Clemastine
Sedating first generation H1 antihistamine
Clemastine is a first generation antihistamine from the ethanolamine class. Sandoz introduced the compound in 1967 under the trade name Tavegil. In Germany Tavegil is available as tablets, syrup and injection solution, and generics also exist. Over the counter dispensing is usual for the oral forms, while the injection solution is reserved for clinical emergency medicine. Clemastine shows pronounced antihistamine activity and a relevant sedating component.
In everyday practice clemastine is used more cautiously today than it used to be, because non sedating second generation antihistamines such as cetirizine, loratadine or fexofenadine are better tolerated in most allergic indications. In acute and emergency medicine, in severe allergic reactions with a strong pruritus component and in sleep disorders with nocturnal itch, clemastine remains an option. The intravenous form is also still kept in the emergency trolley of many hospitals as adjunctive therapy during anaphylaxis alongside adrenaline.
Mechanism of Action
Clemastine competitively blocks H1 histamine receptors. Histamine is released from mast cells and basophils during allergic reactions and binds to H1 receptors on endothelial cells, smooth muscle and peripheral nerve fibres. The consequences are vasodilation, increased vascular permeability, bronchoconstriction and transmission of itch. Clemastine prevents this binding and thereby reduces wheals, itch, lacrimation, sneezing and mucosal oedema.
As a lipophilic ethanolamine clemastine crosses the blood brain barrier and acts centrally on H1 receptors. These receptors in the brain contribute to wakefulness and attention. The central blockade explains the pronounced sedation that is absent with modern second generation antihistamines. The half life is about 20 hours, which can prolong sedation into the following day.
Clemastine is also moderately anticholinergic, alpha adrenergic blocking and antiemetic. These accompanying effects explain both desirable side effects (sedation in pruritus, antiemetic action in motion sickness) and adverse effects (dry mouth, urinary retention, accommodation disturbances, orthostatic hypotension).
Indications
- Allergic rhinitis and conjunctivitis as short term therapy, especially for nocturnal itch
- Chronic and acute urticaria particularly for intense night time pruritus
- Pruritic dermatoses (atopic eczema, insect stings) in combination with topical therapy
- Anaphylactic and pseudo allergic reactions as adjunctive intravenous therapy alongside adrenaline and glucocorticoids
- Drug induced allergic reactions for symptomatic relief
- Premedication before contrast medium administration in patients at increased risk of allergoid reactions
Dosage and Administration
Adults and adolescents from 12 years of age: 1 mg (one tablet or 10 ml of syrup) twice daily, morning and evening. In severe cases up to 6 mg per day. Children aged 6 to 12 years: 0.5 to 1 mg twice daily. Children aged 1 to 6 years: 0.25 to 0.5 mg twice daily as syrup, on medical indication.
Intravenous use: 2 mg (one 5 ml ampoule) slowly over at least two minutes. Combination with adrenaline and a glucocorticoid in anaphylaxis according to emergency protocol. The intravenous form does not replace adrenaline when there is cardiovascular involvement but supplements treatment to relieve itch and urticaria.
Renal impairment: no formal dose adjustment, caution in severe impairment. Hepatic impairment: dose reduction, slowed metabolism. Elderly patients: reduced dose because of intensified anticholinergic and sedating effects and an increased risk of delirium and falls.
Side Effects
Very common and common: tiredness, sedation, drowsiness, impaired reaction capacity, dry mouth, constipation, blurred vision, urinary difficulty, headache.
Uncommon: dizziness, orthostatic hypotension, tachycardia, appetite changes, nausea, diarrhoea, rash, paradoxical reactions in children and elderly people (restlessness, insomnia, nightmares).
Rare and serious: blood count changes (leukopenia, thrombocytopenia, agranulocytosis), anaphylaxis (paradoxical), seizures through lowering of the seizure threshold, elevated liver enzymes, severe anticholinergic delirium in elderly patients.
Important: fitness to drive is often limited under clemastine. Residual fatigue and slowed reactions can persist on the day after administration. In combination with alcohol the impairment is markedly intensified.
Interactions
- Centrally depressant substances (alcohol, benzodiazepines, opioids, barbiturates): strongly increased sedation, risk of respiratory depression
- Anticholinergics (tricyclic antidepressants, atropine, biperiden, scopolamine): additive anticholinergic adverse effects up to anticholinergic delirium
- MAO inhibitors: intensified anticholinergic effects, the combination should be avoided
- Antihypertensives: intensified hypotension
- CYP3A4 inhibitors (ketoconazole, erythromycin): theoretically increased plasma levels, clinical relevance usually low
Special Notes
Contraindications: known hypersensitivity, narrow angle glaucoma, urinary retention in prostatic hypertrophy, acute asthma attack, porphyria, children under one year of age (paradoxical reactions, hyperthermia, respiratory depression). Caution in epilepsy and in severe hepatic disease.
Elderly patients: clemastine is on the Priscus list of potentially inappropriate medications. The risk of anticholinergic induced confusion, falls and urinary retention is increased. Where possible, second generation antihistamines such as desloratadine or levocetirizine should be preferred.
Pregnancy: experience in the first trimester is limited; use is possible for an acceptable indication after a clear benefit risk assessment. At the end of pregnancy caution is advised because of possible sedation or paradoxical effects in the newborn. Breastfeeding: clemastine passes into breast milk with possible sedation of the infant and a reduction in milk production; breastfeeding during therapy should be approached with caution.
Driving ability: patients must be explicitly informed that clemastine can impair driving ability and the operation of machinery. This applies in particular in the first days of therapy, during dose escalation and with concomitant alcohol intake.
Monitoring: clinical review of the allergic symptoms, attention to cognitive effects in elderly patients. Long term use should only be undertaken on a strict indication.
You might also be interested in
- Cetirizine, a less sedating second generation antihistamine
- Levocetirizine, the R enantiomer of cetirizine
- Desloratadine, an antihistamine with low sedation
- Fexofenadine, a non sedating antihistamine
- Diphenhydramine, a related ethanolamine antihistamine
Frequently Asked Questions
Why does Tavegil make you so tired?
Clemastine crosses the blood brain barrier and blocks central H1 receptors which are responsible for wakefulness. This produces pronounced sedation. Modern second generation antihistamines are less lipophilic and scarcely penetrate the brain, so they cause much less drowsiness and are preferred by drivers and working professionals.
Is clemastine an anaphylaxis medicine?
Clemastine is given intravenously as adjunctive therapy in anaphylaxis but is not the main pillar. The life saving first measure is intramuscular adrenaline. Antihistamines and glucocorticoids complement treatment and above all ease the cutaneous symptoms. Adrenaline must not be omitted under any circumstances.
May I combine clemastine and alcohol?
No. The combination considerably intensifies central depression, driving ability drops drastically and the risk of falls rises. With higher amounts of alcohol respiratory depression may occur. As long as you are taking clemastine you should avoid alcohol as far as possible.
Should I avoid clemastine in old age?
In geriatrics caution applies. The Priscus list of potentially inappropriate medications for elderly patients includes sedating H1 antihistamines because of the risk of confusion, delirium, falls and urinary retention. Where antihistamine therapy is needed, non sedating second generation substances are clearly to be preferred.
Sources
- EMA, European Medicines Agency
- AWMF, S3 Guidelines on Urticaria and Anaphylaxis
- Gelbe Liste, Clemastine active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
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The information provided on this page is for general informational purposes only and does not constitute medical advice, diagnosis or treatment recommendation. It does not replace consultation with a licensed physician or pharmacist. Medicines should only be taken on medical prescription or via a pharmacy. All information is based on product information and recognised scientific sources published at the time of creation; the manufacturer's current summary of product characteristics is always authoritative. Sanoliste assumes no liability for the completeness, timeliness or accuracy of the information presented. In a medical emergency, call the emergency number 112 (Europe).