Chlorphenamine: Effects as an antihistamine
Chlorphenamine (internationally also known as Chlorpheniramine, brand names Codipront in combination preparations and generics) is a classic first generation antihistamine. Since the 1950s it has been part of the treatment of allergic diseases. In Germany, chlorphenamine is mainly found in combination preparations for colds containing codeine or antitussives. Monotherapy with pure chlorphenamine is rare today because modern second generation antihistamines such as cetirizine, loratadine and fexofenadine have less sedating effects.
Characteristic of first generation antihistamines is the pronounced blood brain barrier penetration. This makes chlorphenamine sedating and therefore suitable for acute allergies with marked itching or nocturnal allergic symptoms, but at the same time problematic for daytime use. The anticholinergic side effect can lead to confusion, falls and urinary retention in elderly patients, which is why chlorphenamine is used very restrictively in geriatrics.
Mechanism of action
Chlorphenamine competitively blocks the histamine H1 receptor and thus inhibits allergic symptoms triggered by histamine such as itching, vasodilation, mucus secretion and bronchoconstriction. Unlike modern H1 antagonists of the second generation, chlorphenamine crosses the blood brain barrier and works centrally. This explains the sedating effect with drowsiness, sleepiness and reduced responsiveness.
Additionally, chlorphenamine blocks muscarinic acetylcholine receptors, which leads to typical anticholinergic effects: dry mouth, accommodation disorders, constipation, tachycardia, urinary retention. These side effects are usually tolerable with short term use, but with longer therapy and in elderly people they can force discontinuation of treatment.
Oral bioavailability is approximately 25 to 50 percent. The half life is 13 to 27 hours, which allows for one to two times daily administration. Chlorphenamine is metabolized hepatically via CYP2D6 and CYP3A4. Genetic variants and comedications can relevantly influence levels.
Indications
- Allergic reactions such as hay fever, urticaria, food allergies, insect bite reactions
- Allergic conjunctivitis and rhinitis, especially when sedation at night is desired
- Pruritus in atopy, eczema and allergic skin diseases, often as nocturnal as needed medication
- Adjuvant in anaphylaxis therapy after epinephrine and glucocorticoids
- Cold preparations in fixed combinations with codeine, pseudoephedrine or other active ingredients, to relieve runny nose and cough
- Off label for sleep disorders, in emergency medicine or with short term use
Chlorphenamine is not first line therapy in chronic treatment of allergic rhinitis or urticaria because modern non sedating antihistamines like cetirizine or loratadine are better tolerated. In elderly people, chlorphenamine is listed on the Priscus list of potentially inappropriate medications.
Dosage and administration
Adults: 4 mg three to four times daily or 8 mg twice daily (extended release form). Maximum dose 24 mg per day.
Children between 6 and 12 years: 2 mg three to four times daily, individual adjustment based on weight.
Children between 2 and 6 years: 1 mg four times daily, child appropriate syrup form.
Children under 2 years: Use very restrictive and only under medical supervision.
In acute allergic reaction: 10 mg intramuscularly or intravenously, in emergency medicine.
Administration: with or without meals, sufficient water. Tablets generally at bedtime because sedation is desired then. Extended release form can be taken in the morning and evening if daytime use is necessary.
Renal insufficiency: cautious dosing in case of impaired function. Hepatic insufficiency: dose reduction in case of moderate to severe impairment.
Adverse effects
Very common: Drowsiness, sleepiness, reduced attention.
Common: Dry mouth, accommodation disorders with blurred vision, constipation, dizziness, headache, tachycardia, urinary retention in patients with benign prostatic hyperplasia.
Uncommon: paradoxical excitation in children and elderly people, confusion, hallucinations at higher doses.
Rare: Rash, allergic reactions, bone marrow suppression, photosensitivity, gastrointestinal complaints.
In elderly people: increased risk of falls, confusion, cognitive deterioration, acute angle closure glaucoma attack in narrow angle glaucoma, urinary retention in benign prostatic hyperplasia. Use should be very restrictive.
In children: paradoxical excitation with hyperactivity, irritability or sleep disorders is possible.
Drug interactions
- Other centrally depressing substances (benzodiazepines, Z substances, opioids, alcohol, antipsychotics, tricyclics): increased sedation, fall risk, respiratory depression possible.
- Other anticholinergics: additive anticholinergic effect with confusion, tachycardia, constipation, urinary retention.
- MAO inhibitors: prolonged and enhanced anticholinergic effect, avoid combination.
- Beta blockers: no specific interaction.
- QT prolonging substances: theoretically additive effect, clinical significance at standard doses is low.
- CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion): increased chlorphenamine levels.
- Food: no relevant interactions, however a fat rich meal may slightly slow resorption.
Special notes
Pregnancy: Limited data. In case of compelling indication, use after individual risk benefit assessment. Modern antihistamines with better data are preferred, such as loratadine or cetirizine. Breast feeding: Transfer into breast milk, sedating effect in the infant possible. Use not recommended.
Children and adolescents: possible from 1 year of age in pediatric indications, if used at all. In small children consider paradoxical excitation.
Elderly patients: critical due to blood brain barrier penetration and anticholinergic effect. Priscus 2.0 list classifies first generation antihistamines as potentially inadequate. If at all, then lowest dose and shortest duration of therapy.
Preexisting conditions: contraindicated in manifest narrow angle glaucoma, severe benign prostatic hyperplasia with residual urine, gastrointestinal stenoses, paralytic ileus, myasthenia gravis.
Ability to drive: significantly impaired by sedation, especially in the early phase of therapy. Before activities requiring increased attention (driving, operating machinery) check responsiveness individually.
Alcohol: enhances sedation, therefore avoid.
Lifestyle: for chronic allergies modern non sedating antihistamines, allergen avoidance, if necessary specific immunotherapy.
You may also be interested in
- Cetirizine, modern second generation antihistamine
- Loratadine, another second generation antihistamine
- Fexofenadine, also an H1 antihistamine
- Dimetindene, classic H1 antihistamine
- Diphenhydramine, another sedating H1 antihistamine
Frequently asked questions
How does chlorphenamine differ from modern antihistamines?
Chlorphenamine is a first generation antihistamine with pronounced blood brain barrier penetration, therefore sedating and anticholinergic. Modern H1 antagonists of the second generation such as cetirizine, loratadine and fexofenadine are less sedating, well tolerated for daytime use and more suitable for long term therapy.
Does chlorphenamine cause dependence?
There is no classical physical dependence. With longer use, tolerance to the sedating effect may develop. When used as a sleep aid, short term use makes sense because better sleep aids and non pharmacological strategies are more effective in chronic sleep disorders.
Why is chlorphenamine critical in elderly people?
First generation antihistamines have anticholinergic effects that can lead to falls, confusion and cognitive deterioration in elderly people. Geriatric lists such as Priscus classify these substances as potentially inappropriate. For allergies, modern non sedating antihistamines should be preferred.
May I drive a car while taking chlorphenamine?
During the initial dosing phase and with any daytime use, responsiveness is often significantly impaired. Sedation can vary greatly between individuals. Before driving a vehicle or operating machinery, individual responsiveness should be checked. Evening administration reduces daytime risk.
Sources
- Gelbe Liste, Chlorphenamine active ingredient profile
- BfArM, Federal Institute for Drugs and Medical Devices
- AWMF, Guidelines for allergic diseases
- Priscus 2.0 List, potentially inappropriate medication in the elderly
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