Brompheniramine Maleate, Dexbrompheniramine Maleate

Class: First Generation Antihistamines
ATC Class: R06AB01
VA Class: AH104
CAS Number: 980-71-2
Brands: Bromaline, Bromfed, Dimetapp

Introduction

First generation antihistamines; alkylamine (propylamine) derivatives.101 102 103 106 107 109 110 111

Uses for Brompheniramine Maleate, Dexbrompheniramine Maleate

Allergic Rhinitis or Other Upper Respiratory Allergies

Used in fixed combination with other agents (e.g., dextromethorphan, guaifenesin, phenylephrine, pseudoephedrine) 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) or other upper respiratory allergies.104 105 108 113

Use fixed-combination preparations only when symptoms amenable to each ingredient are present concurrently.

Common Cold

Used in fixed combination with other agents (e.g., phenylephrine, pseudoephedrine) for temporary relief of rhinorrhea, sneezing, lacrimation, itching eyes, oronasopharyngeal itching, and/or other symptoms associated with the common cold (e.g., nasal congestion).104 105 108 113

Brompheniramine Maleate, Dexbrompheniramine Maleate Dosage and Administration

Administration

Oral Administration

Administer orally with food, water, or milk to minimize gastric irritation.102 103 106 107

Brompheniramine maleate oral solution: Use only the measuring device (e.g., calibrated dropper, cup, spoon) provided by the manufacturer.109

Dosage

Brompheniramine: Available as brompheniramine maleate; dosage expressed in terms of the salt.101 102 107

Dexbrompheniramine: Available as dexprompheniramine maleate; dosage expressed in terms of the salt.112 Dexbrompheniramine maleate available only in fixed-combination preparations.a

Individualize dosage according to patient’s response and tolerance.a

Fixed-combination preparations do not permit individual titration of dosages. When used in fixed combination with other agents (e.g., dextromethorphan, guaifenesin, phenylephrine, pseudoephedrine), select a dosage that is within the usual therapeutic range for each ingredient. Because combinations and dosage strengths vary for fixed-combination preparations, consult manufacturer’s product labeling for appropriate dosage of the specific preparation.

Pediatric Patients

Allergic Rhinitis, Other Upper Respiratory Allergies, or the Common Cold
Brompheniramine Maleate
Oral

Children 2 to <6 years of age: 1 mg every 4 hours.113

Self-medication in children 6 to <12 years of age: 2 mg every 4 hours.104 105 113

Self-medication in children ≥12 years of age: 4 mg every 4 hours.105 113

Adults

Allergic Rhinitis, Other Upper Respiratory Allergies, or the Common Cold
Brompheniramine Maleate
Oral

Self-medication: 4 mg every 4 hours.105 113

Prescribing Limits

Pediatric Patients

Allergic Rhinitis, Other Upper Respiratory Allergies, or the Common Cold
Brompheniramine Maleate
Oral

Children 2 to <6 years of age: Maximum 6 mg in 24 hours.113

Children 6 to <12 years of age: Maximum 12 mg in 24 hours.104 105 113 When used for self-medication, discontinue therapy if symptoms persist for >7 days or are accompanied by fever.104 105

Children ≥12 years of age: Maximum 24 mg in 24 hours.105 113 When used for self-medication, discontinue therapy if symptoms persist for >7 days or are accompanied by fever.105

Adults

Allergic Rhinitis, Other Upper Respiratory Allergies, or the Common Cold
Brompheniramine Maleate
Oral

Maximum 24 mg in 24 hours.105 When used for self-medication, discontinue therapy if symptoms persist for >7 days or are accompanied by fever.105

Special Populations

Geriatric Patients

Patients ≥60 years of age: Select dosage 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.101 102 103 106 107

Cautions for Brompheniramine Maleate, Dexbrompheniramine Maleate

Contraindications

Warnings/Precautions

Warnings

Concomitant Diseases

Use with caution in patients with increased IOP, bronchial asthma, hyperthyroidism, diabetes mellitus, cardiovascular disease (e.g., hypertension, ischemic heart disease), or prostatic hypertrophy.b 101 102 103 106 107 109 111

CNS Effects

Risk of drowsiness.101 105 106 107 Concurrent use of other CNS depressants may have additive CNS depressant effects.101 102 103 104 106 107 109 110 111 112 (See CNS Depressants under Interactions and also see Advice to Patients.)

Possible excitability (especially in children).101 102 103 104 105 106 107 109 111 112 (See Pediatric Use under Cautions.)

General Precautions

Anticholinergic Effects

Possible anticholinergic effects (e.g., severe dryness of mouth, nose, and throat; dysuria; urinary retention).b 102 106 Use with caution, if at all, in patients with prostatic hypertrophy, pyloroduodenal obstruction, or bladder neck obstruction.b (See Contraindications under Cautions.)

Use of Fixed Combinations

When used in fixed combination with other agents (e.g., dextromethorphan, guaifenesin, phenylephrine, pseudoephedrine), consider the cautions, precautions, and contraindications associated with the concomitant agent(s).101 103 104 105 107

Specific Populations

Pregnancy

Category C.101 102 103 106 107 109 110 111 Use not recommended during the third trimester because of risk of severe reactions (e.g., seizures) in neonates and premature infants.a 102 103 106 107

Lactation

Not known if brompheniramine is distributed into milk.102 103 106 107 110 Discontinue nursing or the drug because of potential risk to nursing infants.a 102 103 106 107 110 (See Contraindications under Cautions.)

Pediatric Use

Possible paradoxical irritability or excitement (e.g., restlessness, insomnia, tremors, euphoria, nervousness, delirium, palpitation, seizures), especially in children.b 101 106 107

Brompheniramine maleate: Safety and efficacy of brompheniramine in fixed combination with pseudoephedrine and dextromethorphan not established in children <6 months of age.113 For self-medication, do not use brompheniramine in fixed combination with phenylephrine in children <6 years of age.104 105

Risk of overdosage and toxicity (including death) in children <2 years of age receiving OTC preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection. Limited evidence of efficacy for these preparations in this age group; appropriate dosages not established. Therefore, FDA recommended not to use such preparations in children <2 years of age; safety and efficacy in older children currently under evaluation. 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 recently agreed to voluntarily revise the product labeling to state that such preparations should not be used in children <4 years of age. During the transition period, some preparations on pharmacy shelves will have the new recommendation (“do not use in children <4 years of age”), while others will have the previous recommendation (“do not use in children <2 years of age”). FDA recommends that parents and caregivers adhere to dosage instructions and warnings on the product labeling that accompanies the preparation and consult a clinician about any concerns. Clinicians should ask caregivers about use of nonprescription cough/cold preparations to avoid overdosage.

Geriatric Use

Possible increased risk of confusion, dizziness, sedation, hypotension, hyperexcitability, and anticholinergic effects (e.g., dry mouth, urinary retention [particularly in men]) in patients ≥60 years of age.101 102 103 106 107 (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Sedation (e.g., drowsiness, dizziness),101 102 103 106 107 109 110 111 CNS stimulation (e.g., restlessness, insomnia, anxiety, tension, nervousness),101 102 103 106 107 110 vertigo,102 103 106 107 weakness,102 103 106 107 confusion,102 103 106 107 blurred vision,110 nausea,101 102 dry mouth,101 109 110 111 cardiac palpitations,101 102 103 106 107 flushing,101 increased thickening of bronchial secretions.109 111

Interactions for Brompheniramine Maleate, Dexbrompheniramine Maleate

Specific Drugs and Laboratory Tests

Drug or Laboratory Test

Interaction

Comments

CNS depressants (alcohol, hypnotics, sedatives, tranquilizers, tricyclic antidepressants)

Possible additive CNS depression101 102 103 106 107 109 110 111 112

Tricyclic antidepressants prolong and intensify anticholinergic effects of antihistamines102 103 106 107

Avoid concomitant use102 103 106 107

MAO inhibitors

MAO inhibitors prolong and intensify anticholinergic effects of antihistamines102 103 106 107 109 b

Contraindicated during or within 2 weeks of MAO-inhibitor therapy101 105 106 107 109

Test, antigen or histamine

Inhalation-challenge testing with histamine or antigen: Possible suppression of test response

Antigen skin testing: Possible suppression of wheal and flare reactions

Brompheniramine Maleate, Dexbrompheniramine Maleate Pharmacokinetics

Absorption

Bioavailability

Brompheniramine and dexbrompheniramine appear to be well absorbed from the GI tract.109 110 111

Brompheniramine: Peak concentrations generally occur within 2–5 hours following oral administration.109 110 111

Onset

Brompheniramine: Antihistamine effect appears to be maximal within 3–9 hours. Antipruritic effect appears to be maximal within 9–24 hours.

Duration

Brompheniramine: Suppression of the flare response may persist for up to at least 48 hours.

Distribution

Extent

Brompheniramine: Distribution not fully characterized; appears to be widely distributed.

Elimination

Metabolism

Brompheniramine: Metabolic and excretory fate not fully characterized. Undergoes N-dealkylation and other metabolic processes to several metabolites.

Elimination Route

Brompheniramine: Excreted in urine (about 40%) and feces (about 2%) as unchanged drug and metabolites within 72 hours.

Half-life

Brompheniramine: 11.8–34.7 hours.

Dexbrompheniramine: Approximately 22 hours.

Stability

Storage

Oral

Brompheniramine Maleate Chewable Tablets and Oral Solution

20–25°C.104 105

Actions

  • Blocks H1-receptor sites, thereby preventing the action of histamine on the effector cell.109 110 111

  • Antagonizes the allergic response (vasodilation, increased vascular permeability, increased mucus secretion) of nasal tissue.109 110 111

  • Suppresses flare and pruritus that accompany the endogenous release of histamine.b

  • Has anticholinergic and sedative effects.109 110 111

  • Causes less drowsiness than some other first-generation antihistamines.101 102 106

  • Antihistamines do not block the stimulating effect of histamine on gastric acid secretion, which is mediated by H2-receptors of the parietal cells.b

Advice to Patients

  • Risk of drowsiness or dizziness;105 110 112 avoid driving, operating machinery, or engaging in other hazardous tasks if these adverse effects occur.102 103 106 107

  • Importance of avoiding alcoholic beverages during antihistamine therapy.102 103 105 106 107 108 112

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.101 102 103 106 107 110 111 Importance of patients already receiving another CNS depressant (e.g., sedative, tranquilizer) not undertaking self-medication without first consulting a clinician.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.101 102 103 106 107 110 111

  • Importance of informing patients of other important precautionary information.101 102 103 106 107 110 111 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Many prescription cough, cold, and allergy preparations commercially available in the US have not been approved by FDA.500 Because of the potentially serious health risks associated with unapproved preparations, FDA announced on March 3, 2011, that it would take enforcement action (e.g., seizure, injunction, other judicial or administrative proceeding) against any currently marketed and listed unapproved cough, cold, and allergy preparation manufactured on or after June 1, 2011 or shipped on or after August 30, 2011.500 For additional information and for a complete list of unapproved cough, cold, and allergy preparations affected by this FDA notice, see FDA website ().

Brompheniramine Maleate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

1 mg/5 mL with Phenylephrine Hydrochloride 2.5 mg/5 mL

Children’s Dimetapp Cold & Allergy

Pfizer

1 mg/5 mL with Dextromethorphan Hydrobromide 5 mg/5 mL and Phenylephrine Hydrochloride 2.5 mg/5 mL

Children’s Dimetapp Cold & Cough

Pfizer

1 mg/5 mL with Pseudoephedrine Hydrochloride 15 mg/5 mL

Bromaline

Rugby

1 mg/5 mL with Dextromethorphan Hydrobromide 5 mg/5 mL and Pseudoephedrine Hydrochloride 15 mg/5 mL

Bromaline DM Elixir

Rugby

2 mg/5 mL with Dextromethorphan Hydrobromide 10 mg/5 mL and Pseudoephedrine Hydrochloride 30 mg/5 mL

Bromfed DM Cough Syrup

Morton Grove

Tablets, chewable

1 mg with Phenylephrine Hydrochloride 2.5 mg

Children’s Dimetapp Cold & Allergy Chewable Tablets

Pfizer

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 30, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

101. Ethex Corporation. Bromfenex and Bromfenex PD (brompheniramine maleate and pseudoephedrine hydrochloride) capsules prescribing information. St. Louis, MO; 1999 Apr.

102. Larken Laboratories, Inc. LoHist 12 Hour (brompheniramine maleate) tablets prescribing information. Canton, MS; 2007 Aug.

103. Larken Laboratories. LoHist 12D (brompheniramine maleate and pseudoephedrine hydrochloride) extended-release tablets prescribing information. Madison, MS; 2005 Aug.

104. Wyeth. Dimetapp Cold & Allergy (brompheniramine maleate and phenylephrine hydrochloride) chewable tablets product information. From Wyeth Consumer Healthcare web site (). Accessed 2011 Jun 21.

105. Wyeth. Dimetapp Cold & Allergy (brompheniramine maleate and phenylephrine hydrochloride) elixir product information. From Wyeth Consumer Healthcare web site (). Accessed 2011 Jun 21.

106. ECR Pharmaceuticals. Lodrane 24 (brompheniramine maleate) extended release capsules prescribing information. Richmond, VA; 2004 Oct.

107. ECR Pharmaceuticals. Lodrane 24 D (brompheniramine maleate and pseudoephedrine hydrochloride) extended release capsules prescribing information. Richmond, VA; 2006 Jun.

108. Schering-Plough. Kenilworth, NJ: Personal communication.

109. Cypress Pharmaceutical, Inc. Bromhist PDX (brompheniramine maleate, dextromethorphan hydrobromide, and pseudoephedrine hydrochloride) drops prescribing information. Madison, MS; 2006 Jan.

110. Larken Laboratories, Inc. LoHist PD (brompheniramine maleate and pseudoephedrine hydrochloride) pediatric drops prescribing information. Canton, MS; 2007 Oct.

111. Cypress Pharmaceutical, Inc. Bromhist-DM (brompheniramine maleate, dextromethorphan hydrobromide, pseudoephedrine hydrochloride, and guaifenesin) pediatric syrup prescribing information. Madison, MS; 2006 Jan.

112. Schering-Plough Corporation. Drixoral Cold & Allergy (dexbrompheniramine maleate and pseudoephedrine sulfate) tablets product information. Kenilworth, NJ; Undated.

113. Morton Grove Pharmaceuticals, Inc. Bromfed DM (brompheniramine maleate, pseudoephedrine hydrochloride, and dextromethorphan hydrobromide) syrup prescribing information. Morton Grove, IL; 2010 Feb.

500. Food and Drug Administration. Drugs for human use; unapproved and misbranded oral drugs labeled for prescription use and offered for relief of symptoms of cold, cough, or allergy, enforcement action dates. Notice. [Docket No. FDA-2011-N-0100] Fed Regist. 2011; 76:11794-8.

a. AHFS Drug Information 2008. McEvoy GK, ed. Brompheniramine Maleate and Dexbrompheniramine Maleate. Bethesda, MD: American Society of Health-System Pharmacists; 2008:9-10.

b. AHFS Drug Information 2008. McEvoy GK, ed. Antihistamines General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2008:1-8.

Hide
(web5)