Please note: Astemizole has been withdrawn from the market in many countries, including the US, due to the risk of serious cardiac side effects, including QT prolongation and torsades de pointes. This information is for historical and educational purposes only and should not be interpreted as a recommendation for its use. Safer alternative antihistamines are available.
Usage
- Medical Conditions: Astemizole was previously prescribed for the relief of symptoms associated with seasonal allergic rhinitis (hay fever) and chronic idiopathic urticaria (hives). It was also used for other allergic conditions like conjunctivitis, eczema, reactions to insect bites, and some food allergies.
- Pharmacological Classification: Antihistamine (H1 receptor antagonist).
- Mechanism of Action: Astemizole selectively blocks the effects of histamine at the H1 receptor. Histamine is a chemical mediator responsible for many of the symptoms of allergic reactions. By blocking histamine’s action, astemizole reduces symptoms such as sneezing, runny nose, itching, and watery eyes.
Alternate Names
- International/Regional Variations: Hismanal (brand name - discontinued)
- Brand Names: Hismanal (discontinued), and various generic formulations (no longer marketed in many countries).
How It Works
- Pharmacodynamics: Astemizole acts as a selective H1 receptor antagonist, competitively inhibiting the binding of histamine to its receptors. It has little to no effect on other receptors, such as muscarinic or serotonergic receptors, leading to fewer side effects compared to first-generation antihistamines.
- Pharmacokinetics:
- Absorption: Readily absorbed from the gastrointestinal tract.
- Metabolism: Extensively metabolized in the liver, primarily by the CYP3A4 enzyme system. This metabolism produces the active metabolite, desmethylastemizole.
- Elimination: Metabolites are slowly eliminated through both urinary and fecal routes, with an elimination half-life of approximately 24 hours for astemizole itself, extending to several days or weeks for its metabolites. This long half-life contributes to its once-daily dosing.
- Mode of Action: Astemizole acts by competitively and reversibly binding to the histamine H1 receptor on the surface of cells, preventing histamine from binding and triggering the allergic cascade.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: It primarily involves H1 receptor antagonism.
Dosage (Historical - Not Recommended)
It is crucial to understand that astemizole is no longer recommended for use due to safety concerns. The following dosage information is provided for historical context only.
Standard Dosage
Adults: 10 mg orally once daily.
Children (6-12 years): 5 mg orally once daily.
Children (under 6 years): Not recommended.
Special Cases:
- Elderly Patients: Use with caution due to potential for prolonged elimination. Dosage adjustments may be required.
- Patients with Renal Impairment: Use with caution. Clinical studies evaluating dosage adjustments have not been adequately performed.
- Patients with Hepatic Dysfunction: Contraindicated due to potential for increased drug levels and adverse cardiovascular events.
- Patients with Comorbid Conditions: Pre-existing cardiac disease or conditions that can prolong the QT interval are contraindications.
Clinical Use Cases
Astemizole is not recommended for use in any clinical setting.
Dosage Adjustments
No specific dosage adjustments are available due to the withdrawal of the drug. Historically, dose adjustments were not typically necessary for renal impairment, but hepatic impairment was a contraindication.
Side Effects
Common Side Effects
- Increased appetite
- Weight gain
- Headache
- Drowsiness
- Fatigue
- Dry mouth
Rare but Serious Side Effects
- Cardiac arrhythmias: QT prolongation, torsades de pointes, ventricular tachycardia, cardiac arrest. These are the primary reasons for the drug’s withdrawal.
Long-Term Effects
The long half-life means potential long-term persistence of side effects, especially cardiac effects, even after discontinuation.
Adverse Drug Reactions (ADR)
Cardiac arrhythmias are the most significant ADRs, potentially leading to life-threatening complications.
Contraindications
- Hypersensitivity to astemizole
- Concomitant use of ketoconazole, itraconazole, erythromycin, clarithromycin, troleandomycin, or other drugs that inhibit CYP3A4 metabolism
- Pre-existing cardiac conditions, including QT prolongation
- Hepatic impairment
- Hypokalemia or other electrolyte imbalances
- Pregnancy and breastfeeding (unless the potential benefit justifies the risk to the fetus or infant)
Drug Interactions
- CYP3A4 Inhibitors: Antifungal agents (ketoconazole, itraconazole), macrolide antibiotics (erythromycin, clarithromycin), and certain other drugs can significantly increase astemizole levels, increasing the risk of cardiac arrhythmias. These combinations are contraindicated.
- Other Drugs that Prolong the QT Interval: Concurrent use increases the risk of additive QT prolongation.
- Grapefruit Juice: May inhibit metabolism and increase astemizole levels.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Risk cannot be ruled out). Use during pregnancy is generally contraindicated due to potential risks to the fetus.
- Breastfeeding: Astemizole can be excreted in breast milk. Breastfeeding while taking astemizole is contraindicated.
Drug Profile Summary (Historical)
- Mechanism of Action: H1 receptor antagonist.
- Side Effects: Increased appetite, weight gain, headache, drowsiness, fatigue, dry mouth. Rare but serious: Cardiac arrhythmias (QT prolongation, torsades de pointes).
- Contraindications: Hypersensitivity, concomitant use of CYP3A4 inhibitors, pre-existing cardiac conditions, hepatic impairment.
- Drug Interactions: CYP3A4 inhibitors, QT-prolonging drugs.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: 10 mg once daily; children (6-12 yrs): 5 mg once daily.
- Monitoring Parameters: ECG (for QT interval), electrolyte levels.
Popular Combinations (Historical)
Astemizole is not recommended in combination with any other drugs.
Precautions (Historical)
- Assess for pre-existing cardiac conditions and electrolyte imbalances.
- Monitor ECG for QT prolongation during therapy.
- Caution in patients with renal impairment and the elderly.
FAQs (Frequently Asked Questions) (Historical)
Q1: What is the recommended dosage for Astemizole?
A: Historically, the recommended dosage for adults was 10 mg orally once daily. For children aged 6-12 years, it was 5 mg orally once daily. Astemizole is no longer recommended for use due to safety concerns.
Q2: What are the main side effects of Astemizole?
A: Common side effects included increased appetite, weight gain, headache, drowsiness, and dry mouth. However, rare but serious cardiac arrhythmias, including QT prolongation and torsades de pointes, led to its withdrawal from the market.
Q3: Why was Astemizole withdrawn from the market?
A: Astemizole was withdrawn due to the risk of serious, potentially fatal cardiac arrhythmias, particularly QT prolongation and torsades de pointes. These risks were amplified when taken with certain other medications.
Q4: What are the contraindications for Astemizole?
A: Contraindications included hypersensitivity, concomitant use of certain medications (like ketoconazole, itraconazole, and erythromycin), pre-existing cardiac conditions, hepatic impairment, and hypokalemia.
Q5: Can Astemizole be used during pregnancy or breastfeeding?
A: Astemizole is generally contraindicated during pregnancy and breastfeeding due to potential risks to the fetus or infant.
Q6: What are some safer alternatives to Astemizole?
A: Several safer second-generation antihistamines are available, including loratadine, cetirizine, fexofenadine, and desloratadine. Consult with a physician for appropriate alternatives.
Q7: How does Astemizole work differently from first-generation antihistamines?
A: Astemizole is more selective for the H1 receptor and does not readily cross the blood-brain barrier, resulting in fewer sedative and anticholinergic side effects compared to first-generation antihistamines like diphenhydramine.
Q8: What should a patient do if they are currently taking Astemizole?
A: They should discontinue use immediately and contact their physician for a safer alternative.
Q9: Does Astemizole interact with any foods?
A: Grapefruit juice can inhibit the metabolism of astemizole, potentially leading to higher drug levels and increased risk of side effects.
