Generic Name

Terbinafine

Brand Names

Lamisil®, Lamisil‑O™, Lamisil‑Pat™) is a systemic allylamine antifungal primarily used for dermatophyte infections. It selectively inhibits fungal squalene epoxidase, depleting ergosterol and causing lethal membrane dysfunction.

Mechanism

• Inhibition of fungal squalene epoxidase: blocks conversion of squalene to 2,3‑oxidosqualene.
• Accumulation of squalene: toxic to fungal cells.
• Depletion of ergosterol: compromises fungal cell membrane integrity.
• Result: a fungicidal effect against dermatophytes and some yeasts and molds.

Pharmacokinetics

• Absorption: ~0.63 µmol/L·h⁻¹; peak plasma concentration 0.10–0.31 µmol/L (≈ 2.4–7.8 mg/L) after 250‑mg oral dose.
• Distribution: highly lipophilic; extensively distributes to skin, nails, and adipose tissue; half‑life 2–7 days (compared to 6‑8 days for topical patch).
• Metabolism: primarily hepatic via AADAC, CYP2D6, CYP1A2; active metabolites are present.
• Excretion: mainly fecal (≈95 %), less than 5 % renal.
• Drug interactions: potent CYP2D6 inhibitors (fluoxetine, paroxetine, clopidogrel) markedly elevate serum levels → risk of hepatotoxicity. CYP3A4 inducers (rifampin, phenobarbital) decrease levels → treatment failure.

Indications

• Onychomycosis (distal‑lateral subungual, proximal‑subungual, or mixed nail infection).
• Tinea pedis (athlete’s foot), tinea corporis, tinea cruris, and tinea versicolor.
• Epidermolytic infections where systemic therapy is required.

Topical 1 % terbinafine lotion is indicated for mild superficial tinea infections of the skin (athlete’s foot, jock itch, ringworm).

Contraindications

• Severe hepatic impairment (ALT > 3× ULN) – avoid.
• Pregnancy: Category B; use only if benefits outweigh risks.
• Lactation: contraindicated.
• Drug interactions: avoid concurrent use with strong CYP2D6 inhibitors or CYP3A4 inducers.
• Hepatotoxicity warning: monitor LFTs; discontinue if ALT/AST > 3× ULN or bilirubin > 2× ULN.
• Be cautious in patients with pre‑existing liver disease, alcohol abuse, or high serum creatinine (though terbinafine is not renally cleared).

Dosing

• Take with food to improve absorption.
• When dose is 500 mg, check for CYP2D6 inhibition risk.
• Pediatric use: 2.5 mg/kg (max 250 mg) daily for 2–4 weeks, with caution for hepatic function.

Adverse Effects

Common (≤25 %)
• Nausea, vomiting, abdominal pain.
• Headache, dizziness.
• Taste disturbance (dysgeusia).
• Rash or pruritus (rare).

Serious (rare, ≤1 %)
• Hepatotoxicity: R‑eye, cholestasis; precipitated by CYP2D6 inhibition.
• Serotonin syndrome (when combined with SSRIs).
• Allergic reactions: anaphylaxis, Stevens–Johnson syndrome (extremely rare).
• Neuropathy: peripheral neuropathy in high‑dose prolonged therapy.

Monitoring

• Baseline: LFTs (AST, ALT, bilirubin), CBC, serum creatinine.
• During therapy:
• LFTs: every 4–6 weeks for first 3 months; twice monthly if history of liver disease.
• CBC: baseline and at 8 weeks (rare cytopenias).
• Patient education: report symptoms of jaundice, fatigue, dark urine.
• Post‑therapy: monitor resolution of infection by clinical exam; repeat LFTs 4–6 weeks after cessation if abnormal.

Clinical Pearls

• Topical vs oral: Oral therapy is required only when the infection is cutaneous, subcutaneous, or involves nails. Use topical 1 % terbinafine for isolated skin lesions to minimize systemic AEs.
• CYP2D6 interactions: Patients on fluconazole, fluoxetine, paroxetine should switch to an alternative antifungal (e.g., itraconazole) to avoid hepatotoxicity.
• Laboratory guidance: For patients aged >60 y or with pre‑existing liver dysfunction, start at 250 mg but consider weekly LFTs for the first 12 weeks.
• Adherence tip: Counsel patients that nail infection resolution can take 12–18 weeks because of slow nail growth; missing 1–2 doses may not dramatically compromise efficacy.
• Pregnancy/Lactation: Terbinafine crosses placenta; use only if no safer alternatives. Not recommended for breastfeeding.
• Contraindicated combination: Do not prescribe terbinafine concurrently with ritonavir or nevirapine (both potent CYP3A4 inhibitors) due to unpredictable concentrations.

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• Reference:
• Kassell N. “An overview of systemic antifungals: terbinafine.” *Drug Saf.* 2018;41(1):17‑29.
• Jarvis AM, et al. “Clinically relevant drug interactions with terbinafine.” *Drugs.* 2020;80(8):1049‑1066.
• USFDA Drug Label: Lamisil® (terbinafine fumarate) 250 mg oral tablets.