Lamisil AT Athletes Foot

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Lamisil AT Athletes Foot

Classes

Other Systemic Antifungals
Topical Dermatological Antifungals

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

May be taken with or without food.

Extemporaneous Compounding-Oral

NOTE: Extemporaneously compounded oral terbinafine suspension is not FDA-approved.
Shake well before administering. Measure dosage with calibrated measuring device.
Extemporaneous preparation of 25 mg/mL terbinafine oral suspension†
Using a mortar and pestle, grind twenty 250-mg terbinafine tablets into a fine powder.
Add a small volume of the vehicle (1:1 mixture of Ora-Plus and Ora-Sweet) and triturate to make a smooth paste.
Add increasing volumes of the vehicle to make the terbinafine liquid pourable.
Transfer the liquid to a graduated cylinder.
Add enough vehicle to the graduated cylinder to bring the final volume to 200 mL.
Transfer to amber plastic bottle.
Label the bottle with 'Shake well before use' and 'Protect from light'.
Storage: The oral suspension is stable for 42 days when stored at room temperature or refrigerated.

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.
Improvement of dermal tinea infection is gradual, and improvements in the treated condition may continue for the 2 to 6 weeks after terbinafine therapy is discontinued.

Adverse Reactions
Severe

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

Moderate

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

Mild

headache / Early / 7.0-12.9
diarrhea / Early / 3.0-6.0
rash / Early / 5.6-5.6
vomiting / Early / 5.0-5.0
dyspepsia / Early / 4.0-4.3
abdominal pain / Early / 2.0-4.0
dysgeusia / Early / 2.8-3.0
nausea / Early / 2.0-3.0
pruritus / Rapid / 0.2-2.8
flatulence / Early / 2.2-2.2
urticaria / Rapid / 1.1-1.1
skin irritation / Early / 1.0-1.0
xerosis / Delayed / 0.2-0.2
photosensitivity / Delayed / Incidence not known
alopecia / 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
paresthesias / Delayed / Incidence not known
hypoesthesia / Delayed / Incidence not known
tinnitus / Delayed / Incidence not known
malaise / Early / Incidence not known
vertigo / Early / Incidence not known
arthralgia / Delayed / Incidence not known
fatigue / Early / Incidence not known
myalgia / Early / Incidence not known

Common Brand Names

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

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

Dosage And 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 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 tinea capitis†. Oral dosage Adults

250 mg PO once daily for 2 to 6 weeks for Trichophyton infections and 8 to 12 weeks for Microsporum infections.

Children and Adolescents weighing more than 40 kg

250 mg PO once daily for 2 to 6 weeks for Trichophyton infections and 8 to 12 weeks for Microsporum infections.

Children and Adolescents weighing 20 to 40 kg

4 to 6 mg/kg/dose PO once daily or 125 mg PO once daily for 2 to 6 weeks for Trichophyton infections and 8 to 12 weeks for Microsporum infections.

Children weighing 10 to 20 kg

4 to 6 mg/kg/dose PO once daily or 62.5 mg PO once daily for 2 to 6 weeks for Trichophyton infections and 8 to 12 weeks for Microsporum infections.

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.

For the treatment of cutaneous or lymphocutaneous sporotrichosis†. Oral dosage Adults

500 mg PO twice daily for 2 to 4 weeks after all lesions have resolved, usually for a total of 3 to 6 months in patients who do not respond to itraconazole.[50784]

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

Oral terbinafine is contraindicated in persons with chronic or active liver disease. In persons with hepatic cirrhosis, oral terbinafine clearance is reduced by approximately 50% compared to normal volunteers.

Renal Impairment

CrCl more than 50 mL/minute: No dosage adjustment needed.
CrCl 50 mL/minute or less: The use of oral terbinafine has not been adequately studied. Oral terbinafine clearance is reduced by approximately 50% compared to normal volunteers.

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; Caffeine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with terbinafine may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of terbinafine could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If terbinafine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Terbinafine is a strong inhibitor of CYP2D6. (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
Acetaminophen; Caffeine; Pyrilamine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with terbinafine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of terbinafine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If terbinafine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Terbinafine is a strong inhibitor of CYP2D6.
Acetaminophen; Dextromethorphan: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with terbinafine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of terbinafine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If terbinafine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Terbinafine is a strong inhibitor of CYP2D6.
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.
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.
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; 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.
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: (Major) Recommendations for managing aripiprazole and terbinafine vary by aripiprazole dosage form. For aripiprazole oral dosage forms, administer half of the usual dose. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; terbinafine is a strong CYP2D6 inhibitor. (Major) Recommendations for managing aripiprazole and terbinafine vary by aripiprazole dosage form. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg or for patients known to be poor metabolizers of CYP2D6. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP3A inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP2D6 and CYP3A substrate; terbinafine is a strong CYP2D6 inhibitor.
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.
Asciminib: (Moderate) Monitor for an increase in terbinafine-related adverse reactions if coadministration with asciminib is necessary. Terbinafine is a CYP2C9 and CYP3A substrate; asciminib is a dual CYP2C9 and CYP3A inhibitor. Coadministration with a moderate CYP2C9 and CYP3A inhibitor increased the Cmax and AUC of terbinafine by 52% and 69%, respectively.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
Aspirin, ASA; Caffeine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
Aspirin, ASA; Caffeine; Orphenadrine: (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: (Moderate) Concomitant use of codeine with terbinafine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of terbinafine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If terbinafine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Terbinafine is a strong inhibitor of CYP2D6.
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) Dosage reduction of atomoxetine is recommended in patients receiving terbinafine due to the potential for increased atomoxetine exposure and related adverse effects. In children and adolescents up to 70 kg receiving terbinafine, atomoxetine should be initiated at 0.5 mg/kg/day and only increased to the usual target dose of 1.2 mg/kg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. In children and adolescents over 70 kg and adults receiving terbinafine, atomoxetine should be initiated at 40 mg/day and only increased to the usual target dose of 80 mg/day if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. Terbinafine is a strong CYP2D6 inhibitor; atomoxetine is a CYP2D6 substrate. Coadministration of a strong CYP2D6 inhibitor and atomoxetine in extensive metabolizers of CYP2D6, increased atomoxetine steady-state plasma concentrations by approximately 6 to 8-fold. This increase is similar to exposures observed in poor metabolizers. Concurrent use of a strong CYP2D6 inhibitor with atomoxetine in poor metabolizers is not expected to increase atomoxetine exposure.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Butalbital; Acetaminophen; Caffeine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with terbinafine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of terbinafine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If terbinafine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Terbinafine is a strong inhibitor of CYP2D6. (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with terbinafine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of terbinafine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If terbinafine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Terbinafine is a strong inhibitor of CYP2D6. (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
Caffeine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
Caffeine; Sodium Benzoate: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
Carvedilol: (Minor) Inhibitors of the hepatic CYP450 isozyme CYP 2D6, including terbinafine, may inhibit the hepatic oxidative metabolism of carvedilol.
Celecoxib; 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.
Ceritinib: (Major) Monitor for an increase in terbinafine-related adverse reactions if coadministration with ceritinib is necessary. Terbinafine is a CYP3A4 and CYP2C9 substrate. Ceritinib is a strong CYP3A4 inhibitor and a weak CYP2C9 inhibitor. Coadministration with a moderate 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.
Chlordiazepoxide; 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.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with terbinafine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of terbinafine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If terbinafine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Terbinafine is a strong inhibitor of CYP2D6.
Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with terbinafine may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of terbinafine could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If terbinafine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Terbinafine is a strong inhibitor of CYP2D6.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with terbinafine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of terbinafine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If terbinafine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Terbinafine is a strong inhibitor of CYP2D6.
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.
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.
Clozapine: (Moderate) Consider a clozapine dose reduction if coadministered with terbinafine and monitor for adverse reactions. If terbinafine is discontinued, monitor for lack of clozapine effect and increase dose if necessary. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is partially metabolized by CYP2D6 and terbinafine is a strong CYP2D6 inhibitor.
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.
Codeine: (Moderate) Concomitant use of codeine with terbinafine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of terbinafine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If terbinafine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Terbinafine is a strong inhibitor of CYP2D6.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with terbinafine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of terbinafine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If terbinafine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Terbinafine is a strong inhibitor of CYP2D6.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with terbinafine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of terbinafine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If terbinafine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Terbinafine is a strong inhibitor of CYP2D6.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with terbinafine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of terbinafine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If terbinafine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Terbinafine is a strong inhibitor of CYP2D6.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with terbinafine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of terbinafine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If terbinafine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Terbinafine is a strong inhibitor of CYP2D6.
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.
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.
Darunavir; Cobicistat; 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) 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.
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.
Desogestrel; 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.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Dextromethorphan: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Dextromethorphan; Bupropion: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Dextromethorphan; Guaifenesin: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Dextromethorphan; Quinidine: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
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.
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.
Duloxetine: (Moderate) Monitor for increased duloxetine-related adverse effects if coadministered with terbinafine. Concurrent use may result in increased duloxetine exposure resulting in excessive serotonin activity. Terbinafine is a strong CYP2D6 inhibitor; duloxetine is a CYP2D6 substrate. Coadministration with another strong CYP2D6 inhibitor increased the duloxetine AUC by about 60%.
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 Disoproxil Fumarate: (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; Lamivudine; Tenofovir Disoproxil Fumarate: (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.
Elexacaftor; tezacaftor; 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.
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; Cobicistat; 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.
Elvitegravir; Cobicistat; 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.
Ergotamine; Caffeine: (Minor) Terbinafine has been shown to inhibit the clearance of caffeine. The clinical significance of this interaction has not been determined.
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.
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.
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; 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.
Ethynodiol Diacetate; 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.
Etonogestrel; 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.
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.
Fenfluramine: (Major) Do not exceed a maximum dose of fenfluramine 20 mg per day if coadministered with terbinafine; for patients also receiving stiripentol plus clobazam, do not exceed a maximum dose of fenfluramine 17 mg per day. Concomitant use may increase fenfluramine plasma concentrations and the risk of adverse reactions. Fenfluramine is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Coadministration with another strong CYP2D6 inhibitor increased fenfluramine overall exposure by 81% and decreased norfenfluramine overall exposure by 13%.
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.
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.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with terbinafine is necessary; the risk is increased in CYP2D6 poor metabolizers. Based on in vitro data, gefitinib is metabolized to O-desmethyl gefitinib by CYP2D6 and terbinafine is a strong CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends precautions based on exposure in patients with poor CYP2D6 metabolism.
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.
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.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with terbinafine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of terbinafine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If terbinafine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Terbinafine is a strong inhibitor of CYP2D6.
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: (Moderate) Concomitant use of hydrocodone with terbinafine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of terbinafine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If terbinafine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Terbinafine is a strong inhibitor of CYP2D6.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with terbinafine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of terbinafine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If terbinafine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Terbinafine is a strong inhibitor of CYP2D6.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with terbinafine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of terbinafine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If terbinafine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Terbinafine is a strong inhibitor of CYP2D6.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with terbinafine may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of terbinafine could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If terbinafine is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Terbinafine is a strong inhibitor of CYP2D6.
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.
Iloperidone: (Major) Reduce the iloperidone dose by one-half if coadministered with terbinafine. If terbinafine is discontinued, increase the iloperidone dose to the previous level. Increased iloperidone exposure may occur with concurrent use. Iloperidone is a CYP2D6 substrate. Terbinafine is a strong inhibitor of CYP2D6. Coadministration of other strong CYP2D6 inhibitors increased mean steady-state peak concentrations of iloperidone and its metabolite P88, by up to 3-fold, and decreased mean steady-state peak concentrations of its metabolite P95 by one-half.
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; 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.
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.
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 CYP3A4; ketoconazole is a CYP3A4 inhibitor. 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 CYP2C19; lansoprazole is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
Lansoprazole; Amoxicillin; 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. (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 CYP2C19; lansoprazole is an inhibitor of this enzyme. 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.
Levoketoconazole: (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 CYP3A4; ketoconazole is a CYP3A4 inhibitor. Monitor patients for adverse reactions if these drugs are coadministered.
Levonorgestrel; 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.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (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.
Levonorgestrel; Ethinyl Estradiol; 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.
Lofexidine: (Moderate) Monitor for orthostatic hypotension and bradycardia during concurrent use of lofexidine and terbinafine. Coadministration may increase lofexidine exposure. Lofexidine is a CYP2D6 substrate; terbinafine is a strong CYP2D6 inhibitor. Coadministration with a strong CYP2D6 inhibitor increased the lofexidine AUC by 28%.
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 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.
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.
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.
Metoclopramide: (Major) Metoclopramide is a substrate of CYP2D6 and terbinafine is a strong CYP2D6 inhibitor; due to the risk of increased metoclopramide plasma concentrations and extrapyramidal adverse reactions, dose adjustments of oral metoclopramide are recommended when administered in combination with strong CYP2D6 inhibitors. In patients with gastroesophageal reflux receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers (PMs), the recommended dose of metoclopramide is 5 mg PO four times daily or 10 mg PO three times daily. In patients with diabetic gastroparesis receiving a strong CYP2D6 inhibitor or who are known CYP2D6 poor metabolizers (PMs), the recommended dose of metoclopramide is 5 mg PO four times daily times daily.
Metoprolol: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure and decrease its cardioselectivity. Metoprolol is a CYP2D6 substrate; terbinafine is a strong CYP2D6 inhibitor. In the presence of another strong CYP2D6 inhibitor, the concentration of S-metoprolol was tripled and the metoprolol elimination half-life doubled.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure and decrease its cardioselectivity. Metoprolol is a CYP2D6 substrate; terbinafine is a strong CYP2D6 inhibitor. In the presence of another strong CYP2D6 inhibitor, the concentration of S-metoprolol was tripled and the metoprolol elimination half-life doubled.
Mexiletine: (Moderate) Mexiletine is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, including terbinafine, could theoretically impair mexiletine metabolism.
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.
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.
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.
Nirmatrelvir; 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.
Norethindrone Acetate; Ethinyl Estradiol; 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.
Norethindrone; 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.
Norethindrone; Ethinyl Estradiol; 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.
Norgestimate; 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.
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.
Olanzapine; 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.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and terbinafine is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and terbinafine may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If terbinafine is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor.
Omeprazole; Amoxicillin; 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.
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.
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.
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.
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.
Pimozide: (Contraindicated) Coadministration of pimozide and terbinafine is contraindicated due to the potential for increased pimozide exposure. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death. Terbinafine is a strong CYP2D6 inhibitor; pimozide is a CYP2D6 substrate. Coadministration of pimozide with another strong CYP2D6 inhibitor increased the pimozide AUC by 151%.
Pitolisant: (Major) Initiate pitolisant at 8.9 mg once daily in patients taking terbinafine; increase pitolisant after 7 days to a maximum dosage of 17.8 mg once daily. If terbinafine is initiated in a patient on a stable dose of pitolisant, reduce the pitolisant dose by half. Pitolisant is a CYP2D6 substrate; terbinafine is a strong CYP2D6 inhibitor. Coadministration of strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold.
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.
Promethazine; Dextromethorphan: (Moderate) Monitor for dextromethorphan-related side effects, such as dizziness or drowsiness, if concomitant use of terbinafine is necessary. For patients receiving combination dextromethorphan; bupropion, do not exceed a maximum dose of 45 mg dextromethorphan; 105 mg bupropion once daily. Concomitant use may increase dextromethorphan exposure and side effects. Dextromethorphan is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with another strong CYP2D6 inhibitor increased dextromethorphan overall exposure by 2.69-fold.
Propranolol: (Minor) Propranolol is significantly metabolized by CYP2D6 isoenzymes. CYP2D6 inhibitors, such as terbinafine, could theoretically impair propranolol metabolism.
Propranolol; Hydrochlorothiazide, HCTZ: (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 coadministered with CYP2D6 inhibitors.
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.
Risperidone: (Moderate) Monitor for an increase in risperidone-related adverse effects if concomitant use with terbinafine is necessary and reduce risperidone dosage as appropriate based on response. For patients receiving long-acting risperidone dosage forms, an anticipatory dosage decrease may be considered prior to initiation of terbinafine. Concomitant use may increase risperidone exposure. Risperidone is a CYP2D6 substrate and terbinafine is a strong CYP2D6 inhibitor. Concomitant use with other strong CYP2D6 inhibitors increased risperidone overall exposure by 2.5- to 9-fold.
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 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.
Segesterone Acetate; 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.
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 no t known. Topical forms of terbinafine do not interact.
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.
Tamoxifen: (Moderate) Monitor for decreased efficacy of tamoxifen if coadministration with terbinafine is necessary. Tamoxifen is metabolized by CYP2D6 to endoxifen and 4-hydroxytamoxifen, both of which are minor metabolites but have 100-fold greater affinity for the estrogen receptor and 30- to 100-fold greater potency in suppressing estrogen-dependent cell proliferation than tamoxifen. Terbinafine is a strong CYP2D6 inhibitor. In one study, the mean steady-state endoxifen plasma concentration was significantly reduced in patients taking CYP2D6 inhibitors compared to those not taking concomitant CYP2D6 inhibitors. In another study, the mean steady-state plasma concentration of endoxifen in CYP2D6 normal metabolizers who were not receiving CYP2D6 inhibitors were 3.6-fold higher compared to normal metabolizers who were receiving strong CYP2D6 inhibitors; plasma levels in CYP2D6 normal metabolizers receiving strong CYP2D6 inhibitors were similar to levels observed in CYP2D6 poor metabolizers taking no CYP2D6 inhibitors. Some studies have shown that the efficacy of tamoxifen may be reduced when concomitant drugs decrease the levels of potent active metabolites; however, others have failed to demonstrate such an effect. The clinical significance is not well established.
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.
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.
Telmisartan; Amlodipine: (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.
Telmisartan; Hydrochlorothiazide, HCTZ: (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.
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.
Tezacaftor; 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.
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.
Thioridazine: (Contraindicated) 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.
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.
Tramadol; Acetaminophen: (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.
Vonoprazan; Amoxicillin; 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.
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.

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

Maximum Dosage
Adults

250 mg/day PO is FDA-approved maximum; however, doses up to 1,000 mg/day PO have been used off-label; specific maximum dosage information is not available for topical preparations.

Geriatric

250 mg/day PO is FDA-approved maximum; however, doses up to 1,000 mg/day PO have been used off-label; specific maximum dosage information is not available for topical preparations.

Adolescents

Weight 40 kg or more: Safety and efficacy have not been established; however, doses up to 250 mg/day PO have been used off-label.
Weight 21 to 40 kg: Safety and efficacy have not been established; however, doses up to 125 mg/day PO have been used off-label.

Children

Weight 40 kg or more: Safety and efficacy have not been established; however, doses up to 250 mg/day PO have been used off-label.
Weight 21 to 40 kg: Safety and efficacy have not been established; however, doses up to 125 mg/day PO have been used off-label.
Weight 10 to 20 kg: Safety and efficacy have not been established; however, doses up to 62.5 mg/day PO have been used off-label.
Weight less than 10 kg: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Terbinafine, an allylamine antifungal, inhibits biosynthesis of ergosterol, an essential component of fungal cell membrane, via inhibition of squalene epoxidase enzyme. This results in fungal cell death primarily due to the increased membrane permeability mediated by the accumulation of high concentrations of squalene but not due to ergosterol deficiency. Depending on the concentration of the drug and the fungal species test in vitro, terbinafine may be fungicidal.

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.

Pregnancy And Lactation
Pregnancy

Data from postmarketing use of oral terbinafine in human pregnancy are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, terbinafine did not cause malformations or fetal harm when administered orally to pregnant rats or rabbits during organogenesis at doses up to 23-times the maximum recommended human dose. There are no adequate and well-controlled studies with topical terbinafine in pregnant women. Use topical terbinafine during pregnancy only if clearly indicated.[43881] [43883]

After oral administration, terbinafine is present in human breast milk. After a single terbinafine 500 mg oral dose to 2 volunteers, the total excretion of terbinafine in human milk was 0.03% to 0.13%. There are no data on the effects on the breast-fed child or milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for oral terbinafine and any potential adverse effects on the breast-fed child from oral terbinafine or the underlying maternal condition. Advise breast-feeding mothers to avoid topical application of terbinafine to the breast. Further, given the limited data on neonatal exposure, discontinue breast-feeding or discontinue topical terbinafine, taking into account the importance of the drug to the mother.[43881] [43883]