Terbinafine

Terbinafine (allylamine)

  • Pregnancy Category B (low risk)
  • Not routinely recommended during lactation

Formulations

Tablets, oral granules

(oral granules should be sprinkled on non-acidic foods such as pudding, mashed potatoes)

Dosing

Onychomycosis:

  • 250 mg daily x 6-12 weeks

Tinea capitis (children):

  • <25kg – 125 mg daily
  • 25-35kg – 187.5 mg daily
  • >35kg-250 mg daily
  • Duration – 6 weeks

Note: Alternative regimen for children (if tablets & not granules):

  • <20kg 62.5 mg
  • <40kg 125 mg
  • >40kg 250 mg
  • Duration 2-4 weeks

Tinea corporis

  • 250mg daily x 1 week

Tinea pedis

  • 250mg daily x 2 weeks

  • Inhibition of squalene epoxidase leading to:

    1. increased squalene which is toxic (fungicidal) 

    2. decreased ergosterol for cell wall synthesis (fungistatic)

  • Skin: delivered through sebum
  • Nails: migrates through nail bed & matrix
  • Hair: by sebum (incorporation into shaft targets endothrix infections)
  • Bioavailability ~40%
  • Half-life 36 hours, longer in keratinized tissues
  • First-pass hepatic metabolism by: CYP-2C9, 1A2, 3A4, 2C8, 2C19
  • Renal clearance 70%

FDA

  • Dermatophyte onychomycosis 
  • Tinea capitis (oral granules only, in > 4 years old)

    (Treatment of choice for T. tonsurans tinea capitis)

Off-label

  • Candida & non-dermatophyte onychomycosis
  • Tinea cruris, corporis, pedis
  • Seborrheic dermatitis
  • Other deep/systemic fungal: chromoblastomycosis, aspergillosis, sporotrichosis, black piedra

Absolute

  • Known allergy
  • Chronic or active liver disease

Relative

  • Creatinine clearance < 50 mL/min

Common

  • Nasopharyngitis (most common) headache, GI (nausea, diarrhea, vomiting, abdominal pain, flatulence)

Dermatologic

  • Pruritus, urticaria, erythema multiforme, Steven Johnson/Toxic epidermal necrolysis, drug rash with eosinophilia & systemic symptoms (DRESS), acute generalized exanthematous pustulosis, serum-sickness lik e reaction, psoriasis, lupus (systemic & subacute cutaneous lupus), alopecia

Rare

  • Hepatitis (4-6 weeks), hepatic failure, reversible cytopenias (neutropenia), thrombotic microangiopathy (HUS, TTP), depression

Other

  • Increased liver function tests (>2x upper limit of normal), taste & visual disturbance

Inhibits CYP2D6

High risk

  • Increase levels of tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), beta-blockers, antiarrhythmics (Amiodarone) monoamine oxidase inhibitor, Narcotics

Low risk

  • Increase levels of nonsteroidal anti-inflammatory drugs (NSAIDs), cyclosporine, caffeine, rifampin, antimalarials, cimetidine

  • Liver function tests before starting treatment (ALT, AST)
  • Symptoms to monitor include nausea, anorexia, fatigue, vomiting, abdominal pain; discontinue & do complete liver profile; 
  • If patient with immunodeficiency: Liver function tests + complete blood work (CBC) due to cytopenia rare side effect of Terbinafine