LAMISIL AT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LAMISIL AT (LAMISIL AT).
Terbinafine inhibits squalene epoxidase, an enzyme in the fungal ergosterol biosynthesis pathway. This leads to accumulation of squalene and depletion of ergosterol, disrupting fungal cell membrane integrity and causing cell death.
| Metabolism | Extensively metabolized in the liver via CYP1A2, CYP2C9, CYP2C19, CYP3A4, and CYP2D6 to inactive metabolites. |
| Excretion | Terbinafine is extensively metabolized in the liver; approximately 80% of a dose is excreted in urine as metabolites, and 20% in feces. Less than 1% is excreted unchanged in urine. |
| Half-life | The terminal elimination half-life is approximately 11-17 hours in healthy adults; however, it increases to about 200-400 hours in the distribution phase from tissues (e.g., skin, adipose). Steady-state is reached after 10-14 days of oral dosing. |
| Protein binding | Terbinaine is highly bound to plasma proteins, primarily albumin; binding is >99%. |
| Volume of Distribution | The apparent volume of distribution (Vd) is approximately 900–1000 L (about 13–14 L/kg for a 70 kg person), indicating extensive tissue distribution, particularly into skin, hair, and nails. |
| Bioavailability | Oral terbinafine: approximately 70-80% (first-pass metabolism reduces it; absolute bioavailability is 40-50% based on AUC comparisons). Topical: absorption is negligible (<5% of applied dose is systemically absorbed). |
| Onset of Action | Topical: clinical improvement in tinea infections noted within 1-2 weeks of application; oral: clinical effect in dermatophytosis observed after 2-4 weeks; however, drug levels in stratum corneum are detected within 24 hours of oral administration. |
| Duration of Action | After a standard 1-week oral course for tinea unguium, drug persists in nails above therapeutic levels for up to 30 weeks; for topical, clinical cure may be achieved within 2-4 weeks, but residual drug in skin persists for 2-3 weeks. |
| Molecular Weight | 291.43 |
Terbinafine 250 mg orally once daily for 6 weeks for fingernail onychomycosis or 12 weeks for toenail onychomycosis. Topical: 1% cream applied once daily for 1 week for tinea pedis; 1% solution applied once daily for 1 week for tinea corporis/cruris.
| Dosage form | SOLUTION |
| Renal impairment | Contraindicated in patients with CrCl <50 mL/min. For CrCl 50-80 mL/min, reduce dose by 50% (e.g., 125 mg orally once daily). |
| Liver impairment | Contraindicated in patients with chronic or active liver disease (Child-Pugh Class B or C). For mild hepatic impairment (Child-Pugh Class A), reduce dose by 50% and monitor liver function tests closely. |
| Pediatric use | Oral formulation not approved. Topical: 1% cream applied once daily for 1 week in children ≥12 years for tinea pedis, tinea corporis, tinea cruris; safety in children <12 years not established. |
| Geriatric use | No specific dose adjustment recommended; however, monitor renal function (CrCl) as elderly more likely to have decreased renal function. Use with caution. |
| 1st trimester | Limited human data; animal studies show no teratogenicity at systemic levels; use only if potential benefit outweighs risk. |
| 2nd trimester | Limited human data; no known fetal harm; exercise caution. |
| 3rd trimester | Limited human data; no known fetal harm; exercise caution. |
Clinical note
Comprehensive clinical and safety monograph for LAMISIL AT (LAMISIL AT).
| Placental transfer | Oral terbinafine crosses placenta; topical absorption minimal; plasma levels 1-5% after topical application. |
| Breastfeeding | Topical application results in minimal systemic absorption ( <5% ), unlikely to reach significant levels in breast milk; however, avoid application to breast area to prevent infant ingestion. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to terbinafine or any componentChronic or active liver disease (for oral use; topical not contraindicated but caution)
| Precautions | Hepatotoxicity (rare but severe; monitor liver function before and during therapy); taste disturbance (including taste loss, reversible); exacerbation of lupus; neutropenia (rare); pregnancy category B (use only if clearly needed). |
| Food/Dietary | High-fat meals increase bioavailability. Avoid grapefruit juice as it may decrease metabolism. |
| Clinical Pearls |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | Topical terbinafine (Lamisil AT) has minimal systemic absorption; animal studies show no teratogenicity. No adequate human studies exist. Use during pregnancy only if clearly needed. First trimester: risk cannot be excluded. Second/third trimester: low risk due to negligible absorption. |
| Fetal Monitoring | No specific monitoring required due to minimal systemic absorption. Observe for local irritation or allergic reactions. |
| Fertility Effects | No evidence of impaired fertility in animal studies at topical doses. Systemic effects unlikely due to low absorption. |
| Terbinafine is fungicidal against dermatophytes due to inhibition of squalene epoxidase. For nail infections, treatment duration is 6 weeks for fingernails and 12 weeks for toenails. Hepatic toxicity is rare but requires monitoring LFTs in patients with pre-existing liver disease. Avoid in patients with chronic or active liver disease. |
| Patient Advice | Take with food to improve absorption and reduce GI upset. · Complete full course even if symptoms improve. · Report signs of liver issues: dark urine, pale stools, jaundice, fatigue. · Avoid alcohol during treatment to reduce hepatotoxicity risk. · May cause taste disturbance (usually reversible). · Keep medication at room temperature, away from moisture. |