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Chlorpheniramine

Class: First Generation Antihistamines
VA Class: AH104
CAS Number: 113-92-8
Brands: Advil Allergy Sinus, Alka-Seltzer Plus, Aller-Chlor, Chlor-Trimeton, Coricidin, Dimetapp, Dristan, Flu-Relief, Kolephrin, Protid, Sine-Off, Triaminic, Tylenol

Introduction

First generation antihistamine; a propylamine-derivative.

Uses for Chlorpheniramine

Allergic Rhinitis

Symptomatic relief of allergic symptoms (e.g., rhinorrhea, sneezing, oronasopharyngeal irritation or itching, lacrimation, red, irritated, or itching eyes) caused by histamine release.

Used in fixed combination with other agents (e.g., acetaminophen, dextromethorphan, guaifenesin, ibuprofen, 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).

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

Chlorpheniramine Dosage and Administration

Administration

Oral Administration

Administer orally.

May be administered as self-medication in adults and children >6 years of age.

Administer to children 2 to ≤6 years of age under the direction of a clinician.

Dosage

Individualize dosage according to patient’s response and tolerance.

Fixed-combination preparations do not permit individual titration of dosages. When used in fixed combination with other agents (e.g., acetaminophen, dextromethorphan, guaifenesin, ibuprofen, phenylephrine, pseudoephedrine), select a dosage that is within the usual therapeutic range for each ingredient. Lower maximum daily chlorpheniramine dosages may be necessary because of other ingredients included in the formulations. 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
Oral

Children 2 to <6 years of age: 1 mg every 4–6 hours (as conventional formulations).

Children 6 to <12 years of age: 2 mg every 4–6 hours (as conventional formulations) or 8 mg (as extended-release tablets) once daily at bedtime or during the day, as indicated.

Children ≥12 years of age: 4 mg every 4–6 hours (as conventional formulations) or 8 or 12 mg (as extended-release tablets) twice daily in the morning and evening.

Adults

Allergic Rhinitis
Oral

4 mg every 4–6 hours (as conventional formulations) or 8 or 12 mg (as extended-release tablets) twice daily in the morning and evening.

Prescribing Limits

Pediatric Patients

Allergic Rhinitis
Oral

Children 2 to <6 years of age: Maximum 6 mg daily (as conventional formulations).

Children 6 to <12 years of age: Maximum 12 mg daily (as conventional formulations) or maximum 8 mg daily (as extended-release tablets).

Children ≥12 years of age: Maximum 24 mg daily (as immediate-release formulations or extended-release tablets).

Adults

Allergic Rhinitis
Oral

Maximum 24 mg daily (as conventional formulations or extended-release tablets).

Cautions for Chlorpheniramine

Warnings/Precautions

Sensitivity Reactions

Tartrazine Sensitivity

Some commercially available preparations may contain the dye tartrazine (FD&C yellow No. 5); possible allergic reactions in susceptible individuals (e.g., those sensitive to aspirin).

General Precautions

CNS Effects

Possible CNS depression (e.g., drowsiness, dizziness, weakness).

Caution when driving a motor vehicle or operating machinery. (See CNS Depressants under Interactions.)

Anticholinergic Effects

Possible anticholinergic effects (e.g., dryness of mouth, nose, and throat; dysuria; urinary retention). Use with caution, if at all, in patients with angle-closure glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, or bladder neck obstruction.

Bronchopulmonary Effects

Possible bronchopulmonary effects (e.g., tightness of the chest, thickening of bronchial secretions, wheezing). Use not recommended, unless under the direction of a clinician, in patients who have a breathing problem (e.g., emphysema, chronic bronchitis). Use generally not recommended in asthmatics who previously experienced a serious antihistamine-induced adverse bronchopulmonary effect.

Phenylketonuria

Some commercially available preparations may contain aspartame (e.g., NutraSweet) which is metabolized in the GI tract to phenylalanine.

Use of Fixed Combinations

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

Specific Populations

Pregnancy

Category B. Use not recommended during the third trimester.

Lactation

Not known whether chlorpheniramine is distributed into milk; discontinue nursing or chlorpheniramine because of potential risk to nursing infants.

Pediatric Use

Possible severe reactions (e.g., seizures) in neonates; use not recommended in premature or full-term neonates. Possible paradoxical excitement (e.g., restlessness, insomnia, tremors, euphoria, nervousness, delirium, palpitation, seizures).

Use conventional and extended-release preparations only under the direction and supervision of a clinician in children <6 years of age and in those <12 years of age, respectively.

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 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 agreed to voluntarily revise the product labeling to state that such preparations should not be used in children <4 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 dizziness, sedation, and hypotension.

Common Adverse Effects

Sedation (e.g., drowsiness, dizziness, weakness), CNS stimulation (e.g., restlessness, insomnia, nervousness).

Interactions for Chlorpheniramine

CNS Depressants

Potential pharmacologic interaction (additive CNS depression) with alcohol and other CNS depressants (e.g., hypnotics, sedatives, tranquilizers).

Laboratory Test Interferences

Antihistamines may suppress inhalation-challenge testing with histamine or antigen as well as the wheal and flare reactions to antigen skin testing.

Specific Drugs

Drug

Interaction

Comments

MAO inhibitors

MAO inhibitors prolong and intensify anticholinergic effects of antihistamines

Chlorpheniramine Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration, but only 25–45% (conventional tablets) or 35–60% (solution) of a single oral dose reaches the systemic circulation as unchanged drug.

Bioavailability of extended-release preparations is reduced compared to conventional tablets or solution.

Peak plasma concentrations generally occur within 2–6 hours following oral administration of conventional tablets or solution.

Onset

Antihistamine effect is apparent within 6 hours after a single dose.

Duration

Antihistamine effect may persist for ≥24 hours.

Distribution

Extent

Undergoes rapid and extensive distribution; however, distribution has not been characterized fully.

Plasma Protein Binding

Approximately 69–72%.

Elimination

Metabolism

Undergoes substantial metabolism in the GI mucosa during absorption and on first pass through the liver. Rapidly and extensively metabolized principally to at least 2 unidentified metabolites and monodesmethylchlorpheniramine and didesmethylchlorpheniramine.

Elimination Route

Excreted in urine.

Half-life

Terminal elimination half-life of chlorpheniramine is about 12–43 hours.

Special Populations

Terminal elimination half-life in children is about 9.6–13.1 hours (range: 5.2–23.1 hours).

Terminal elimination half-life in patients with chronic renal failure undergoing hemodialysis is about 280–330 hours.

Stability

Storage

Oral

Tablets

Tight containers at 15–30°C.

Extended-release Tablets

Well-closed containers at 15–30°C.

Oral Solution

Tight, light-resistant containers at 15–30°C; avoid freezing.

Actions and Spectrum

  • Blocks H1-receptor sites and prevents the action of histamine on the cell.

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

  • Exhibits some activities common to anticholinergics, ganglionic and adrenergic blocking agents, local anesthetics, and antispasmodics.

  • Causes less drowsiness and more CNS stimulation than some other first generation antihistamines.

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

Advice to Patients

  • Importance of informing individuals who perform potentially hazardous tasks requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle) about possible drowsiness, dizziness, or weakness.

  • Importance of avoiding alcoholic beverages during antihistamine therapy.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses. Importance of patients already receiving another CNS depressant (e.g., sedatives, tranquilizers) 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.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Chlorpheniramine Maleate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Oral

Solution

2 mg/5 mL*

Aller-Chlor Syrup

Rugby

Chlorpheniramine Maleate Solution

Tablets

4 mg*

Aller-Chlor

Rugby

Chlorpheniramine Maleate Tablets

Chlor-Trimeton 4 Hour Allergy (scored)

Schering-Plough

Tablets, extended-release

8 mg*

Chlorpheniramine Maleate Extended-release Tablets

12 mg*

Chlorpheniramine Maleate Extended-release Tablets

Chlorpheniramine Maleate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, liquid-filled

2 mg with Acetaminophen 325 mg, Dextromethorphan Hydrobromide 10 mg, and Phenylephrine Hydrochloride 5 mg

Alka-Seltzer Plus Cold & Cough Formula

Bayer

Solution

1 mg/5 mL with Acetaminophen 160 mg/5 mL and Dextromethorphan Hydrobromide 7.5 mg/5 mL

Triaminic Multi-Symptom Fever

Novartis

1 mg/5 mL with Acetaminophen 160 mg/5 mL, Dextromethorphan Hydrobromide 5 mg/ 5 mL, and Phenylephrine Hydrochloride 2.5 mg/5 mL

Children’s Tylenol Plus Multi-Symptom Cold

McNeil

1 mg/5 mL with Dextromethorphan Hydrobromide 7.5 mg/5 mL

Dimetapp Long Acting Cough Plus Cold

Pfizer

Tablets

2 mg with Acetaminophen 325 mg

Coricidin HBP Cold & Flu

Schering-Plough

2 mg with Acetaminophen 500 mg and Phenylephrine Hydrochloride 5 mg

Sine-Off Sinus/Cold Caplets

Gemini

4 mg with Dextromethorphan Hydrobromide 30 mg

Coricidin HBP Cough & Cold

Schering-Plough

Tablets, extended-release

8 mg with Acetaminophen 500 mg and Phenylephrine Hydrochloride 40 mg

Protid

Lunsco

Tablets, film-coated

2 mg with Acetaminophen 325 mg and Phenylephrine Hydrochloride 5 mg

Dristan Cold

Pfizer

2 mg with Acetaminophen 325 mg and Pseudoephedrine Hydrochloride 30 mg

Flu-Relief Caplets

Pfeiffer

Kolephrin Caplets

Pfeiffer

2 mg with Ibuprofen 200 mg and Pseudoephedrine Hydrochloride 30 mg

Advil Allergy Sinus Caplets

Pfizer

AHFS DI Essentials™. © Copyright 2022, Selected Revisions February 1, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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