Usage
Terbinafine is an antifungal medication primarily prescribed for the treatment of fungal infections affecting the skin, hair, and nails. These include:
- Onychomycosis: Fungal infection of the fingernails or toenails (tinea unguium).
- Tinea corporis: Ringworm of the body.
- Tinea cruris: Jock itch (ringworm of the groin).
- Tinea pedis: Athlete’s foot (ringworm of the foot).
- Tinea capitis: Ringworm of the scalp (primarily in children).
Pharmacological Classification: Antifungal (allylamine class)
Mechanism of Action: Terbinafine inhibits squalene epoxidase, a fungal enzyme essential for ergosterol synthesis. Ergosterol is a crucial component of the fungal cell membrane. Disruption of ergosterol biosynthesis leads to increased membrane permeability, causing fungal cell death.
Alternate Names
While “terbinafine” is the generic name, it is marketed under various brand names, including Lamisil, Terbinex and Deolate.
How It Works
Pharmacodynamics: Terbinafine accumulates in the keratin precursor cells of the skin, hair, and nails, achieving fungicidal concentrations. It disrupts fungal cell membrane integrity by inhibiting squalene epoxidase.
Pharmacokinetics:
- Absorption: Well-absorbed orally, with bioavailability around 80%. Food does not significantly affect absorption.
- Distribution: Highly lipophilic and distributes extensively into skin, nails, and adipose tissue.
- Metabolism: Extensively metabolized in the liver, primarily by CYP2D6, 1A2, 3A4, and 2C9 enzymes.
- Elimination: Excreted mainly in urine and feces.
Mode of Action:
Terbinafine acts by inhibiting squalene epoxidase in the fungal cell membrane. This enzyme is essential in the biosynthesis of ergosterol, a vital component of fungal cell membranes. The inhibition of squalene epoxidase leads to:
- Depletion of ergosterol: Compromising the structural integrity and function of the fungal cell membrane.
- Accumulation of squalene: Further disrupting membrane function and leading to fungal cell death.
Terbinafine does not affect human steroid hormone synthesis.
Dosage
Standard Dosage
Adults:
- Onychomycosis: 250 mg orally once daily. Fingernails: 6 weeks; Toenails: 12 weeks.
- Tinea corporis/cruris/pedis: 250 mg orally once daily for 2-6 weeks, depending on the infection site and severity.
- Tinea capitis: 250 mg orally once daily for 4 weeks.
Children:
Dosing is based on body weight:
- <20 kg: 62.5 mg daily.
- 20-40 kg: 125 mg daily.
- >40 kg: 250 mg daily.
Special Cases:
- Elderly Patients: No specific dosage adjustments unless renal or hepatic impairment is present.
- Patients with Renal Impairment (CrCl <50 mL/min): Dose reduction to 125 mg daily is recommended. Avoid use if CrCl <20 mL/min.
- Patients with Hepatic Dysfunction: Contraindicated in patients with chronic or active liver disease.
- Patients with Comorbid Conditions: Monitor for potential drug interactions, particularly with drugs metabolized by CYP enzymes. Caution advised in patients with pre-existing autoimmune conditions like lupus.
Clinical Use Cases
Terbinafine’s clinical use is primarily focused on the treatment of fungal infections. It’s not typically used in the clinical settings mentioned (intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations).
Side Effects
Common Side Effects:
Headache, gastrointestinal upset (nausea, diarrhea, abdominal pain), rash, taste disturbance, and altered sense of smell.
Rare but Serious Side Effects:
Severe liver injury (hepatotoxicity), including liver failure, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, neutropenia, angioedema, and anaphylaxis.
Long-Term Effects:
Long-term effects are rare with typical treatment durations. Monitor for persistent taste or smell disturbances.
Adverse Drug Reactions (ADR):
Any signs of hepatotoxicity (jaundice, dark urine, right upper quadrant pain), severe skin reactions, or blood dyscrasias require immediate discontinuation of terbinafine and prompt medical evaluation.
Contraindications
- Chronic or active liver disease.
- Hypersensitivity to terbinafine.
Drug Interactions
Terbinafine is metabolized by several CYP450 enzymes (mainly CYP2D6, 1A2, 3A4, and 2C9). It can interact with drugs that inhibit or induce these enzymes:
- CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): May increase terbinafine levels.
- CYP2D6 inducers (e.g., rifampin): May decrease terbinafine levels.
- Cimetidine: May increase terbinafine levels.
- Rifampin: May decrease terbinafine levels.
Also consider interactions with:
- Caffeine: Terbinafine may increase caffeine levels.
- Ciclosporin: Terbinafine may increase ciclosporin levels.
Pregnancy and Breastfeeding
- Pregnancy: Terbinafine is classified as Pregnancy Category B. Limited human data suggest no major fetal risks, but use only if clearly needed.
- Breastfeeding: Terbinafine is excreted in breast milk. Potential risks to the infant are unknown. Consider alternative antifungals or discontinue breastfeeding.
Drug Profile Summary
- Mechanism of Action: Inhibits squalene epoxidase, disrupting fungal cell membrane synthesis.
- Side Effects: Headache, GI upset, rash, taste/smell disturbances; rarely, hepatotoxicity, severe skin reactions.
- Contraindications: Chronic/active liver disease, hypersensitivity.
- Drug Interactions: CYP2D6 and other CYP enzyme inhibitors/inducers; cimetidine, rifampin, caffeine, ciclosporin.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
- Dosage: Adults: 250 mg/day; Pediatrics: weight-based dosing; adjust for renal impairment.
- Monitoring Parameters: Liver function tests (baseline and periodically during treatment), complete blood count (if indicated).
Popular Combinations
Terbinafine is generally used as monotherapy. Topical antifungals may be used concomitantly for onychomycosis.
Precautions
- General Precautions: Assess liver function before starting treatment. Monitor for adverse effects.
- Specific Populations: See above in “Special Cases”
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Terbinafine?
A: Adults: 250 mg orally once daily. Pediatric dosing is weight-based (see above). Adjust dose for renal impairment.
Q2: How long does Terbinafine take to work?
A: Clinical improvement may take several weeks to months, even after the infection is cleared, especially with nail infections due to slow nail growth.
Q3: What are the most common side effects of Terbinafine?
A: Headache, gastrointestinal disturbances (nausea, diarrhea), rash, and taste/smell changes.
Q4: Is Terbinafine safe for patients with liver disease?
A: No. It’s contraindicated in patients with chronic or active liver disease due to the risk of hepatotoxicity.
Q5: Can Terbinafine interact with other medications?
A: Yes. It can interact with drugs metabolized by CYP enzymes (e.g., some antidepressants, antifungals). Inform your patients to report all concomitant medications.
Q6: Can Terbinafine be used during pregnancy or breastfeeding?
A: Use cautiously if benefits outweigh risks. Consider the potential for fetal exposure and infant exposure through breast milk.
Q7: What should I do if a patient develops a rash while taking Terbinafine?
A: Evaluate the rash. If it’s mild, it may be managed symptomatically. If it’s severe or suggestive of a serious skin reaction (e.g., Stevens-Johnson syndrome), discontinue Terbinafine immediately and refer to a dermatologist.
Q8: How is Terbinafine different from other antifungals?
A: Terbinafine belongs to the allylamine class and has a unique mechanism of action compared to azoles like itraconazole or fluconazole. It specifically targets squalene epoxidase. It tends to have good penetration into keratinized tissues like skin and nails.
Q9: What patient education is crucial for Terbinafine therapy?
A: Advise patients about potential side effects, drug interactions, the importance of completing the full course of treatment, and the need to report any signs of liver dysfunction or severe skin reactions promptly. Emphasize that clinical improvement may take time, especially with nail infections.
Q10: When should liver function tests be monitored during terbinafine therapy?
A: Obtain baseline liver function tests before initiating therapy and periodically during treatment, especially if treatment is prolonged. Consider monitoring at 4-6 weeks after starting treatment or if any signs or symptoms of hepatic dysfunction appear.
