terbinafine (Rx)

>10%

Headache (13%)

1-10%

Rash (6%)

Pruritus (3%)

Nausea (3%)

Diarrhea (6%)

Dyspepsia (4%)

Abdominal pain (2%)

Taste disturbance (3%)

Elevated liver function test results (3%)

Visual disturbance (1%)

Postmarketing Reports

Idiosyncratic and symptomatic hepatic injury; more rarely, cases of liver failure, some leading to death or liver transplant

Skin and subcutaneous tissue disorders (eg, Stevens-Johnson Syndrome and toxic epidermal necrolysis), drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome

Anaphylaxis, angioedema

Severe neutropenia, thrombocytopenia, agranulocytosis, pancytopenia, anemia

Psoriasiform eruptions or exacerbation of psoriasis, acute generalized exanthematous pustulosis, precipitation and exacerbation of cutaneous and systemic lupus erythematosus

Taste and smell disturbances

Malaise, fatigue, vomiting, arthralgia, myalgia, rhabdomyolysis, reduced visual acuity, visual field defect, hair loss, serum sickness-like reaction, vasculitis, pancreatitis, influenzalike illness, pyrexia, increased blood creatine phosphokinase, photosensitivity reactions

Hearing impairment, vertigo

Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

Contraindications

Hypersensitivity

Chronic or active liver disease

Cautions

Discontinue if the following develop: Liver disease, neutropenia (absolute neutrophil count <1000 mcL); skin rash; signs or symptoms of SLE

Changes in ocular lens and retina reported; may require discontinuation of therapy

Use caution in renal and liver impairment

Periodic monitoring of liver function tests is recommended

Ask patients and caregivers to report immediately to healthcare provider any symptoms or signs of persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain or jaundice, dark urine, or pale stools; if these symptoms occur discontinue taking oral terbinafine, and immediately evaluate patient’s liver function

Serious skin/hypersensitivity reactions (eg, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms [DRESS] syndrome); manifestations of DRESS syndrome may include cutaneous reaction (eg, rash, exfoliative dermatitis), eosinophilia, and 1 or more organ complications (eg, hepatitis, pneumonitis, nephritis, myocarditis, pericarditis)

Due to potential toxicity, confirmation of onychomycosis or dermatomycosis recommended

Smell disturbance reported; discontinue therapy if symptoms occur

CYP2D6 inhibitor; may also convert CYP2D6 extensive metabolizers to poor metabolizer status

Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, reported with terbinafine; discontinue terbinafine if clinical symptoms and laboratory findings consistent with TMA occur; the findings of unexplained thrombocytopenia and anemia should prompt further evaluation and consideration of diagnosis of TMA

Pregnancy

Available data from postmarketing cases in pregnant women are insufficient to evaluate drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Animal data

• In animal reproduction studies, the drug did not cause malformations or any harm to fetus when administered to pregnant rabbits and rats during period of organogenesis at oral doses up to 12 and 23 times the maximum recommended human dose (MRHD) of 250 mg/day, respectively

Because treatment of onychomycosis can be postponed until after pregnancy is completed, it is recommended that oral terbinafine not be initiated during pregnancy

Lactation

After oral administration, terbinafine is present in human milk; however, there are no data on effects on breastfed child or on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy; tablets and any potential adverse effects on breastfed child from therapy or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Inhibits squalene epoxidase, reducing cell membrane ergosterol synthesis, causing inhibition of fungal cell-wall synthesis and subsequently fungal cell death

Absorption

Absorption >70%

Bioavailability: 40% (Adults); 36-64% (children)

Peak plasma time: 1-2 hr

Peak plasma concentration (250-mg dose): 1 mcg/mL

Distribution

Predominantly distributed to sebum and skin

Protein bound: >99%

Vd: 2000 L

Metabolism

Metabolized in liver by several CYP450 enzymes; first-pass effect (40%)

Metabolites: Inactive

Enzymes inhibited: CYP2D6

Elimination

Half-life: 36 hr (drug released very slowly from skin and adipose tissues)

Excretion: Urine (~70%)