Chlorpheniramine - Drug Monograph

Introduction

Chlorpheniramine is a first-generation alkylamine antihistamine that has been widely used for over 60 years in the management of allergic conditions. As a histamine H1-receptor antagonist, it remains a common component in both prescription and over-the-counter medications for allergic rhinitis, urticaria, and other hypersensitivity reactions. Despite the development of newer, less sedating antihistamines, chlorpheniramine continues to be clinically relevant due to its efficacy, low cost, and established safety profile.

Mechanism of Action

Chlorpheniramine competitively antagonizes histamine at H1-receptor sites. By blocking the action of histamine on capillaries, smooth muscle, and sensory nerves, it prevents the characteristic symptoms of allergic reactions including vasodilation, increased capillary permeability, bronchoconstriction, and sensory nerve stimulation. Unlike second-generation antihistamines, chlorpheniramine readily crosses the blood-brain barrier, resulting in significant central nervous system effects including sedation and anticholinergic activity.

Indications

• Allergic rhinitis (seasonal and perennial)
• Allergic conjunctivitis
• Urticaria (hives)
• Angioedema
• Mild allergic skin reactions
• As an adjunct in anaphylactic reactions (after epinephrine)
• Component in cold and allergy combination products

Dosage and Administration

• Immediate-release: 4 mg every 4-6 hours (maximum 24 mg/day)
• Extended-release: 8-12 mg every 8-12 hours (maximum 24 mg/day)

• 2 mg every 4-6 hours (maximum 12 mg/day)

• 1 mg every 4-6 hours (maximum 4 mg/day)

• Hepatic impairment: Reduce dose by 50%
• Renal impairment: Use with caution; consider dose reduction
• Geriatric patients: Start with lower doses due to increased sensitivity

Pharmacokinetics

Contraindications

• Hypersensitivity to chlorpheniramine or related compounds
• Neonates and premature infants
• Patients with narrow-angle glaucoma
• Patients with bladder neck obstruction
• Patients with symptomatic prostatic hypertrophy
• Patients with severe respiratory depression
• Concurrent use with MAO inhibitors (risk of hypertensive crisis)

Warnings and Precautions

• CNS depression: May impair mental and physical abilities; caution when operating machinery
• Anticholinergic effects: Use with caution in patients with cardiovascular disease, hypertension, or hyperthyroidism
• Respiratory conditions: May thicken secretions and impair expectoration in asthma patients
• Pregnancy: Category B - use only if clearly needed
• Lactation: Excreted in breast milk; may cause sedation in infants
• Elderly: Increased risk of dizziness, sedation, and hypotension

Drug Interactions

• MAO inhibitors: Increased anticholinergic effects and risk of hypertensive crisis
• CNS depressants: Additive sedation with alcohol, benzodiazepines, opioids
• Anticholinergic drugs: Additive effects with tricyclic antidepressants, antipsychotics
• Hepatic enzyme inhibitors: May increase chlorpheniramine levels (cimetidine, macrolides)
• Hepatic enzyme inducers: May decrease efficacy (rifampin, carbamazepine)

Adverse Effects

• Sedation, drowsiness
• Dry mouth, nose, and throat
• Dizziness
• Gastrointestinal disturbances
• Thickening of bronchial secretions

• Headache
• Photosensitivity
• Urinary retention
• Blurred vision
• Tachycardia
• Hypotension
• Paradoxical excitation (especially in children)

• Anaphylaxis
• Blood dyscrasias
• Severe hypotension
• Cardiac arrhythmias
• Acute angle-closure glaucoma

Monitoring Parameters

• Therapeutic response and symptom control
• Signs of excessive sedation or CNS depression
• Anticholinergic effects (dry mouth, urinary retention)
• Blood pressure and heart rate in susceptible patients
• Mental status changes in elderly patients
• Signs of paradoxical excitation in children

Patient Education

• Take as directed; do not exceed recommended dosage
• Avoid alcohol and other CNS depressants during therapy
• Be aware of potential drowsiness; avoid driving or operating machinery
• Use sugar-free products if diabetic (many formulations contain sugar)
• Report severe drowsiness, palpitations, or difficulty urinating
• Use caution in hot environments (reduced sweating capacity)
• Chewable tablets should be chewed thoroughly before swallowing
• Extended-release tablets should be swallowed whole

References

1. Simons FER, Simons KJ. H1 Antihistamines: Current Status and Future Directions. World Allergy Organ J. 2008;1(9):145-155. 2. Church MK, Maurer M, Simons FER, et al. Risk of first-generation H1-antihistamines: a GA²LEN position paper. Allergy. 2010;65(4):459-466. 3. Golightly LK, Grell HA. Second-generation antihistamines: actions and efficacy in the management of allergic disorders. Drugs. 2005;65(3):341-384. 4. Drug Facts and Comparisons. Facts & Comparisons [database online]. St. Louis, MO: Wolters Kluwer Health Inc; 2023. 5. American Society of Health-System Pharmacists. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2023. 6. FDA Label: Chlorpheniramine Maleate. Accessdata.fda.gov. Revised 2022.