Terbinafine

Topical Management (Lamisil, Terbinafine HCl 1%)
1. Resistant dermatophyte infection
2. Tinea Pedis
3. Tinea Cruris
4. Tinea Corporis
5. Tinea Versicolor
Systemic Management (Terbinafine oral)
1. Onychomycosis
  1. Highly active in vitro against dermatophytes (more than Itraconazole)
  2. Does not cover all yeast forms that cause Onychomycosis

Synthetic Allylamine Antifungal
Blocks Ergosterol synthesis (key component in the fungal cell wall)
1. Inhibits squalene epoxidase, the enzyme that converts squalene to ergosterol

Terbinafine Oral
1. Tablets: 250 mg
2. Pharmacists can compound into oral suspensions for children
Terbinafine Topical (Lamisil AT)
1. Available as a 1% cream, spray or gel
2. Minimal systemic absorption (3%)

Dose
1. Adult (and child >40 kg): 250 mg orally daily
2. Child weight 20 to 40 kg: 125 mg (up to 187.5 mg) orally daily
3. Child (age> 4 years) and weight <20 kg: 67.5 mg (up to 125 mg) orally daily
Duration
1. Tinea Capitis: 6 weeks (longer course if culture grows Microsporum)
2. Fingernail Onychomycosis: 6 weeks
3. Toenail Onychomycosis: 12 weeks

Common
1. Headache
2. Gastrointestinal upset (Diarrhea, Dyspepsia, Abdominal Pain)
3. Taste Dysfunction
Uncommon
1. Rash (including Urticaria and Pruritus)
  1. Typically mild with spontaneous resolution
Serious (rare)
1. Anaphylaxis
2. Cholestatic hepatitis
3. Blood dyscrasia
  1. Pancytopenia
  2. Neutropenia
4. Stevens-Johnson Syndrome
5. Toxic Epidermal Necrolysis
6. Drug-induced Lupus (or exacerbation of pre-existing Systemic Lupus Erythematosus)
7. Hepatotoxicity
  1. Increased serum transaminases
  2. Significant liver injury has been reported
8. Ocular findings
  1. Ocular lens changes
  2. Retinal changes

Oral Bioavailability: High
1. Peak serum concentrations within 2 hours
Distribution
1. Terbinafine is lipophilic and keratophilic
2. Reaches high concentrations in the Stratum Corneum, sebum, hair and nails
  1. Nail clippings contain Terbinafine within 1 week of first dose
  2. Nail clippings contain Terbinafine for up to 36 weeks after last dose
Hepatic Metabolism
Excreted in urine and stool
1. Decreased clearance in renal and hepatic Impairment

CYP2D6 Inhibitor
Terbinafine increases other drug levels (esp. as CYP2D6 Inhibitor)
1. Warfarin (may increase INR)
Terbinafine decreases other drug levels
1. Cyclosporine (15% reduction in levels)
Drugs that increase Terbinafine levels
1. Cimetidine
2. Fluconazole
Drugs that decrease Terbinafine levels
1. Rifampin (doubles clearance rates)

Protocol
1. Baseline AST and ALT
2. Repeat CBC after 6 weeks of continuous use if Immunodeficiency
  1. Discontinue if Neutrophil Count <1000 cells/mm3
3. New guidelines do not require repeat LFT testing routinely
  1. Obtain repeat testing if higher risk of liver abnormality, concurrent use of Hepatotoxic Medications, or symptoms
  2. In past, LFTs have been monitored every 4 to 6 weeks
  3. Stop agent if AST or ALT increased >2x normal
Labs
1. Complete Blood Count and Platelet Count (if Immunodeficiency)
2. Aspartate Aminotransferase (AST)
3. Alanine Aminotransferase (ALT)
4. Serum Creatinine