Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Erleada: 60 mg
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
Distribution
~276 L
Metabolism
Hepatic; primarily via CYP2C8 and CYP3A4 to form the active metabolite N-desmethyl apalutamide
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)
Time to Peak
2 hours (range: 1 to 5 hours)
Half-Life Elimination
~3 days
Protein Binding
Apalutamide: 96%; N-desmethyl apalutamide: 95%; to plasma proteins
Use: Labeled Indications
Prostate cancer:
Treatment of metastatic, castration-sensitive prostate cancer.
Treatment of nonmetastatic, castration-resistant prostate cancer.
Contraindications
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.
Dosage and Administration
Dosing: Adult
Prostate cancer, metastatic, castration sensitive: Oral: 240 mg once daily (in combination with continuous androgen deprivation therapy) (Chi 2019).
Prostate cancer, nonmetastatic, castration resistant: Oral: 240 mg once daily (in combination with continuous androgen deprivation therapy); continue until disease progression or unacceptable toxicity (Smith 2018).
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.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Adjustment for Toxicity
Grade 3 or higher toxicity (or intolerable adverse reaction): Withhold apalutamide dosing 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.
Cardiovascular event (ischemic), grade 3 or 4: Consider discontinuing apalutamide.
Seizure: Permanently discontinue if seizure develops during apalutamide treatment.
Administration
Oral: Administer at the same time each day, either with or without food. Swallow tablets whole.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Store in the original package. Do not discard desiccant; protect from moisture.
Drug Interactions
Abemaciclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abemaciclib. Avoid combination
Abiraterone Acetate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abiraterone Acetate. Management: Avoid whenever possible. If such a combination cannot be avoided, increase abiraterone acetate dosing frequency from once daily to twice daily during concomitant use. Consider therapy modification
Acalabrutinib: CYP3A4 Inducers (Strong) may decrease the 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. Consider therapy modification
Afatinib: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Afatinib. Management: Per US labeling: if requiring chronic use of P-gp inducers, increase afatinib dose by 10 mg as tolerated; reduce to original afatinib dose 2-3 days after stopping P-gp inducers. Per Canadian labeling: avoid combination if possible. Consider therapy modification
Alpelisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Alpelisib. Avoid combination
Antihepaciviral Combination Products: CYP3A4 Inducers (Strong) may decrease the serum concentration of Antihepaciviral Combination Products. Avoid combination
Apixaban: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease the serum concentration of Apixaban. Avoid combination
Apremilast: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apremilast. Avoid combination
Aprepitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Aprepitant. Avoid combination
ARIPiprazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of ARIPiprazole. Management: Double the oral aripiprazole dose and closely monitor. Reduce oral aripiprazole dose to 10-15 mg/day (for adults) if the inducer is discontinued. Avoid use of strong CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Consider therapy modification
ARIPiprazole Lauroxil: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) 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. Consider therapy modification
Artemether: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Artemether. Specifically, dihydroartemisinin concentrations may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Artemether. Avoid combination
Asunaprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Asunaprevir. Avoid combination
Avapritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Avapritinib. Avoid combination
Axitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib. Avoid combination
Bedaquiline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bedaquiline. Avoid combination
Benperidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Benperidol. Monitor therapy
Benzhydrocodone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Monitor therapy
Betrixaban: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Betrixaban. Avoid combination
Bictegravir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bictegravir. Management: Rifampin is specifically contraindicated, and the use of carbamazepine, phenytoin, or phenobarbital is not recommended when alternatives are acceptable Monitor therapy
Bortezomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib. Avoid combination
Bosutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bosutinib. Avoid combination
Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Monitor therapy
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Monitor therapy
Brexpiprazole: CYP3A4 Inducers (Strong) may decrease the 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. Consider therapy modification
Brigatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brigatinib. Avoid combination
Buprenorphine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Buprenorphine. Monitor therapy
BusPIRone: CYP3A4 Inducers (Strong) may decrease the 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. Consider therapy modification
Cabozantinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, cabozantinib dose adjustments are recommended and vary based on the cabozantinib product used and the indication for use. See monograph for details. Consider therapy modification
Calcifediol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Calcifediol. Monitor therapy
Cannabidiol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabidiol. Monitor therapy
Cannabidiol: CYP2C19 Inducers (Strong) may decrease the serum concentration of Cannabidiol. Monitor therapy
Cannabis: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Monitor therapy
CarBAMazepine: CYP3A4 Inducers (Strong) may decrease the serum concentration of CarBAMazepine. Monitor therapy
Cariprazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cariprazine. Avoid combination
Celiprolol: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Celiprolol. Monitor therapy
Ceritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ceritinib. Avoid combination
ChlorproPAMIDE: CYP3A4 Inducers (Strong) may decrease the serum concentration of ChlorproPAMIDE. Monitor therapy
Choline C 11: Antiandrogens may diminish the therapeutic effect of Choline C 11. Monitor therapy
Cladribine: BCRP/ABCG2 Inducers may decrease the serum concentration of Cladribine. Monitor therapy
Cladribine: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Cladribine. Monitor therapy
Clarithromycin: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Clarithromycin. Clarithromycin may increase the serum concentration of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and may impair clarithromycin efficacy. Consider therapy modification
Clindamycin (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Clindamycin (Systemic). Refer to the specific clindamycin (systemic) - rifampin drug interaction monograph for information concerning that combination. Monitor therapy
Clopidogrel: CYP2C19 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Clopidogrel. Monitor therapy
CloZAPine: CYP3A4 Inducers (Strong) may decrease the serum concentration of CloZAPine. Avoid combination
Cobimetinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cobimetinib. Avoid combination
Codeine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Codeine. Monitor therapy
Copanlisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Copanlisib. Avoid combination
Corticosteroids (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Corticosteroids (Systemic). Exceptions: Hydrocortisone (Systemic); PrednisoLONE (Systemic); PredniSONE. Monitor therapy
Crizotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib. Avoid combination
CYP2C19 Substrates (High risk with Inducers): CYP2C19 Inducers (Strong) may increase the metabolism of CYP2C19 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP2C8 Inhibitors (Strong): May increase the serum concentration of Apalutamide. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Apalutamide. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Apalutamide. Monitor therapy
CYP3A4 Substrates (High risk with Inducers): CYP3A4 Inducers (Strong) may increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Exceptions: Benzhydrocodone; Buprenorphine; CarBAMazepine; Etizolam; HYDROcodone; Mirtazapine; TraMADol; Zolpidem. Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Dabigatran Etexilate. Management: Avoid concurrent use of dabigatran with P-glycoprotein inducers whenever possible. Avoid combination
Dabrafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dabrafenib. Monitor therapy
Daclatasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Daclatasvir. Avoid combination
Darolutamide: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease the serum concentration of Darolutamide. Avoid combination
Dasabuvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasabuvir. Avoid combination
Dasatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Consider therapy modification
Deflazacort: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Avoid combination
Delamanid: CYP3A4 Inducers (Strong) may decrease the serum concentration of Delamanid. Avoid combination
DexAMETHasone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of DexAMETHasone (Systemic). Management: Consider dexamethasone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced dexamethasone efficacy. Consider avoiding this combination when treating life threatening conditions (ie, multiple myeloma). Consider therapy modification
Dienogest: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dienogest. Management: Avoid use of dienogest for contraception when using medications that induce CYP3A4 and for at least 28 days after discontinuation of a CYP3A4 inducer. An alternative form of contraception should be used during this time. Avoid combination
Diethylstilbestrol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Diethylstilbestrol. Monitor therapy
Doravirine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Doravirine. Avoid combination
Doxercalciferol: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Doxercalciferol. Monitor therapy
DOXOrubicin (Conventional): CYP3A4 Inducers (Strong) may decrease the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP3A4 inducers in patients treated with doxorubicin. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inducers in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Dronabinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronabinol. Monitor therapy
Dronedarone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone. Avoid combination
Duvelisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Duvelisib. Avoid combination
Edoxaban: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Edoxaban. Monitor therapy
Elagolix: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elagolix. Monitor therapy
Elbasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elbasvir. Avoid combination
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Avoid combination
Eliglustat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eliglustat. Avoid combination
Encorafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Encorafenib. Avoid combination
Enfortumab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Monitor therapy
Entrectinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Entrectinib. Avoid combination
Enzalutamide: CYP3A4 Inducers (Strong) may decrease the serum concentration 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. Consider therapy modification
Eravacycline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eravacycline. Management: Increase the eravacycline dose to 1.5 mg/kg every 12 hours when combined with strong CYP3A4 inducers. Consider therapy modification
Erdafitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Erdafitinib. Avoid combination
Erlotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Erlotinib. Management: Avoid combination if possible. If combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Consider therapy modification
Estriol (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Estriol (Systemic). Monitor therapy
Estriol (Topical): CYP3A4 Inducers (Strong) may decrease the serum concentration of Estriol (Topical). Monitor therapy
Etoposide: CYP3A4 Inducers (Strong) may decrease the 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. Consider therapy modification
Etoposide Phosphate: CYP3A4 Inducers (Strong) may decrease the 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. Consider therapy modification
Etravirine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etravirine. Avoid combination
Everolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus. Management: Avoid concurrent use of strong CYP3A4 inducers if possible. If coadministration cannot be avoided, double the daily dose of everolimus using increments of 5 mg or less. Monitor everolimus serum concentrations closely when indicated. Consider therapy modification
Evogliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Evogliptin. Monitor therapy
Exemestane: CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane. Management: Exemestane U.S. product labeling recommends using an increased dose (50 mg/day) in patients receiving concurrent strong CYP3A4 inducers. The Canadian product labeling does not recommend a dose adjustment with concurrent use of strong CYP3A4 inducers. Consider therapy modification
Fedratinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fedratinib. Avoid combination
FentaNYL: CYP3A4 Inducers (Strong) may decrease the serum concentration of FentaNYL. Monitor therapy
Fexofenadine: Apalutamide may decrease the serum concentration of Fexofenadine. Monitor therapy
Flibanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Flibanserin. Avoid combination
Fosaprepitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite aprepitant. Avoid combination
Fosnetupitant: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fosnetupitant. Avoid combination
Fostamatinib: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fostamatinib. Avoid combination
Gefitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase 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. Consider therapy modification
Gemigliptin: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Gemigliptin. CYP3A4 Inducers (Strong) may decrease the serum concentration of Gemigliptin. Avoid combination
Gilteritinib: Combined Inducers of CYP3A4 and P-glycoprotein may decrease the serum concentration of Gilteritinib. Avoid combination
Glasdegib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Glasdegib. Avoid combination
Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy
Grazoprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Grazoprevir. Avoid combination
GuanFACINE: CYP3A4 Inducers (Strong) may decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating guanfacine in a patient taking a strong CYP3A4 inducer. Increase guanfacine dose gradually over 1 to 2 weeks if initiating strong CYP3A4 inducer therapy in a patient already taking guanfacine. Consider therapy modification
HYDROcodone: CYP3A4 Inducers (Strong) may decrease the serum concentration of HYDROcodone. Monitor therapy
Hydrocortisone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Hydrocortisone (Systemic). Monitor therapy
Ibrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrutinib. Avoid combination
Idelalisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Idelalisib. Avoid combination
Ifosfamide: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy
Imatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with 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. Consider therapy modification
Indium 111 Capromab Pendetide: Antiandrogens may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Avoid combination
Irinotecan Products: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan Products. Avoid combination
Isavuconazonium Sulfate: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Avoid combination
Istradefylline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Istradefylline. Avoid combination
Itraconazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole. Avoid combination
Ivabradine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivabradine. Avoid combination
Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor. Avoid combination
Ivosidenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivosidenib. Avoid combination
Ixabepilone: CYP3A4 Inducers (Strong) may decrease the 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. Consider therapy modification
Ixazomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixazomib. Avoid combination
Lapatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib. Management: If therapy overlap cannot be avoided, consider titrating 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. Avoid combination
Larotrectinib: CYP3A4 Inducers (Strong) may decrease the 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 half-life. Consider therapy modification
Ledipasvir: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Ledipasvir. Avoid combination
Lefamulin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with strong CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification
Lefamulin: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with P-glycoprotein/ABCB1 inducers unless the benefits outweigh the risks. Consider therapy modification
Lefamulin (Intravenous): CYP3A4 Inducers (Strong) may decrease the serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin intravenous infusion with strong CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification
Lefamulin (Intravenous): P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with P-glycoprotein/ABCB1 inducers unless the benefits outweigh the risks. Consider therapy modification
Lemborexant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lemborexant. Avoid combination
Letermovir: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Letermovir. Avoid combination
LinaGLIPtin: CYP3A4 Inducers (Strong) may decrease the 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. Consider therapy modification
LinaGLIPtin: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any strong 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. Consider therapy modification
Lopinavir: Apalutamide may decrease the serum concentration of Lopinavir. Avoid combination
Lorlatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lorlatinib. Avoid combination
Lumacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Avoid combination
Lumateperone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumateperone. Avoid combination
Lumefantrine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumefantrine. Avoid combination
Lurasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone. Avoid combination
Macimorelin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Macimorelin. Avoid combination
Macitentan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Macitentan. Avoid combination
Manidipine: CYP3A4 Inducers (Strong) may decrease the 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. Consider therapy modification
Maraviroc: CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice daily when used with strong CYP3A4 inducers. This does not apply to patients also receiving strong CYP3A4 inhibitors. Do not use maraviroc with strong CYP3A4 inducers in patients with CrCl less than 30 mL/min. Consider therapy modification
Meperidine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Meperidine. Monitor therapy
MethylPREDNISolone: CYP3A4 Inducers (Strong) may decrease the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Consider therapy modification
Midostaurin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Midostaurin. Avoid combination
MiFEPRIStone: CYP3A4 Inducers (Strong) may decrease the serum concentration of MiFEPRIStone. Avoid combination
Mirodenafil: CYP3A4 Inducers (Strong) may decrease the 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. Consider therapy modification
Mirtazapine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mirtazapine. Monitor therapy
Naldemedine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naldemedine. Avoid combination
Naloxegol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naloxegol. Avoid combination
Neratinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Neratinib. Avoid combination
Netupitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Netupitant. Avoid combination
NIFEdipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NIFEdipine. Avoid combination
Nilotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib. Avoid combination
NiMODipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NiMODipine. Avoid combination
Nintedanib: Combined Inducers of CYP3A4 and P-glycoprotein may decrease the serum concentration of Nintedanib. Avoid combination
Nisoldipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine. Avoid combination
Olaparib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Olaparib. Avoid combination
Osimertinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Osimertinib. Consider therapy modification
OXcarbazepine: CYP3A4 Inducers (Strong) may decrease the serum concentration of OXcarbazepine. Specifically, the concentrations of the 10-monohydroxy active metabolite of oxcarbazepine may be decreased. Monitor therapy
Palbociclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Palbociclib. Avoid combination
Paliperidone: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease the serum concentration of Paliperidone. Management: Avoid using the 3-month extended-release injectable suspension (Invega Trinza) with inducers of both CYP3A4 and P-glycoprotein during the 3-month dosing interval if possible. If combination is necessary, consider using extended-release tablets. Consider therapy modification
Panobinostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Panobinostat. Avoid combination
PAZOPanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of PAZOPanib. Avoid combination
Perampanel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. Consider therapy modification
Pexidartinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pexidartinib. Avoid combination
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Exceptions: Betrixaban; Edoxaban. Monitor therapy
Pimavanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pimavanserin. Avoid combination
Piperaquine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Piperaquine. Avoid combination
Pitolisant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pitolisant. Management: For patients who are stable on pitolisant doses of 8.9 mg or 17.8 mg/day and who are also taking a strong CYP3A4 inducer, increase the pitolisant dose over 7 days to double the original dose (ie, to either 17.8 mg/day or 35.6 mg/day, respectively). Consider therapy modification
Polatuzumab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be decreased. Monitor therapy
PONATinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of PONATinib. Avoid combination
Praziquantel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel. Management: Use of praziquantel with strong CYP3A4 inducers is contraindicated. Discontinue rifampin 4 weeks prior to initiation of praziquantel therapy. Rifampin may be resumed the day following praziquantel completion. Avoid combination
PrednisoLONE (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of PrednisoLONE (Systemic). Monitor therapy
PredniSONE: CYP3A4 Inducers (Strong) may decrease the serum concentration of PredniSONE. Monitor therapy
Pretomanid: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pretomanid. Avoid combination
Propafenone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Propafenone. Monitor therapy
QUEtiapine: CYP3A4 Inducers (Strong) may decrease the 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 7-14 days of discontinuing the inducer. Consider therapy modification
Radotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Radotinib. Management: Consider alternatives to this combination when possible as the risk of radotinib treatment failure may be increased. Consider therapy modification
Ramelteon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ramelteon. Monitor therapy
Ranolazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine. Avoid combination
Reboxetine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Reboxetine. Monitor therapy
Regorafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib. Avoid combination
Ribociclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ribociclib. Avoid combination
RisperiDONE: CYP3A4 Inducers (Strong) may decrease the serum concentration of RisperiDONE. Management: Consider increasing the dose of oral risperidone (to no more than double the original dose) if a strong CYP3A4 inducer is initiated. For patients on IM risperidone, consider an increased IM dose or supplemental doses of oral risperidone. Consider therapy modification
Rivaroxaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban. Avoid combination
Roflumilast: CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast. Management: Roflumilast U.S. prescribing information recommends against combining strong CYP3A4 inducers with roflumilast. The Canadian product monograph makes no such recommendation but notes that such agents may reduce roflumilast therapeutic effects. Avoid combination
Rolapitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rolapitant. Management: Avoid rolapitant use in patients requiring chronic administration of strong CYP3A4 inducers. Monitor for reduced rolapitant response and the need for alternative or additional antiemetic therapy even with shorter-term use of such inducers. Consider therapy modification
RomiDEPsin: CYP3A4 Inducers (Strong) may decrease the serum concentration of RomiDEPsin. Avoid combination
Rosuvastatin: Apalutamide may decrease the serum concentration of Rosuvastatin. Monitor therapy
Ruxolitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ruxolitinib. Monitor therapy
SAXagliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of SAXagliptin. Monitor therapy
Sertraline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sertraline. Monitor therapy
Simeprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir. Avoid combination
Sirolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sirolimus. 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. Consider therapy modification
Sofosbuvir: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Sofosbuvir. Avoid combination
Sonidegib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sonidegib. Avoid combination
SORAfenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SORAfenib. Avoid combination
SUFentanil: CYP3A4 Inducers (Strong) may decrease the serum concentration of SUFentanil. Monitor therapy
SUNItinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SUNItinib. Management: Avoid when possible. If such a combination cannot be avoided, sunitinib dose increases are recommended, and vary by indication. See full monograph for details. Consider therapy modification
Tadalafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil. Management: Erectile dysfunction: monitor for decreased effectiveness - no standard dose adjustments recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Consider therapy modification
Tamoxifen: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. CYP3A4 Inducers (Strong) may decrease the serum concentration of Tamoxifen. Management: Consider alternatives to concomitant use of strong CYP3A4 inducers and tamoxifen. If the combination cannot be avoided, monitor for reduced therapeutic effects of tamoxifen. Consider therapy modification
Tasimelteon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tasimelteon. Avoid combination
Tazemetostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tazemetostat. Avoid combination
Telithromycin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Telithromycin. Avoid combination
Temsirolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Temsirolimus. Management: Consider increasing the dose of temsirolimus to 50 mg IV/week (from 25 mg IV/week) if a concomitant CYP3A4 strong inducer is necessary. Consider therapy modification
Tetrahydrocannabinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol. Monitor therapy
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol. Monitor therapy
Tezacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tezacaftor and Ivacaftor. Avoid combination
Thiotepa: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inducers (Strong) may decrease the 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. Consider therapy modification
Thyroid Products: Apalutamide may diminish the therapeutic effect of Thyroid Products. Monitor therapy
TiaGABine: CYP3A4 Inducers (Strong) may decrease the serum concentration of TiaGABine. Management: Approximately 2-fold higher tiagabine doses and a more rapid dose titration will likely be required in patients concomitantly taking a strong CYP3A4 inducer. Consider therapy modification
Ticagrelor: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ticagrelor. Avoid combination
Tofacitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tofacitinib. Avoid combination
Tolvaptan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Management: If concurrent use is necessary, increased doses of tolvaptan (with close monitoring for toxicity and clinical response) may be needed. Avoid combination
Toremifene: CYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene. Avoid combination
Trabectedin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Trabectedin. Avoid combination
TraMADol: CYP3A4 Inducers (Strong) may decrease the serum concentration of TraMADol. Monitor therapy
Tropisetron: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tropisetron. Monitor therapy
Ubrogepant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ubrogepant. Avoid combination
Udenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Udenafil. Monitor therapy
Ulipristal: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal. Avoid combination
Upadacitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Upadacitinib. Avoid combination
Valbenazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Valbenazine. Avoid combination
Vandetanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib. Avoid combination
Velpatasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Velpatasvir. Avoid combination
Velpatasvir: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Velpatasvir. Avoid combination
Vemurafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib. Management: Avoid concurrent use of vemurafenib with a strong CYP3A4 inducer and replace with another agent when possible. If a strong CYP3A4 inducer is indicated and unavoidable, the dose of vemurafenib may be increased by 240 mg (1 tablet) as tolerated. Consider therapy modification
Venetoclax: CYP3A4 Inducers (Strong) may decrease the serum concentration of Venetoclax. Avoid combination
Vilazodone: CYP3A4 Inducers (Strong) may decrease the 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 1-2 weeks after inducer discontinuation. Consider therapy modification
VinCRIStine (Liposomal): CYP3A4 Inducers (Strong) may decrease the serum concentration of VinCRIStine (Liposomal). Avoid combination
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of VinCRIStine (Liposomal). Avoid combination
Vinflunine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vinflunine. Avoid combination
Vorapaxar: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vorapaxar. Avoid combination
Vortioxetine: CYP3A4 Inducers (Strong) may decrease the 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. Consider therapy modification
Voxelotor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and strong CYP3A4 inducers. If concomitant use is unavoidable, increase the voxelotor dose to 2,500 mg once daily. Consider therapy modification
Voxilaprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Voxilaprevir. Avoid combination
Warfarin: Apalutamide may decrease the serum concentration of Warfarin. Monitor therapy
Zaleplon: CYP3A4 Inducers (Strong) may decrease the 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 zalephon is combined with a strong CYP3A4 inducer, monitor for decreased effectiveness of zaleplon. Consider therapy modification
Zanubrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zanubrutinib. Avoid combination
Zolpidem: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zolpidem. Monitor therapy
Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol. Monitor therapy
Adverse Reactions
>10%:
Cardiovascular: Hypertension (18% to 25%), peripheral edema (11%)
Central nervous system: Fatigue (26% to 39%), falling (16%)
Dermatologic: Skin rash (25% to 28%), pruritus (6% to 11%)
Endocrine & metabolic: Hypercholesterolemia (76%), hyperglycemia (70%), hypertriglyceridemia (17% to 67%), hyperkalemia (32%), increased thyroid stimulating hormone level (25%), hot flash (14% to 23%), weight loss (16%)
Gastrointestinal: Diarrhea (9% to 20%), nausea (18%), decreased appetite (12%)
Hematologic & oncologic: Anemia (70%; grades 3/4: <1%), leukopenia (47%; grades 3/4: <1%), lymphocytopenia (41%; grades 3/4: 2%)
Neuromuscular & skeletal: Arthralgia (16% to 17%), bone fracture (9% to 12%)
1% to 10%:
Cardiovascular: Ischemic heart disease (4%), cardiac failure (2%)
Endocrine & metabolic: Hypothyroidism (4% to 8%)
Gastrointestinal: Dysgeusia (3%)
Neuromuscular & skeletal: Muscle spasm (3%)
<1%, postmarketing, and/or case reports: Seizure
Warnings/Precautions
Concerns related to adverse effects:
- Cardiac events: Ischemic cardiovascular events (including fatal events) have been observed with apalutamide. Optimize management of hypertension, diabetes, dyslipidemia, and other cardiovascular risk factors. Patients with current evidence of unstable angina, myocardial infarction, or heart failure (within 6 months of randomization) were excluded from clinical trials. Monitor for signs/symptoms of ischemic heart disease; consider discontinuing apalutamide therapy for grade 3 or 4 events. 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: 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 was usually managed with oral antihistamines and topical corticosteroids; some patients required systemic corticosteroids to manage rash. May require apalutamide treatment interruption and/or dose reduction. 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. Evaluate patients for fracture risk; patients at risk for fractures should be monitored and managed according to established management guidelines. Consider the use of bone-modifying agents.
- Seizures: Seizures occurred in patients receiving apalutamide. It is not known if antiepileptic 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. Discontinue apalutamide permanently if seizures develop during treatment.
- 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; if clinically indicated, thyroid replacement therapy should be initiated and/or dose-adjusted.
Disease-related concerns:
- Cardiovascular disease: Androgen-deprivation therapy may increase the risk for cardiovascular disease (Levine 2010).
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Elderly: Elderly patients are at an increased risk for falls and grade 3 or 4 adverse reactions (compared to younger patients).
Monitoring Parameters
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, seizure, and dermatologic toxicity. Assess for fall and fracture risk. Monitor adherence.
Pregnancy
Pregnancy Considerations
Based on the mechanism of action, in utero exposure to apalutamide may cause fetal harm and potential fetal loss.
Males with female partners of reproductive potential should use effective contraception during therapy and for 3 months after the last apalutamide dose.
Patient Education
What is this drug used for?
- It is used to treat prostate cancer.
- It may be given for other reasons. Talk with the doctor.
Frequently reported side effects of this drug
- Joint pain
- Loss of strength and energy
- Lack of appetite
- Weight loss
- Hot flash
- Diarrhea
- Nausea
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Severe headache
- Dizziness
- Passing out
- Vision changes
- High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
- High potassium like abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, or numbness or tingling feeling
- Low thyroid level like constipation; difficulty handling heat or cold; trouble with memory; mood changes; or burning, numbness, or tingling feeling
- Chest pain
- Shortness of breath
- Seizures
- Swelling of arms or legs
- Bone pain
- Infection
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
