Version July 2025
Note: Optimize management of cardiovascular risk factors (including hypertension, diabetes, or dyslipidemia) prior to and during treatment.
Prostate cancer, metastatic, castration sensitive: Oral: 240 mg once daily (in combination with continuous androgen deprivation therapy); continue until disease progression or unacceptable toxicity (Ref). Note: Continuous androgen deprivation therapy is either treatment with a concurrent gonadotropin-releasing hormone analog agonist/antagonist or prior bilateral orchiectomy.
Prostate cancer, nonmetastatic, castration resistant: Oral: 240 mg once daily (in combination with continuous androgen deprivation therapy); continue until disease progression or unacceptable toxicity (Ref). Note: Continuous androgen deprivation therapy is either treatment with a concurrent gonadotropin-releasing hormone analog agonist/antagonist or prior bilateral orchiectomy.
Missed doses: If a daily dose is missed, administer as soon as possible on the same day and return to the normal dosing schedule the following day; do not administer extra tablets to make up a missed dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Renal function estimated by the modification of diet in renal disease (MDRD) equation.
eGFR 30 to 89 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling. However, no clinically significant pharmacokinetic differences were observed in mild or moderate renal impairment; therefore, dosage adjustment is not likely necessary.
eGFR ≤29 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (effect on apalutamide pharmacokinetics is unknown).
Mild to moderate impairment (Child-Pugh classes A and B): There are no dosage adjustments provided in the manufacturer's labeling. However, no clinically significant pharmacokinetic differences were observed in mild or moderate hepatic impairment; therefore, dosage adjustment is not likely necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (effect on apalutamide pharmacokinetics is unknown).
Grade 3 or higher toxicity (or intolerable adverse reactions): Withhold apalutamide until symptoms improve to baseline or to grade 1 or lower, then resume either at the same dose or (if warranted) with the dose reduced to 180 mg or 120 mg.
Cerebrovascular and ischemic cardiovascular events, grade 3 or 4: Consider permanently discontinuing apalutamide.
Dermatologic toxicity:
Severe cutaneous adverse reactions: If a severe cutaneous adverse reaction (SCAR) is suspected, withhold apalutamide until the etiology of the reaction has been identified; consultation with a dermatologist is recommended. Permanently discontinue apalutamide for confirmed SCARs.
Rash: Rash may be managed with oral antihistamines and topical corticosteroids; some patients may require systemic corticosteroids. May require apalutamide treatment interruption and/or dose reduction.
Other grade 4 skin reactions: Permanently discontinue apalutamide.
Fracture: Patients at risk for fractures should be managed according to established management guidelines; consider the use of bone-modifying agents.
Interstitial lung disease/Pneumonitis: If interstitial lung disease (ILD)/pneumonitis is suspected, withhold apalutamide. Permanently discontinue apalutamide for severe ILD/pneumonitis or if no other causes of ILD/pneumonitis are identified.
Seizure: Permanently discontinue if seizure develops during apalutamide treatment.
Thyroid dysfunction: May require thyroid replacement therapy; if clinically indicated, thyroid replacement therapy should be initiated and/or dose-adjusted.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Hypertension (18% to 25%), peripheral edema (11%)
Dermatologic: Pruritus (6% to 11%), skin rash (25% to 28%; including maculopapular rash)
Endocrine & metabolic: Hot flash (14% to 23%), hypercholesterolemia (76%), hyperglycemia (70%), hyperkalemia (32%), hypertriglyceridemia (17% to 67%), increased thyroid stimulating hormone level (25%), weight loss (16%)
Gastrointestinal: Decreased appetite (12%), diarrhea (9% to 20%; grades 3/4: 1%), nausea (18%)
Hematologic & oncologic: Anemia (70%; grades 3/4: <1%), leukopenia (47%; grades 3/4: <1%), lymphocytopenia (41%; grades 3/4: 2%)
Nervous system: Falling (16%), fatigue (39%)
Neuromuscular & skeletal: Arthralgia (16% to 17%), bone fracture (9% to 12%)
1% to 10%:
Cardiovascular: Heart failure (2%), ischemic heart disease (4%)
Endocrine & metabolic: Hypothyroidism (4% to 8%)
Gastrointestinal: Dysgeusia (3%)
Nervous system: Cerebrovascular disease (3%)
Neuromuscular & skeletal: Muscle spasm (3%)
Respiratory: Interstitial lung disease (≤1%), pneumonitis (≤1%)
<1%: Nervous system: Seizure
Postmarketing:
Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to apalutamide or any component of the formulation; use in females who are or may become pregnant.
Concerns related to adverse effects:
• Cardiac events: Cerebrovascular and ischemic cardiovascular events (including fatal events) have been observed with apalutamide. Patients with history of unstable angina, myocardial infarction, heart failure, stroke, or transient ischemic attack (within 6 months of randomization) were excluded from clinical trials. Based on exposure-QT analysis in an uncontrolled, single-arm, dedicated QTc interval assessment study, a concentration-dependent increase in QTcF was noted with apalutamide (and the active metabolite). The maximum mean QTcF change from baseline was 12.4 msec.
• Dermatologic toxicity: Life-threatening (and fatal) cases of severe cutaneous adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms, have occurred. Rashes (usually macular or maculo-papular) were reported in nearly one-fourth of patients who received apalutamide; including some that were grade 3. Rash onset usually occurred at median of 83 days and typically resolved within a median of 78 days in most patients. Rash recurred in over half of patients who were rechallenged with apalutamide.
• Falls: Evaluate patients for fall risk. Falls have occurred in patients receiving apalutamide; elderly patients are at increased risk for falls.
• Fractures: Fractures have occurred in patients receiving apalutamide. Grade 3 or 4 fractures have been reported. In clinical studies, the median time to onset of fracture was ~2 to 10 months (range: 2 to 953 days); the studies did not perform routine bone density assessments or osteoporosis treatment with bone-modifying agents.
• Interstitial lung disease: Interstitial lung disease or pneumonitis may occur; may be life-threatening or fatal.
• Seizures: Seizures occurred in patients receiving apalutamide. It is not known if antiseizure medications can prevent apalutamide-related seizures. In clinical studies, a small number of patients experienced seizures, with the onset occurring from ~5 to 22 months after treatment initiation. Patients with a history of seizure, predisposing factors for seizure, or receiving medications known to reduce seizure threshold or to induce seizures were excluded from the studies. There is no experience in reinitiating apalutamide in patients who experienced a seizure. Advise patients of the risk of seizures during apalutamide treatment and of the risk of engaging in activities where sudden loss of consciousness could cause serious harm to themselves or others.
• Thyroid dysfunction: Hypothyroidism and elevated thyroid stimulating hormone (TSH) have been reported with apalutamide; the median onset was ~4 months (there were no grade 3 or 4 hypothyroid events). Thyroid replacement therapy was initiated in some patients.
Disease-related concerns:
• Cardiovascular disease: Androgen-deprivation therapy may increase the risk for cardiovascular disease (Levine 2010).
Special populations:
• Older adult: Patients ≥65 years of age experienced an increased incidence of falls and grade 3 or 4 adverse reactions (compared to patients <65 years of age).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Erleada: 60 mg, 240 mg
No
Tablets (Erleada Oral)
60 mg (per each): $153.00
240 mg (per each): $612.02
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Erleada: 60 mg, 240 mg
Apalutamide is available through a specialty pharmacy network. Refer to https://www.janssencarepath.com/hcp/erleada or call 877-227-3728 for more information.
Oral: Administer at the same time each day, either with or without food. Swallow tablets whole; do not crush or split.
For patients unable to swallow whole tablet(s):
240 mg tablet: Place whole 240 mg tablet in a cup (do not crush or split tablet). Add ~10 mL noncarbonated water, making sure tablet is completely immersed in the water. Wait 2 minutes until the tablet is broken up and spread out, then stir the mixture. Add 30 mL of orange juice, applesauce, or additional water and stir, then administer immediately. Rinse cup with additional water to make sure entire dose is administered and have patient drink immediately. Do not save apalutamide mixed with noncarbonated water, orange juice, or applesauce for later.
60 mg tablets: Place enough tablets for prescribed dose (120 mg, 180 mg, or 240 mg) in a cup (do not crush or split tablets). Add ~20 mL noncarbonated water, making sure tablet is completely immersed in the water. Wait 2 minutes until the tablets are broken up and spread out, then stir the mixture. Add 30 mL of orange juice, applesauce, or additional water and stir, then administer immediately. Rinse cup with additional water to make sure entire dose is administered and have patient drink immediately. Do not save apalutamide mixed with noncarbonated water, orange juice, or applesauce for later.
For feeding tube administration (≥8 French):
240 mg tablet: Place one 240 mg tablet in the barrel of a syringe (use at least a 20 mL syringe that is appropriate for a feeding tube) and draw up 10 mL noncarbonated water into the syringe. Wait 10 minutes and then shake vigorously to completely disperse contents. Administer immediately through feeding tube. Refill syringe with noncarbonated water and administer; repeat until no tablet residue is left in syringe or feeding tube.
60 mg tablets: Place enough tablets for prescribed dose (120 mg, 180 mg, or 240 mg) in the barrel of a syringe (use at least a 50 mL syringe that is appropriate for a feeding tube) and draw up 20 mL noncarbonated water into the syringe. Wait 10 minutes and then shake vigorously to completely disperse contents. Administer immediately through feeding tube. Refill syringe with noncarbonated water and administer; repeat until no tablet residue is left in syringe or feeding tube.
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Apalutamide may cause reproductive toxicity, teratogenicity, and has a structural/toxicity profile similar to existing hazardous agents.
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).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Prostate cancer:
Treatment of metastatic, castration-sensitive prostate cancer.
Treatment of nonmetastatic, castration-resistant prostate cancer.
Apalutamide may be confused with abiraterone, bicalutamide, darolutamide, dutasteride, enzalutamide, flutamide, nilutamide.
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 Settings).
Substrate of CYP2C8 (Major with inhibitors), CYP2C8 (Minor with inducers), CYP3A4 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces BCRP, CYP2C19 (Strong), CYP3A4 (Strong), OATP1B1/1B3, P-glycoprotein;
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.
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
Abrocitinib: CYP2C19 Inducers (Strong) may decrease serum concentration of Abrocitinib. Risk X: Avoid
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
Afatinib: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Afatinib. Management: Increase the afatinib dose by 10 mg as tolerated in patients requiring chronic coadministration of P-gp inducers with afatinib. Reduce afatinib dose back to the original afatinib dose 2 to 3 days after discontinuation of the P-gp inducer. Risk D: Consider Therapy Modification
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
Aliskiren: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Aliskiren. Risk C: Monitor
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
Androgens: Hypertension-Associated Agents may increase hypertensive effects of Androgens. Risk C: Monitor
Antihepaciviral Combination Products: CYP3A4 Inducers (Strong) may decrease serum concentration of Antihepaciviral Combination Products. Risk X: Avoid
Apixaban: Apalutamide may decrease serum concentration of Apixaban. Risk X: Avoid
Apremilast: CYP3A4 Inducers (Strong) may decrease serum concentration of Apremilast. Risk X: Avoid
Aprepitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Aprepitant. 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: May increase serum concentration of Apalutamide. Apalutamide 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
Berotralstat: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Berotralstat. Risk X: Avoid
Beta-Acetyldigoxin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Beta-Acetyldigoxin. 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
Brivaracetam: CYP2C19 Inducers (Strong) may decrease serum concentration of Brivaracetam. Management: Increase the brivaracetam dose by up to 100% (ie, double the dose) if used with rifampin and consider the same dose adjustment if used with other strong CYP2C19 inducers. Monitor for reduced brivaracetam efficacy. Risk D: Consider Therapy Modification
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: CYP2C19 Inducers (Strong) may decrease serum concentration of Cannabidiol. CYP2C19 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
Carisoprodol: CYP2C19 Inducers (Strong) may decrease serum concentration of Carisoprodol. CYP2C19 Inducers (Strong) may increase active metabolite exposure of Carisoprodol. Risk C: Monitor
Celiprolol: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Celiprolol. Risk C: Monitor
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
Choline C 11: Antiandrogens may decrease therapeutic effects of Choline C 11. 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
Cladribine: BCRP/ABCG2 Inducers may decrease serum concentration of Cladribine. Risk C: Monitor
Cladribine: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Cladribine. 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
Clopidogrel: CYP2C19 Inducers (Strong) may increase active metabolite exposure of Clopidogrel. Management: Consider alternatives to this combination when possible. If combined, monitor for increased clopidogrel effects and toxicities (eg, bleeding) if clopidogrel is combined with a strong CYP2C19 inducer. Risk D: Consider Therapy Modification
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
CYP2C8 Inhibitors (Strong): May increase serum concentration of Apalutamide. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Apalutamide. Risk C: Monitor
Cyproterone: CYP3A4 Inducers (Strong) may decrease serum concentration of Cyproterone. Risk C: Monitor
Dabigatran Etexilate: Apalutamide may decrease serum concentration of Dabigatran Etexilate. Risk X: Avoid
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
Darolutamide: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Darolutamide. 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
Dexlansoprazole: CYP2C19 Inducers (Strong) may decrease serum concentration of Dexlansoprazole. Risk X: Avoid
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
Digitoxin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Digitoxin. Risk C: Monitor
Digoxin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Digoxin. 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
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inducers 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
Edoxaban: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Edoxaban. Management: Avoid coadministration of edoxaban and P-glycoprotein (P-gp) inducers if possible. If concomitant use is required, be aware the edoxaban efficacy may be decreased. Risk D: Consider Therapy Modification
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
Esomeprazole: CYP2C19 Inducers (Strong) may decrease serum concentration of Esomeprazole. Risk X: Avoid
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: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Everolimus. Management: Afinitor: Double the everolimus daily dose, using increments of 5 mg or less, with careful monitoring; multiple increments may be necessary. Zortress: Avoid if possible and monitor for decreased everolimus concentrations if combined. 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
Fexofenadine: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Fexofenadine. Risk C: Monitor
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
Flotufolastat F18: Coadministration of Antiandrogens and Flotufolastat F18 may alter diagnostic results. Management: Therapies targeting the androgen pathway may result in changes in the uptake of flotufolastat F18 in prostate cancer. The impact of these therapies on the performance of flotufolastat F18 is unknown; consider use of alternative agents. Risk D: Consider Therapy Modification
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
Fosaprepitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite aprepitant. Risk X: Avoid
Fosnetupitant: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fosnetupitant. Risk X: Avoid
Fosphenytoin-Phenytoin: CYP2C19 Inducers (Strong) may decrease serum concentration of Fosphenytoin-Phenytoin. 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: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Futibatinib. Risk X: Avoid
Gallium Ga 68 PSMA-11: Antiandrogens may decrease therapeutic effects of Gallium Ga 68 PSMA-11. Management: Therapies targeting the androgen pathway may result in changes in the uptake of gallium Ga 68 PSMA-11 (gozetotide) in prostate cancer. The impact on the performance of gallium Ga 68 PSMA-11 (gozetotide) is unknown; consider use of alternative agents. Risk D: Consider Therapy Modification
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: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Gilteritinib. Risk X: Avoid
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: CYP3A4 Inducers (Strong) may decrease serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a strong CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider Therapy Modification
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
Indium 111 Capromab Pendetide: Coadministration of Antiandrogens and Indium 111 Capromab Pendetide may alter diagnostic results. Risk X: Avoid
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
Lansoprazole: CYP2C19 Inducers (Strong) may decrease serum concentration of Lansoprazole. Risk X: Avoid
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
Ledipasvir: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Ledipasvir. 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 (Intravenous): P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with P-glycoprotein/ABCB1 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
Lefamulin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with P-glycoprotein/ABCB1 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
Letermovir: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Letermovir. Risk X: Avoid
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
LinaGLIPtin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any P-glycoprotein 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: Apalutamide may decrease serum concentration of Lopinavir. Risk X: Avoid
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
Netupitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Netupitant. 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: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Nintedanib. Risk X: Avoid
Niraparib: Apalutamide may increase adverse/toxic effects of Niraparib. Apalutamide may decrease serum concentration of Niraparib. Management: Consider alternatives to this combination when possible. If combined, monitor for decreased niraparib concentrations and efficacy, as well as for increased niraparib toxicities. Risk D: Consider Therapy Modification
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
Omeprazole: CYP2C19 Inducers (Strong) may decrease serum concentration of Omeprazole. 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
Ospemifene: Apalutamide may decrease serum concentration of Ospemifene. Risk C: Monitor
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: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Paliperidone. Management: Avoid coadministration of extended-release injectable paliperidone and P-gp inducers. If coadministration is required, consider use of paliperidone extended-release tablets, monitor for reduced paliperidone 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
PHENobarbital: CYP2C19 Inducers (Strong) may decrease serum concentration of PHENobarbital. Risk C: Monitor
Piflufolastat F18: Coadministration of Antiandrogens and Piflufolastat F18 may alter diagnostic results. Management: Therapies targeting the androgen pathway may result in changes in the uptake of piflufolastat F18 in prostate cancer. The impact of these therapies on the performance of piflufolastat F18 is unknown; consider use of alternative agents. Risk D: Consider Therapy Modification
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
Relugolix, Estradiol, and Norethindrone: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Relugolix, Estradiol, and Norethindrone. Risk X: Avoid
Relugolix: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Relugolix. Management: Avoid use of relugolix with drugs that are both strong CYP3A4 and P-glycoprotein (P-gp) inducer. If combined, increase the dose of relugolix to 240 mg once daily. Reduce back to 120 mg daily once the combined inducer is discontinued. Risk D: Consider Therapy Modification
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: Apalutamide may decrease serum concentration of Rivaroxaban. Risk X: Avoid
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
Rolapitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Rolapitant. Risk X: Avoid
RomiDEPsin: CYP3A4 Inducers (Strong) may decrease serum concentration of RomiDEPsin. Risk X: Avoid
Rosuvastatin: Apalutamide may decrease serum concentration of Rosuvastatin. Risk C: Monitor
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
Sofosbuvir: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Sofosbuvir. Risk X: Avoid
Solifenacin: CYP3A4 Inducers (Strong) may decrease serum concentration of Solifenacin. Risk C: Monitor
Solriamfetol: May increase hypertensive effects of Hypertension-Associated Agents. 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
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
Tenofovir Alafenamide: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Tenofovir Alafenamide. Management: Consider alternatives to the use of P-gp inducers with tenofovir alafenamide. If combined, monitor for reduced tenofovir alafenamide concentrations and efficacy, and for the development of resistance. Risk D: Consider Therapy Modification
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
Thyroid Products: Apalutamide may decrease therapeutic effects of Thyroid Products. Risk C: Monitor
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
Vitamin K Antagonists: CYP2C9 Inducers (Weak) may decrease serum concentration of Vitamin K Antagonists. 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
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
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inducers may decrease serum concentration of Zavegepant. 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
Patients with partners who could become pregnant should use effective contraception during therapy and for 3 months after the last apalutamide dose.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to apalutamide may cause fetal harm and potential fetal loss.
It is not known if apalutamide is present in breast milk.
Monitor thyroid function (eg, thyroid-stimulating hormone [TSH]) as clinically necessary (TSH was monitored at baseline and every 4 months in studies). Monitor for signs/symptoms of cardiovascular events (including ischemic heart disease), cerebrovascular events, seizure, and dermatologic toxicity. Monitor for signs/symptoms of interstitial lung disease/pneumonitis (eg, cough, dyspnea, fever) and severe cutaneous adverse reactions (eg, prodrome of fever, flu-like symptoms, mucosal lesions, progression skin rash, or lymphadenopathy). Assess for fall and fracture risk. Monitor adherence.
Cardiovascular monitoring for patients with prostate cancer: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; baseline and serial ECGs are recommended in patients at risk of QTc prolongation during androgen deprivation therapy (ADT); estimate 10-year cardiovascular disease risk in patients without cardiovascular disease at baseline; assess cardiovascular risk annually during ADT (ASCO [Armenian 2017]; ESC [Lyon 2022]).
Apalutamide is a nonsteroidal androgen receptor inhibitor; apalutamide binds directly to the androgen receptor ligand-binding domain to prevent androgen-receptor translocation, DNA binding, and receptor-mediated transcription (Smith 2018). Androgen receptor inhibition results in decreased proliferation of tumor cells and increased apoptosis, leading to a decrease in tumor volume.
Distribution: ~276 L.
Protein binding: Apalutamide: 96%; N-desmethyl apalutamide: 95%; to plasma proteins.
Metabolism: Hepatic; primarily via CYP2C8 and CYP3A4 to form the active metabolite N-desmethyl apalutamide.
Bioavailability: ~100%.
Half-life elimination: ~3 days.
Time to peak: 2 hours (range: 1 to 5 hours).
Excretion: Urine (65%; 1.2% as apalutamide and 2.7% as N-desmethyl apalutamide); Feces (24%; 1.5% as apalutamide and 2% as N-desmethyl apalutamide).
Clearance: 1.3 L/hour (after single dose); 2 L/hour (steady state).
