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  • CLASSES

    Other Systemic Antifungals
    Topical Dermatological Antifungals

    DEA CLASS

    OTC, Rx

    DESCRIPTION

    Oral and topical antifungal
    Fungicidal activity against dermatophytes; less active against Candida sp.
    Used topically and orally for tinea infections; oral form effective for onychomycosis or for refractory aspergillosis

    COMMON BRAND NAMES

    Desenex Max, Lamisil, Lamisil AT, Lamisil AT Athletes Foot, Lamisil AT Jock Itch, Terbinex

    HOW SUPPLIED

    Desenex Max/Lamisil AT/Lamisil AT Athletes Foot/Lamisil AT Jock Itch/Terbinafine/Terbinafine Hydrochloride Topical Cream: 1%
    Lamisil AT Athletes Foot/Lamisil AT Jock Itch Topical Spray: 1%
    Lamisil AT Topical Gel: 1%
    Lamisil/Terbinafine/Terbinafine Hydrochloride/Terbinex Oral Tab: 250mg

    DOSAGE & INDICATIONS

    For the treatment of tinea pedis.
    Topical dosage (1% OTC spray or topical solution)
    Adults, Adolescents, and Children >= 12 years

    Apply to affected areas between the toes twice daily for 1 week. Use for tinea pedis on the bottom or sides of the foot has not been studied. Change shoes and socks at least once daily.

    Topical dosage (1% prescription gel; Lamisil Dermagel)
    Adults

    Apply to affected areas and surrounding skin once daily for 1 week. Change shoes and socks at least once daily.

    Topical dosage (1% OTC gel)
    Adults, Adolescents, and Children >= 12 years

    Apply to affected areas between the toes once daily at bedtime for 1 week. Use for tinea pedis on the bottom or sides of the foot has not been studied. Change shoes and socks at least once daily.

    Topical dosage (1% OTC cream)
    Adults, Adolescents, and Children >= 12 years

    Apply to affected areas twice daily. For tinea pedis between the toes, treat for 1 week. For tinea pedis affecting the bottom or sides of the foot, treat for 2 weeks. Change shoes and socks at least once daily.

    Oral dosage†
    Adults

    A dosage of 250 mg PO once daily for 7 days has been suggested. In a clinical trial for interdigital tinea pedis, patients receiving oral terbinafine administered for 1 week achieved the same cure rates as those who received 4 weeks of topical clotrimazole 1% cream application (71%). Signs and symptoms of infection responded more quickly to oral terbinafine. For moccasin-type plantar tinea pedis, a dose of terbinafine 250 mg PO once daily has been recommended. In a comparison with oral itraconazole, significantly higher mycological cure rates and clinical improvement were seen with oral terbinafine after 2 weeks of therapy for interdigital or extensive tinea pedis.

    For the treatment of tinea cruris or tinea corporis.
    Topical dosage (1% OTC spray, solution, gel, or cream)
    Adults, Adolescents, and Children >= 12 years

    Apply to affected areas once daily for 1 week.

    Topical dosage (1% prescription gel; Lamisil DermaGel)
    Adults

    Apply to affected areas and surrounding skin once daily for 1 week.

    For the treatment of tinea capitis.
    Oral dosage (Lamisil oral granules)
    Adults

    A dose of 250 mg PO once daily is recommended. Treatment should continue for 6 weeks.

    Children and Adolescents >= 4 years and > 35 kg

    250 mg PO once daily. Treatment should continue for 6 weeks.

    Children and Adolescents >= 4 years and 25—35 kg

    187.5 mg PO once daily for 6 weeks.

    Children and Adolescents >= 4 years and < 25 kg

    125 mg PO once daily for 6 weeks.

    For the treatment of tinea versicolor due to Malassezia furfur.
    Topical dosage (1% prescription gel; Lamisil DermaGel)
    Adults

    Apply to affected areas and surrounding skin once daily for 1 week.

    Topical dosage (1% prescription topical solution)
    Adults

    Apply to affected areas twice daily for 1 week.

    For the treatment of onychomycosis.
    For the routine treatment of onychomycosis (tinea unguium).
    Oral dosage (tablet)
    Adults

    The recommended dosage is 250 mg PO once daily. Treatment should continue for 6 weeks for treatment of fingernails, and 12 weeks for treatment of toenails. Alternatively, an intermittent dosage† of 500 mg PO once daily for 7 days during the first week of each month for 3 months was found to be equivalent to the standard continuous dosage.

    Children >= 2 years† and Adolescents†

    Safety and efficacy have not been established. Although experience is limited, a published review suggested a dose of 62.5 mg/day PO for children under 20 kg, and 125 mg/day PO for children between 20 and 40 kg.

    For the treatment of onychomycosis due to Candida parapsilosis†.
    Oral dosage
    Adults

    In a study of 20 patients, terbinafine 250 mg PO once daily for 16 weeks was utilized. At the end of the trial, 60% of target nails were cured clinically and mycologically.

    For the treatment of refractory bronchopulmonary aspergillosis† due to various Aspergillus sp.†, including Aspergillus fumigatus†, in non-immunocompromised patients.
    Oral dosage
    Adults

    A dosage of 5—15 mg/kg PO once daily for 3—5 months has been utilized in compassionate use trials. Eradication of Aspergillus was obtained in 3 patients; clinical improvement was seen in all seven patients.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    250 mg PO daily, although a higher dose of 500 mg/day PO has been used off-label for onychomycosis; specific maximum dosage information is not available for topical preparations.

    Elderly

    250 mg PO daily, although a higher dose of 500 mg/day PO has been used off-label for onychomycosis; specific maximum dosage information is not available for topical preparations.

    Adolescents

     > 35 kg: 250 mg/day PO of oral granules; safety and efficacy have not been established for other dosage forms.
     25—35 kg: 187.5 mg/day PO of oral granules; safety and efficacy have not been established for other dosage forms.
     < 25 kg: 125 mg/day PO of oral granules; safety and efficacy have not been established for other dosage forms.

    Children

     >= 4 years and > 35 kg: 250 mg/day PO of oral granules; safety and efficacy have not been established for other dosage forms.
     >= 4 years and 25—35 kg: 187.5 mg/day PO of oral granules; safety and efficacy have not been established for other dosage forms.
     >= 4 years and < 25 kg: 125 mg/day PO of oral granules; safety and efficacy have not been established for other dosage forms.
     < 4 years: Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Avoid use of oral terbinafine in patients with hepatic disease. In patients with hepatic cirrhosis, oral terbinafine clearance is reduced by approximately 50% compared to normal volunteers.

    Renal Impairment

    CrCl > 50 ml/min: no dosage adjustment needed.
    CrCl <= 50 ml/min: Use of oral terbinafine is not recommended. Oral terbinafine clearance is reduced by approximately 50% compared to normal volunteers.

    ADMINISTRATION

    Oral Administration

    The optimal clinical effect in onychomycosis is seen some months after mycological cure and treatment due to the time needed for outgrowth of healthy nails.

    Oral Solid Formulations

    Oral tablets: May be taken with or without food.
    Oral granules: Take with food. Sprinkle the contents of each packet on a spoonful of pudding or other soft, non-acidic food such as mashed potatoes. Swallow the entire spoonful without chewing; do NOT use applesauce or fruit-based foods. If two packets (250 mg) are required with each dose, either the content of both packets may be sprinkled on one spoonful, or the contents of both packets may be sprinkled on two spoonfuls of non-acidic food as directed above.

    Topical Administration

    For topical dermatologic use only; not for ophthalmic, oral, or intravaginal use.
    Wash hands before and after application. When treating hand or fingernail infections, do not wash patient's hands after application. Use gloves if required by universal precautions.
    Rub cream, topical solution, or topical gel gently into the affected area(s). Apply an amount sufficient to cover the affected area and the immediate surrounding skin. Avoid getting in the eyes, nose, mouth, or other mucous membranes.
    Avoid occlusive dressing of the affected areas unless otherwise directed by the prescriber.
    Improvement of dermal tinea infection is gradual, and improvements in the treated condition may continue for the 2—6 weeks after terbinafine therapy is discontinued. The manufacturer recommends that patients not be considered therapeutic failures until 2—6 weeks off therapy have passed.

    STORAGE

    Desenex Max:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Lamisil:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Lamisil AT:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Lamisil AT Athletes Foot:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Lamisil AT Jock Itch:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Terbinex:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Changes in the ocular lens and retina have been reported following the use of oral terbinafine in controlled trials. The clinical significance of these changes is unknown.

    Onychomycosis

    As with many other topical antifungal drugs, terbinafine cream is not effective for onychomycosis. This condition usually requires treatment with an oral (systemic) antifungal drug, like systemic (oral) terbinafine.

    Human immunodeficiency virus (HIV) infection, immunosuppression, neutropenia

    Transient lymphopenia and neutropenia have occurred with oral terbinafine therapy. In patients with known or suspected immunodeficiency syndromes (e.g., human immunodeficiency virus (HIV) infection), or immunosuppression, complete blood counts are recommended at baseline and with any treatment lasting greater than 6 weeks. If signs or symptoms of secondary infection occur, a complete blood count should be obtained to rule out lymphopenia or neutropenia. If the neutrophil count is less than 1000/mm3, oral terbinafine should be discontinued.

    Pregnancy

    Terbinafine, in both dermatologic and oral formulations, is rated FDA pregnancy risk category B. Although adequate, well-controlled studies have not been performed in humans, studies in animals using large oral and topical dosages did not reveal teratogenic effects. Terbinafine should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. Treatment of onychomycosis can be postponed until after pregnancy is completed; it is recommended that terbinafine not be initiated for this indication during pregnancy.

    Breast-feeding

    Orally administered terbinafine is excreted in breast milk and is not recommended for use during breast-feeding. Human data from two lactating volunteers found total excretion into breast milk to be 0.13% and 0.03% of the administered dose (500 mg PO once). Topical use during breast-feeding has not been studied; because of the low absorption, significant excretion in breast milk is considered unlikely. Instruct nursing mothers to avoid topical application to the breast, as this would be expected to increase infant exposure. A decision should be made whether to discontinue nursing or to discontinue terbinafine, taking into account the importance of the medication to the mother. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Anxiety, children, depression, insomnia, suicidal ideation

    Neuropsychiatric adverse reactions consisting of depression, suicidal ideation, and self-harm, have been reported in 3 children (ages 13 to 16 years) while taking oral terbinafine. Other symptoms included anxiety, insomnia, nausea, forgetfulness, and social withdrawal. Symptoms in all 3 children resolved after the discontinuation of the medication.

    Hepatic disease, hepatitis, jaundice

    Oral terbinafine is contraindicated for use in patients with chronic or active hepatic disease (i.e., cirrhosis, hepatitis), as the systemic clearance may be decreased by approximately 50%; topical formulations are unlikely to be affected. In addition, use of oral terbinafine has been associated with serious hepatotoxicity (i.e., hepatic failure, some resulting in death or liver transplant). Although the majority of cases have been reported in patients with serious underlying conditions, hepatotoxicity has been reported in patients with and without preexisting hepatic disease. Prior to initiating therapy and periodically during therapy, monitor liver function tests. If elevations in liver function test are observed, immediately discontinue therapy. Counsel patients to discontinue use of the drug and immediately report any symptoms of persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain or jaundice, dark urine, or pale stools as these may indicate hepatotoxicity.

    Renal failure, renal impairment

    In patients with renal impairment or renal failure (i.e., creatinine clearance 50 mL/min or less), the use of oral terbinafine formulations has not been studied, and therefore, is not recommended.

    Serious rash

    Terbinafine is contraindicated in patients that have a known or suspected hypersensitivity to terbinafine or any of its components. Occasionally the use of oral terbinafine has been associated with serious rash or hypersensitivity skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, and bullous dermatitis. If irritation, skin rash, or sensitivity occurs during use of terbinafine, treatment should be discontinued and appropriate therapy administered. Topical terbinafine formulations should be kept away from the eyes, nose, and mouth during treatment.

    Hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura (TTP)

    Treatment with oral terbinafine has been associated with serious, and sometimes fatal, cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome. Closely evaluate drug recipients who develop unexplained thrombocytopenia and anemia. If clinical symptoms and laboratory findings are consistent with TMA, discontinue terbinafine therapy.

    ADVERSE REACTIONS

    Severe

    visual impairment / Early / 1.0-5.0
    angioedema / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
    hemolytic-uremic syndrome / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    serum sickness / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known

    Moderate

    elevated hepatic enzymes / Delayed / 3.3-3.3
    lymphopenia / Delayed / 1.7-1.7
    psoriaform rash / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known

    Mild

    headache / Early / 7.0-12.9
    pharyngitis / Delayed / 10.0-10.0
    fever / Early / 7.0-7.0
    rash (unspecified) / Early / 2.0-6.0
    diarrhea / Early / 3.0-6.0
    cough / Delayed / 6.0-6.0
    vomiting / Early / 5.0-5.0
    infection / Delayed / 5.0-5.0
    dyspepsia / Early / 4.0-4.3
    abdominal pain / Early / 2.0-4.0
    nausea / Early / 2.0-3.0
    dysgeusia / Early / 2.8-3.0
    pruritus / Rapid / 0.2-2.8
    flatulence / Early / 2.2-2.2
    skin irritation / Early / 1.0-2.0
    rhinorrhea / Early / 2.0-2.0
    nasal congestion / Early / 2.0-2.0
    urticaria / Rapid / 1.1-1.1
    dental pain / Delayed / 1.0-1.0
    xerosis / Delayed / 0.2-0.2
    photosensitivity / Delayed / Incidence not known
    anorexia / Delayed / Incidence not known
    weight loss / Delayed / Incidence not known
    anosmia / Delayed / Incidence not known
    anxiety / Delayed / Incidence not known
    dizziness / Early / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known
    fatigue / Early / Incidence not known
    alopecia / Delayed / Incidence not known
    arthralgia / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    vertigo / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    malaise / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
    Acetaminophen; Butalbital: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections. (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections. (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined. (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Terbinafine may interfere with the conversion of codeine to morphine; a corresponding decrease in analgesia may be seen.
    Acetaminophen; Caffeine; Dihydrocodeine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Codeine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Terbinafine may interfere with the conversion of codeine to morphine; a corresponding decrease in analgesia may be seen.
    Acetaminophen; Dextromethorphan: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Acetaminophen; Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Acetaminophen; Oxycodone: (Moderate) Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as terbinafine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Acetaminophen; Propoxyphene: (Moderate) Propoxyphene is a substrate and an inhibitor of CYP2D6. Increased serum concentrations of propoxyphene would be expected from concurrent use of a CYP2D6 inhibitor like terbinafine.
    Acetaminophen; Tramadol: (Moderate) As terbinafine inhibits CYP2D6 and tramadol is partially metabolized by CYP2D6, concurrent therapy may decrease tramadol metabolism. This interaction may result in decreased tramadol efficacy and/or increased tramadol-induced risks of serotonin syndrome or seizures. The analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), and M1 formation is dependent on CYP2D6. Therefore, use of tramadol with a CYP2D6-inhibitor may alter tramadol efficacy. In addition, inhibition of CYP2D6 metabolism is expected to result in reduced metabolic clearance of tramadol. This in turn may increase the risk of tramadol-related adverse events including serotonin syndrome and seizures. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Aldesleukin, IL-2: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering aldesleukin, IL-2. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; aldesleukin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Alogliptin; Pioglitazone: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with pioglitazone. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; pioglitazone induces this enzyme. Monitor patients for breakthrough fungal infections.
    Amiodarone: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering amiodarone. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may substantially increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9 and CYP3A4; amiodarone is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Amitriptyline: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as tricyclic antidepressants.
    Amitriptyline; Chlordiazepoxide: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as tricyclic antidepressants.
    Amlodipine; Telmisartan: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering telmisartan. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19; telmisartan is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Amobarbital: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections.
    Amoxapine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as amoxapine.
    Amoxicillin; Clarithromycin; Lansoprazole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering clarithromycin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; clarithromycin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered. (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering lansoprazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9 and CYP2C19; lansoprazole is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering clarithromycin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; clarithromycin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Amprenavir: (Moderate) Caution is advised when administering terbinafine with amprenavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4. Amprenavir is a substrate of CYP2D6, an inhibitor of CYP3A4. Monitor patients for adverse reactions if these drugs are coadministered.
    Aprepitant, Fosaprepitant: (Moderate) Use caution if terbinafine and aprepitant, fosaprepitant are used concurrently, and monitor for an increase in terbinafine-related adverse effects for several days after administration of a multi-day aprepitant regimen. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may substantially increase the systemic exposure of terbinafine. Terbinafine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of terbinafine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Aprepitant is also a CYP2C9 inducer and terbinafine is a CYP2C9 substrate. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant.
    Aripiprazole: (Moderate) Because aripiprazole is partially metabolized by CYP2D6, patients should be carefully monitored for aripiprazole-related adverse reactions during concurrent use of a CYP2D6 inhibitor such as terbinafine. Because aripiprazole is also metabolized by CYP3A4, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada during use of a mild to moderate CYP2D6 inhibitor. Topical terbinafine preparations are unlikely to result in a clinically significant interaction with aripiprazole.
    Armodafinil: (Moderate) Caution is advised when administering terbinafine with armodafinil. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2, CYP2C8, CYP2C9, CYP2C19 and CYP3A4; armodafinil is an inhibitor of CYP2C19 and an inducer of CYP1A2 and CYP3A4. Taking these drugs together may increase or decrease the systemic exposure of terbinafine. Monitor patients for breakthrough fungal infections and terbinafine related adverse reactions.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections. (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections. (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined. (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Terbinafine may interfere with the conversion of codeine to morphine; a corresponding decrease in analgesia may be seen.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
    Aspirin, ASA; Carisoprodol; Codeine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Terbinafine may interfere with the conversion of codeine to morphine; a corresponding decrease in analgesia may be seen.
    Aspirin, ASA; Oxycodone: (Moderate) Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as terbinafine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Atazanavir: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering atazanavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C8 and CYP3A4; atazanavir is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Atazanavir; Cobicistat: (Moderate) Caution is advised when administering terbinafine with cobicistat. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4. Cobicistat is a substrate of CYP2D6 and an inhibitor of CYP3A4. Monitor patients for adverse reactions if these drugs are coadministered. Topical terbinafine formulations would not be expected to interact. (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering atazanavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C8 and CYP3A4; atazanavir is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Atomoxetine: (Major) Because atomoxetine is primarily metabolized by CYP2D6, concurrent use of CYP2D6 inhibitors such as systemic terbinafine may increase the risk of atomoxetine-induced adverse effects. Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, increased pulse rate, QT prolongation).
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections.
    Barbiturates: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections.
    Basiliximab: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering basiliximab. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; basiliximab is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections.
    Bexarotene: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with bexarotene. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; bexarotene induces this enzyme. Monitor patients for breakthrough fungal infections.
    Boceprevir: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering boceprevir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; boceprevir is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Bosentan: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with bosentan. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9 and CYP3A4; bosentan induces these enzymes. Monitor patients for breakthrough fungal infections.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Brompheniramine; Guaifenesin; Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Butabarbital: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections.
    Cabozantinib: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering cabozantinib. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C8, CYP2C9, CYP2C19, and CYP3A4; cabozantinib is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Caffeine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
    Caffeine; Ergotamine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
    Capecitabine: (Moderate) Use caution if coadministration of capecitabine with terbinafine is necessary, and monitor for an increase in terbinafine-related adverse reactions. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP2C9 and CYP3A4; capecitabine and/or its metabolites are thought to be inhibitors of CYP2C9. In a drug interaction study, the mean AUC of another CYP2C9 substrate, S-warfarin (single dose), significantly increased after coadministration with capecitabine; the maximum observed INR value also increased by 91%.
    Carbamazepine: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with carbamazepine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2, CYP2C9, and CYP3A4; carbamazepine induces these enzymes. Monitor patients for breakthrough fungal infections.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Carvedilol: (Minor) Inhibitors of the hepatic CYP450 isozyme CYP 2D6, including terbinafine, may inhibit the hepatic oxidative metabolism of carvedilol.
    Ceritinib: (Major) Avoid coadministration of ceritinib with systemic administration of terbinafine due to increased terbinafine exposure. If coadministration is unavoidable, monitor for terbinafine-related adverse reactions. Ceritinib is a CYP3A4 and CYP2C9 inhibitor; terbinafine is metabolized by both CYP3A4 and CYP2C9. Coadministration with another dual CYP3A4 and CYP2C9 inhibitor increased the Cmax and AUC of terbinafine by 52% and 69%, respectively.
    Cevimeline: (Moderate) Cevimeline is partially metabolized by CYP2D6. Inhibitors of this isoenzyme, like terbinafine, would be expected to lead to an increase in cevimeline plasma concentrations.
    Chloramphenicol: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering chloramphenicol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; chloramphenicol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Chlorpheniramine; Codeine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Terbinafine may interfere with the conversion of codeine to morphine; a corresponding decrease in analgesia may be seen.
    Chlorpheniramine; Dextromethorphan: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Cimetidine: (Minor) According to the manufacturer, cimetidine decreases the clearance of terbinafine by one-third. Studies were performed in normal volunteers. It is unknown if this interaction would be clinically significant; the exact mechanisms are not known.
    Ciprofloxacin: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ciprofloxacin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2; ciprofloxacin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Citalopram: (Moderate) Systemic terbinafine inhibits hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as selective serotonin reuptake inhibitors (SSRIs). The clinical relevance of the interaction is not known. Topical forms of terbinafine do not interact.
    Clarithromycin: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering clarithromycin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; clarithromycin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Class IC Antiarrhythmics: (Major) Class IC antiarrhythmics are metabolized by CYP2D6 isoenzymes. Caution is recommended when administering them with CYP2D6 inhibitors, such as terbinafine; Class IC antiarrhythmics exhibit a narrow therapeutic range and large increases in serum concentrations may be associated with severe adverse reactions.
    Clobazam: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with clobazam. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; clobazam induces this enzyme. Monitor patients for breakthrough fungal infections.
    Clomipramine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as tricyclic antidepressants.
    Clopidogrel: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering clopidogrel. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C8, CYP2C19, and CYP2C9; clopidogrel is a strong inhibitor of CYP2C8, an inhibitor of CYP2C19, and at high concentrations in vitro, clopidogrel inhibits the activity of CYP2C9. Monitor patients for adverse reactions if these drugs are coadministered.
    Clozapine: (Moderate) Caution is advisable during concurrent use of terbinafine and clozapine. Terbinafine is an inhibitor of CYP2D6, one of the isoenzymes responsible for the metabolism of clozapine.Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Elevated plasma concentrations of clozapine occurring through inhibition of CYP1A2, CYP2D6, or CYP3A4 may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with an inhibitor of CYP2D6 should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
    Cobicistat: (Moderate) Caution is advised when administering terbinafine with cobicistat. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4. Cobicistat is a substrate of CYP2D6 and an inhibitor of CYP3A4. Monitor patients for adverse reactions if these drugs are coadministered. Topical terbinafine formulations would not be expected to interact.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is advised when administering terbinafine with cobicistat. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4. Cobicistat is a substrate of CYP2D6 and an inhibitor of CYP3A4. Monitor patients for adverse reactions if these drugs are coadministered. Topical terbinafine formulations would not be expected to interact. (Moderate) Caution is advised when administering terbinafine with elvitegravir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may lower the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9. Elvitegravir is an inducer of CYP2C9. Monitor patients for breakthrough fungal infections if these drugs are coadministered.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering terbinafine with cobicistat. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4. Cobicistat is a substrate of CYP2D6 and an inhibitor of CYP3A4. Monitor patients for adverse reactions if these drugs are coadministered. Topical terbinafine formulations would not be expected to interact. (Moderate) Caution is advised when administering terbinafine with elvitegravir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may lower the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9. Elvitegravir is an inducer of CYP2C9. Monitor patients for breakthrough fungal infections if these drugs are coadministered.
    Codeine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Terbinafine may interfere with the conversion of codeine to morphine; a corresponding decrease in analgesia may be seen.
    Codeine; Guaifenesin: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Terbinafine may interfere with the conversion of codeine to morphine; a corresponding decrease in analgesia may be seen.
    Codeine; Phenylephrine; Promethazine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Terbinafine may interfere with the conversion of codeine to morphine; a corresponding decrease in analgesia may be seen.
    Codeine; Promethazine: (Minor) The activity of codeine is due to its conversion to morphine via the cytochrome P450 2D6 hepatic isoenzyme. Terbinafine may interfere with the conversion of codeine to morphine; a corresponding decrease in analgesia may be seen.
    Conivaptan: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering conivaptan. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; conivaptan is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Cyclobenzaprine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as cyclobenzaprine.
    Cyclosporine: (Moderate) Terbinafine has been found to increase the clearance of cyclosporine. As decreased cyclosporine serum concentrations and thus, an increased risk of organ rejection are possible, monitoring of cyclosporine concentrations is recommended during terbinafine use.
    Dalfopristin; Quinupristin: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering dalfopristin; quinupristin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; quinupristin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Danazol: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering danazol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; danazol is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Darifenacin: (Minor) Terbinafine inhibits hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme including darifenacin. Monitor patients for increased anticholinergic effects when CYP2D6 inhibitors are coadministered with darifenacin.
    Darunavir: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering darunavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; darunavir is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Darunavir; Cobicistat: (Moderate) Caution is advised when administering terbinafine with cobicistat. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4. Cobicistat is a substrate of CYP2D6 and an inhibitor of CYP3A4. Monitor patients for adverse reactions if these drugs are coadministered. Topical terbinafine formulations would not be expected to interact. (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering darunavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; darunavir is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Caution is advised when administering terbinafine with ritonavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2, CYP2C9, and CYP3A4; ritonavir is an inducer of CYP1A2 and CYP2C9, and an inhibitor/inducer of CYP3A4. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Dasatinib: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering dasatinib. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; dasatinib is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Delavirdine: (Moderate) Caution is advised when administering terbinafine with delavirdine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9, CYP2C19, and CYP3A4; delavirdine is a substrate of CYP2D6 and an inhibitor of CYP2C9, CYP2C19, and CYP3A4. Monitor patients for adverse reactions if these drugs are coadministered.
    Desipramine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as tricyclic antidepressants.
    Dexamethasone: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with dexamethasone. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; dexamethasone induces this enzyme. Monitor patients for breakthrough fungal infections.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Guaifenesin: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Promethazine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dextromethorphan; Quinidine: (Minor) Terbinafine has been shown to inhibit hepatic CYP2D6 enzymes and thus, dextromethorphan metabolism. Dextromethorphan toxicity can result, although the clinical significance of this is uncertain.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and terbinafine together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including antifungals. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dichlorphenamide dose or discontinuing dichlorphenamide therapy.
    Diltiazem: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering diltiazem. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; diltiazem is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Disulfiram: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering disulfiram. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2; disulfiram is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Donepezil: (Minor) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as donepezil.
    Donepezil; Memantine: (Minor) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as donepezil.
    Doxepin: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as tricyclic antidepressants.
    Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as terbinafine, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Dronedarone: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering dronedarone. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; dronedarone is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Drospirenone; Ethinyl Estradiol: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Dutasteride; Tamsulosin: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as terbinafine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Efavirenz: (Moderate) Caution is advised when administering terbinafine with efavirenz. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9, CYP2C19, and CYP3A4; efavirenz is inhibitor of CYP2C9 and CYP2C19, and an inhibitor/inducer of CYP3A4. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Caution is advised when administering terbinafine with efavirenz. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9, CYP2C19, and CYP3A4; efavirenz is inhibitor of CYP2C9 and CYP2C19, and an inhibitor/inducer of CYP3A4. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Elbasvir; Grazoprevir: (Moderate) Administering terbinafine with elbasvir; grazoprevir may result in elevated terbinafine plasma concentrations. Terbinafine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Eliglustat: (Major) In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of terbinafine and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily; however, coadministration of eliglustat with both terbinafine and a strong or moderate CYP3A inhibitor is contraindicated. Terbinafine is a moderate CYP2D6 inhibitor; eliglustat is a CYP2D6 and CYP3A substrate. Coadministration with CYP2D6 inhibitors, such as terbinafine, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). Physiology-based pharmacokinetic (PBPK) models suggest that terbinafine may increase the Cmax and AUC of eliglustat 3.8- and 4.5-fold, respectively, in EMs and 1.6-fold (both Cmax and AUC) in IMs. In addition, PBPK modeling suggests concomitant use of eliglustat (84 mg PO twice daily) with terbinafine (moderate 2D6 inhibitor) and a moderate 3A4 inhibitor may increase the Cmax and AUC of eliglustat 10.2- and 13.6-fold, respectively, in EMs and 4.2- and 5-fold, respectively, in IMs.
    Elvitegravir: (Moderate) Caution is advised when administering terbinafine with elvitegravir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may lower the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9. Elvitegravir is an inducer of CYP2C9. Monitor patients for breakthrough fungal infections if these drugs are coadministered.
    Erythromycin: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering erythromycin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; erythromycin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Erythromycin; Sulfisoxazole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering erythromycin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; erythromycin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Escitalopram: (Moderate) Systemic terbinafine inhibits hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as selective serotonin reuptake inhibitors (SSRIs). The clinical relevance of the interaction is not known. Topical forms of terbinafine do not interact.
    Eslicarbazepine: (Moderate) Caution is advised when administering terbinafine with eslicarbazepine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; eslicarbazepine is an inducer of CYP3A4 and an inhibitor of CYP2C19. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Ethanol: (Moderate) Caution is advised when administering terbinafine with ethanol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9 and CYP3A4; ethanol is an inducer of CYP3A4 and an inhibitor of CYP2C9. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Ethinyl Estradiol: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ethinyl Estradiol; Desogestrel: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ethinyl Estradiol; Etonogestrel: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ethinyl Estradiol; Levonorgestrel: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ethinyl Estradiol; Norelgestromin: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ethinyl Estradiol; Norethindrone: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ethinyl Estradiol; Norgestimate: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ethinyl Estradiol; Norgestrel: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ethinyl estradiol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; ethinyl estradiol is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Etravirine: (Moderate) Caution is advised when administering terbinafine with etravirine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9, CYP2C19, and CYP3A4; etravirine is an inducer of CYP3A4 and an inhibitor of CYP2C9 and CYP2C19. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Felbamate: (Moderate) Caution is advised when administering terbinafine with felbamate. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; felbamate is an inducer of CYP3A4 and an inhibitor of CYP2C19. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Fluconazole: (Moderate) Caution is advised when using terbinafine concurrently with fluconazole. The Cmax and AUC of terbinafine is increased by 52% and 69%, respectively, when administered with a single 100 mg dose of fluconazole. Predictions about this interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9, CYP2C19, and CYP3A4; fluconazole is an inhibitor of these enzymes. Taking these drugs together may increase the risk for terbinafine related adverse effects. However, in vitro studies suggest that use of terbinafine in combination with fluconazole may have synergistic activity against certain fungal species, including Candida sp. Clinical study is needed to elucidate the potential utility of terbinafine combinations with other antifungal agents.
    Fluorouracil, 5-FU: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering fluorouracil, 5-FU. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9; fluorouracil is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Fluoxetine: (Moderate) Systemic terbinafine inhibits hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as selective serotonin reuptake inhibitors (SSRIs). The clinical relevance of the interaction is not known. Topical forms of terbinafine do not interact.
    Fluoxetine; Olanzapine: (Moderate) Systemic terbinafine inhibits hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as selective serotonin reuptake inhibitors (SSRIs). The clinical relevance of the interaction is not known. Topical forms of terbinafine do not interact.
    Fluphenazine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as fluphenazine.
    Flutamide: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with flutamide. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; flutamide induces this enzyme. Monitor patients for breakthrough fungal infections.
    Fluvastatin: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering fluvastatin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9; fluvastatin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Fluvoxamine: (Moderate) Systemic terbinafine inhibits hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as selective serotonin reuptake inhibitors (SSRIs). The clinical relevance of the interaction is not known. Topical forms of terbinafine do not interact.
    Fosamprenavir: (Moderate) Caution is advised when administering terbinafine with fosamprenavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4. Fosamprenavir is a substrate of CYP2D6 and an inhibitor/inducer of CYP3A4. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Fosphenytoin: (Moderate) Caution is advised when administering terbinafine with phenytoin or fosphenytoin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9, CYP2C19, and CYP3A4; phenytoin is an inducer of CYP2C19 and CYP3A4, and a substrate and inducer of CYP2C9. Monitor patients for breakthrough fungal infections if these drugs are coadministered.
    Gefitinib: (Major) Monitor for an increased incidence of gefitinib-related adverse effects if gefitinib and terbinafine are used concomitantly. Gefitinib is metabolized significantly by CYP3A4 and to a lesser extent by CYP2D6; terbinafine is a CYP2D6 inhibitor. Coadministration may decrease the metabolism of gefitinib and increase gefitinib concentrations. While the manufacturer has provided no guidance regarding the use of gefitinib with CYP2D6 inhibitors, in patients with poor CYP2D6 metabolism, the mean exposure to gefitinib was 2-fold higher when compared to extensive metabolizers; the contribution of drugs that inhibit CYP2D6 on gefitinib exposure has not been evaluated.
    Gemfibrozil: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering gemfibrozil. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9; gemfibrozil is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Glimepiride; Pioglitazone: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with pioglitazone. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; pioglitazone induces this enzyme. Monitor patients for breakthrough fungal infections.
    Grapefruit juice: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering grapefruit juice. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, administration may increase the systemic exposure of terbinafine. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9 and CYP3A4; grapefruit juice is an inhibitor of these enzymes. Monitor patients for adverse reactions.
    Green Tea: (Moderate) Some green tea products contain caffeine. Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
    Griseofulvin: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with griseofulvin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; griseofulvin induces this enzyme. Monitor patients for breakthrough fungal infections.
    Guaifenesin; Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Guarana: (Moderate) Terbinafine is an inhibitor of the hepatic CYP450 isoenzyme CYP1A2 and may inhibit the hepatic oxidative metabolism of caffeine, which is an active component of guarana. No specific management is recommended except in patients who complain of caffeine-related side effects like nausea, tremor, or palpitations. Such patients should reduce their intake of guarana.
    Haloperidol: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as haloperidol.
    Homatropine; Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Minor) Metoprolol is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as terbinafine, could theoretically impair metoprolol metabolism. Clinicians should be alert to exaggerated beta-blocker effects if metoprolol is given with terbinafine.
    Hydrochlorothiazide, HCTZ; Propranolol: (Minor) Propranolol is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as terbinafine, could theoretically impair propranolol metabolism.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering telmisartan. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19; telmisartan is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Hydrocodone: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Ibuprofen: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Phenylephrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydrocodone; Pseudoephedrine: (Minor) The metabolism of hydrocodone to its active metabolite, hydromorphone, is dependent on CYP2D6. Theoretically, coadministration of hydrocodone and a CYP2D6 inhibitor, such as terbinafine, may result in a reduction in the analgesic effect of hydrocodone.
    Hydroxyprogesterone: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with hydroxyprogesterone. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2; hydroxyprogesterone induces this enzyme. Monitor patients for breakthrough fungal infections.
    Ibuprofen; Oxycodone: (Moderate) Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as terbinafine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with terbinafine, a CYP3A substrate, as terbinafine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Imatinib: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering imatinib, STI-571. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9 and CYP3A4; imatinib is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Imipramine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as tricyclic antidepressants.
    Indinavir: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering indinavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; indinavir is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Isavuconazonium: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering isavuconazonium. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; isavuconazole, the active moiety of isavuconazonium, is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Isoniazid, INH: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering isoniazid, INH. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; isoniazid is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) According to the manufacturer, rifampin doubles terbinafine's clearance systemically. Studies were performed in normal volunteers. It is unknown if this interaction would be clinically significant; the exact mechanisms are not known. When terbinafine is administered to patients who are prescribed rifampin, patients should be monitored for decreased responses to terbinafine therapy. (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering isoniazid, INH. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; isoniazid is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Isoniazid, INH; Rifampin: (Moderate) According to the manufacturer, rifampin doubles terbinafine's clearance systemically. Studies were performed in normal volunteers. It is unknown if this interaction would be clinically significant; the exact mechanisms are not known. When terbinafine is administered to patients who are prescribed rifampin, patients should be monitored for decreased responses to terbinafine therapy. (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering isoniazid, INH. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; isoniazid is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Itraconazole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering itraconazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; itraconazole is an inhibitor of this enzyme. Taking these drugs together may increase the risk for terbinafine related adverse effects. However, in vitro studies suggest that use of terbinafine in combination with itraconazole may have synergistic activity against certain fungal species, including Candida sp. Clinical study is needed to elucidate the potential utility of terbinafine combinations with other antifungal agents.
    Ivacaftor: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ivacaftor. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9 and CYP3A4; ivacaftor is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ketoconazole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ketoconazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may substantially increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9, CYP2C19, and CYP3A4; ketoconazole is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Lansoprazole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering lansoprazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9 and CYP2C19; lansoprazole is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Lansoprazole; Naproxen: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering lansoprazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9 and CYP2C19; lansoprazole is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Lapatinib: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering lapatinib. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C8 and CYP3A4; lapatinib is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Leflunomide: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering leflunomide. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9; leflunomide is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Loperamide: (Moderate) The plasma concentration of loperamide, a CYP2D6 substrate, may be increased when administered concurrently with terbinafine, a CYP2D6 inhibitor. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
    Loperamide; Simethicone: (Moderate) The plasma concentration of loperamide, a CYP2D6 substrate, may be increased when administered concurrently with terbinafine, a CYP2D6 inhibitor. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
    Lopinavir; Ritonavir: (Moderate) Caution is advised when administering terbinafine with ritonavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2, CYP2C9, and CYP3A4; ritonavir is an inducer of CYP1A2 and CYP2C9, and an inhibitor/inducer of CYP3A4. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Luliconazole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering luliconazole. Although this interaction has not been studied by the manufacturer and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4. In vitro data suggest luliconazole is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Lumacaftor; Ivacaftor: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with lumacaftor; ivacaftor. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C8, CYP2C9, CYP2C19 and CYP3A4; lumacaftor is a strong CYP3A inducer. In vitro data also suggest that lumacaftor; ivacaftor may induce CYP2C19 and induce and/or inhibit CYP2C8 and CYP2C9. Monitor patients for breakthrough fungal infections. (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ivacaftor. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9 and CYP3A4; ivacaftor is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Lumacaftor; Ivacaftor: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with lumacaftor; ivacaftor. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C8, CYP2C9, CYP2C19 and CYP3A4; lumacaftor is a strong CYP3A inducer. In vitro data also suggest that lumacaftor; ivacaftor may induce CYP2C19 and induce and/or inhibit CYP2C8 and CYP2C9. Monitor patients for breakthrough fungal infections.
    Maprotiline: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as maprotiline.
    Meperidine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as meperidine.
    Meperidine; Promethazine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as meperidine.
    Mephobarbital: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections.
    Metformin; Pioglitazone: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with pioglitazone. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; pioglitazone induces this enzyme. Monitor patients for breakthrough fungal infections.
    Methadone: (Moderate) Coadministration of methadone and terbinafine may result in increased methadone concentrations. Systemic terbinafine inhibits hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme.
    Methamphetamine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as methamphetamine.
    Methohexital: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections.
    Metoprolol: (Minor) Metoprolol is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as terbinafine, could theoretically impair metoprolol metabolism. Clinicians should be alert to exaggerated beta-blocker effects if metoprolol is given with terbinafine.
    Metyrapone: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with metyrapone. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; metyrapone induces this enzyme. Monitor patients for breakthrough fungal infections.
    Mexiletine: (Moderate) Mexiletine is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, including terbinafine, could theoretically impair mexiletine metabolism.
    Mifepristone, RU-486: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering mifepristone, RU-486. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; mifepristone is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Mirabegron: (Moderate) Caution is advised when administering terbinafine with mirabegron. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4. Mirabegron is a substrate of CYP2D6 and an inhibitor of CYP3A4. Monitor patients for adverse reactions if these drugs are coadministered.
    Mitotane: (Major) Avoid the concomitant use of mitotane with terbinafine due to decreased terbinafine exposure and possible decreases in efficacy. Mitotane is a strong CYP3A4 inducer and terbinafine is a CYP3A4 substrate. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Terbinafine clearance was increased 100% by rifampin, another strong CYP450 inducer.
    Modafinil: (Moderate) Caution is advised when administering terbinafine with modafinil. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9, CYP2C19, and CYP3A4; modafinil is an inducer of CYP3A4 and an inhibitor of CYP2C9 and CYP2C19. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Montelukast: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering montelukast. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C8; montelukast is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Nafcillin: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with nafcillin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; nafcillin induces this enzyme. Monitor patients for breakthrough fungal infections.
    Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with terbinafine. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as terbinafine, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
    Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with terbinafine. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as terbinafine, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
    Nefazodone: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering nefazodone. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; nefazodone is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Nelfinavir: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering nelfinavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; nelfinavir is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Nevirapine: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with nevirapine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; nevirapine induces this enzyme. Monitor patients for breakthrough fungal infections.
    Nicardipine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering nicardipine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C8, CYP2C19, and CYP3A4; nicardipine is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Norfloxacin: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering norfloxacin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2; norfloxacin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Nortriptyline: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as tricyclic antidepressants.
    Octreotide: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering octreotide. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; octreotide is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Caution is advised when administering terbinafine with ritonavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2, CYP2C9, and CYP3A4; ritonavir is an inducer of CYP1A2 and CYP2C9, and an inhibitor/inducer of CYP3A4. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Oritavancin: (Moderate) Coadministration of oritavancin and systemic terbinafine may result in increases or decreases in terbinafine exposure and may increase side effects or decrease efficacy of terbinafine. Terbinafine is metabolized by CYP3A4, CYP2C9, and CYP2C19. Oritavancin weakly induces CYP3A4, while weakly inhibiting CYP2C9 and CYP2C19. If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy. Topical formulations are not extensively absorbed and are unlikely to exhibit significant drug interactions.
    Oxcarbazepine: (Moderate) Caution is advised when administering terbinafine with oxcarbazepine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; oxcarbazepine is an inhibitor of CYP2C19 and an inducer of CYP3A4. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Oxycodone: (Moderate) Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone, which represents < 15% of the total administered dose. Potent inhibitors of CYP2D6, such as terbinafine, may potentially increase the effects of oxycodone; however, such blockade has not been shown to be of clinical significance during oxycodone treatment. Clinicians should be aware of this possible interaction.
    Pantoprazole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering pantoprazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9, CYP2C19, and CYP3A4; pantoprazole is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Paroxetine: (Moderate) Systemic terbinafine inhibits hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as selective serotonin reuptake inhibitors (SSRIs). The clinical relevance of the interaction is not known. Topical forms of terbinafine do not interact.
    Peginterferon Alfa-2b: (Moderate) Caution is advised when administering terbinafine with peginterferon alfa-2b. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of systemic terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, including CYP1A2, which is inhibited by peginterferon alfa-2b. Monitor patients for adverse reactions if these drugs are coadministered.
    Pentobarbital: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections.
    Perampanel: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with perampanel. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; perampanel induces this enzyme. Monitor patients for breakthrough fungal infections.
    Perphenazine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as perphenazine.
    Perphenazine; Amitriptyline: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as perphenazine. (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as tricyclic antidepressants.
    Phenobarbital: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections.
    Phentermine; Topiramate: (Moderate) Caution is advised when administering terbinafine with topiramate. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; topiramate is an inducer of CYP3A4 and an inhibitor of CYP2C19. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Phenytoin: (Moderate) Caution is advised when administering terbinafine with phenytoin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9, CYP2C19, and CYP3A4; phenytoin is an inducer of CYP2C19 and CYP3A4, and an inhibitor of CYP2C9. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Pimozide: (Major) Concurrent use of pimozide and terbinafine should be avoided if possible. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. Terbinafine is an inhibitor of CYP2D6. Elevated pimozide concentrations occurring through inhibition of CYP3A4, CYP2D6, and/or CYP1A2 can lead to QT prolongation, ventricular arrhythmias, and sudden death. Concurrent use of potent CYP2D6 inhibitors and pimozide is contraindicated by the manufacturer of pimozide.
    Pioglitazone: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with pioglitazone. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; pioglitazone induces this enzyme. Monitor patients for breakthrough fungal infections.
    Posaconazole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering posaconazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; posaconazole is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Primidone: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections.
    Propoxyphene: (Moderate) Propoxyphene is a substrate and an inhibitor of CYP2D6. Increased serum concentrations of propoxyphene would be expected from concurrent use of a CYP2D6 inhibitor like terbinafine.
    Propranolol: (Minor) Propranolol is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as terbinafine, could theoretically impair propranolol metabolism.
    Protriptyline: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as tricyclic antidepressants.
    Quinine: (Moderate) Caution is advised when administering terbinafine with quinine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of both drugs. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is an inhibitor of CYP2D6 and is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2, CYP2C19, and CYP3A4; quinine is a substrate of CYP2D6, an inhibitor of CYP2C19, an inducer of CYP1A2, and an inhibitor/inducer of CYP3A4. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Rabeprazole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering rabeprazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19; rabeprazole is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Ranolazine: (Moderate) Coadministration of terbinafine and ranolazine may result in increased plasma concentrations of ranolazine. Ranolazine is metabolized mainly by CYP3A and to a lesser extent by CYP2D6. Terbinafine is a known CYP2D6 inhibitor. Cautiously monitor the concurrent use of ranolazine and significant CYP2D6 inhibitors since potential increases in plasma concentrations of ranolazine may result in adverse effects.The manufacturer specifies that no dosage adjustment of ranolazine is necessary when coadministering CYP2D6 inhibitors.
    Regorafenib: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering regorafenib. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C8, CYP2C9, CYP2C19, and CYP3A4; regorafenib is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Ribociclib: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ribociclib. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP3A4; ribociclib is a moderate inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Ribociclib; Letrozole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ribociclib. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP3A4; ribociclib is a moderate inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Rifabutin: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with rifabutin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; rifabutin induces this enzyme. Monitor patients for breakthrough fungal infections.
    Rifampin: (Moderate) According to the manufacturer, rifampin doubles terbinafine's clearance systemically. Studies were performed in normal volunteers. It is unknown if this interaction would be clinically significant; the exact mechanisms are not known. When terbinafine is administered to patients who are prescribed rifampin, patients should be monitored for decreased responses to terbinafine therapy.
    Ritonavir: (Moderate) Caution is advised when administering terbinafine with ritonavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2, CYP2C9, and CYP3A4; ritonavir is an inducer of CYP1A2 and CYP2C9, and an inhibitor/inducer of CYP3A4. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Saccharomyces boulardii: (Major) Because Saccharomyces boulardii is an active yeast, it would be expected to be inactivated by any antifungals. The manufacturer does not recommend taking in conjunction with any antifungal agents. Patients should avoid use of this probiotic yeast until the patient's fungal or yeast infection is completely treated.
    Saquinavir: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering saquinavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; saquinavir is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Secobarbital: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections.
    Selective serotonin reuptake inhibitors: (Moderate) Systemic terbinafine inhibits hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as selective serotonin reuptake inhibitors (SSRIs). The clinical relevance of the interaction is not known. Topical forms of terbinafine do not interact.
    Sertraline: (Moderate) Systemic terbinafine inhibits hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as selective serotonin reuptake inhibitors (SSRIs). The clinical relevance of the interaction is not known. Topical forms of terbinafine do not interact.
    St. John's Wort, Hypericum perforatum: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with St. John's Wort, hypericum perforatum. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; St. John's Wort induces these enzymes. Monitor patients for breakthrough fungal infections.
    Streptogramins: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering dalfopristin; quinupristin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; quinupristin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering sulfamethoxazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9; sulfamethoxazole is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered. (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering trimethoprim. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP2C8; trimethoprim is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Sulfinpyrazone: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering sulfinpyrazone. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9; sulfinpyrazone is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Tacrine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering tacrine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2; tacrine is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Tamoxifen: (Major) Concomitant use may result in decreased concentrations of the active metabolites of tamoxifen, which can compromise efficacy. Monitor patients for changes in the therapeutic efficacy of tamoxifen. Terbinafine is a moderate CYP2D6 inhibitor. Tamoxifen is metabolized by CYP2D6 to the potent active metabolite 4-hydroxytamoxifen. 4-hydroxytamoxifen is further metabolized to endoxifen by CYP3A4/5. Active metabolite, N-desmethyl-tamoxifen, is also metabolized to endoxifen by CYP2D6. Terbinafine may inhibit the metabolism of tamoxifen to these metabolites, which have up to 33 times more affinity for the estrogen receptor than tamoxifen. Some data suggest that the efficacy of tamoxifen is reduced when coadministered with CYP2D6 inhibitors. A trial of 1,298 patients with breast cancer compared the rate of breast cancer recurrence in patients treated with tamoxifen with or without a CYP2D6 inhibitor. Patients who received tamoxifen in combination with a CYP2D6 inhibitor had a significantly higher rate of breast cancer recurrence at 2 years (13.9% v. 7.5%, p < 0.001). A separate observational study of 1,990 patients assessed event free time with adjuvant tamoxifen treatment for breast cancer. Only 215 of these patients were administered a CYP2D6 inhibitor, however no clinically significant differences were observed with the addition of a CYP2D6 inhibitor.
    Tamsulosin: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as terbinafine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Telaprevir: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering telaprevir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; telaprevir is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Telithromycin: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering telithromycin. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; telithromycin is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Telmisartan: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering telmisartan. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19; telmisartan is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Telotristat Ethyl: (Minor) Use caution if coadministration of telotristat ethyl and terbinafine is necessary, as the systemic exposure of terbinafine may be decreased resulting in reduced efficacy; however, published literature suggests the potential for interactions to be low. If these drugs are used together, monitor patients for suboptimal efficacy of terbinafine; consider increasing the dose of terbinafine if necessary. Terbinafine is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Teriflunomide: (Moderate) Caution is advised when administering terbinafine with teriflunomide. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2 and CYP2C8; teriflunomide is an inducer of CYP1A2 and an inhibitor of CYP2C8. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Theophylline, Aminophylline: (Minor) Oral terbinafine is reported to decrease theophylline clearance by 14%. It is unknown if this interaction would be clinically significant. Patients who receive aminophylline concurrently with terbinafine should be monitored for increased or decreased effects of these narrow therapeutic window drugs. (Minor) Oral terbinafine is reported to decrease theophylline clearance by 14%. It is unknown if this interaction would be clinically significant. Patients who receive theophylline or aminophylline concurrently with terbinafine should be monitored for increased or decreased effects of these narrow therapeutic window drugs.
    Thiabendazole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering thiabendazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2; thiabendazole is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Thiopental: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with barbiturates. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP1A2, CYP2C9, CYP2C19 and CYP3A4; barbiturates induce these enzymes. Monitor patients for breakthrough fungal infections.
    Thioridazine: (Severe) Coadministration of terbinafine, a CYP2D6 inhibitor, and thioridazine, a CYP2D6 substrate, is contraindicated, as concurrent use may result in increased exposure to thioridazine. Elevated thioridazine concentrations would be expected to augment the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsade de pointes.
    Ticagrelor: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ticagrelor. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; ticagrelor is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Ticlopidine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering ticlopidine. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19; ticlopidine is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Tipranavir: (Moderate) Caution is advised when administering terbinafine with tipranavir. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2, CYP2C19, and CYP3A4; tipranavir is an inducer of CYP1A2 and CYP2C19, and an inhibitor of CYP3A4. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Tobacco: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine to someone who smokes tobacco. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, administration may decrease the systemic exposure of terbinafine. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2; tobacco smoking induces this enzyme. Monitor patients for breakthrough fungal infections.
    Topiramate: (Moderate) Caution is advised when administering terbinafine with topiramate. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; topiramate is an inducer of CYP3A4 and an inhibitor of CYP2C19. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Tramadol: (Moderate) As terbinafine inhibits CYP2D6 and tramadol is partially metabolized by CYP2D6, concurrent therapy may decrease tramadol metabolism. This interaction may result in decreased tramadol efficacy and/or increased tramadol-induced risks of serotonin syndrome or seizures. The analgesic activity of tramadol is due to the activity of both the parent drug and the O-desmethyltramadol metabolite (M1), and M1 formation is dependent on CYP2D6. Therefore, use of tramadol with a CYP2D6-inhibitor may alter tramadol efficacy. In addition, inhibition of CYP2D6 metabolism is expected to result in reduced metabolic clearance of tramadol. This in turn may increase the risk of tramadol-related adverse events including serotonin syndrome and seizures. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Trandolapril; Verapamil: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering verapamil. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP3A4; verapamil is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Tricyclic antidepressants: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as tricyclic antidepressants.
    Trimethoprim: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering trimethoprim. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP2C8; trimethoprim is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Trimipramine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as tricyclic antidepressants.
    Valproic Acid, Divalproex Sodium: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering valproic acid. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9; valproic acid is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Vemurafenib: (Moderate) Caution is advised when administering terbinafine with vemurafenib. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2, CYP2C9 and CYP3A4; vemurafenib is an inducer of CYP3A4 and an inhibitor of CYP1A2 and CYP2C9. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered.
    Venlafaxine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as venlafaxine.
    Verapamil: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering verapamil. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP3A4; verapamil is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Voriconazole: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering voriconazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9, CYP2C19, and CYP3A4; voriconazole is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Warfarin: (Minor) Terbinafine has been associated with an increase in the activity of warfarin.
    Zafirlukast: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering zafirlukast. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2, CYP2C8, CYP2C9, and CYP3A4; zafirlukast is an inhibitor of these enzymes. Monitor patients for adverse reactions if these drugs are coadministered.
    Zileuton: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering zileuton. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP1A2; zileuton is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Zolpidem: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as zolpidem.

    PREGNANCY AND LACTATION

    Pregnancy

    Terbinafine, in both dermatologic and oral formulations, is rated FDA pregnancy risk category B. Although adequate, well-controlled studies have not been performed in humans, studies in animals using large oral and topical dosages did not reveal teratogenic effects. Terbinafine should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. Treatment of onychomycosis can be postponed until after pregnancy is completed; it is recommended that terbinafine not be initiated for this indication during pregnancy.

    Orally administered terbinafine is excreted in breast milk and is not recommended for use during breast-feeding. Human data from two lactating volunteers found total excretion into breast milk to be 0.13% and 0.03% of the administered dose (500 mg PO once). Topical use during breast-feeding has not been studied; because of the low absorption, significant excretion in breast milk is considered unlikely. Instruct nursing mothers to avoid topical application to the breast, as this would be expected to increase infant exposure. A decision should be made whether to discontinue nursing or to discontinue terbinafine, taking into account the importance of the medication to the mother. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Terbinafine, an allylamine antifungal, displays activity against dermatophytes (Trichophyton mentagrophytes and T. rubrum), as well as in vitro activity against Candida albicans, Epidermophyton floccosum, and Scopulariopsis brevicaulis. The drug exerts its antifungal effect through interfering with fungal sterol biosynthesis by inhibiting the enzyme squalene epoxidase. Squalene epoxidase is a key enzyme in fungal sterol biosynthesis that is required to convert squalene to ergosterol (an essential component of fungal cell membranes). By blocking squalene monooxygenase, terbinafine creates a deficiency in ergosterol, thereby resulting in increased cell membrane permeability and fungal cell death.

    PHARMACOKINETICS

    Terbinafine is administered orally and topically. Although more than 99% protein-bound, the drug is widely distributed, including in the CNS, hair, and nail beds. It is detectable within the stratum corneum in as little as 24 hours after the initiation of therapy. After 2 weeks at the recommended doses, terbinafine remains in the skin for up to 3 months. The elimination half-life ranges from 26 to 36 hours. The terminal half-life is about 200 to 400 hours, representing the slow redistribution from skin and adipose tissue. The Drug may be detected in the nails within 1 week of starting therapy and last for up to 90 days after treatment has stopped. Terbinafine is extensively metabolized in the liver by at least 7 CYP isoenzymes, with major contributions from CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP3A4. Most of the oral dose is metabolized through N-demethylation, alkyl oxidation, and hydrolysis to 15 known metabolites that lack antifungal activity. The primary metabolite is N-desmethyl-terbinafine (10% to 15%). Roughly 70% to 80% of an oral dose is excreted in the urine as these conjugated and unconjugated metabolites; 20% is eliminated via the feces.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6, CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4
    Systemic terbinafine has been shown in vitro and in vivo to inhibit the CYP2D6 isoenzyme. In addition, systemically it is a substrate for hepatic isoenzymes CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP3A4. Topical formulations are not extensively absorbed and are unlikely to exhibit significant drug interactions.

    Oral Route

    Oral terbinafine is well absorbed from the gut, reaching peak plasma concentrations within 2 hours; bioavailability is roughly 40% due to first-pass metabolism. Administration with food increases the serum AUC by 20%. Steady-state concentrations are achieved within 10 to 14 days.

    Topical Route

    Systemic absorption of terbinafine from the topical formulation was highly variable in a study of 16 patients, 8 of whose sites of application were compromised by stripping the stratum corneum. In many patients, there were no measurable amounts of the metabolite or the parent drug. Systemic absorption of topically administered terbinafine is 37 times lower than that which occurs with oral administration.