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Monday, July 28, 2025

Terbinafine


Generic Name: Terbinafine
Chemical Class: Allylamine antifungal
Drug Formulations:
– Oral tablets (250 mg)
– Oral granules (for pediatric use)
– Topical 1% cream, spray, gel, or solution

Route of Administration: Oral, topical
Primary Therapeutic Action: Fungicidal agent active against dermatophytes and some yeasts
Classification: Antifungal – Allylamine group

Terbinafine is a lipophilic antifungal compound primarily used to treat superficial fungal infections involving skin, nails, and hair. It works by interfering with sterol biosynthesis in fungal cells, thereby impairing membrane integrity and causing cell death. Because of its accumulation in keratin-rich tissues, terbinafine is effective in eradicating dermatophytes from areas such as nails and skin, even after treatment has been stopped.

2. Mechanism of Action

Terbinafine selectively inhibits the fungal enzyme squalene epoxidase, a key component in the ergosterol biosynthetic pathway. Ergosterol is essential for the structural and functional integrity of fungal cell membranes. Inhibition of squalene epoxidase leads to:

  • Accumulation of squalene, a toxic metabolite at high concentrations

  • Depletion of ergosterol

  • Disruption of the fungal cell membrane

  • Rapid fungal cell death

Unlike azole antifungals that inhibit the synthesis of lanosterol demethylase (CYP450-dependent), terbinafine's mechanism is earlier in the sterol pathway and is not dependent on fungal cytochrome P450 enzymes.

3. Antifungal Spectrum

Highly Sensitive Organisms:

  • Trichophyton species (e.g., T. rubrum, T. mentagrophytes)

  • Microsporum canis

  • Epidermophyton floccosum

Moderately Sensitive:

  • Candida albicans (fungistatic effect)

  • Malassezia furfur (variable response)

Ineffective:

  • Some non-dermatophyte molds

  • Most systemic pathogenic fungi (e.g., Aspergillus, Cryptococcus)

4. Pharmacokinetics

  • Absorption: Rapid absorption after oral administration; absolute bioavailability ~70% due to first-pass metabolism

  • Distribution: Highly lipophilic; accumulates in keratinized tissues (skin, hair, nails, adipose tissue)

  • Protein Binding: >99%

  • Metabolism: Extensively metabolized in the liver by cytochrome P450 isoenzymes (primarily CYP2C9, CYP1A2, CYP3A4, CYP2C8, CYP2C19)

  • Half-life: Initial plasma half-life ~12 hours; terminal half-life from tissue stores ~200–400 hours due to depot effect in skin/nails

  • Excretion: Metabolites excreted via urine (major route) and bile (minor route)

5. Indications

5.1 Onychomycosis (Nail Fungus)

  • Fingernails: 250 mg orally once daily for 6 weeks

  • Toenails: 250 mg orally once daily for 12 weeks

Success rates include clinical cure in 38–57% of patients and mycologic cure (negative culture or microscopy) in up to 88%, depending on organism and compliance.

5.2 Tinea Capitis (Scalp Ringworm)

  • Pediatric patients aged ≥4 years

  • Dosing based on body weight (granules or tablets)

  • Duration: typically 6 weeks, up to 8 weeks for Microsporum infections

5.3 Tinea Corporis (Body Ringworm)

  • Oral: 250 mg once daily for 2–4 weeks

  • Topical: once or twice daily for 1–2 weeks

5.4 Tinea Cruris (Jock Itch)

  • Topical: once daily for 1–2 weeks

  • Oral: 250 mg daily for 2–4 weeks in extensive disease

5.5 Tinea Pedis (Athlete’s Foot)

  • Topical: 1–2 times daily for 1 week

  • Oral: 250 mg daily for 2–6 weeks in severe cases

5.6 Pityriasis Versicolor

  • Topical formulations used daily for 1–2 weeks

6. Dosage and Administration

6.1 Oral (Adults)

  • Standard dose: 250 mg once daily

  • Food: May be taken with or without meals

  • Missed dose: Take as soon as remembered unless close to next scheduled dose; do not double dose

6.2 Oral (Pediatric – Tinea Capitis)

  • <20 kg: 62.5 mg/day

  • 20–40 kg: 125 mg/day

  • 40 kg: 250 mg/day

  • Granules to be sprinkled onto a non-acidic food (e.g., mashed potatoes or pudding), not mixed in liquid

6.3 Topical

  • Clean and dry affected area before application

  • Apply thin film of cream to affected and surrounding skin

  • Wash hands after use

  • Avoid contact with eyes and mucous membranes

  • Treatment durations range from 1 to 4 weeks depending on location and severity

7. Contraindications

  • Hypersensitivity to terbinafine or any component of the formulation

  • Chronic or active liver disease

  • Severe renal impairment (caution)

  • History of hepatic dysfunction related to terbinafine

8. Warnings and Precautions

8.1 Hepatic Toxicity

  • Rare but potentially severe hepatotoxicity

  • Baseline liver function testing recommended before oral treatment

  • Monitor LFTs periodically during long-term therapy

  • Discontinue immediately if signs of liver injury (e.g., fatigue, dark urine, jaundice) occur

8.2 Taste and Smell Disturbances

  • Reversible taste disturbance (dysgeusia) reported in up to 2% of users

  • Complete loss of taste (ageusia) rare but may persist for weeks

  • Loss of smell (anosmia) extremely rare

8.3 Psychiatric Effects

  • Anxiety, depression, suicidal ideation reported infrequently

  • Monitor mood and mental health status during treatment

8.4 Visual and Auditory Effects

  • Blurred vision, diplopia, photophobia, tinnitus, and rarely hearing loss

  • Stop treatment if persistent sensory symptoms occur

8.5 Hematological Effects

  • Rare reports of neutropenia, leukopenia, thrombocytopenia, agranulocytosis

  • Monitor CBC in long-term use or if infection signs present

9. Adverse Effects

9.1 Common (≥1%)

  • Diarrhea

  • Dyspepsia

  • Nausea

  • Headache

  • Rash

  • Elevated liver enzymes

  • Taste changes

9.2 Less Common (<1%)

  • Fatigue

  • Arthralgia, myalgia

  • Depression or anxiety

  • Visual disturbances

  • Urticaria

  • Pruritus

9.3 Rare / Serious

  • Hepatitis

  • Liver failure

  • Stevens–Johnson syndrome

  • Toxic epidermal necrolysis

  • Anaphylaxis

  • Seizures

  • Severe neutropenia

10. Drug Interactions

  • CYP2D6 substrates: Terbinafine inhibits this enzyme and may increase plasma levels of antidepressants (e.g., tricyclics, SSRIs), antipsychotics, beta-blockers, antiarrhythmics

  • CYP inducers (e.g., rifampin): May decrease terbinafine concentration

  • CYP inhibitors (e.g., cimetidine): May increase terbinafine levels

  • Caffeine metabolism: Slightly slowed by terbinafine

  • Warfarin: No major interaction, but INR monitoring advised

  • Oral contraceptives: No effect on efficacy, but breakthrough bleeding may occur

11. Special Populations

11.1 Pregnancy

  • Category B (oral); avoid unless benefit outweighs risk

  • No teratogenicity observed in animal studies

  • Topical terbinafine considered safe during pregnancy due to minimal systemic absorption

11.2 Lactation

  • Excreted in breast milk

  • Oral use not recommended while breastfeeding

  • Topical use allowed with caution; avoid applying to nipple area

11.3 Pediatrics

  • Approved for use in children ≥4 years for tinea capitis

  • Safety and efficacy in younger children not established

11.4 Geriatric

  • No dosage adjustment needed

  • Monitor hepatic and renal function

  • Elderly may be more sensitive to adverse effects

11.5 Hepatic Impairment

  • Contraindicated in chronic or active liver disease

  • Monitor LFTs if mild impairment is suspected

11.6 Renal Impairment

  • Use with caution in patients with severe renal dysfunction (CrCl <50 mL/min)

12. Overdose Management

12.1 Symptoms

  • Headache

  • Nausea

  • Epigastric pain

  • Dizziness

  • Rash

12.2 Management

  • Supportive treatment

  • Activated charcoal if recent ingestion

  • Symptom monitoring (liver enzymes, CNS effects)

  • No specific antidote

13. Monitoring Parameters

  • Liver function tests before starting and during oral therapy

  • Complete blood count if systemic signs of infection or adverse effects occur

  • Clinical evaluation of symptom resolution in skin and nail conditions

  • Neurological, visual, or psychiatric status in case of sensory complaints

  • Patient adherence and response to topical formulations

14. Storage and Handling

  • Oral tablets: store at 20–25 °C; protect from light and moisture

  • Topical cream: store below 25 °C; keep cap tightly closed

  • Do not freeze topical products

  • Keep all forms out of reach of children



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