Version July 2025
Patients treated with mitotane are at increased risk for developing adrenal crisis in the setting of shock, severe trauma or infection that may lead to death. If shock, severe trauma or infection occurs or develops, temporarily discontinue mitotane and administer exogenous steroids. Monitor patients closely for infections and instruct patients to contact their physician immediately if injury, infection, or any other concomitant illness occurs.
Note: Mitotane is associated with a moderate emetic potential; antiemetics may be needed to prevent nausea and vomiting.
Adrenocortical carcinoma (stage III or IV): Limited data available; efficacy results variable; optimal dose not established: Children and Adolescents: Oral: Initial: 0.5 to 1 g/day in 3 divided doses, titrate dose to target serum concentration range of 14 to 20 mcg/mL (see Reference Range)
Mitotane has been used in combination with CED regimen (cisplatin, etoposide, and doxorubicin). An initial dose of 0.5 to 1 g/day divided 3 times a day, increased weekly to a target dose of 4 g/m2/day (divided 3 times a day) was used in an open-label, prospective study (n=11; age range: 2 to 15 years); however, the reported range to initially achieve a serum concentration of 14 ± 2 mcg/mL was 1.6 to 7.3 g/m2/day; and then further reductions to 1 to 5.3 g/m2/day were required to maintain therapeutic concentrations (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients; specific recommendations for pediatric patients are limited. Refer to specific protocol for management in pediatric patients if available.
Adult:
Adrenal crisis in the setting of shock or severe trauma: Discontinue mitotane until recovery occurs.
CNS toxicity: Discontinue mitotane until symptoms resolve; 7 to 10 days after symptoms resolve, restart at a lower dose (eg, decrease dose by 0.5 to 1 g).
Significant neuropsychiatric adverse effects: Withhold treatment for at least 1 week and restart at a lower dose (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling. However, accumulation may occur in patients with hepatic impairment; use with caution.
(For additional information see "Mitotane: Drug information")
Dosage guidance:
Safety: Withhold mitotane prior to planned surgeries. Temporarily withhold mitotane (and administer exogenous steroids) during shock, trauma, infection, or adrenal suppression.
Clinical considerations: Mitotane is associated with a moderate or high emetic potential; antiemetics may be needed to prevent nausea and vomiting.
Adrenocortical carcinoma:
Inoperable (single-agent therapy): Oral: Initial: 2 to 6 g per day in 3 to 4 divided doses, then (based on tolerance and clinical response), increase incrementally to achieve a blood concentration of 14 to 20 mg/L or as tolerated.
Mitotane plasma levels >20 mg/L without toxicity: Consider reducing mitotane dose by 50% to 75%.
Off-label dosing: Oral: Initial: 1 to 2 g per day as a single dose or as divided doses; increase by 1 to 2 g per day at 1- to 2-week intervals as tolerated to achieve a plasma level of 10 to 14 mg/L; usual dose 4 to 6 g per day; maximum of 6 to 10 g per day (Ref).
Inoperable (combination therapy) (off-label):
In combination with streptozocin: Oral : Initial: 1 g per day; increase by 500 mg incrementally (eg, every 3 days) up to 4 g per day as tolerated to achieve a plasma level of 14 to 20 mg/L (Ref) (low starting dose approach); or Initial: 1.5 g per day on day 1; increase to 3 g per day on day two, 4.5 g per day on day three, and 6 g per day on day four as tolerated to achieve a plasma level of 14 to 20 mg/L (Ref) (high starting dose approach); continue until disease progression or unacceptable toxicity (Ref).
In combination with etoposide, doxorubicin, and cisplatin (EDP- M regimen): Oral: Initial: 1 g per day; increase by 500 mg incrementally (eg, every 3 days) up to a total daily dose of 4 g as tolerated to achieve a plasma level of 14 to 20 mg/L (Ref) (low starting dose approach); or Initial: 1.5 g per day on day 1; increase to 3 g per day on day two, 4.5 g per day on day three, and 6 g per day on day four as tolerated to achieve a plasma level of 14 to 20 mg/L (Ref) (high starting dose approach); or Initial: 1 g per day; increase incrementally up to 4 g per day as tolerated (Ref); continue until disease progression or unacceptable toxicity (Ref).
Resected, adjuvant therapy (at high risk of recurrence): Oral: Initial: 500 mg twice daily, increased (as tolerated) every 4 to 7 days up to 4 to 6 g/day in divided doses, with monitoring to achieve a target therapeutic level of 14 to 20 mg/L (Ref) or 1 to 5 g/day (in divided doses); continue until disease progression or unacceptable toxicity (Ref) or 1 to 4 g per day in divided doses, based on tolerance (median dose: 3 g per day); in combination with streptozocin (Ref).
Cushing syndrome (off-label use): Oral:
Initial: Oral: 500 mg 3 times daily (Ref) or 250 to 500 mg/day (Ref).
Maintenance: Oral: May increase dose during the first 4 to 6 weeks up to 2 to 4 g/day in 3 divided doses (Ref). Maximum doses of 4 to 8 g/day in 3 divided doses have been reported (Ref). After achieving control of cortisol secretion, gradually taper to the minimal dose required to maintain remission (Ref). Administer the largest dose in the evening to minimize discomfort or adverse effects (Ref).
Missed doses: If a dose is missed, administer the next dose as scheduled. If patient vomits following a dose, administer the next dose as scheduled.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate kidney impairment: There are no dosage adjustments provided in the manufacturer’s labeling; due to potential for increased risk of adverse effects, monitor mitotane plasma levels more frequently; adjust dosing accordingly.
Severe kidney impairment: Use is not recommended. Mitotane is not likely to be dialyzable.
Hepatic impairment prior to treatment initiation:
Mild to moderate hepatic impairment: There are no dosage adjustments provided in the manufacturer’s labeling; due to potential for increased risk of adverse effects, monitor mitotane plasma levels more frequently; adjust dosing accordingly.
Severe hepatic impairment: Use is not recommended.
Acute hepatotoxicity during treatment:
Grade 3 or 4 hepatotoxicity: Measure mitotane plasma level and adjust dosing accordingly. Withhold mitotane until recovery to grade ≤1 or baseline; resume mitotane at a reduced dose or permanently discontinue after symptom resolution, based on severity.
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Postmarketing:
Cardiovascular: Flushing, hypertension, orthostatic hypotension, prolonged QT interval on ECG
Dermatologic: Pruritus, skin rash
Endocrine & metabolic: Adrenocortical insufficiency (including acute adrenocortical insufficiency), albuminuria, altered hormone level (decreased plasma androstenedione), decreased plasma testosterone (females, males), growth suppression, gynecomastia, hypercholesterolemia, hypertriglyceridemia, hypothyroidism, hypouricemia, increased sex hormone binding globulin (females, males)
Gastrointestinal: Anorexia, diarrhea, dysgeusia, dyspepsia, epigastric discomfort, mucosal swelling, nausea, vomiting
Genitourinary: Hematuria, hemorrhagic cystitis, male hypogonadism, proteinuria
Hematologic & oncologic: Anemia, leukopenia, prolonged bleeding time, thrombocytopenia
Hepatic: Hepatic injury (hepatocellular/cholestatic/mixed), hepatitis, increased liver enzymes
Hypersensitivity: Hypersensitivity reaction
Infection: Opportunistic infection
Nervous system: Asthenia, ataxia, balance impairment, confusion, decreased mental acuity, depression, dizziness, dysarthria, generalized ache or pain, headache, movement disorder, myasthenia, paresthesia, polyneuropathy, vertigo
Neuromuscular & skeletal: Subacute cutaneous lupus erythematosus (Mayor-Ibarguren 2016)
Ophthalmic: Blurred vision, cataract, diplopia, maculopathy, retinopathy
Respiratory: Dyspnea
Miscellaneous: Fever
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to mitotane or any component of the formulation; concomitant use with spironolactone; breastfeeding.
Concerns related to adverse effects:
• Adrenal crisis: Adrenal crisis or adrenal suppression may occur in the setting of shock, severe trauma, or infection in patients treated with mitotane.
• Adrenal insufficiency: Treatment with mitotane may cause adrenal insufficiency or worsen existing adrenal insufficiency; steroid replacement therapy (for glucocorticoid and/or mineralocorticoid insufficiency) may be required.
• CNS toxicity: CNS adverse effects, including lethargy, sedation, and vertigo, may occur; mitotane plasma concentrations >20 mg/L are associated with higher incidence of toxicity. Patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
• Hematologic toxicity: Treatment with mitotane may cause hematologic toxicity, including leukopenia, anemia, and thrombocytopenia.
• Hepatotoxicity: Hepatotoxicity, including liver injury or failure, may occur with mitotane; isolated elevation in gamma-glutamyl transferase (GGT) may also occur.
• Hormone-binding protein elevation: Mitotane can increase levels of hormone-binding proteins (eg, sex hormone-binding globulin [SHBG] and corticosteroid-binding globulin [CBG]); may result in gynecomastia.
• Ovarian macrocysts: Nonmalignant ovarian macrocysts (often bilateral and multiple) have been reported in premenopausal patients receiving mitotane. Ovarian macrocysts may be symptomatic or asymptomatic; symptoms include pelvic pain, discomfort, or menstrual irregularities. Complications due to the cysts have been reported (including adnexal torsion and hemorrhagic cyst rupture). Patients should obtain immediate medical care if they experience gynecologic symptoms such as vaginal bleeding and/or pelvic pain.
• Prolonged bleeding time: Platelet function disorders are observed with mitotane (due to abnormal adenosine-diphosphate (ADP)-induced platelet aggregation); prolonged or normal bleeding time may occur as a result. Routine in vitro bleeding time is not suitable to detect platelet defects and assess bleeding risk; ADP-induced platelet aggregometry should be performed prior to surgery or dental procedures. If currently on anticoagulant therapy, adjust anticoagulant dose as needed.
• Thyroid effects: Mitotane is commonly associated with hypothyroidism, with free T4 levels beginning to fall within the first 3 months; presentation has been reported as low free T4 levels, normal thyrotropin level, and blunted response to thyrotropin-releasing hormone (Burch 2019).
Special populations:
• Obesity/weight loss: Mitotane is lipophilic and accumulates in adipose tissue. Plasma levels may suddenly increase despite maintaining a constant dose, and adipose tissue may continue to release mitotane even after withdrawal/discontinuation. Due to adipose tissue accumulation, close monitoring of mitotane plasma levels is recommended.
• Patients undergoing surgery or procedures: Withhold mitotane prior to planned surgeries to minimize the risk of adrenal crisis.
Growth, motor skill, and speech delays were observed during therapy in an infant treated for adenocarcinoma (DeLeon 2002).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Lysodren: 500 mg
No
Tablets (Lysodren Oral)
500 mg (per each): $19.46
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Lysodren: 500 mg
It has been reported that tablets have been crushed/powdered and dissolved in medium-chain triglyceride (MCT) oil in a pediatric study. Each gram of mitotane was dissolved in 2 mL MCT oil, then mixed with a fat-containing food such as milk (white or chocolate) or yogurt (Zancanella 2006).
Wear impervious gloves when handling; avoid exposure to crushed or broken tablets if possible. Note: Mitotane is associated with a moderate emetic potential; antiemetics may be needed to prevent nausea and vomiting.
Oral: Per the manufacturer, do not crush tablets; however, in pediatric trials, tablets have been crushed and dissolved in MCT (medium-chain triglyceride) oil (ie, each gram mitotane in 2 mL MCT oil); then solution was mixed with a fat-containing food [eg, milk (white or chocolate) or yogurt] (Ref).
Note: Mitotane is associated with a moderate or high emetic potential; antiemetics may be needed to prevent nausea and vomiting.
Oral: Administer in 3 to 4 divided doses per day with food (ensure timing of dose relative to meals is consistent). Do not administer if tablet shows signs of deterioration.
The manufacturer recommends swallowing whole (do not crush, chew, or split). A suspension may be extemporaneously prepared for patients unable to swallow tablets or for NG administration.
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/016885Orig1s032lbl.pdf#page=19, must be dispensed with this medication.
Treatment of inoperable adrenocortical carcinoma (both functional and nonfunctional types) (FDA approved in adults)
Mitotane may be confused with Matulane, mitapivat, mitoMYcin, mitoXANTRONE
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Induces CYP3A4 (Strong);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Abemaciclib: CYP3A4 Inducers (Strong) may decrease serum concentration of Abemaciclib. Risk X: Avoid
Abiraterone Acetate: CYP3A4 Inducers (Strong) may decrease serum concentration of Abiraterone Acetate. Management: Avoid coadministration with strong CYP3A4 inducers. For patients treated with single-agent abiraterone who require therapy with a strong CYP3A4 inducers, abiraterone frequency may increased to twice daily. See full mono for details. Risk D: Consider Therapy Modification
Acalabrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Acalabrutinib. Management: Avoid co-administration of strong CYP3A inducers in patients taking acalabrutinib. If strong CYP3A inducers cannot be avoided, increase the dose of acalabrutinib to 200 mg twice daily. Risk D: Consider Therapy Modification
Acoramidis: CYP3A4 Inducers (Strong) may decrease serum concentration of Acoramidis. Risk X: Avoid
Adagrasib: CYP3A4 Inducers (Strong) may decrease serum concentration of Adagrasib. Risk X: Avoid
Alfacalcidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Alfacalcidol. Risk C: Monitor
ALfentanil: CYP3A4 Inducers (Strong) may decrease serum concentration of ALfentanil. Management: If concomitant use of alfentanil and strong CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Risk D: Consider Therapy Modification
Alpelisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Alpelisib. Risk X: Avoid
ALPRAZolam: CYP3A4 Inducers (Strong) may decrease serum concentration of ALPRAZolam. Risk C: Monitor
Amiodarone: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Amiodarone. CYP3A4 Inducers (Strong) may decrease serum concentration of Amiodarone. Risk C: Monitor
AmLODIPine: CYP3A4 Inducers (Strong) may decrease serum concentration of AmLODIPine. Risk C: Monitor
Antihepaciviral Combination Products: CYP3A4 Inducers (Strong) may decrease serum concentration of Antihepaciviral Combination Products. Risk X: Avoid
Apixaban: CYP3A4 Inducers (Strong) may decrease serum concentration of Apixaban. Management: Avoid concurrent use of apixaban with strong CYP3A4 inducers whenever possible. Use of a strong CYP3A4 inducer with apixaban should be strictly avoided in any patient who is using an agent (either the CYP3A4 inducer or a third drug) that induces P-gp. Risk D: Consider Therapy Modification
Apremilast: CYP3A4 Inducers (Strong) may decrease serum concentration of Apremilast. Risk X: Avoid
ARIPiprazole Lauroxil: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of ARIPiprazole Lauroxil. Management: Patients taking the 441 mg dose of aripiprazole lauroxil increase their dose to 662 mg if used with a strong CYP3A4 inducer for more than 14 days. No dose adjustment is necessary for patients using the higher doses of aripiprazole lauroxil. Risk D: Consider Therapy Modification
ARIPiprazole: CYP3A4 Inducers (Strong) may decrease serum concentration of ARIPiprazole. Management: For indications other than major depressive disorder: double the oral aripiprazole dose over 1 to 2 weeks and closely monitor. Avoid use of strong CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Risk D: Consider Therapy Modification
Artemether and Lumefantrine: CYP3A4 Inducers (Strong) may decrease serum concentration of Artemether and Lumefantrine. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. Risk X: Avoid
Atazanavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Atazanavir. Risk X: Avoid
Atogepant: CYP3A4 Inducers (Strong) may decrease serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider Therapy Modification
Atorvastatin: CYP3A4 Inducers (Strong) may decrease serum concentration of Atorvastatin. Risk C: Monitor
Atrasentan: CYP3A4 Inducers (Strong) may decrease serum concentration of Atrasentan. Risk X: Avoid
Avacopan: CYP3A4 Inducers (Strong) may decrease serum concentration of Avacopan. Risk X: Avoid
Avanafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Avanafil. Risk X: Avoid
Avapritinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Avapritinib. Risk X: Avoid
Axitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Axitinib. Risk X: Avoid
Barnidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Barnidipine. Risk C: Monitor
Bedaquiline: CYP3A4 Inducers (Strong) may decrease serum concentration of Bedaquiline. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Bedaquiline. Risk X: Avoid
Belumosudil: CYP3A4 Inducers (Strong) may decrease serum concentration of Belumosudil. Management: Increase the dose of belumosudil to 200 mg twice daily when coadministered with strong CYP3A4 inducers. Risk D: Consider Therapy Modification
Benidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Benidipine. Risk C: Monitor
Benperidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Benperidol. Risk C: Monitor
Benzhydrocodone: CYP3A4 Inducers (Strong) may decrease serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor
Betamethasone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Betamethasone (Systemic). Risk C: Monitor
Bictegravir: CYP3A4 Inducers (Strong) may decrease serum concentration of Bictegravir. Risk C: Monitor
Bisoprolol: CYP3A4 Inducers (Strong) may decrease serum concentration of Bisoprolol. Risk C: Monitor
Blonanserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Blonanserin. Risk C: Monitor
Bortezomib: CYP3A4 Inducers (Strong) may decrease serum concentration of Bortezomib. Risk X: Avoid
Bosutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Bosutinib. Risk X: Avoid
Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor
Brexpiprazole: CYP3A4 Inducers (Strong) may decrease serum concentration of Brexpiprazole. Management: If brexpiprazole is used together with a strong CYP3A4 inducer, the brexpiprazole dose should gradually be doubled over the course of 1 to 2 weeks. Decrease brexpiprazole to original dose over 1 to 2 weeks if the strong CYP3A4 inducer is discontinued. Risk D: Consider Therapy Modification
Brigatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Brigatinib. Risk X: Avoid
Bromocriptine: CYP3A4 Inducers (Strong) may decrease serum concentration of Bromocriptine. Risk C: Monitor
Bromperidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Bromperidol. Risk C: Monitor
Brotizolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Brotizolam. Risk C: Monitor
Buprenorphine: CYP3A4 Inducers (Strong) may decrease serum concentration of Buprenorphine. Risk C: Monitor
BusPIRone: CYP3A4 Inducers (Strong) may decrease serum concentration of BusPIRone. Management: Consider alternatives to this combination. If coadministration of these agents is deemed necessary, monitor patients for reduced buspirone effects and increase buspirone doses as needed. Risk D: Consider Therapy Modification
Butorphanol: CYP3A4 Inducers (Strong) may decrease serum concentration of Butorphanol. Risk C: Monitor
Cabazitaxel: CYP3A4 Inducers (Strong) may decrease serum concentration of Cabazitaxel. Risk C: Monitor
Cabozantinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, increase cabozantinib capsules (Cometriq) by 40 mg from previous dose, max 180 mg daily. Increase cabozantinib tablets (Cabometyx) by 20 mg from previous dose, max 80 mg daily Risk D: Consider Therapy Modification
Calcifediol: CYP3A4 Inducers (Strong) may increase serum concentration of Calcifediol. Risk C: Monitor
Calcitriol (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Calcitriol (Systemic). Risk C: Monitor
Cannabidiol: CYP3A4 Inducers (Strong) may decrease serum concentration of Cannabidiol. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Cannabidiol. Risk C: Monitor
Cannabis: CYP3A4 Inducers (Strong) may decrease serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor
Capivasertib: CYP3A4 Inducers (Strong) may decrease serum concentration of Capivasertib. Risk X: Avoid
Capmatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Capmatinib. Risk X: Avoid
CarBAMazepine: CYP3A4 Inducers (Strong) may decrease serum concentration of CarBAMazepine. Risk C: Monitor
Cariprazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Cariprazine. Risk X: Avoid
Ceritinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ceritinib. Risk X: Avoid
ChlorproPAMIDE: CYP3A4 Inducers (Strong) may decrease serum concentration of ChlorproPAMIDE. Risk C: Monitor
Cilnidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Cilnidipine. Risk C: Monitor
Citalopram: CYP3A4 Inducers (Strong) may decrease serum concentration of Citalopram. Risk C: Monitor
Clarithromycin: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Clarithromycin. CYP3A4 Inducers (Strong) may decrease serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A4 inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and may impair clarithromycin efficacy. Risk D: Consider Therapy Modification
Clindamycin (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Clindamycin (Systemic). Risk C: Monitor
ClonazePAM: CYP3A4 Inducers (Strong) may decrease serum concentration of ClonazePAM. Risk C: Monitor
CloZAPine: CYP3A4 Inducers (Strong) may decrease serum concentration of CloZAPine. Management: Avoid use with strong CYP3A4 inducers when possible. If combined, monitor patients closely and consider clozapine dose increases. Clozapine dose reduction and further monitoring may be required when strong CYP3A4 inducers are discontinued. Risk D: Consider Therapy Modification
Cobicistat: CYP3A4 Inducers (Strong) may decrease serum concentration of Cobicistat. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced cobicistat efficacy. Risk D: Consider Therapy Modification
Cobimetinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Cobimetinib. Risk X: Avoid
Codeine: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Codeine. Risk C: Monitor
Colchicine: CYP3A4 Inducers (Strong) may decrease serum concentration of Colchicine. Risk C: Monitor
Copanlisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Copanlisib. Risk X: Avoid
Crinecerfont: CYP3A4 Inducers (Strong) may decrease serum concentration of Crinecerfont. Management: Double the morning and evening doses of crinecerfont during coadministration with strong CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider Therapy Modification
Crizotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Crizotinib. Risk X: Avoid
CycloSPORINE (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of CycloSPORINE (Systemic). Management: Monitor closely for reduced cyclosporine concentrations when combined with strong CYP3A4 inducers. Cyclosporine dose increases will likely be required to maintain adequate serum concentrations. Risk D: Consider Therapy Modification
Cyproterone: CYP3A4 Inducers (Strong) may decrease serum concentration of Cyproterone. Risk C: Monitor
Daclatasvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Daclatasvir. Risk X: Avoid
Dapsone (Systemic): May increase adverse/toxic effects of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease serum concentration of Dapsone (Systemic). Management: Consider alternatives to this combination when possible. Monitor for decreased dapsone efficacy if combined with strong CYP3A4 inducers. Risk D: Consider Therapy Modification
Daridorexant: CYP3A4 Inducers (Strong) may decrease serum concentration of Daridorexant. Risk X: Avoid
Darunavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Darunavir. Risk C: Monitor
Dasabuvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Dasabuvir. Risk X: Avoid
Dasatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Dasatinib. Management: Avoid concurrent use of dasatinib with strong CYP3A4 inducers when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Risk D: Consider Therapy Modification
Deflazacort: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Deflazacort. Risk X: Avoid
Delamanid: CYP3A4 Inducers (Strong) may decrease serum concentration of Delamanid. Risk X: Avoid
Deuruxolitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Deuruxolitinib. Risk X: Avoid
DexAMETHasone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of DexAMETHasone (Systemic). Management: Avoid coadministration of dexamethasone and strong CYP3A4 inducers. If concomitant use cannot be avoided, consider dexamethasone dose increases. Risk D: Consider Therapy Modification
DiazePAM: CYP3A4 Inducers (Strong) may decrease serum concentration of DiazePAM. Risk C: Monitor
Dienogest: CYP3A4 Inducers (Strong) may decrease serum concentration of Dienogest. Risk C: Monitor
Digitoxin: CYP3A4 Inducers (Strong) may decrease serum concentration of Digitoxin. Risk C: Monitor
DilTIAZem: CYP3A4 Inducers (Strong) may decrease serum concentration of DilTIAZem. Management: Consider alternatives to this combination when possible. If combined, monitor for decreased diltiazem efficacy. Risk D: Consider Therapy Modification
Disopyramide: CYP3A4 Inducers (Strong) may decrease serum concentration of Disopyramide. Risk C: Monitor
DOCEtaxel: CYP3A4 Inducers (Strong) may decrease serum concentration of DOCEtaxel. Risk C: Monitor
Domperidone: CYP3A4 Inducers (Strong) may decrease serum concentration of Domperidone. Risk C: Monitor
Doravirine: CYP3A4 Inducers (Strong) may decrease serum concentration of Doravirine. Risk X: Avoid
Doxercalciferol: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Doxercalciferol. Risk C: Monitor
DOXOrubicin (Conventional): CYP3A4 Inducers (Strong) may decrease serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DroNABinol: CYP3A4 Inducers (Strong) may decrease serum concentration of DroNABinol. Risk C: Monitor
Dronedarone: CYP3A4 Inducers (Strong) may decrease serum concentration of Dronedarone. Risk X: Avoid
Duvelisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Duvelisib. Risk X: Avoid
Dydrogesterone: CYP3A4 Inducers (Strong) may decrease serum concentration of Dydrogesterone. Risk C: Monitor
Ebastine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ebastine. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Ebastine. Risk C: Monitor
Efavirenz: CYP3A4 Inducers (Strong) may decrease serum concentration of Efavirenz. Risk C: Monitor
Elacestrant: CYP3A4 Inducers (Strong) may decrease serum concentration of Elacestrant. Risk X: Avoid
Elagolix, Estradiol, and Norethindrone: CYP3A4 Inducers (Strong) may decrease serum concentration of Elagolix, Estradiol, and Norethindrone. Risk C: Monitor
Elagolix: CYP3A4 Inducers (Strong) may decrease serum concentration of Elagolix. Risk C: Monitor
Elbasvir and Grazoprevir: CYP3A4 Inducers (Strong) may decrease serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk X: Avoid
Eliglustat: CYP3A4 Inducers (Strong) may decrease serum concentration of Eliglustat. Risk X: Avoid
Encorafenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Encorafenib. Risk X: Avoid
Enfortumab Vedotin: CYP3A4 Inducers (Strong) may decrease serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor
Ensartinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ensartinib. Risk X: Avoid
Entrectinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Entrectinib. Risk X: Avoid
Enzalutamide: CYP3A4 Inducers (Strong) may decrease serum concentration of Enzalutamide. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Enzalutamide. Management: Consider using an alternative agent that has no or minimal CYP3A4 induction potential when possible. If this combination cannot be avoided, increase the dose of enzalutamide from 160 mg daily to 240 mg daily. Risk D: Consider Therapy Modification
Eplerenone: CYP3A4 Inducers (Strong) may decrease serum concentration of Eplerenone. Risk C: Monitor
Eravacycline: CYP3A4 Inducers (Strong) may decrease serum concentration of Eravacycline. Management: Increase the eravacycline dose to 1.5 mg/kg every 12 hours when combined with strong CYP3A4 inducers. Risk D: Consider Therapy Modification
Erdafitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Erdafitinib. Risk X: Avoid
Erlotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Erlotinib. Management: Avoid the combination of erlotinib and strong CYP3A4 inducers whenever possible. If this combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Risk D: Consider Therapy Modification
Escitalopram: CYP3A4 Inducers (Strong) may decrease serum concentration of Escitalopram. Risk C: Monitor
Esketamine (Injection): CYP3A4 Inducers (Strong) may decrease serum concentration of Esketamine (Injection). Risk C: Monitor
Estazolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Estazolam. Risk C: Monitor
Estrogen Derivatives: CYP3A4 Inducers (Strong) may decrease serum concentration of Estrogen Derivatives. Risk C: Monitor
Eszopiclone: CYP3A4 Inducers (Strong) may decrease serum concentration of Eszopiclone. Risk C: Monitor
Ethosuximide: CYP3A4 Inducers (Strong) may decrease serum concentration of Ethosuximide. Risk C: Monitor
Etizolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Etizolam. Risk C: Monitor
Etoposide Phosphate: CYP3A4 Inducers (Strong) may decrease serum concentration of Etoposide Phosphate. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide phosphate. If these combinations cannot be avoided, monitor patients closely for diminished etoposide phosphate response. Risk D: Consider Therapy Modification
Etoposide: CYP3A4 Inducers (Strong) may decrease serum concentration of Etoposide. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide. If combined, monitor patients closely for diminished etoposide response and need for etoposide dose increases. Risk D: Consider Therapy Modification
Etoricoxib: CYP3A4 Inducers (Strong) may decrease serum concentration of Etoricoxib. Risk C: Monitor
Etravirine: CYP3A4 Inducers (Strong) may decrease serum concentration of Etravirine. Risk X: Avoid
Everolimus: CYP3A4 Inducers (Strong) may decrease serum concentration of Everolimus. Management: Concomitant use of everolimus and strong CYP3A4 inducers is generally not recommended. However, if combined, monitor for decreased everolimus concentrations and effects, and adjust everolimus dose as needed. Risk D: Consider Therapy Modification
Evogliptin: CYP3A4 Inducers (Strong) may decrease serum concentration of Evogliptin. Risk C: Monitor
Exemestane: CYP3A4 Inducers (Strong) may decrease serum concentration of Exemestane. Management: Increase the exemestane dose to 50 mg once daily in patients receiving concurrent strong CYP3A4 inducers. Monitor patients closely for evidence of toxicity or inadequate clinical response. Risk D: Consider Therapy Modification
Fedratinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Fedratinib. Risk X: Avoid
Felbamate: CYP3A4 Inducers (Strong) may decrease serum concentration of Felbamate. Risk C: Monitor
Felodipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Felodipine. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced felodipine efficacy and the need for felodipine dose increases. Risk D: Consider Therapy Modification
Fenfluramine: CYP3A4 Inducers (Strong) may decrease serum concentration of Fenfluramine. Management: Avoid concurrent use of strong CYP3A4 inducers with fenfluramine when possible. If combined use cannot be avoided, consider increasing the fenfluramine dose, but do not exceed the fenfluramine maximum daily dose. Risk D: Consider Therapy Modification
FentaNYL: CYP3A4 Inducers (Strong) may decrease serum concentration of FentaNYL. Risk C: Monitor
Fesoterodine: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fesoterodine. Risk C: Monitor
Fexinidazole: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Fexinidazole. Risk X: Avoid
Finerenone: CYP3A4 Inducers (Strong) may decrease serum concentration of Finerenone. Risk X: Avoid
Flibanserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Flibanserin. Risk X: Avoid
Fludrocortisone: CYP3A4 Inducers (Strong) may decrease serum concentration of Fludrocortisone. Risk C: Monitor
Fosamprenavir: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fosamprenavir. Risk C: Monitor
Fostamatinib: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fostamatinib. Risk X: Avoid
Fostemsavir: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fostemsavir. Risk X: Avoid
Fruquintinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Fruquintinib. Risk X: Avoid
Futibatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Futibatinib. Risk C: Monitor
Ganaxolone: CYP3A4 Inducers (Strong) may decrease serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and strong CYP3A4 inducers whenever possible. If combined, consider increasing the dose of ganaxolone, but do not exceed the maximum recommended daily dose. Risk D: Consider Therapy Modification
Gefitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase the gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers; resume 250 mg dose 7 days after discontinuation of the strong inducer. Carefully monitor clinical response. Risk D: Consider Therapy Modification
Gemigliptin: CYP3A4 Inducers (Strong) may decrease serum concentration of Gemigliptin. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Gemigliptin. Risk X: Avoid
Gepirone: CYP3A4 Inducers (Strong) may decrease serum concentration of Gepirone. Risk X: Avoid
Gepotidacin: CYP3A4 Inducers (Strong) may decrease serum concentration of Gepotidacin. Risk X: Avoid
Gilteritinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Gilteritinib. Risk C: Monitor
Glasdegib: CYP3A4 Inducers (Strong) may decrease serum concentration of Glasdegib. Risk X: Avoid
Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
GuanFACINE: CYP3A4 Inducers (Strong) may decrease serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Risk D: Consider Therapy Modification
Haloperidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Haloperidol. Risk C: Monitor
Hormonal Contraceptives: Mitotane may decrease serum concentration of Hormonal Contraceptives. Management: Effective nonhormonal contraception is recommended for those of reproductive potential during treatment with mitotane as well as after discontinuation of mitotane for as long as mitotane plasma levels are detectable. Risk X: Avoid
HYDROcodone: CYP3A4 Inducers (Strong) may decrease serum concentration of HYDROcodone. Risk C: Monitor
Hydrocortisone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Hydrocortisone (Systemic). Risk C: Monitor
Ibrexafungerp: CYP3A4 Inducers (Strong) may decrease serum concentration of Ibrexafungerp. Risk X: Avoid
Ibrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ibrutinib. Risk X: Avoid
Idelalisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Idelalisib. Risk X: Avoid
Ifosfamide: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Ifosfamide. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor
Imatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Imatinib. Management: Avoid use of imatinib and strong CYP3A4 inducers when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Doses up to 1200 mg/day (600 mg twice daily) have been used. Risk D: Consider Therapy Modification
Indinavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Indinavir. Management: Consider avoiding the combination of indinavir and strong CYP3A4 inducers whenever possible due to the risk for decreased indinavir concentrations, reduced efficacy, and development of resistance. If combined, monitor for indinavir treatment failure Risk D: Consider Therapy Modification
Irinotecan Products: CYP3A4 Inducers (Strong) may decrease serum concentration of Irinotecan Products. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. Management: Avoid administration of strong CYP3A4 inducers during irinotecan treatment, and substitute non-CYP3A4 inducing agents at least 2 weeks prior to irinotecan initiation, whenever possible. If combined, monitor for reduced irinotecan efficacy. Risk D: Consider Therapy Modification
Isavuconazonium Sulfate: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Risk X: Avoid
Isradipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Isradipine. Risk C: Monitor
Istradefylline: CYP3A4 Inducers (Strong) may decrease serum concentration of Istradefylline. Risk X: Avoid
Itraconazole: CYP3A4 Inducers (Strong) may decrease serum concentration of Itraconazole. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Itraconazole. Risk X: Avoid
Ivabradine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ivabradine. Risk X: Avoid
Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Ivacaftor. Risk X: Avoid
Ivosidenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ivosidenib. Risk X: Avoid
Ixabepilone: CYP3A4 Inducers (Strong) may decrease serum concentration of Ixabepilone. Management: Avoid this combination whenever possible. If this combination must be used, a gradual increase in ixabepilone dose from 40 mg/m2 to 60 mg/m2 (given as a 4-hour infusion), as tolerated, should be considered. Risk D: Consider Therapy Modification
Ixazomib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ixazomib. Risk X: Avoid
Ketamine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ketamine. Risk C: Monitor
Ketoconazole (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Ketoconazole (Systemic). Management: The use of ketoconazole concurrently with or within 2 weeks of a strong CYP3A4 inducer is not recommended. If such a combination cannot be avoided, monitor patients closely for evidence of diminished clinical response to ketoconazole. Risk D: Consider Therapy Modification
Lacidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Lacidipine. Risk C: Monitor
Lapatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Lapatinib. Management: If concomitant use cannot be avoided, titrate lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Risk D: Consider Therapy Modification
Larotrectinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inducers with larotrectinib. If this combination cannot be avoided, double the larotrectinib dose. Reduced to previous dose after stopping the inducer after a period of 3 to 5 times the inducer's half-life. Risk D: Consider Therapy Modification
Lazertinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Lazertinib. Risk X: Avoid
Lefamulin (Intravenous): CYP3A4 Inducers (Strong) may decrease serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin intravenous infusion with strong CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification
Lefamulin: CYP3A4 Inducers (Strong) may decrease serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with strong CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification
Lemborexant: CYP3A4 Inducers (Strong) may decrease serum concentration of Lemborexant. Risk X: Avoid
Lenacapavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Lenacapavir. Risk X: Avoid
Leniolisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Leniolisib. Risk X: Avoid
Lercanidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Lercanidipine. Risk C: Monitor
Leuprolide and Norethindrone: CYP3A4 Inducers (Strong) may decrease serum concentration of Leuprolide and Norethindrone. Specifically, norethindrone concentrations may be decreased. Risk C: Monitor
Levamlodipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Levamlodipine. Risk C: Monitor
Levoketoconazole: CYP3A4 Inducers (Strong) may decrease serum concentration of Levoketoconazole. Risk X: Avoid
Levomethadone: CYP3A4 Inducers (Strong) may decrease serum concentration of Levomethadone. Risk C: Monitor
Levonorgestrel (IUD): CYP3A4 Inducers (Strong) may decrease therapeutic effects of Levonorgestrel (IUD). CYP3A4 Inducers (Strong) may decrease serum concentration of Levonorgestrel (IUD). Risk C: Monitor
Lidocaine (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Lidocaine (Systemic). Risk C: Monitor
LinaGLIPtin: CYP3A4 Inducers (Strong) may decrease serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Risk D: Consider Therapy Modification
Lonafarnib: CYP3A4 Inducers (Strong) may decrease serum concentration of Lonafarnib. Risk X: Avoid
Lopinavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Lopinavir. Risk C: Monitor
Lorlatinib: CYP3A4 Inducers (Strong) may increase hepatotoxic effects of Lorlatinib. CYP3A4 Inducers (Strong) may decrease serum concentration of Lorlatinib. Risk X: Avoid
Lovastatin: CYP3A4 Inducers (Strong) may decrease serum concentration of Lovastatin. Risk C: Monitor
Lumacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Lumacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk X: Avoid
Lumateperone: CYP3A4 Inducers (Strong) may decrease serum concentration of Lumateperone. Risk X: Avoid
Lurasidone: CYP3A4 Inducers (Strong) may decrease serum concentration of Lurasidone. Risk X: Avoid
Lurbinectedin: CYP3A4 Inducers (Strong) may decrease serum concentration of Lurbinectedin. Risk X: Avoid
Macimorelin: CYP3A4 Inducers (Strong) may decrease serum concentration of Macimorelin. Risk X: Avoid
Macitentan: CYP3A4 Inducers (Strong) may decrease serum concentration of Macitentan. Risk X: Avoid
Manidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inducers. If combined, monitor closely for decreased manidipine effects and loss of efficacy. Increased manidipine doses may be required. Risk D: Consider Therapy Modification
Maraviroc: CYP3A4 Inducers (Strong) may decrease serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice/day, but only if not receiving a strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Contraindicated in patients with CrCl less than 30 mL/min. Risk D: Consider Therapy Modification
Maribavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Maribavir. Risk X: Avoid
Mavacamten: CYP3A4 Inducers (Strong) may decrease serum concentration of Mavacamten. Risk X: Avoid
Mavorixafor: CYP3A4 Inducers (Strong) may decrease serum concentration of Mavorixafor. Risk X: Avoid
Mefloquine: CYP3A4 Inducers (Strong) may decrease serum concentration of Mefloquine. Risk C: Monitor
Meperidine: CYP3A4 Inducers (Strong) may decrease serum concentration of Meperidine. CYP3A4 Inducers (Strong) may increase active metabolite exposure of Meperidine. Specifically, concentrations of normeperidine, the CNS stimulating metabolite, may be increased. Risk C: Monitor
Methadone: CYP3A4 Inducers (Strong) may decrease serum concentration of Methadone. Risk C: Monitor
Methylergonovine: CYP3A4 Inducers (Strong) may decrease serum concentration of Methylergonovine. Risk C: Monitor
MethylPREDNISolone: CYP3A4 Inducers (Strong) may decrease serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Risk D: Consider Therapy Modification
Mianserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Mianserin. Risk C: Monitor
Midazolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Midazolam. Risk C: Monitor
Midostaurin: CYP3A4 Inducers (Strong) may decrease serum concentration of Midostaurin. Risk X: Avoid
MiFEPRIStone: CYP3A4 Inducers (Strong) may decrease serum concentration of MiFEPRIStone. Management: Avoid combined use in patients treated for Cushing's disease. When used for pregnancy termination, mifepristone efficacy may be reduced and an alternative pregnancy termination procedure may be warranted. Ensure a follow-up assessment after combined use. Risk D: Consider Therapy Modification
Mirabegron: CYP3A4 Inducers (Strong) may decrease serum concentration of Mirabegron. Risk C: Monitor
Mirodenafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Mirodenafil. Management: Consider avoiding the concomitant use of mirodenafil and strong CYP3A4 inducers. If combined, monitor for decreased mirodenafil effects. Mirodenafil dose increases may be required to achieve desired effects. Risk D: Consider Therapy Modification
Mirtazapine: CYP3A4 Inducers (Strong) may decrease serum concentration of Mirtazapine. Risk C: Monitor
Mitapivat: CYP3A4 Inducers (Strong) may decrease serum concentration of Mitapivat. Risk X: Avoid
Mobocertinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Mobocertinib. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Mobocertinib. Risk X: Avoid
Montelukast: CYP3A4 Inducers (Strong) may decrease serum concentration of Montelukast. Risk C: Monitor
Naldemedine: CYP3A4 Inducers (Strong) may decrease serum concentration of Naldemedine. Risk X: Avoid
Naloxegol: CYP3A4 Inducers (Strong) may decrease serum concentration of Naloxegol. Risk X: Avoid
Nateglinide: CYP3A4 Inducers (Strong) may decrease serum concentration of Nateglinide. Risk C: Monitor
Nelfinavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Nelfinavir. Risk C: Monitor
Neratinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Neratinib. Risk X: Avoid
Nevirapine: CYP3A4 Inducers (Strong) may decrease serum concentration of Nevirapine. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced nevirapine efficacy. Risk D: Consider Therapy Modification
NiCARdipine: CYP3A4 Inducers (Strong) may decrease serum concentration of NiCARdipine. Risk C: Monitor
NIFEdipine (Topical): CYP3A4 Inducers (Strong) may decrease serum concentration of NIFEdipine (Topical). Risk C: Monitor
NIFEdipine: CYP3A4 Inducers (Strong) may decrease serum concentration of NIFEdipine. Management: Avoid coadministration of nifedipine with strong CYP3A4 inducers when possible and if combined, monitor patients closely for clinical signs of diminished nifedipine response. Risk D: Consider Therapy Modification
Nilotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Nilotinib. Risk X: Avoid
Nilvadipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Nilvadipine. Risk C: Monitor
NiMODipine: CYP3A4 Inducers (Strong) may decrease serum concentration of NiMODipine. Risk X: Avoid
Nintedanib: CYP3A4 Inducers (Strong) may decrease serum concentration of Nintedanib. Risk C: Monitor
Nirmatrelvir and Ritonavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Nirmatrelvir and Ritonavir. Risk X: Avoid
Nirogacestat: CYP3A4 Inducers (Strong) may decrease serum concentration of Nirogacestat. Risk X: Avoid
Nisoldipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Nisoldipine. Risk X: Avoid
Nitrazepam: CYP3A4 Inducers (Strong) may decrease serum concentration of Nitrazepam. Risk C: Monitor
Olaparib: CYP3A4 Inducers (Strong) may decrease serum concentration of Olaparib. Risk X: Avoid
Oliceridine: CYP3A4 Inducers (Strong) may decrease serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Olmutinib. Risk C: Monitor
Olutasidenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Olutasidenib. Risk X: Avoid
Omaveloxolone: CYP3A4 Inducers (Strong) may decrease serum concentration of Omaveloxolone. Risk X: Avoid
Ondansetron: CYP3A4 Inducers (Strong) may decrease serum concentration of Ondansetron. Risk C: Monitor
Osilodrostat: CYP3A4 Inducers (Strong) may decrease serum concentration of Osilodrostat. Risk C: Monitor
Osimertinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Osimertinib. Management: Avoid coadministration of osimertinib and strong CYP3A4 inducers if possible. If coadministration is unavoidable, increase osimertinib to 160 mg daily. Reduce osimertinib to 80 mg daily 3 weeks after discontinuation of the strong CYP3A4 inducer. Risk D: Consider Therapy Modification
OXcarbazepine: CYP3A4 Inducers (Strong) may decrease serum concentration of OXcarbazepine. Specifically, the concentrations of the 10-monohydroxy active metabolite of oxcarbazepine may be decreased. Risk C: Monitor
OxyCODONE: CYP3A4 Inducers (Strong) may decrease serum concentration of OxyCODONE. Risk C: Monitor
PACLitaxel (Conventional): CYP3A4 Inducers (Strong) may decrease serum concentration of PACLitaxel (Conventional). Risk C: Monitor
PACLitaxel (Protein Bound): CYP3A4 Inducers (Strong) may decrease serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor
Pacritinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pacritinib. Risk X: Avoid
Palbociclib: CYP3A4 Inducers (Strong) may decrease serum concentration of Palbociclib. Risk X: Avoid
Paliperidone: CYP3A4 Inducers (Strong) may decrease serum concentration of Paliperidone. Management: Avoid coadministration of extended-release injectable paliperidone and strong CYP3A4 inducers. If coadministration is required consider use of paliperidone extended-release tablets, monitor for reduced effects, and increase the dose as needed. Risk D: Consider Therapy Modification
Palovarotene: CYP3A4 Inducers (Strong) may decrease serum concentration of Palovarotene. Risk X: Avoid
Panobinostat: CYP3A4 Inducers (Strong) may decrease serum concentration of Panobinostat. Risk X: Avoid
PAZOPanib: CYP3A4 Inducers (Strong) may decrease serum concentration of PAZOPanib. Risk X: Avoid
Pemigatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pemigatinib. Risk X: Avoid
Perampanel: CYP3A4 Inducers (Strong) may decrease serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with strong CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider Therapy Modification
Perazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Perazine. Risk C: Monitor
Pexidartinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pexidartinib. Risk X: Avoid
Pimavanserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Pimavanserin. Risk X: Avoid
Piperaquine: CYP3A4 Inducers (Strong) may decrease serum concentration of Piperaquine. Risk X: Avoid
Pirtobrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pirtobrutinib. Risk X: Avoid
Pitolisant: CYP3A4 Inducers (Strong) may decrease serum concentration of Pitolisant. Management: If on a stable pitolisant dose of 8.9 mg or 17.8 mg/day and starting a strong CYP3A4 inducer, double the pitolisant dose over 7 days (ie, to either 17.8 mg/day or 35.6 mg/day, respectively). Reduce pitolisant dose by 50% when the inducer is discontinued. Risk D: Consider Therapy Modification
Polatuzumab Vedotin: CYP3A4 Inducers (Strong) may decrease serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be decreased. Risk C: Monitor
PONATinib: CYP3A4 Inducers (Strong) may decrease serum concentration of PONATinib. Management: Avoid coadministration of ponatinib with strong CYP3A4 inducers unless the potential benefit of concomitant treatment outweighs the risk of reduced ponatinib exposure. Monitor patients for reduced ponatinib efficacy if combined. Risk D: Consider Therapy Modification
Pralsetinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pralsetinib. Management: Avoid concomitant use of pralsetinib with strong CYP3A4 inducers when possible. If combined, increase the starting dose of pralsetinib to double the current pralsetinib dosage starting on day 7 of coadministration. Risk D: Consider Therapy Modification
Praziquantel: CYP3A4 Inducers (Strong) may decrease serum concentration of Praziquantel. Risk X: Avoid
PrednisoLONE (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of PrednisoLONE (Systemic). Risk C: Monitor
PredniSONE: CYP3A4 Inducers (Strong) may decrease serum concentration of PredniSONE. Risk C: Monitor
Pretomanid: CYP3A4 Inducers (Strong) may decrease serum concentration of Pretomanid. Risk X: Avoid
Propafenone: CYP3A4 Inducers (Strong) may decrease serum concentration of Propafenone. Risk C: Monitor
Pyrimethamine: CYP3A4 Inducers (Strong) may decrease serum concentration of Pyrimethamine. Risk C: Monitor
QUEtiapine: CYP3A4 Inducers (Strong) may decrease serum concentration of QUEtiapine. Management: An increase in quetiapine dose (as much as 5 times the regular dose) may be required to maintain therapeutic benefit. Reduce the quetiapine dose back to the previous/regular dose within 7 to 14 days of discontinuing the inducer. Risk D: Consider Therapy Modification
QuiNIDine: CYP3A4 Inducers (Strong) may decrease serum concentration of QuiNIDine. Risk C: Monitor
QuiNINE: CYP3A4 Inducers (Strong) may decrease serum concentration of QuiNINE. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced quinine efficacy and treatment failure. Risk D: Consider Therapy Modification
Quizartinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Quizartinib. Risk X: Avoid
Radotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Radotinib. Management: Consider alternatives to this combination when possible as the risk of radotinib treatment failure may be increased. Risk D: Consider Therapy Modification
Ramelteon: CYP3A4 Inducers (Strong) may decrease serum concentration of Ramelteon. Risk C: Monitor
Ranolazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ranolazine. Risk X: Avoid
Reboxetine: CYP3A4 Inducers (Strong) may decrease serum concentration of Reboxetine. Risk C: Monitor
Regorafenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Regorafenib. CYP3A4 Inducers (Strong) may increase active metabolite exposure of Regorafenib. Risk X: Avoid
Repaglinide: CYP3A4 Inducers (Strong) may decrease serum concentration of Repaglinide. Risk C: Monitor
Repotrectinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Repotrectinib. Risk X: Avoid
Revumenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Revumenib. Risk X: Avoid
Ribociclib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ribociclib. Risk X: Avoid
Rifabutin: CYP3A4 Inducers (Strong) may decrease serum concentration of Rifabutin. Risk C: Monitor
Rilpivirine: CYP3A4 Inducers (Strong) may decrease serum concentration of Rilpivirine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced rilpivirine efficacy (eg, loss of virologic response or resistance). Risk X: Avoid
Rimegepant: CYP3A4 Inducers (Strong) may decrease serum concentration of Rimegepant. Risk X: Avoid
Riociguat: CYP3A4 Inducers (Strong) may decrease serum concentration of Riociguat. Risk C: Monitor
Ripretinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ripretinib. Risk X: Avoid
RisperiDONE: CYP3A4 Inducers (Strong) may decrease serum concentration of RisperiDONE. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of RisperiDONE. Management: Careful monitoring for reduced risperidone efficacy and possible dose adjustment are recommended when combined with strong CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider Therapy Modification
Ritlecitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ritlecitinib. Risk X: Avoid
Ritonavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Ritonavir. Risk X: Avoid
Rivaroxaban: CYP3A4 Inducers (Strong) may decrease serum concentration of Rivaroxaban. Management: Consider alternatives to use of rivaroxaban with strong CYP3A4 inducers. Use of a strong CYP3A4 inducer with rivaroxaban should be strictly avoided in any patient who is using an agent (either the CYP3A4 inducer or a third drug) that induces P-gp. Risk D: Consider Therapy Modification
Roflumilast (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Roflumilast (Systemic). CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Roflumilast (Systemic). Risk X: Avoid
RomiDEPsin: CYP3A4 Inducers (Strong) may decrease serum concentration of RomiDEPsin. Risk X: Avoid
Ruxolitinib (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Ruxolitinib (Systemic). CYP3A4 Inducers (Strong) may increase active metabolite exposure of Ruxolitinib (Systemic). Risk C: Monitor
Samidorphan: CYP3A4 Inducers (Strong) may decrease serum concentration of Samidorphan. Risk X: Avoid
Saquinavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Saquinavir. Management: Consider alternatives to strong CYP3A4 inducers in patients treated with saquinavir. If combined, monitor closely for signs of decreased saquinavir concentrations and effects. Risk D: Consider Therapy Modification
SAXagliptin: CYP3A4 Inducers (Strong) may decrease serum concentration of SAXagliptin. Risk C: Monitor
Selpercatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Selpercatinib. Risk X: Avoid
Selumetinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Selumetinib. Risk X: Avoid
Sertindole: CYP3A4 Inducers (Strong) may decrease serum concentration of Sertindole. Risk C: Monitor
Sertraline: CYP3A4 Inducers (Strong) may decrease serum concentration of Sertraline. Risk C: Monitor
Sildenafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Sildenafil. Risk C: Monitor
Simeprevir: CYP3A4 Inducers (Strong) may decrease serum concentration of Simeprevir. Risk X: Avoid
Simvastatin: CYP3A4 Inducers (Strong) may decrease serum concentration of Simvastatin. Risk C: Monitor
Sirolimus (Conventional): CYP3A4 Inducers (Strong) may decrease serum concentration of Sirolimus (Conventional). Management: Avoid concomitant use of strong CYP3A4 inducers and sirolimus if possible. If combined, monitor for reduced serum sirolimus concentrations. Sirolimus dose increases will likely be necessary to prevent subtherapeutic sirolimus levels. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): CYP3A4 Inducers (Strong) may decrease serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Solifenacin: CYP3A4 Inducers (Strong) may decrease serum concentration of Solifenacin. Risk C: Monitor
Sonidegib: CYP3A4 Inducers (Strong) may decrease serum concentration of Sonidegib. Risk X: Avoid
SORAfenib: CYP3A4 Inducers (Strong) may decrease serum concentration of SORAfenib. Risk X: Avoid
Sotorasib: CYP3A4 Inducers (Strong) may decrease serum concentration of Sotorasib. Risk X: Avoid
Sparsentan: CYP3A4 Inducers (Strong) may decrease serum concentration of Sparsentan. Risk X: Avoid
Spironolactone: May decrease serum concentration of Mitotane. Risk X: Avoid
Stiripentol: CYP3A4 Inducers (Strong) may decrease serum concentration of Stiripentol. Management: Avoid concomitant use of stiripentol and strong CYP3A4 inducers when possible. If combined, monitor for reduced stiripentol efficacy and increase the stiripentol dose as needed. Risk D: Consider Therapy Modification
SUFentanil: CYP3A4 Inducers (Strong) may decrease serum concentration of SUFentanil. Management: If a strong CYP3A4 inducer is initiated in a patient on sufentanil, consider a sufentanil dose increase and monitor for decreased sufentanil effects and opioid withdrawal symptoms. Risk D: Consider Therapy Modification
SUNItinib: CYP3A4 Inducers (Strong) may decrease serum concentration of SUNItinib. Management: Avoid when possible. If combined, increase sunitinib dose to a max of 87.5 mg daily when treating GIST or RCC. Increase sunitinib dose to a max of 62.5 mg daily when treating PNET. Monitor patients for both reduced efficacy and increased toxicities. Risk D: Consider Therapy Modification
Suvorexant: CYP3A4 Inducers (Strong) may decrease serum concentration of Suvorexant. Risk C: Monitor
Suzetrigine: CYP3A4 Inducers (Strong) may decrease serum concentration of Suzetrigine. Risk X: Avoid
Tacrolimus (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Tacrolimus (Systemic). Management: Tacrolimus dose increases will likely be needed during concomitant use with strong CYP3A4 inducers. Monitor more closely and frequently for decreased tacrolimus concentrations and effects when combined. Risk D: Consider Therapy Modification
Tadalafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Tadalafil. Management: Erectile dysfunction or benign prostatic hypertrophy: monitor for decreased effectiveness - no standard dose adjustment is recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Risk D: Consider Therapy Modification
Tamoxifen: CYP3A4 Inducers (Strong) may decrease serum concentration of Tamoxifen. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Tamoxifen. Risk X: Avoid
Tasimelteon: CYP3A4 Inducers (Strong) may decrease serum concentration of Tasimelteon. Risk X: Avoid
Tazemetostat: CYP3A4 Inducers (Strong) may decrease serum concentration of Tazemetostat. Risk X: Avoid
Temsirolimus: CYP3A4 Inducers (Strong) may decrease serum concentration of Temsirolimus. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Temsirolimus. Specifically, concentrations of sirolimus may be decreased. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inducers. If coadministration is unavoidable, increase temsirolimus dose to 50 mg per week. Resume previous temsirolimus dose after discontinuation of the strong CYP3A4 inducer. Risk D: Consider Therapy Modification
Teniposide: CYP3A4 Inducers (Strong) may decrease serum concentration of Teniposide. Risk C: Monitor
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Strong) may decrease serum concentration of Tetrahydrocannabinol and Cannabidiol. Management: Avoid use of the tetrahydrocannabinol/cannabidiol oromucosal spray and strong CYP3A4 inducers when possible. If combined use is necessary, careful titration is recommended, notably within the two weeks following discontinuation of the inducer. Risk D: Consider Therapy Modification
Tetrahydrocannabinol: CYP3A4 Inducers (Strong) may decrease serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Tezacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Tezacaftor and Ivacaftor. Risk X: Avoid
Thiotepa: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Thiotepa. CYP3A4 Inducers (Strong) may decrease serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inducers. If concomitant use is unavoidable, monitor for adverse effects. Risk D: Consider Therapy Modification
TiaGABine: CYP3A4 Inducers (Strong) may decrease serum concentration of TiaGABine. Risk C: Monitor
Ticagrelor: CYP3A4 Inducers (Strong) may decrease serum concentration of Ticagrelor. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Ticagrelor. Risk X: Avoid
Tipranavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Tipranavir. Risk C: Monitor
Tivozanib: CYP3A4 Inducers (Strong) may decrease serum concentration of Tivozanib. Risk X: Avoid
Tofacitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Tofacitinib. Risk X: Avoid
Tolvaptan: CYP3A4 Inducers (Strong) may decrease serum concentration of Tolvaptan. Risk X: Avoid
Toremifene: CYP3A4 Inducers (Strong) may decrease serum concentration of Toremifene. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Toremifene. Risk X: Avoid
Trabectedin: CYP3A4 Inducers (Strong) may decrease serum concentration of Trabectedin. Risk X: Avoid
TraMADol: CYP3A4 Inducers (Strong) may decrease serum concentration of TraMADol. Risk C: Monitor
TraZODone: CYP3A4 Inducers (Strong) may decrease serum concentration of TraZODone. Management: Consider increasing the trazodone dose during coadministration with strong CYP3A4 inducers. Risk D: Consider Therapy Modification
Tretinoin (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Tretinoin (Systemic). Management: Avoid use of tretinoin and strong CYP3A4 inducers when possible. If combined, monitor for reduced tretinoin concentrations and efficacy. Risk D: Consider Therapy Modification
Triamcinolone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Triamcinolone (Systemic). Risk C: Monitor
Triazolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Triazolam. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced triazolam efficacy. Substantial triazolam dose increases will likely be required. Risk D: Consider Therapy Modification
Tropisetron: CYP3A4 Inducers (Strong) may decrease serum concentration of Tropisetron. Risk C: Monitor
Tucatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Tucatinib. Risk X: Avoid
Ubrogepant: CYP3A4 Inducers (Strong) may decrease serum concentration of Ubrogepant. Risk X: Avoid
Udenafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Udenafil. Risk C: Monitor
Ulipristal: CYP3A4 Inducers (Strong) may decrease serum concentration of Ulipristal. Risk X: Avoid
Upadacitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Upadacitinib. Risk X: Avoid
Valbenazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Valbenazine. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Valbenazine. Risk X: Avoid
Vandetanib: CYP3A4 Inducers (Strong) may decrease serum concentration of Vandetanib. CYP3A4 Inducers (Strong) may increase active metabolite exposure of Vandetanib. Risk X: Avoid
Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Risk X: Avoid
Velpatasvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Velpatasvir. Risk X: Avoid
Vemurafenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Vemurafenib. Management: Avoid coadministration of vemurafenib and strong CYP3A4 inducers if possible. If coadministration is unavoidable, increase the vemurafenib dose by 240 mg as tolerated. Resume prior vemurafenib dose 2 weeks after discontinuation of strong CYP3A4 inducer. Risk D: Consider Therapy Modification
Venetoclax: CYP3A4 Inducers (Strong) may decrease serum concentration of Venetoclax. Risk X: Avoid
Verapamil: CYP3A4 Inducers (Strong) may decrease serum concentration of Verapamil. Management: Consider alternatives to this combination. If combined, monitor for reduced verapamil efficacy. Verapamil dose increases may be necessary. Risk D: Consider Therapy Modification
Vilazodone: CYP3A4 Inducers (Strong) may decrease serum concentration of Vilazodone. Management: Consider increasing vilazodone dose by as much as 2-fold (do not exceed 80 mg/day), based on response, in patients receiving strong CYP3A4 inducers for > 14 days. Reduce to the original vilazodone dose over 1 to 2 weeks after inducer discontinuation. Risk D: Consider Therapy Modification
VinCRIStine: CYP3A4 Inducers (Strong) may decrease serum concentration of VinCRIStine. Risk X: Avoid
Vinflunine: CYP3A4 Inducers (Strong) may decrease serum concentration of Vinflunine. Risk X: Avoid
Vinorelbine: CYP3A4 Inducers (Strong) may decrease serum concentration of Vinorelbine. Risk C: Monitor
Voclosporin: CYP3A4 Inducers (Strong) may decrease serum concentration of Voclosporin. Risk X: Avoid
Vonoprazan: CYP3A4 Inducers (Strong) may decrease serum concentration of Vonoprazan. Risk X: Avoid
Vorapaxar: CYP3A4 Inducers (Strong) may decrease serum concentration of Vorapaxar. Risk X: Avoid
Voriconazole: CYP3A4 Inducers (Strong) may decrease serum concentration of Voriconazole. Management: Consider alternatives to this combination when possible. If combined, monitor for decreased voriconazole concentrations and effects. Risk D: Consider Therapy Modification
Vortioxetine: CYP3A4 Inducers (Strong) may decrease serum concentration of Vortioxetine. Management: Consider increasing the vortioxetine dose to no more than 3 times the original dose when used with a strong drug metabolism inducer for more than 14 days. The vortioxetine dose should be returned to normal within 14 days of stopping the strong inducer. Risk D: Consider Therapy Modification
Voxelotor: CYP3A4 Inducers (Strong) may decrease serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and strong CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,500 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider Therapy Modification
Voxilaprevir: CYP3A4 Inducers (Strong) may decrease serum concentration of Voxilaprevir. Risk X: Avoid
Warfarin: Mitotane may decrease anticoagulant effects of Warfarin. Risk C: Monitor
Zaleplon: CYP3A4 Inducers (Strong) may decrease serum concentration of Zaleplon. Management: Consider the use of an alternative hypnotic that is not metabolized by CYP3A4 in patients receiving strong CYP3A4 inducers. If zaleplon is combined with a strong CYP3A4 inducer, monitor for decreased effectiveness of zaleplon. Risk D: Consider Therapy Modification
Zanubrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Zanubrutinib. Risk X: Avoid
Ziprasidone: CYP3A4 Inducers (Strong) may decrease serum concentration of Ziprasidone. Risk C: Monitor
Zolpidem: CYP3A4 Inducers (Strong) may decrease serum concentration of Zolpidem. Risk C: Monitor
Zonisamide: CYP3A4 Inducers (Strong) may decrease serum concentration of Zonisamide. Risk C: Monitor
Zopiclone: CYP3A4 Inducers (Strong) may decrease serum concentration of Zopiclone. Risk C: Monitor
Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease serum concentration of Zuclopenthixol. Risk C: Monitor
Zuranolone: CYP3A4 Inducers (Strong) may decrease serum concentration of Zuranolone. Risk X: Avoid
Administration of mitotane with high-fat food enhances absorption. Management: Ensure consistent timing of dose relative to meals.
Evaluate pregnancy status prior to treatment in patients who could become pregnant.
Patients who could become pregnant should use effective nonhormonal contraception during treatment and until mitotane is discontinued and plasma levels are no longer detectable. Estrogen-containing contraceptives may facilitate tumor development in patients treated for adrenocortical carcinoma (ESE [Fassnacht 2018]). In addition, mitotane may decrease the efficacy of some hormonal contraceptives. Consult drug interactions database for more detailed information related to the use of mitotane and specific contraceptives.
Fertility counseling is recommended for patients of reproductive potential who require use of mitotane (ESE [Fassnacht 2018]). Menstrual changes and nonmalignant ovarian macrocysts have been reported in premenopausal patients receiving mitotane and may resolve once treatment is stopped. Normal menstrual cycles and conception may occur once mitotane is discontinued (Abrahamsson 2020; Basile 2020; Salenave 2015).
Agents other than mitotane are preferred for the treatment of Cushing syndrome in patients planning a future pregnancy (PS [Fleseriu 2021]).
Mitotane crosses the placenta (Gerl 1992).
Outcome data following maternal use of mitotane during pregnancy are limited (de Corbière 2015; Magkou 2018). Preterm births and pregnancy loss have been reported.
Management of adrenocortical carcinoma during pregnancy should be made as part of a shared decision-making process. Pregnancy in patients treated for adrenocortical carcinoma is not recommended until after mitotane is discontinued and maternal plasma levels are no longer detectable (possibly 3 to 12 months). Withhold mitotane if pregnancy occurs during therapy (ESE [Fassnacht 2018]). Agents other than mitotane are preferred for the treatment of Cushing syndrome during pregnancy (PS [Fleseriu 2021]).
Serum concentration; adrenal function; neurologic assessments (including behavioral) at regular intervals with chronic (>2 years) use.
Adult: Urinary free cortisol levels; TSH and free thyroxine every few months (Veytsman 2009)
Pediatric: Monitor mitotane serum concentrations initially every 2 to 4 weeks until serum concentration of 10 mcg/mL is achieved, then monitor every 1 to 2 weeks (even after target concentration of 14 to 20 mcg/mL is reached) and use conservative dose adjustments due to drug accumulation and narrow therapeutic window (Zancanella 2006)
Adult: Monitor mitotane serum concentrations (gas chromatography-flame ionization assay) every 4 to 8 weeks until levels at 10 to 14 mg/L are attained, then monitor every 3 months
Mitotane is an adrenolytic agent that suppresses (directly) the adrenal cortex and alters the peripheral metabolism of steroids.
Onset of action: Antitumor response: Achieved at serum concentrations ≥14 mg/L; target mitotane plasma levels usually reached within 3 to 5 months; Pediatric patients: In experience with treatment of adenocarcinoma reported 1.5 to 12.5 months to reach 10 mcg/mL with subsequent rapid escalation of serum concentration, clinical response may be observed earlier (Rodriguez-Galindo 2005; Zancanella 2006).
Duration: Measurable serum levels may persist for months after discontinuation (Veytsman 2009).
Absorption: Oral: 40%; absorption is enhanced with high-fat foods.
Distribution: Distributed primarily in fat tissue but is found in most body tissues.
Metabolism: Hepatic and extrahepatic; converted to a water-soluble metabolite.
Half-life elimination: Median: 53 days (range: 18 to 159 days).
Excretion: Urine (~10%, as metabolites); feces (1% to 17%, as metabolites).
Obesity: Mitotane is lipophilic and accumulates in adipose tissue.
