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terbinafine (Lamisil)

Tradename: Lamisil. (terbinafine hydrochloride) Indications: - onychomycosis caused by dermatophytes - Tinea capitis, Tinea cruris, Tinea pedis, Tinea corporis, Tinea versicolor - chromoblastomycosis - cutaneous candidiasis [8] Contraindications: Pregnancy category B. Not recommended in pregnant women. Not recommended in nursing mothers. Dosage: 1) Tinea: apply 1% cream BID. 2) Onychomycosis: - 250 mg PO QD - 6 weeks (fingernails) - 12 weeks (toenails) - pulse dose: 500 mg PO QD for 1st week of month - 2 months for fingernails - 4 months for toenails Tabs: 250 mg. Pharmacokinetics: 1) well absorbed orally 2) extensively metabolized by the liver 3) highly protein bound 4) elimination 1/2 life a) phase 1: 11-16 hours b) phase 2: 200-400 hours (due to slow release from skin & tissue 5) clearance is decreased in hepatic & renal impairment Monitor: - baseline & at 6 weeks of therapy a) renal function tests b) liver function tests c) complete blood count (CBC) Antibiotic susceptiblity: - susceptible organisms: - E. floccosum - T. mentagrophytes - T. rubrum - less active against yeast than azole antifungal agents Adverse effects: (% vs placebo) 1) general a) headache (12.9% vs. 9.5%) b) malaise c) fatigue 2) gastrointestinal a) diarrhea (5.6% vs 2.9%) b) dyspepsia (4.3% vs 2.9%) c) abdominal pain (2.4% vs 1.5%) d) nausea/vomiting 3) skin a) rash (5.6% vs 2.2%) b) pruritus (2.8% vs 1.5%) c) urticaria (1.1% vs 0%) d) hair loss 4) abnormal liver function tests: (3.3% vs 1.4%) 5) taste disturbance (2.8% vs 0.7%) 6) musculoskeletal a) arthralgia b) myalgia 7) rare adverse effects: a) cholestatic hepatitis b) serious skin reactions 1] Stevens-Johnson syndrome 2] toxic epidermal necrolysis c) severe neutropenia d) thrombocytopenia e) severe allergic reactions including anaphylaxis Overdose: 1) doses of up to 5 grams have been taken without serious adverse effects 2) symptoms of toxicity a) nausea/vomiting b) abdominal pain c) dizziness d) rash e) frequent urination f) headache 3) treatment is decontinuation & supportive [3] * see hepatotoxicity for management of toxicity Drug interactions: 1) increases the potency of sulfonylureas 2) terfenadine, astemizole: metabolism inhibited resulting in prolongation of the QT interval 3) cisapride: prolongation of QT interval 4) cyclosporine: decreased concentration of cyclosporine (15%) 5) rifampin increases metabolism of terbinafine 6) cimetidine decreases metabolism of terbinafine Mechanism of action: 1) allyamine derivative that inhibits squalene epoxidase, a key enzyme involved in membrane sterol synthesis in fungi 2) results in ergosterol deficiency in fungi & accumulation of squalene resulting in fungal cell death 3) fungicidal 4) remains active in the skin for at least a week after cessation of use [4] 5) 50% long-term success in fungal eradication [5]

Interactions

drug interactions

General

antifungal agent

Properties

SIZE: MW = 291.4 G/M MISC-INFO: elimination route LIVER KIDNEY 1/2life 11-16 HOURS 8-16 DAYS pregnancy-category B safety in lactation - ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996.
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 19, American College of Physicians, Philadelphia 1998, 2022
  4. Prescriber's Letter 11(3):15 2004
  5. Prescriber's Letter 11(4):21 2004
  6. deprecated reference
  7. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  8. Deprecated Reference