What is Toterabin?

What is Terbinafine?

Terbinafine is an oral and topical antifungal medication that inhibits fungal ergosterol biosynthesis by blocking squalene epoxidase, resulting in both fungistatic (ergosterol depletion) and fungicidal (toxic squalene accumulation) effects, primarily used to treat dermatophyte onychomycosis (fungal nail infections). 1

Mechanism of Action

• Terbinafine blocks squalene epoxidase, the enzyme responsible for converting squalene to ergosterol in fungal cell membranes 1
• This dual mechanism creates ergosterol-depleted fungal cell membranes (fungistatic effect) and causes toxic intracellular squalene accumulation (fungicidal effect) 1
• The drug demonstrates excellent fungicidal activity against dermatophytes and variable activity against yeasts and non-dermatophyte molds in vitro 1

Pharmacokinetics and Distribution

• Following oral administration, terbinafine is rapidly absorbed and widely distributed to body tissues, including the poorly perfused nail matrix 1
• Nail terbinafine concentrations are detectable within 1 week after starting therapy and persist for at least 30 weeks after treatment completion 1
• The drug is primarily cleared by the kidney, with decreased clearance in patients with severe kidney disease 2

Clinical Efficacy

• Oral terbinafine 250 mg/day for 12-16 weeks is more efficacious than itraconazole, fluconazole, and griseofulvin for dermatophyte toenail onychomycosis 1
• In the L.I.ON. study at 72 weeks' follow-up, mycologic cure rates were approximately twice as high with terbinafine (76-81%) compared to intermittent itraconazole (38-49%) 1
• The 5-year L.I.ON. Icelandic Extension study demonstrated superior complete cure rates (35% vs 14%), mycologic cure rates (46% vs 13%), and clinical cure rates (42% vs 18%) for terbinafine versus itraconazole 1

Common Adverse Effects

• Gastrointestinal disturbances (nausea, diarrhea, taste disturbance) occur in 49% of reported side effects 2
• Dermatological events (rash, pruritus, urticaria, eczema) occur in 23% of reported side effects 2
• Adverse events were experienced by 10.5% of terbinafine recipients in post-marketing surveillance, with gastrointestinal complaints being most common 1
• A very rare taste disturbance that can potentially be permanent has been reported 2

Serious but Rare Adverse Reactions

• Rare serious cutaneous reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis 2
• Hepatotoxicity is rare but can occur, particularly in patients with pre-existing liver disease 2
• Rare hematologic effects include occasional isolated neutropenia 2

Critical Contraindications

Terbinafine is absolutely contraindicated in patients with renal impairment (creatinine clearance ≤50 mL/min), as it is primarily cleared by the kidneys. 2

• The drug should be avoided in patients with active or chronic liver disease 2
• For patients with chronic kidney disease requiring antifungal therapy, topical treatments (amorolfine 5% lacquer or ciclopirox 8% lacquer) are the preferred approach 2

Baseline Monitoring Requirements

• Baseline liver function tests (ALT and AST) and complete blood count should be obtained before prescribing terbinafine 2
• High-risk patients with a history of heavy alcohol consumption, hepatitis, hematological abnormalities, or children require baseline testing 2
• Hepatic function tests should be monitored during therapy, particularly if treatment extends beyond one month in high-risk patients 2

Drug Interaction Profile

• Unlike azole antifungals, terbinafine has a low potential for drug-drug interactions 1
• Monitoring for interactions with medications metabolized by cytochrome P450 2D6 isoenzyme is recommended 2

Alternative Agents When Terbinafine is Contraindicated

• For patients with renal impairment and normal hepatic function, itraconazole may be considered if systemic therapy is absolutely necessary 2
• Topical therapy with amorolfine 5% lacquer (once or twice weekly for 6-12 months) or ciclopirox 8% lacquer (once daily for up to 48 weeks) are safer alternatives for patients with contraindications 2
• If severe or progressive cutaneous reaction occurs, discontinue terbinafine and consider itraconazole as an alternative 3