LAMISIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LAMISIL (LAMISIL).
Allylamine antifungal that inhibits squalene epoxidase, an enzyme in the ergosterol biosynthesis pathway, leading to accumulation of squalene and disruption of fungal cell membrane function.
| Metabolism | Hepatic via CYP2D6, CYP1A2, and CYP3A4; extensive first-pass metabolism; active metabolite is N-desmethylterbinafine. |
| Excretion | Approximately 70% of the administered dose is excreted in the urine as metabolites, with less than 5% as unchanged drug. About 20% is eliminated via feces. Terbinafine undergoes extensive hepatic metabolism; renal elimination of metabolites is the primary route. |
| Half-life | Terminal elimination half-life is approximately 17-24 hours in healthy adults. However, it can prolong to about 36-40 hours in patients with renal or hepatic impairment. The prolonged half-life allows for once-daily dosing. Due to extensive tissue distribution, the functional half-life (terminal phase from tissues) may be longer. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is about 2000 L (approximately 25-30 L/kg based on 70 kg), indicating extensive tissue distribution with high affinity for adipose tissue, skin, and nails. |
| Bioavailability | Oral bioavailability is approximately 70-80% when taken with food. Topical bioavailability is minimal (<5%) due to low percutaneous absorption. |
| Onset of Action | Oral: Onset of clinical effect (symptom relief) typically occurs within 1-2 weeks for dermatophyte infections; however, noticeable improvement may take 4-6 weeks. Topical: Onset of action is within 1-2 days for tinea infections, but clinical resolution may require 1-4 weeks. |
| Duration of Action | Oral: Duration of action persists for several weeks after therapy discontinuation due to high drug concentration in keratinous tissues (skin, hair, nails). For dermatophytosis, clinical cure may persist for up to 6-12 months. Topical: Duration varies; typically requires application for 1-4 weeks. |
| Molecular Weight | 291.43 |
250 mg orally once daily for 2-6 weeks for dermatophyte infections; 250 mg orally once daily for 12 weeks for onychomycosis.
| Dosage form | SOLUTION |
| Renal impairment | Creatinine clearance <50 mL/min: contraindicated (no data); >50 mL/min: no adjustment. |
| Liver impairment | Child-Pugh class A: caution, reduce dose by 50%? limited data; Child-Pugh B or C: contraindicated. |
| Pediatric use | >2 years and <20 kg: 62.5 mg orally once daily; 20-40 kg: 125 mg orally once daily; >40 kg: 250 mg orally once daily. Duration: 6 weeks for tinea capitis. |
| Geriatric use | No dose adjustment required based on age alone; assess renal function (CrCl) and hepatic function before use. |
| 1st trimester | Avoid due to potential risk; limited human data but animal studies show embryotoxicity at high doses. |
| 2nd trimester | Limited data; use only if clearly needed and benefit outweighs risk. |
| 3rd trimester | Limited data; use only if clearly needed and benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for LAMISIL (LAMISIL).
| Placental transfer | Crosses placenta; animal studies indicate transfer. Human data limited but shows fetal tissue distribution at lower concentrations than maternal plasma. |
| Breastfeeding | Terbinafine is excreted into breast milk in small amounts; levels are approximately 0.5% of maternal dose. Caution if breastfeeding a preterm or low-birth-weight infant. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to terbinafineChronic or active liver disease
| Precautions | Hepatotoxicity (rare but severe), taste disturbance (often reversible), Stevens-Johnson syndrome, toxic epidermal necrolysis, drug-induced lupus, hepatobiliary dysfunction, monitoring of liver function tests recommended. |
| Food/Dietary | Avoid grapefruit juice as it may increase terbinafine serum concentrations. Alcohol should be avoided during therapy and for at least 2 weeks after cessation due to risk of hepatotoxicity. No significant food interactions with standard meals; absorption is not affected by food. |
| Clinical Pearls |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; however, adequate human studies are lacking. Administer during pregnancy only if clearly needed. |
| Fetal Monitoring | No specific maternal-fetal monitoring required; standard prenatal care is advised. |
| Fertility Effects | No adverse effects on fertility observed in animal studies. Human data insufficient. |
| LAMISIL (terbinafine) is a fungicidal allylamine that inhibits squalene epoxidase, leading to accumulation of squalene and fungal cell death. It achieves high concentrations in keratin-rich tissues (skin, hair, nails) and remains detectable for weeks after therapy cessation. For onychomycosis, efficacy is highest with continuous dosing; pulse dosing is not FDA-approved. Monitor hepatic function at baseline and during prolonged therapy (>6 weeks). Avoid in patients with pre-existing liver disease or chronic alcoholism. Drug interactions: CYP2D6 substrates (e.g., tricyclic antidepressants, SSRIs, beta-blockers) may have increased levels. Caution with CYP2D6 poor metabolizers. |
| Patient Advice | Take exactly as prescribed; do not stop early even if symptoms improve. · Complete full course of therapy; nail infections may take months to clear. · Avoid alcohol during treatment and for 2 weeks after due to rare liver effects. · Report signs of liver problems: dark urine, pale stools, jaundice, persistent nausea. · Use sunscreen as terbinafine may increase photosensitivity. · Inform your doctor if you have psoriasis or lupus history; may exacerbate. · Do not take if pregnant, planning pregnancy, or breastfeeding unless approved. · Taste disturbance (dysgeusia) may occur and usually resolves after stopping. |