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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LAMISIL (LAMISIL).
| Breastfeeding | Terbinafine is excreted in human milk; M/P ratio not determined. Breastfeeding is not recommended during treatment due to potential for infant exposure. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to terbinafine, chronic or active liver disease, severe renal impairment (CrCl <50 mL/min), lactation (excreted in breast milk).
| 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. |
Loading safety data…
| Fertility Effects | No adverse effects on fertility observed in animal studies. Human data insufficient. |