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Terbinafine

For medical students2 min readUpdated 2026-10-10

Terbinafine is a synthetic antifungal agent belonging to the allylamine class (N-methylnaphthalene derivatives). It is highly effective in treating superficial mycoses and dermatophytoses due to its fungicidal action against causative pathogens.

Pharmacological classAntifungals (allylamines / N-methylnaphthalene derivatives)

FormulationsTablets 0.125 g and 0.25 g; 1% ointment/cream (15 g and 30 g)

Biochemical targetInhibition of fungal squalene epoxidase

PharmacokineticsHigh plasma protein binding (99%), cumulative tissue distribution, $T_{1/2} \approx 300\text{ hours}$

Mechanism of Action

Terbinafine is a synthetic antimycotic that acts at early stages of sterol synthesis in the fungal cell. It selectively and reversibly inhibits the cytoplasmic membrane enzyme squalene epoxidase (squalene-2,3-epoxidase).

This blocks the conversion of squalene to squalene epoxide (and subsequently to lanosterol), leading to a deficiency of ergosterol—a vital component of the fungal cell membrane—and the intracellular accumulation of toxic squalene, which causes pathogen death. An important difference from azole antifungals is that allylamines do not affect the 14-α-demethylase enzyme and do not directly depend on the cytochrome P-450 system, although they are metabolized with the participation of hepatic enzymes.

Pharmacological Profile and Pharmacokinetics

Upon oral administration, the bioavailability of terbinafine is approximately 40% due to presystemic metabolism (first-pass hepatic effect). The drug features high plasma protein binding (99%).

Due to its lipophilic properties, the active substance is actively distributed and accumulates in keratin-containing tissues (skin, nails) and adipose tissues. The elimination half-life ($T_{1/2}$) is approximately 300 hours, ensuring prolonged circulation and deposition of the drug in sites of infection.

Indications for Use

The spectrum of clinical activity of terbinafine focuses on superficial mycosis pathogens. The drug is a drug of choice for dermatophytoses (infections of the skin and its appendages—nails and hair) caused by dermatophytic fungi (trichophytosis, microsporia, epidermophytosis).

Indications for systemic use (oral):

Onychomycosis (fungal nail plate infections).
Tinea capitis and tinea corporis (ringworm of the scalp and smooth skin).
Pityriasis versicolor.

Topical use (1% cream/ointment): Applied cutaneously for fungal skin infections and epidermophytosis.

Safety Profile, Adverse Effects, and Contraindications

The drug is contraindicated in severe renal or hepatic impairment, as well as during pregnancy.

Adverse Effects:

Common: dyspeptic symptoms (nausea, abdominal pain, diarrhea, loss of appetite), cutaneous allergic reactions (rash).
Rare but severe: hepatotoxicity (requires regular monitoring of liver enzymes during the course), hematological disorders (neutropenia), severe skin reactions (including Stevens-Johnson syndrome), and possible exacerbation of autoimmune conditions (psoriasis, subacute cutaneous lupus erythematosus).
Local reactions (with topical application): skin hyperemia, burning, and itching at the application site.

Drug Interactions:

Cimetidine (a CYP450 inhibitor) can increase plasma concentrations of terbinafine.
Rifampin (a hepatic enzyme inducer), conversely, decreases blood levels of the drug.

Clinical Administration and Prescribing

In clinical practice, terbinafine is available as 0.125 g and 0.25 g tablets, as well as 1% cream/ointment (in 15 g and 30 g tubes).

Example of a Latin prescription:

Rp.: Unguenti Terbinafini 1% - 30 g
D. S. Apply topically to affected skin areas 1–2 times daily.

Systemic oral administration:

Rp.: Tab. Terbinafini 0.25 N. 28
D. S. Oral: 1 tablet (0.25 g) once daily.

Mnemonic

Allylamine TERBINAFINE hits the enemy at an early stadium: squalene epoxidase it blocks in nails and skin!

Frequently asked questions

What laboratory parameters must be monitored during long-term systemic terbinafine therapy?

During systemic terbinafine therapy, liver enzyme levels must be monitored. This laboratory monitoring is required throughout the entire course of treatment due to the risk of hepatotoxicity.

Additionally, it should be kept in mind that the drug can cause rare but severe adverse effects:

Hepatotoxicity — requires mandatory liver enzyme monitoring.
Hematological disorders — include the development of neutropenia.

While direct instructions for mandatory regular complete blood count monitoring are not specified in all guidelines, liver function monitoring is strictly mandatory.

What is the metabolic and elimination pathway of terbinafine from the body?

Terbinafine undergoes presystemic metabolism in the liver, leading to a first-pass effect. Due to hepatic elimination, the oral bioavailability of the drug is about 40%.

During distribution and elimination, the drug accumulates in the following structures:

Keratin-containing tissues — skin and nails.
Adipose tissues — fat cells.

Elimination of terbinafine from the body is slow. The drug is characterized by prolonged circulation, with a half-life of approximately 300 hours.

Which microbial cell enzyme is blocked by terbinafine?

Terbinafine selectively inhibits squalene epoxidase, disrupting the early stage of ergosterol synthesis and leading to the accumulation of toxic squalene.

Why is terbinafine effective in treating onychomycosis?

The drug has high lipophilicity and the ability to accumulate in keratin-containing tissues (nails and hair), while its long half-life (about 300 hours) ensures a sustained therapeutic concentration at the site of infection.

How does terbinafine's mechanism of action differ from azole derivatives?

Allylamines (terbinafine) block ergosterol synthesis at an earlier stage by inhibiting squalene epoxidase, whereas azoles inhibit 14-α-demethylase, which depends on cytochrome P-450.

Go deeper

Comparative pharmacodynamics of allylamines (naftifine, butenafine, terbinafine)
The effect of cytochrome P-450 inducers and inhibitors on antimycotic pharmacokinetics
Biochemical consequences of squalene accumulation in the fungal cell
Laboratory monitoring (hepatic transaminases, complete blood count) during systemic therapy
Peculiarities of pharmacotherapy for onychomycosis in patients with concomitant GI and hepatic pathology