AHFS Class:

• First Generation Antihistamines 4:04

Generic Name(s):

• Brompheniramine Maleate

• Brompheniramine Maleate and Pseudoephedrine Sulfate

• Dexbrompheniramine Maleate

Associated Monographs

• Antihistamines General Statement

Brompheniramine and dexbrompheniramine are alkylamine (propylamine)-derivative first generation antihistamines.

Brompheniramine and dexbrompheniramine share the actions and uses of other antihistamines. Preparations containing brompheniramine maleate or dexbrompheniramine maleate in fixed combination with other agents (e.g., dextromethorphan, guaifenesin, phenylephrine, pseudoephedrine) are used for relief of rhinorrhea, sneezing, lacrimation, itching eyes, oronasopharyngeal itching, and/or other symptoms (e.g., nasal/sinus congestion, cough) associated with allergic rhinitis (e.g., hay fever), other upper respiratory allergies, or the common cold. Combination preparations generally should only be used when symptoms amenable to each ingredient are present concurrently.

Administration

Brompheniramine maleate and dexbrompheniramine maleate are administered orally. These agents should be administered with food, water, or milk to minimize gastric irritation.

Doses of brompheniramine maleate oral solution should be measured using the measuring device (e.g., calibrated dropper, cup, spoon) provided by the manufacturer.

Dosage

Dosage of brompheniramine maleate and dexbrompheniramine maleate is expressed in terms of the salt. Dosage of brompheniramine maleate and dexbrompheniramine maleate should be individualized according to the patient's response and tolerance.

Fixed-ratio combination preparations do not permit individual titration of dosages; if a fixed combination is used, the precautions and contraindications associated with each drug must be considered.

Brompheniramine Maleate

When brompheniramine maleate is used in fixed combination with other agents (e.g., dextromethorphan, guaifenesin, phenylephrine, pseudoephedrine), the dosage of the fixed-ratio combination should be within the range for the usual therapeutic dosage of each ingredient.

Dosage of brompheniramine maleate in patients 60 years of age and older should be selected with caution, starting at the lower end of the usual dosage range, because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

The usual dosage of brompheniramine maleate in adults and children 12 years of age and older is 4 mg every 4 hours, not to exceed 24 mg in 24 hours. When used for self-medication , therapy should be discontinued if symptoms persist for more than 7 days or are accompanied by fever.

Children 6 to younger than 12 years of age may receive brompheniramine maleate at a dosage of 2 mg every 4 hours, not to exceed 12 mg in 24 hours. When used for self-medication , therapy should be discontinued if symptoms persist for more than 7 days or are accompanied by fever.

When used under the direction of a clinician, children 2 to younger than 6 years of age may receive 1 mg of brompheniramine maleate every 4 hours, not to exceed 6 mg in 24 hours.

Brompheniramine and dexbrompheniramine share the toxic potentials of other antihistamines, and the usual precautions of antihistamine therapy should be observed. (See Cautions in the Antihistamines General Statement 4:00.)

Pediatric Precautions

Safety and efficacy of brompheniramine maleate in fixed combination with pseudoephedrine and dextromethorphan have not been established in children younger than 6 months of age. Brompheniramine maleate in fixed combination with phenylephrine should not be used for self-medication in children younger than 6 years of age.

Overdosage and toxicity (including death) have been reported in children younger than 2 years of age receiving nonprescription (over-the-counter, OTC) preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection. There is limited evidence of efficacy for these preparations in this age group, and appropriate dosages (i.e., approved by the US Food and Drug Administration [FDA]) for the symptomatic treatment of cold and cough have not been established. Therefore, FDA stated that nonprescription cough and cold preparations should not be used in children younger than 2 years of a the agency continues to assess safety and efficacy of these preparations in older children. Meanwhile, because children 2-3 years of age also are at increased risk of overdosage and toxicity, some manufacturers of oral nonprescription cough and cold preparations agreed to voluntarily revise the product labeling to state that such preparations should not be used in children younger than 4 years of age. FDA recommends that parents and caregivers adhere to the dosage instructions and warnings on the product labeling that accompanies the preparation if administering to children and consult with their clinician about any concerns. Clinicians should ask caregivers about use of nonprescription cough and cold preparations to avoid overdosage. For additional information on precautions associated with the use of cough and cold preparations in pediatric patients, see Cautions: Pediatric Precautions in the Antihistamines General Statement 4:00.

Geriatric Precautions

Geriatric patients (60 years of age and older) may be particularly susceptible to confusion, dizziness, sedation, hypotension, hyperexcitability, and anticholinergic effects (e.g., dry mouth, urinary retention [particularly in men]). Geriatric patients should receive lower initial dosages of brompheniramine maleate.

Mutagenicity and Carcinogenicity

Long-term studies to determine the mutagenic and carcinogenic potentials of brompheniramine and dexbrompheniramine have not been performed to date.

Pregnancy, Fertility, and Lactation

Pregnancy

There is inadequate experience with use of brompheniramine or dexbrompheniramine in pregnant women to determine whether the potential for harm to the fetus exists. Because of the risk of severe reactions (e.g., seizures) to antihistamines in neonates, brompheniramine or dexbrompheniramine should not be used during the third trimester; the drugs should be used during the first 2 trimesters only when the potential benefits justify the possible risks to the fetus.

Fertility

Reproduction studies in rats and mice using brompheniramine dosages up to 16 times the maximum human dosage have not revealed evidence of impaired fertility or harm to the fetus. It is not known whether the drug can affect fertility in humans.

Lactation

It is not known if brompheniramine is distributed into milk. Because of the potential for serious adverse reactions to antihistamines in nursing infants, a decision should be made whether to discontinue nursing or brompheniramine or dexbrompheniramine, taking into account the importance of the drug to the woman. Excessive crying, irritability, and sleep disturbances occurred in one breast-fed infant whose mother was receiving dexbrompheniramine combined with pseudoephedrine; normal behavior in the infant resumed within 12 hours after the mother discontinued the drug and the infant received 2 formula feedings.

Pharmacokinetics

Absorption

Brompheniramine and dexbrompheniramine maleates appear to be well absorbed from the GI tract.

Following oral administration of a single 0.13-mg/kg dose of brompheniramine maleate in healthy, fasting adults in one study, peak serum brompheniramine concentrations of 7.7-15.7 ng/mL occurred within 2-5 hours; in most of these individuals, a second lower peak, possibly secondary to enterohepatic circulation, also was observed. The antihistamine effect of brompheniramine, as determined by suppression of the wheal and flare responses induced by intradermal administration of histamine, appears to be maximal within 3-9 hours after a single oral dose of the drug, but suppression of the flare response may persist for up to at least 48 hours; the antipruritic effect appears to be maximal within 9-24 hours.

Following oral administration of 2 mg of dexbrompheniramine maleate every 4 hours in healthy adults, mean peak plasma concentrations of the drug were about 22 ng/mL on the sixth and seventh days of dosing and mean trough concentrations were about 17 and 18 ng/mL on the sixth and seventh days, respectively.

Distribution

Distribution of brompheniramine into human body tissues and fluids has not been fully characterized, but the drug appears to be widely distributed. Following oral administration of a single dose of the drug in healthy adults, the apparent volume of distribution reportedly averaged 11.7 L/kg.

Elimination

In healthy adults, the half-life of brompheniramine reportedly ranges from 11.8-34.7 hours. The metabolic and excretory fate of the drug has not been fully characterized. Brompheniramine undergoes N -dealkylation to form monodesmethylbrompheniramine and didesmethylbrompheniramine, and is metabolized to the propionic acid derivative, which is partially conjugated with glycine, and to other unidentified metabolites. Brompheniramine and its metabolites are excreted principally in urine. About 40% of an oral dose of brompheniramine is excreted in urine and about 2% in feces within 72 hours in healthy individuals. In healthy individuals, about 5-10% of an oral dose is excreted in urine as unchanged drug, 6-10% as monodesmethylbrompheniramine, 6-10% as didesmethylbrompheniramine, small amounts as the propionic acid derivative and its glycine conjugate, and the remainder as unidentified metabolites.

In healthy adults, dexbrompheniramine reportedly has an elimination half-life of about 22 hours.

Chemistry and Stability

Chemistry

Brompheniramine and dexbrompheniramine are alkylamine (propylamine)-derivative antihistamines. The drugs differ from chlorpheniramine in the substitution of a bromine atom for the chlorine atom of the latter compound. Dexbrompheniramine, the dextro isomer, is approximately twice as active as racemic brompheniramine on a weight basis. Brompheniramine maleate occurs as a white, odorless, crystalline powder and has solubilities of approximately 200 mg/mL in water and 66.7 mg/mL in alcohol at 25°C. Dexbrompheniramine maleate occurs as a white, odorless, crystalline powder, existing in 2 polymorphic forms, and has solubilities of approximately 833 mg/mL in water and 400 mg/mL in alcohol at 25°C. Brompheniramine has pK_a values of 3.59 and 9.12.

Stability

Preparations containing brompheniramine maleate generally should be stored in tight, light-resistant containers at a controlled room temperature between 15-30°C. The manufacturer's product information should be consulted for specific recommendations.

Additional Information

For further information on chemistry, pharmacology, pharmacokinetics, uses, cautions, acute toxicity, drug interactions, laboratory test interferences, and dosage and administration of brompheniramine and dexbrompheniramine, see the Antihistamines General Statement 4:00.

Please see the general statement for a list of references.