Terfenadine, a non-sedating antihistamine, was widely used to treat allergic rhinitis (hay fever) and urticaria (hives). However, due to the risk of serious cardiac side effects, including torsades de pointes and cardiac arrest, it has been withdrawn from the market in many countries, including the United States. Fexofenadine, its active metabolite, is now preferred as it lacks these cardiac risks. This information is for historical and educational purposes only and should not be used for current clinical decision-making.
Usage
- Medical Conditions: Terfenadine was previously prescribed for the relief of symptoms associated with seasonal allergic rhinitis (hay fever), other allergic conditions like skin allergies and urticaria (hives), and allergic reactions to insect bites.
- Pharmacological Classification: Antihistamine (H1-receptor antagonist).
- Mechanism of Action: Selectively blocks histamine H1-receptors, preventing the actions of histamine released during allergic reactions. This reduces symptoms like itching, sneezing, runny nose, and hives.
Alternate Names
- International/Regional Variations: Terfenadine.
- Brand Names: Seldane (withdrawn).
How It Works
- Pharmacodynamics: Terfenadine acts as a selective histamine H1-receptor antagonist in peripheral tissues. It competes with histamine for binding at H1 receptors, thus reducing the effects of histamine during an allergic response.
- Pharmacokinetics:
- Absorption: Rapidly absorbed from the gastrointestinal tract.
- Metabolism: Extensively metabolized in the liver, primarily by the CYP3A4 enzyme, to its active metabolite, fexofenadine. Terfenadine itself has little or no H1-receptor antagonist activity. Impaired metabolism can lead to increased terfenadine levels and serious cardiac side effects.
- Elimination: Excreted in urine and feces.
- Mode of Action: Terfenadine’s metabolite, fexofenadine, competitively inhibits histamine binding to the H1 receptor. This prevents histamine-mediated vasodilation, bronchoconstriction, and increased capillary permeability.
- Receptor Binding/Enzyme Inhibition: Fexofenadine, the active metabolite of terfenadine, binds selectively to peripheral H1 receptors. Terfenadine itself is a prodrug and inhibits the CYP3A4 enzyme, leading to potential drug interactions.
- Elimination Pathways: Primarily hepatic metabolism via CYP3A4, followed by excretion in urine and feces.
Terfenadine is no longer recommended for use due to safety concerns. The dosage information below is for historical reference only.
Standard Dosage
Adults: 60 mg twice daily or 120 mg once daily. Maximum: 120 mg daily.
Children: (Use not recommended.) Historically, dosing was based on age:
- 3-5 years: 15 mg twice daily.
- 6-12 years: 30-60 mg twice daily.
Special Cases:
- Elderly Patients: Dose adjustments may be necessary due to age-related changes in metabolism and organ function.
- Patients with Renal Impairment: Dosage reduction is recommended for patients with creatinine clearance less than 40 mL/min.
- Patients with Hepatic Dysfunction: Contraindicated due to increased risk of cardiotoxicity.
- Patients with Comorbid Conditions: Use with caution in patients with heart disease.
Clinical Use Cases (Not Applicable - Drug Withdrawn)
Dosage Adjustments (Not Applicable - Drug Withdrawn)
Side Effects
Common Side Effects
- Drowsiness, fatigue
- Headache
- Nausea, vomiting
- Dry mouth
Rare but Serious Side Effects
- Cardiac arrhythmias, including torsades de pointes, ventricular fibrillation, and cardiac arrest (especially with drug interactions or overdose).
- QT interval prolongation.
- Seizures.
- Hepatotoxicity.
Long-Term Effects (Limited data available due to withdrawal)
Adverse Drug Reactions (ADR)
- Severe allergic reactions (anaphylaxis).
- Liver dysfunction.
- Life-threatening cardiac arrhythmias.
Contraindications
- Hypersensitivity to terfenadine.
- Liver disease.
- Concomitant use of medications that inhibit CYP3A4 (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin).
- History of cardiac arrhythmias or QT prolongation.
- Porphyria.
Drug Interactions
- CYP3A4 Inhibitors: Ketoconazole, itraconazole, erythromycin, clarithromycin, grapefruit juice significantly increase terfenadine levels, increasing the risk of cardiac side effects.
- Other Medications: Certain antibiotics, antifungals, antiarrhythmics, and other drugs may interact with terfenadine.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (historical). Limited human data; potential fetal risks. Use only if benefits outweigh risks.
- Breastfeeding: Limited data; the active metabolite fexofenadine is excreted in breast milk in small amounts. Monitor infant for potential side effects.
Popular Combinations (Not Applicable - Drug Withdrawn)
Precautions (Not Applicable - Drug Withdrawn)
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Terfenadine?
A: Terfenadine is no longer recommended for use due to the risk of serious cardiac side effects.
Q2: Why was Terfenadine withdrawn from the market?
A: Terfenadine was withdrawn due to its potential to cause serious cardiac arrhythmias, particularly torsades de pointes, especially when taken with certain other medications or in overdose.
Q3: What are the major side effects of Terfenadine?
A: Major side effects included cardiac arrhythmias, QT prolongation, headache, drowsiness, fatigue, nausea, and dry mouth.
Q4: What are the contraindications for Terfenadine use?
A: Contraindications included liver disease, concomitant use of CYP3A4 inhibitors (like ketoconazole, itraconazole, erythromycin), and a history of cardiac arrhythmias.
Q5: What is the mechanism of action of Terfenadine?
A: Terfenadine is a prodrug that is metabolized to fexofenadine. Fexofenadine acts as a selective H1-receptor antagonist, blocking the effects of histamine.
Q6: Can Terfenadine be used during pregnancy or breastfeeding?
A: Terfenadine was generally avoided during pregnancy and breastfeeding due to limited safety data.
Q7: What drug interactions are important to consider with Terfenadine?
A: Co-administration with CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, grapefruit juice) could significantly increase terfenadine levels, leading to dangerous cardiac side effects.
Q8: What is a safer alternative to Terfenadine?
A: Fexofenadine, the active metabolite of Terfenadine, is a safer alternative and is now widely used for treating allergies. It does not have the same cardiac risks as terfenadine.
Q9: Is Terfenadine still available?
A: Terfenadine has been withdrawn from the market in many countries due to safety concerns.
