosages.16 A common ingredient in cold and allergy products,
diphenhydramine is available in multiple dosage formulations, including an alcohol-free syrup specifically indicated for cough.
Symptoms of diphenhydramine overdose include mild to severe CNS depression (e.g., mental confusion, sedation, or
respiratory depression), hypotension, and CNS stimulation (e.g., hallucinations or convulsions).
Side effects of diphenhydramine include drowsiness, disturbed coordination, respiratory depression, blurred vision, urinary
retention, dry mouth, and dry respiratory secretions. Uncommon side effects reported with diphenhydramine include acute
dystonic reactions such as oculogyric crisis (rotation of the eyeballs), torticollis (contraction of neck muscles), and catatonia-like
states, as well as allergic and photoallergic reactions. Diphenhydramine may cause excitability, especially in children.
Diphenhydramine potentiates the depressant effects of narcotics, nonnarcotic analgesics, benzodiazepines, tranquilizers, and
alcohol on the CNS, and it intensifies the anticholinergic effect of MAOIs and other anticholinergics. Diphenhydramine is
contraindicated in patients with known hypersensitivity to diphenhydramine or structurally similar antihistamines.
Diphenhydramine should be used with caution in patients with diseases potentially exacerbated by drugs with anticholinergic
activity, including narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic
hypertrophy, bladder-neck obstruction, asthma and other lower respiratory tract disease, elevated intraocular pressure,
hyperthyroidism, cardiovascular disease, or hypertension. Because of the increased risk of toxicity, diphenhydramine-containing
antitussives should not be used with any other diphenhydramine-containing product, including topical products.
Chlophedianol
Chlophedianol is a centrally acting oral antitussive originally marketed in 1960 as a prescription antitussive. Reintroduced as a
nonprescription product in late 2009, chlophedianol is an alkylamine antihistamine derivative with antitussive, moderate local
anesthetic, and mild anticholinergic effects. Chlophedianol is indicated for the suppression of nonproductive cough caused by
chemical or mechanical respiratory tract irritation. Table 12-3 lists the FDA-approved chlophedianol dosage.16 Chlophedianol is
marketed in the form of oral liquids, solutions, and syrups. Sugar-, alcohol-, dye-, and gluten-free products are available.
Published data for chlophedianol are limited. It has a slower onset of maximal effect (4 hours vs. 30 minutes) and a longer
duration of action than does codeine.25 Chlophedianol is metabolized hepatically and eliminated renally. Side effects include

5 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

excitation, hyperirritability, nightmares, hallucinations, hypersensitivity, and urticaria. Dry mouth, vertigo, visual disturbances,
nausea, vomiting, and drowsiness have been associated with large doses. If the patient takes MAOIs, chlophedianol should not
be administered for at least 14 days after the MAOIs are halted. Chlophedianol is contraindicated in patients with known
chlophedianol hypersensitivity.

Protussives (Expectorants)

Guaifenesin (glyceryl guaiacolate), the only FDA-approved expectorant, is indicated for the symptomatic relief of acute,
ineffective productive cough.16 Guaifenesin is not indicated for chronic cough associated with chronic lower respiratory tract
diseases such as asthma, COPD, emphysema, or smokers cough. Guaifenesin loosens and thins lower respiratory tract
secretions, making minimally productive coughs more productive. However, few data support its efficacy, especially at
nonprescription dosages. Although the pharmacokinetics of guaifenesin is not well described, guaifenesin appears to be well
absorbed after oral administration, with a half-life of about 1 hour.
Table 12-3 lists FDA-approved dosages of guaifenesin.16 Guaifenesin is marketed as oral liquids, syrups, caplets, granules, and
immediate-release and extended-release tablets. Alcohol-, sucrose-, and dye-free formulations are also available. Most reports
of guaifenesin overdosages involve combinations of drugs and therefore are difficult to assess. However, signs and symptoms
of overdosages appear to be extensions of the side effects.
Guaifenesin is generally well tolerated. Side effects include nausea, vomiting, dizziness, headache, rash, diarrhea, drowsiness,
and stomach pain. Large doses, either singly or in combination with ephedrine or pseudoephedrine, have been associated with
renal calculi.26 Guaifenesin is contraindicated in patients with a known hypersensitivity to guaifenesin.

Topical Antitussives

Camphor and menthol are the only FDA-approved topical antitussives.16 Other volatile oils (e.g., eucalyptus), common in many
cough and cold preparations, impart a strong medicinal odor to products but are not FDA-approved antitussives. At
subtherapeutic doses, menthol is a common flavoring agent. Although the mechanism of action is not well described, inhaled
camphor and menthol vapors stimulate sensory nerve endings within the nose and mucosa, creating a local anesthetic
sensation and a sense of improved airflow. However, there is little objective evidence of clinical efficacy. A possible drug
interaction with menthol cough drops and warfarin resulting in reduced warfarin response has been reported.27Table 12-4
provides administration guidelines for these agents.
TABLE 12-4 Administration Guidelines for Nonprescription Topical Antitussives (Adults and Children 2 Yearsa)

Formulation Administration

Ointmentsb Rub on the throat and chest in a thick layer; application may be repeated up to 3 times daily or as directed by
primary care provider; loosen clothing around throat and chest so vapors reach the nose and mouth; cover
with a warm, dry cloth (optional). Do not use in the nostrils, under the nose, by the mouth, on damaged skin, or
with tight bandages.

Lozengesc Allow lozenge to dissolve slowly in mouth; repeat hourly or as needed or as directed by a primary care
provider.

Inhalationd For products intended to be added directly to cold water for use in a steam vaporizer: add measured solution
to cold water; place the mixture in the vaporizer; breathe in the medicated vapors up to 3 times daily.
For products to be placed in the medication chamber of a hot steam vaporizer: place water in vaporizer; place
solution in medication chamber; breathe in the medicated vapors up to 3 times daily.

a For children ages < 2 years, consult a primary care provider.

b Camphor 4.7%-5.3%; menthol 2.6%-2.8%.

c Menthol lozenges, 5-10 mg lozenge; repeat hourly as needed.

d Camphor 6.2%; menthol 3.2%.

Source: Reference 16.

Camphor- and menthol-containing ointments, creams, and solutions may splatter and cause serious burns if used near an open

6 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

flame or placed in hot water or in a microwave oven. Camphor and menthol vapors may be ciliotoxic and proinflammatory,
especially in young children.28 These products are also toxic if ingested. Toxicities include burning sensations in the mouth,
nausea and vomiting, epigastric distress, restlessness, excitation, delirium, seizures, and death. Ingestion of as little as 4
teaspoons of products containing 5% camphor may be lethal for children.29

Product Selection Guidelines

Efficacy
Although antitussives and expectorants have been marketed for decades, efficacy has been difficult to prove and may depend
on the etiology of the cough. There is no good evidence that dextromethorphan, codeine, diphenhydramine, or guaifenesin are
effective treatments of acute cough in adults or children30-33; there is even less evidence for the efficacy of menthol, camphor,
and chlophedianol. There is also a lack of evidence for or against the efficacy of nonprescription antitussives as adjuncts to
antibiotics for the treatment of acute pneumonia.34 Factors such as taste, smell, color, viscosity, sugar content, and personal
expectation may contribute to a large placebo response (up to 85%).35 Proof of efficacy will require data from well-designed
trials of subjects with natural disease who are assessed with standardized objective outcome parameters.
The American College of Chest Physicians (ACCP) published updated evidence-based diagnosis and management of cough
guidelines in 200636; similar international guidelines are available.37,38 The ACCP guidelines state that central cough
suppressants are ineffective in cough associated with the common cold, and they recommend a combination of a first-
generation antihistamine plus a decongestant to treat the virus-induced postnasal drip that is most likely the cause of the cough
(see Chapter 11).39 Also, because viral infection increases upper airway afferent nerve sensitivity, the guidelines suggest that
the anti-inflammatory naproxen may reduce viral-associated cough.39 The guidelines also recommend empiric treatment of
cough associated with chronic upper airway cough syndrome, for which the etiology is unclear, with a first-generation
antihistamine/decongestant combination (see Chapter 11).40 The guidelines recommend codeine or dextromethorphan for the
short-term symptomatic relief of cough associated with acute and chronic bronchitis and postinfectious subacute cough.
Guaifenesin is not recommended for any indication. The guidelines do not address chlophedianol.
Dosage Formulations
Cough products are marketed in a variety of dosage formulations. Efficacy appears to be the same for all dosage formulations;
patients may select a dosage formulation on the basis of preference and convenience. Most products are formulated for dosage
intervals of 4-6 hours, but some liquid dosage forms are specifically formulated for an extended dosage interval. For example,
some dextromethorphan products are formulated with polymer complexes (e.g., sulfonated styrene-divinylbenzene copolymer;
polistirex), conferring an extended dosage interval (8-12 hours). Patients treating nocturnal cough may prefer a product with an
extended dosage interval.
Special Populations
In January 2008, FDA issued a public health advisory recommending that nonprescription cough and cold medicines . . . not be
used to treat infants and children under 2 years of age because several serious and potentially life-threatening side effects can
occur.41 In October 2008, the Consumer Healthcare Products Association (CHPA) announced that manufacturers were
voluntarily updating cough and cold product labels to state do not use in children under 4 years of age.42 FDA announced that
it would not object to the more restrictive labeling.43 To address the issue of inaccurate dosing, FDA released guidelines in May
2011 for liquid nonprescription drug products that include any type of dispensing device (dropper, cup, syringe, or spoon).44,45
These products include liquid analgesics, liquid cough and cold products, and lactase replacement drops. The key points of the
guidance are recommendations that

A dosing device be included with all oral liquid nonprescription products.

The device be calibrated to the dose recommended in the product directions.
The device be used only with the product in which it is packaged.
The markings remain visible even when the liquid is in the device.

The agency continues to assess the safety and efficacy of nonprescription cough and cold medications in children.
Codeine (Pregnancy Category C) should be used during pregnancy only if the potential benefits outweigh the risks.
Nonteratogenic concerns include the risk of neonatal respiratory depression if codeine is taken close to the time of delivery and
neonatal withdrawal if codeine is used regularly during the pregnancy. Codeine is excreted in breast milk and is associated with
drowsiness in nursing infants.46,47 Because the elderly may be more susceptible to the sedating effects of codeine, the dose
should be started at the lower end of the dosage range and titrated as tolerated, with careful monitoring.
Dextromethorphan (Pregnancy Category C) is viewed as probably safe for use during pregnancy.48 It is not known whether
dextromethorphan is excreted in breast milk. Because the elderly may be more susceptible to the sedating effects of
dextromethorphan, the dose should be started at the lower end of the dosage range and titrated as tolerated, with careful
monitoring.

7 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

Diphenhydramine (Pregnancy Category B) is excreted in breast milk and may cause unusual excitation and irritability in the
infant; it may also decrease the flow of milk. Compared with the general population, the elderly are more likely to experience
dizziness, excessive sedation, syncope, confusion, and hypotension with diphenhydramine. The 2012 American Geriatrics
Society Beers Criteria identify diphenhydramine, along with four other nonprescription first-generation H1-antihistamines and
seven prescription first-generation H 1-antihistamines, as potentially inappropriate medications in older adults.49 Children and the
elderly may experience paradoxical excitation, restlessness, and irritability with diphenhydramine. Dosing for the latter group
should be started at the lower end of the dosage range and titrated as tolerated, with careful monitoring.
There are no controlled data regarding the use of guaifenesin (Pregnancy Category C) or chlophedianol (Pregnancy Category
N) during pregnancy or breast-feeding. There are no special considerations for use of guaifenesin by the elderly. Chlophedianol
should be used with caution in sedated or debilitated patients.
Patient Factors
Cough is a symptom of many acute and chronic diseases. Patients with identified exclusions for self-care (Figure 12-1) should
be referred for further evaluation. Patients with known, or signs and symptoms of, chronic diseases associated with cough
(Table 12-5) should not attempt to self-treat cough, even cough caused by an acute viral upper respiratory tract infection (URTI)
because the acute infection may exacerbate the underlying disease. Patients with smokers cough should be counseled
regarding smoking cessation options; antitussives and expectorants are not indicated (see Chapter 47).
Dextromethorphan, diphenhydramine, and chlophedianol should not be taken concurrently with MAOIs. Diphenhydramine is
highly sedating and should be avoided by patients at risk from the anticholinergic properties of the drug. First-generation
antihistamines and decongestants should be used only if the potential benefit outweighs the risk (see Chapter 11).
Complementary Therapies
Hundreds of herbal and other complementary therapies are marketed for cough. However, evidence does not support the use of
complementary therapies for treating cough, and some products have potential safety issues. (See Chapter 51 for information
on those therapies.) For example, honey, a common but unproven home remedy, should not be given to children younger than 1
year owing to the risk of botulism from ingestion of honey contaminated with Clostridium botulinum.50

Assessment of Cough: A Case-Based Approach

Before recommending any treatment, the health care provider needs to inquire about the duration of the cough, whether the
cough is productive, and whether it is associated with a chronic illness (Table 12-5). The provider should also obtain a list of all
the patients current medications to identify possible drug-drug or drug-disease interactions. In addition, the provider should find
out how the patient has treated the current cough, as well as previous coughs, and whether these treatments were satisfactory
or effective.
TABLE 12-5 Signs and Symptoms of Diseases Associated with Cough

Disease Signs and Symptoms

Acute bronchitis Purulent sputum; cough that lasts 1-3 weeks; mild dyspnea, mild bronchospasm and wheezing;
usually afebrile though may have a low-grade fever

Asthma Wheezing or chest tightness; shortness of breath, coughing predominantly at night; cough in
response to specific irritants, such as dust, smoke, or pollen

CHF Fatigue; dependent edema, breathlessness

Chronic bronchitis Productive cough most days of the month at least 3 months of the year for at least 2 consecutive
years

COPD Persistent, progressive dyspnea; chronic cough (may be intermittent or unproductive), chronic
sputum production

GERD Heartburn; sour taste in mouth; worsening of symptoms when supine; improvement with
acid-lowering drugs

Lower respiratory tract Fever (mild to high); thick, purulent, discolored phlegm; tachypnea, tachycardia
infection

UACS Mucus drainage from nose; frequent throat clearing

Viral URTI Sneezing; sore throat; rhinorrhea; low-grade temperature

8 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

Key: CHF = Congestive heart failure; COPD = chronic obstructive pulmonary disease; GERD = gastroesophageal reflux
disease; UACS = upper airway cough syndrome; URTI = upper respiratory tract infection.

Cases 12-1 and 12-2 provide examples of the assessment of patients with cough.

Case 12-1

Relevant Evaluation Criteria Scenario/Model Outcome

Information Gathering

1. Gather essential information about the

patients symptoms and medical history,
including:

a. description of symptom(s) (i.e., nature, onset, The patient has been coughing for about a week. The cough started about
duration, severity, associated symptoms) 3 days after she got a cold. Her cold symptoms (sore throat, nasal
congestion, rhinorrhea) are mostly resolved, but the dry, hacking,
nonproductive cough persists.

b. description of any factors that seem to The cough is worse at night or when she lies down.
precipitate, exacerbate, and/or relieve the
patients symptom(s)

c. description of the patients efforts to relieve The patient tried menthol cough drops and a combination of
the symptoms dextromethorphan and guaifenesin cough syrup without relief.

d. patients identity Janet Carter

e. age, sex, height, and weight 25 years old, female, 5 ft 5 in., 125 lb

f. patients occupation High school math teacher

g. patients dietary habits Generally eats a well-balanced diet with lots of fresh fruits and vegetables.

h. patients sleep habits Sleeps 8-9 hours a night.

i. concurrent medical conditions, prescription No concurrent medical conditions. No routine nonprescription medications
and nonprescription medications, and dietary or dietary supplements. Is currently taking Yasmin (ethinyl estradiol 30
supplements mcg, drospirenone 3 mg) for oral contraception; started about 5 years ago.

j. allergies NKA

k. history of other adverse reactions to None

medications

l. other (describe) _______ None

Assessment and Triage

9 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough
Relevant Evaluation Criteria
Information Gathering
2. Differentiate patients signs/symptoms and
correctly identify the patients primary
problem(s).
3. Identify exclusions for self-treatment (Figure
12-1).
4. Formulate a comprehensive list of therapeutic
alternatives for the primary problem to
determine if triage to a health care provider is
required, and share this information with the
patient or caregiver.
Plan
5. Select an optimal therapeutic alternative to
address the patients problem, taking into
account patient preferences.
6. Describe the recommended therapeutic
approach to the patient or caregiver.
7. Explain to the patient or caregiver the
rationale for selecting the recommended
therapeutic approach from the considered
therapeutic alternatives.
Patient Education
8. When recommending self-care with
nonprescription medications and/or nondrug
therapy, convey accurate information to the
patient or caregiver.
Solicit follow-up questions from the patient or
caregiver.
Answer the patients or caregivers questions.
10 of 17
http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...
Scenario/Model Outcome
Janet is likely experiencing UACS secondary to the upper respiratory tract
viral infection.
None
Options include:
(1) Take no action.
(2) Recommend that the patient see her PCP for further evaluation and
treatment.
(3) Recommend nondrug treatment (inhale warm steamy vapors, elevate
head of bed at night to promote nasal and sinus drainage).
(4) Recommend self-care with a first-generation antihistamine and
decongestant combination product.
Janet should treat her cough with a first-generation oral antihistamine (e.g.,
diphenhydramine) and decongestant (e.g., pseudoephedrine,
phenylephrine) combination product; elevating the head of the bed at night
or inhaling warm steamy vapors may provide some nondrug symptomatic
relief.
The upper airway cough syndrome is treated by a combination of the
drying effects of an oral first-generation antihistamine and decongestant
action of an oral decongestant.
Centrally active antitussives such as dextromethorphan and codeine and
the expectorant guaifenesin have little efficacy in cough associated with
viral infections such as the common cold.
See the box Patient Education for Cough.
How long can I take the antihistamine/decongestant medication?
You may take the antihistamine/decongestant medication as needed for
relief of symptoms until the cough resolves. Contact your PCP if the cough
persists for longer than 7 days; if you develop a high fever 103F (39.4C);
or if you cough up blood, develop chest pain, or have trouble breathing.
3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

Relevant Evaluation Criteria Scenario/Model Outcome

Information Gathering

Evaluation of Patient Outcome

9. Assess patient outcome. Ask Janet to call to update you on her response to treatment.

Key: NKA = No known allergies; UACS = upper airway cough syndrome; PCP = primary care provider.

Case 12-2

Relevant Evaluation Criteria Scenario/Model Outcome

Information Gathering

1. Gather essential information about the

patients symptoms and medical history,
including:

a. description of symptom(s) (i.e., nature, The patient has a cough that is slowly getting worse. He states that he has had a
onset, duration, severity, associated cough for years. Initially the cough was a dry morning cough, but over the past
symptoms) few months it has become productive of clear phlegm and persists throughout
the day and night.

b. description of any factors that seem to The cough is worse in the morning when he gets up and persists throughout the
precipitate, exacerbate, and/or relieve the day and night. The patient thinks it may be a smokers cough.
patients symptom(s)

c. description of the patients efforts to The patient has tried hard candy, menthol cough drops, Echinacea cough drops,
relieve the symptoms and horehound drops, but nothing stops the cough.

d. patients identity Martin Lansford

e. age, sex, height, and weight 45 years old, male, 5 ft 11 in., 75 kg

f. patients occupation Accountant

g. patients dietary habits Mostly eats a meat and potatoes diet with little fresh fruit or vegetables.

h. patients sleep habits Sleeps 9 hours a night.

i. concurrent medical conditions, Intermittent heartburn and/or sour taste in mouth; has symptoms 3-4 times per
prescription and nonprescription year. The patient takes Prilosec (omeprazole) 20 mg once a day for 3-5 days 3-4
medications, and dietary supplements times per year. He has no other known medical condition and is not taking any
routine nonprescription or dietary supplements.

j. allergies None

11 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough
Relevant Evaluation Criteria
Information Gathering
k. history of other adverse reactions to
medications
l. other (describe) _______
Assessment and Triage
2. Differentiate patients signs/symptoms
and correctly identify the patients primary
problem(s).
3. Identify exclusions for self-treatment
(Figure 12-1).
4. Formulate a comprehensive list of
therapeutic alternatives for the primary
problem to determine if triage to a health
care provider is required, and share this
information with the patient or caregiver.
Plan
5. Select an optimal therapeutic alternative Martin should be referred to his PCP for further evaluation and treatment of his
to address the patients problem, taking
into account patient preferences.
6. Describe the recommended therapeutic
approach to the patient or caregiver.
7. Explain to the patient or caregiver the
rationale for selecting the recommended
therapeutic approach from the considered
therapeutic alternatives.
Patient Education
8. When recommending self-care with
nonprescription medications and/or
nondrug therapy, convey accurate
information to the patient or caregiver.
12 of 17
http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...
Scenario/Model Outcome
None
The patient started smoking at age 16 years. He currently smokes 2 ppd.
The cough appears to be a smokers cough, but may be a symptom of chronic
bronchitis or COPD. Heartburn and dyspepsia may be symptoms of GERD;
GERD may cause chronic cough.
None
Options include:
(1) Take no action.
(2) Recommend that the patient see his PCP for further evaluation and
treatment.
(3) Recommend nondrug treatment (nonmedicated lozenges, inhale warm
steamy vapors).
(4) Recommend self-care with a nonprescription centrally acting antitussive or
expectorant.
(5) Recommend that the patient stop smoking.
chronic cough. Centrally acting antitussives (e.g., codeine, dextromethorphan)
and expectorants (e.g., guaifenesin) are not effective for the management of
smokers cough, COPD, or chronic obstructive pulmonary disease. Recommend
smoking cessation.
You should consult with your primary care provider about your chronic cough.
Chronic productive cough is a symptom associated with smoking but also with
several chronic medical conditions such as chronic bronchitis and COPD.
Chronic cough is also a symptom of lung cancer. Heartburn may trigger cough.
(See Chapter 13 for information on the assessment and self-care of heartburn
and dyspepsia.)
Criterion does not apply in this case.
3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

Relevant Evaluation Criteria Scenario/Model Outcome

Information Gathering

Solicit follow-up questions from the patient What are my choices if I decide to stop smoking?
or caregiver.

Answer the patients or caregivers Nonprescription nicotine replacement choices include nicotine-containing
questions. patches, gums, and lozenges. Prescription medications include nicotine-
containing nasal sprays and inhalers and medications that reduce nicotine
cravings such as bupropion and varenicline. Individual or group counseling are
also available to help you quit smoking. (See Chapter 47 for information on
self-care assessment of and medications for smoking cessation.)

Evaluation of Patient Outcome

9. Assess patient outcome. Ask Martin to call you after he is evaluated by his PCP to update you on his
medical condition and decision regarding smoking cessation.

Key: COPD = Chronic obstructive pulmonary disease; GERD = gastroesophageal reflux disease; PCP = primary care provider;
ppd = acks of cigarettes smoked per day.

Patient Counseling for Cough

The provider should explain the appropriate drug and nondrug measures for treating the patients type of cough. After a product
is recommended, the dosage guidelines; drug administration techniques (for topical drugs); and possible side effects, drug-drug
interactions, and precautions or warnings should be fully explained. The provider should ensure that the patient understands
when self-care of the cough should be discontinued and medical care sought. For patients with underlying medical disorders,
the provider should explain which nonprescription medications are contraindicated and what symptoms indicate the need to
seek medical care. The box Patient Education for Cough lists specific information for patients.
Patient Education for Cough
The goal of self-treatment is to reduce the number and severity of cough episodes and prevent complications. For most patients,
carefully following product instructions and the self-care measures listed here will help ensure optimal therapeutic outcomes.
Nondrug Measures

Stay well hydrated.

Reduce throat irritation by slowly dissolving nonmedicated lozenges and candies in the mouth.
Use humidifiers and vaporizers to increase the moisture in the air and possibly soothe irritated airways.
Treat the underlying cause of cough (e.g., nasal congestion).

Nonprescription Medications

Cough is a symptom of an underlying disorder. Contact your primary care provider if you have any of the exclusions for
self-care listed in Figure 12-1.
Select a product on the basis of the active ingredients and dosage formulation. Brand names frequently change and may
not clearly represent the active ingredients.
Slowly dissolve medicated lozenges in your mouth; do not chew.
Swallow tablets and capsules whole; do not crush or chew.
Follow the recommended dosing guidelines for each medication.
Store all these medications according to the manufacturers recommendations. Do not use any expired drug.

Cough Suppressants (Antitussives)

Cough suppressants control or eliminate cough and are the drugs of choice for nonproductive coughs.
Oral nonprescription cough suppressants include codeine (available without a prescription in some states),
dextromethorphan, diphenhydramine, and chlophedianol.

13 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

Topical nonprescription antitussives include camphor and menthol.

Do not heat, microwave, or add topical antitussives to hot water. Do not use topical antitussives near an open flame.
Topical antitussive ointments and liquids are toxic if ingested.
The most common side effects of codeine include nausea, vomiting, sedation, dizziness, and constipation.
Dextromethorphans side effects are uncommon but may include drowsiness, nausea, vomiting, stomach discomfort,
and constipation.
The most common diphenhydramine side effects include drowsiness, disturbed coordination, decreased respiration,
blurred vision, difficult urination, and dry mouth.
The most common chlophedianol side effects include nausea, dizziness, and drowsiness.
Codeine, dextromethorphan, diphenhydramine, and chlophedianol interact with drugs that cause drowsiness (e.g.,
narcotics, sedatives, some antihistamines, and alcohol).
Dextromethorphan and chlophedianol also interact with monoamine oxidase inhibitors (e.g., phenelzine,
tranylcypromine, and isocarboxazid). Do not take dextromethorphan or chlophedianol within 14 days of taking one of
these medications.
Diphenhydramine and chlophedianol also interact with drugs that have anticholinergic activity.
Patients with impaired respiratory reserve (e.g., asthma or chronic obstructive pulmonary disease) should use codeine
and diphenhydramine with caution.
Patients with narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic
hypertrophy, bladder-neck obstruction, elevated intraocular pressure, hyperthyroidism, heart disease, or hypertension
should use diphenhydramine with caution.
Talk with your doctor before using any medication while pregnant.
Codeine and diphenhydramine are excreted in breast milk and may cause side effects in the child.
Older adults and children may have paradoxical excitation, restlessness, and irritability with diphenhydramine or
chlophedianol. Older adults are more likely than the general population to have side effects from diphenhydramine.

Expectorants (Protussives)

Guaifenesin is the only available nonprescription protussive.

Guaifenesin is generally well tolerated, but side effects may include nausea, vomiting, dizziness, headache, rash,
diarrhea, drowsiness, and stomach pain.
There are no reported drug interactions with guaifenesin.
Guaifenesin is contraindicated in patients with a known hypersensitivity to the medication.
Guaifenesin is not indicated for chronic cough associated with chronic lower respiratory tract diseases such as asthma,
chronic obstructive pulmonary disease, emphysema, or smokers cough.

Note About Pediatric Dosing

Manufacturers of cough and cold medications have revised product labeling to state that these products should not be
used in children younger than 4 years. Health care providers should stress this information to caregivers of infants and
young children.

Evaluation of Patient Outcomes for Cough

For most patients, 7 days of nonprescription drug therapy should relieve cough. If the cough persists but has improved at
follow-up, the patient should continue the therapy until the cough is resolved. Cough associated with viral URTIs usually
resolves within 2 weeks; postviral coughs may persist for 3 weeks or longer. Coughs associated with other respiratory infections
typically resolve in 3-4 weeks. In all cases, the patient should be referred for further medical evaluation if the cough worsens or if
the patient develops other exclusions for self-treatment (Figure 12-1).

Key Points for Cough

Cough is an important respiratory defensive reflex.

Antitussives (cough suppressants) are the drugs of choice for nonproductive coughs.
Protussives (expectorants) are the drugs of choice for coughs that expel thick, tenacious secretions from the lungs with
difficulty.
Neither codeine nor dextromethorphan has been shown to be effective for acute coughs associated with viral URTIs in
either adults or children.
In 2008, manufacturers voluntarily updated labels for cough and cold products to state do not use in children younger
than 4 years.

14 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

Combination products are convenient but are generally more expensive per dose and increase the risk of undesirable
side effects.
Refer patients to their primary care provider if they have cough with thick yellow or green sputum or pus-like secretions,
or cough accompanied by one or more of the following: high fever (adults, 103F; children, >102F), shortness of
breath, chest pain, hemoptysis, chills, night sweats, tight-feeling throat, swollen legs/ankles, cyanosis, unintentional
weight loss, rash, or persistent headache.
Refer patients with cough and a history of or symptoms of chronic underlying disease associated with cough (e.g.,
asthma, COPD, chronic bronchitis, or heart failure) to their primary care provider.

References

1. Hsiao C-J, Cherry DK, Beatty PC, et al. National Ambulatory Medical Care Survey: 2007 Summary. Hyattsville, MD: National
Center for Health Statistics; 2010. National Health Statistics Reports; No. 27. Accessed at http://www.cdc.gov/nchs/data
/nhsr/nhsr027.pdf, January 22, 2013.
2.National Hospital Ambulatory Medical Care Survey: 2010 Emergency Department Summary Tables. Hyattsville, MD: National
Center for Health Statistics. Accessed at http://www.cdc.gov/nchs/data/ahcd/nhames_emergency/2010_ed_web_tables.pdf,
March 5, 2013.
3. Joint Committee on Taxation. Present Law and Background Relating to the Tax Treatment of the Cost of Over-the-Counter
Medicine as a Medical Care Expense (JCX-37-12), April 23, 2012. Accessed at https://www.jct.gov
/publications.html?func=startdown&id=4423, January 22, 2013.
4. Polverino M, Polverino F, Fasolino M, et al. Anatomy and neuro-pathophysiology of the cough reflex arc. Multidiscip Resp
Med. 2012;7:5-12.
5. Nasra J, Belvisi MG. Modulation of sensory nerve function and the cough reflex: understanding disease pathogenesis.
Pharmacol Ther. 2009; 124(3):354-75.
6. Canning BJ. Encoding of the cough reflex. Pulm Pharmacol Ther. 2007; 20(4):396-401.
7. Chang AB. The physiology of cough. Paediatric Respir Rev. 2006;7(1):2-8.
8. Chung KF, Bolser D, Davenport P, et al. Semantics and types of cough. Pulm Pharmacol Ther. 2009;22(2):139-42.
9. Footitt J, Johnston SL. Cough and viruses in airways disease: mechanisms. Pulm Pharmacol Ther. 2009;22(2):108-13.
10. Kwon S-B, Park J, Jang J, et al. Study on the initial velocity distribution of exhaled air from coughing and speaking.
Chemosphere. 2012; 87(11):1260-4. PubMed
11. Irwin RS. Introduction to the diagnosis and management of cough. Chest. 2006;129(1):25S-7S.
12. Chang AB. Pediatric cough: children are not miniature adults. Lung. 2010;188(suppl 1):S33-40.
13. Tumanan-Mendoza BA, Dans AL, et al. Dechallenge and rechallenge method showed different incidences of cough among
four ACE-Is. J Clin Epidemiol. 2007;60(6):547-53. PubMed
14. Snellman L, Adams W, Anderson G, et al. Diagnosis and treatment of respiratory illness in children and adults. Bloomington,
MN: Institute for Clinical Systems Improvement. Updated January 2013. Accessed at https://www.icsi.org/_asset/1wp8x2
/RespIllness.pdf, September 15, 2014.
15. American College of Emergency Physicians Clinical Policies Committee and the Clinical Subcommittee on Pediatric Fever.
Clinical policy for children younger than three years presenting to the emergency department with fever. Annals Emerg Med.
2003;42(4):530-45.
16. U.S. Food and Drug Administration. Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-
counter human use. CFR: Code of Federal Regulations, Title 21, Part 341. Updated April 1, 2012. Accessed at
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=341&showFR=1, January 15, 2013.
17. National Association of Boards of Pharmacy. 2013 Survey of Pharmacy Law. Mount Prospect, IL: National Association of
Boards of Pharmacy; 2012:70-3.
18. U.S. Food and Drug Administration. Controlled Substances Act. Title 21-Food and Drugs, Chapter 13-Drug Abuse
Prevention and Control, Subchapter 1-Control and Enforcement, Part B-Authority to Control; Standards and Schedules.
Accessed at http://www.fda.gov/regulatoryinformation/legislation/ucm148726.htm, March 8, 2013.
19. Peters R Jr, Yacoubian GS Jr, Rhodes W, et al. Beliefs and social norms about codeine and promethazine hydrochloride
cough syrup (CPHCS) use and addiction among multi-ethnic college students. J Psychoactive Drugs. 2007;39(3):277-82.
20. Sharfstein JM, North M, Serwint JR. Over the counter but no longer under the radarpediatric cough and cold medications.
N Engl J Med. 2007;357(23):2321-4.
21. Reissig CJ, Carter LP, Johnson MW, et al. High doses of dextromethorphan, an NMDA antagonist, produce effects similar to
hallucinogens. Psychopharmacology. 2012;223:1-15.
22. Bryner JK, Wang UK, Hui JW, et al. Dextromethorphan abuse in adolescence. Arch Pediatr Adolesc Med.
2006;160:1217-22.
23. Wilson MD, Ferguson RW, Mazer ME, et al. Monitoring trends in dextromethorphan abuse using the National Poison Data

15 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

System: 2000-2010. Clin Toxicol. 2011;49(5):409-15.

24. U.S. Food and Drug Administration. Summary Minutes of the Drug Safety and Risk Management Advisory Committee,
September 14, 2010. Accessed at http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs
/DrugSafetyandRiskManagementAdvisoryCommittee/UCM235010.pdf, July 31, 2013.
25. Chen JYP, Biller HF, Montgomery EG Jr. Pharmacologic studies of a new antitussive, alpha (dimethylaminoethyl)-ortho-
chlorobenzhydrol hydrochloride (SL-501, Bayer B-186). J Pharmacol Exp Ther. 1960;128(4):384-91.
26. Song GY, Lockhart ME, Smith JK, et al. Pseudoephedrine and guaifenesin urolithiasis: widening the differential diagnosis of
radiolucent calculi on abdominal radiograph. Abdom Imaging. 2005;30(5):644-6.
27. Coderre K, Faria C, Dyer E. Probable warfarin interaction with menthol cough drops. Pharmacotherapy. 2010;30(1):110.
28. Abanses JC, Arima S, Rubin BK. Vicks VapoRub induces mucin secretion, decreases ciliary beat frequency, and increases
tracheal mucus transport in the ferret trachea. Chest. 2009;135(1):143-8.
29. American Academy of Pediatrics. Committee on Drugs. Camphor revisited: focus on toxicity. Pediatrics. 1994;94(1):127-8.
30. Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough in children and adults in ambulatory
settings. Cochrane Database Syst Rev. 2012;8:CD001831. doi:10.1002/14651858.CD001831. Accessed at
http://www.thecochranelibrary.com/view/0/index.html.
31. Chang AB, Peake J, McElrea MS. Anti-histamines for prolonged non-specific cough in children. Cochrane Database Syst
Rev. 2010;2:CD005604. doi:10.1002/14651858.CD005604. Accessed at http://www.thecochranelibrary.com/view/0/index.html.
32. Bolser DC, Davenport PW. Codeine and cough: an ineffective gold standard. Curr Opin Allergy Clin Immunol.
2007;7(1):32-6. PubMed
33. Paul IM. Therapeutic options for acute cough due to upper respiratory infections in children. Lung. 2012;190(1):41-4.
34. Chang CC, Cheng AC, Chang AB. Over-the-counter (OTC) medications to reduce cough as an adjunct to antibiotics for
acute pneumonia in children and adults. Cochrane Database Syst Rev. 2012;2:CD006088. doi:10.1002/14651858.CD006088.
Accessed at http://www.thecochranelibrary.com/view/0/index.html.
35. Eccles R. Mechanisms of the placebo effect of sweet cough syrups. Respir Physiol Neurobiol. 2006;152(3):340-8.
36. Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough. Executive summary. Chest.
2006;129(1):1S-23S.
37. Morice AH, McGarvey L, Pavord I. Recommendations for the management of cough in adults. Thorax. 2006;61(suppl
1):i1-24.
38. Shields MD, Bush A, Everard ML, et al. Recommendation for the assessment and management of cough in children.
Thorax. 2008;63(suppl 3):iii1-15.
39. Pratter MR. Cough and the common cold. Chest. 2006;129(1 suppl):72S-4S.
40. Pratter MR. Chronic upper airway cough syndrome secondary to rhinosinus diseases (previously referred to as postnasal
drip syndrome). Chest. 2006;129(1 suppl):63S-71S.
41. U.S. Food and Drug Administration. Public Health Advisory: FDA recommends that over-the-counter (OTC) cough and cold
products not be used for infants and children under 2 years of age. Updated August 20, 2013. Accessed at http://www.fda.gov
/ForConsumers/ConsumerUpdates/ucm051137.htm, September 15, 2014.
42. Consumer Healthcare Products Association. CHPA announces voluntary labeling updates for oral OTC childrens cough and
cold medications. CHPA Executive Newsletter. 2008;Issue No. 21-08. Accessed at http://www.chpa.org/workarea
/downloadasset.aspx?id=911, September 15, 2014.
43. U.S. Food and Drug Administration. FDA statement following CHPAs announcement on nonprescription over-the-counter
cough and cold medicines in children [news release]. October 8, 2008. Accessed at http://www.fda.gov/NewsEvents/Newsroom
/PressAnnouncements/2008/ucm116964.htm, March 8, 2013.
44. U.S. Food and Drug Administration. FDA issues final guidance for liquid OTC drug products with dispensing devices [news
release]. May 4, 2011. Accessed at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm254029.htm, March
8, 2013.
45. U.S. Food and Drug Administration. Guidance for Industry: Dosage Delivery Devices for Orally Ingested OTC Liquid Drug
Products. Rockville, MD: U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug
Evaluation and Research; May 2011. Accessed at http://www.fda.gov/downloads/Drugs
/GuidanceComplianceRegulatoryInformation/Guidances/UCM188992.pdf, March 8, 2013.
46. Berlin CM, Briggs GG. Drugs and chemicals in human milk. Sem Fetal Neonatal Med. 2005;10(2):149-59.
47. Berlin CM Jr, Paul IM, Vesell ES. Safety issues of maternal drug therapy during breastfeeding. Nature. 2009;85(1):20-2.
48. Einarson A, Lyszkiewicz D, Koren G. The safety of dextromethorphan in pregnancy. Chest. 2001;119(2):466-9.
49. The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society updated Beers
criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;
doi:10.111/j.1532-5415.2012.03923.x.
50. Oduwole O, Meremikwu MM, Oyo-Ita A, et al. Honey for acute cough in children. Cochrane Database Syst Rev.
2012;3:CD007094. doi:10.1002/ 14651858.CD007094.

16 of 17 3/15/2015 1:19 AM
PharmacyLibrary | Print: Chapter 12. Cough http://www.pharmacylibrary.com/popup.aspx?aID=787091&print=yes_c...

2015 American Pharmacists Association. All Rights Reserved.

17 of 17 3/15/2015 1:19 AM