Terbinafine

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Mechanism of action

  • Inhibit squalene epoxidase >> accumulation of squalene >> subsequent deficiency of ergosterol >> fungistatic action (fungicidal in vitro).

Indications

  • Tinea pedis (moccasin type)/tinea manuum
    • (adults) :250 mg/day × 2 weeks.
    • (children): 125 mg (<25 kg),187.5 mg (25–35 kg) or250 mg (>35 kg) × 2 weeks.
  • Tinea unguium
    • (adults)(FDA):250 mg/day × 12 weeks(Toe nails) ; 250 mg/day × 6 weeks (finger nails).
    • (children): 62.5 mg/day (<20 kg), 125 mg/day (20–40 kg) or 250 mg/day (>40 kg) × 6 weeks (fingernails)or 12 weeks (toenails).
  • Tinea corporis
    • (extensive, adults) :250 mg/day × 1 week.
    • (extensive, children):125 mg (<25 kg),187.5 mg (25–35 kg) or250 mg (>35 kg) × 1 week.
  • Tinea capitis
    • (adults) : 250 mg/day × 3–4 weeks.
    • (children):125 mg (<25 kg),187.5 mg (25–35 kg) or250 mg (>35 kg) × 3–4 weeks.
  • Majocchi’s granuloma : 250 mg/day po for 2–3 week.
  • Subcutaneous and systemic mycoses : chromoblastomycosis,sporotrichosis, fungal mycetoma, aspergillosis, and histoplasmosis.
  • Tinea imbricata: 250 mg PO qd for 4 weeks.
  • Cutaneous sporotrichosis: 250 mg/day until clinical recovery (at least 3 months).
  • Black piedra :250 mg PO qd for 6 weeks.
  • Aspergillosis: 5–15 mg/kg/d PO for 3–5 months.
  • Chromoblastomycosis : 250 mg daily until clinical recovery.
  • Subcutaneous and systemic mycoses: 500–1000 mg daily.

Dosage

According to diagnosis and age, (revise indications)

  • Oral tablets
    • Adults : 250 mg daily.
    • Children over 2 years old and under 20 kg : 62.5 mg daily.
    • Children over 2 years old and 20–40 kg :125 mg daily.
    • Children over 2 years old and over 40 kg :250 mg daily.
  • Oral granules for tinea capitis
    • Children over 4 years old and under 25 kg : 125 mg daily.
    • Children over 4 years old and 25–35 kg :187.5 mg daily.
    • Children over 4 years old and over 35 kg : 250 mg daily.

Baseline Monitoring

  • Pre-existing liver disease should be assessed before prescribing terbinafine (serum transaminase tests: ALT, AST).

Follow Up Monitoring

  • Liver function test.

Side effects

  • Gastrointestinal
    • Diarrhea (5.6%),dyspepsia(4.3%),abdominal pain (2.4%),nausea (2.6%),flatulence (2.2%).
  • Cutaneous.
    • Rash (5.6%),pruritus(2.8%),urticaria(1.1%).
  • Subacute cutaneous lupus erythematosus.
  • Neurologic
    • Headache.
  • Hepatic
    • LFT ≥ 2 × upper limit of normal.
    • Idiosyncratic hepatobiliary dysfunction(rare).
  • Rare
    • Erythema multiforme, toxic epidermal necrolysis, and Stevens–Johnson syndrome.
  • Blood
    • Transient decreases in absolute lymphocyte count.
    • Neutropenia in immunosuppressed patients.

Contraindications

  • Allergic reaction to terbinafine.
  • Chronic or active liver disease.

Interactions

  • Terbinafine is a CYP2D6 and CYP1A2 inhibitor.
  • It may increase serum levels and toxic effects of ( β-blockers, TCAs, SSRIs, MAO inhibitors,and type B and class IC antiarrhythmics).
  • Terbinafine increases cyclosporine clearance by 15% and decreases caffeine clearance by 19%.
  • It also decreases the efficacy of codeine.
  • Terbinafine used with thioridazine may cause prolonged QT intervals and arrhythmias.
  • Cimetidine increases terbinafine levels, rifampin decreases terbinafine levels by doubling its rate of clearance.

Pregnancy &Lactation

  • It is recommended that oral terbinafine not be initiated during pregnancy.
  • Enters breast milk, not recommended for use in nursing mothers.

Precautions

  • Obtain pre-ttt ALT, AST if suspected liver disease.
  • Avoid if creatinine clearance ≤50 mL/min.
  • Discontinue if:
    • Liver disease.
    • Progressive skin rash occurs.
    • Neutrophil count ≤1,000 cells/mm3.
    • Signs of LE.
    • Taste, smell and visual disturbances.
    • Clinical symptoms and lab findings consistent with thrombotic microangiopathy(unexplained thrombocytopenia -anemia).
  • Use with caution:
    • In renal impairment.
    • Risk factors for CHF.
    • Using calcium channel blockers.
  • Monitor for sings and symptoms of CHF.
  • Use with caution in:
    • Proarrhythmic conditions.
    • Renal and liver impairement.
    • Monitor for depressive symptoms.
  • Patients should be instructed to report any symptoms of liver dysfunction, such as persistent nausea,anorexia, fatigue, vomiting, right upper abdominal pain or jaundice, dark urine, or pale stools.
  • Due to potential toxicity, confirmation of onychomycosis or dermatophytosis recommended.

Drug Info:

  • Granule formulation of terbinafine is also approved for tinea capitis in patients 4 years and older.
  • Terbinafine is less effective when the causative agent of the onychomycosis is Candida species, in particular C. albicans.
  • Both terbinafine and itraconazole have been reported as effective and safe when used off-label for onychomycosis in children.
  • Terbinafine is considered a safe medication for the general population, as well as children, the elderly, transplant patients, diabetics, and HIV patients.
  • Hepatitis produced by terbinafne typically develops within 4–6 weeks of treatment initiation, and has the features of both hepatocellular necrosis and cholestatic injury.
  • In most cases liver functions return to normal several months after stopping the medication.
  • No effects noted on testosterone levels.


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