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.