Dosing & Uses
Dosage Forms & Strengths
tablet
- 300mg
Prostate Cancer
Nonmetastatic Castration-Resistant Prostate Cancer
Indicated for nonmetastatic castration-resistant prostate cancer (nmCRPC)
600 mg PO BID
Continue treatment until disease progression or unacceptable toxicity occurs
Patients should also receive a gonadotropin-releasing hormone analog concurrently or should have had a bilateral orchiectomy
Metastatic Hormone-Sensitive Prostate Cancer
Indicated for metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel
Darolutamide 600 mg PO BID; continue until disease progression or unacceptable toxicity occurs, even if a docetaxel cycle is delayed, interrupted, or discontinued
Docetaxel 75 mg/m2 IV q3Weeks; administer the first of 6 cycles within 6 weeks after initiating darolutamide
Refer to docetaxel prescribing information for additional dosing information, including dosage modifications
Grade ≥3 toxicity or an intolerable adverse reaction
- Withhold dose or reduce to 300 mg PO BID until symptoms improve
- Resume at 600 mg PO BID
- Do not reduce dose below 300 mg BID
Renal impairment
- Mild or moderate (eGFR 30-89 mL/min/1.73 m2): No dosage adjustment necessary
- Severe (eGFR 15-29 mL/min/1.73 m2) who are not receiving hemodialysis: Reduce to 300 mg PO BID
- End-stage renal disease (eGFR ≤15 mL/min/1.73 m2): Pharmacokinetics unknown
Hepatic impairment
- Mild (Child-Pugh Class A): No dosage adjustment necessary
- Moderate (Child-Pugh Class B): Reduce to 300 mg PO BID
- Severe (Child-Pugh Class C): Pharmacokinetics unknown
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (50)
- abametapir
abametapir will increase the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.
- alpelisib
darolutamide will increase the level or effect of alpelisib by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- apalutamide
apalutamide will decrease the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.
- atorvastatin
darolutamide will increase the level or effect of atorvastatin by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- carbamazepine
carbamazepine will decrease the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.
- chlorothiazide
darolutamide will increase the level or effect of chlorothiazide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- cimetidine
darolutamide will increase the level or effect of cimetidine by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- daunorubicin
darolutamide will increase the level or effect of daunorubicin by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- dipyridamole
darolutamide will increase the level or effect of dipyridamole by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- doxorubicin
darolutamide will increase the level or effect of doxorubicin by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- efavirenz
efavirenz will decrease the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.
- fexinidazole
fexinidazole will increase the level or effect of darolutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- fluvastatin
darolutamide will increase the level or effect of fluvastatin by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- fosphenytoin
fosphenytoin will decrease the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.
- glyburide
darolutamide will increase the level or effect of glyburide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- imatinib
darolutamide will increase the level or effect of imatinib by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- irinotecan
darolutamide will increase the level or effect of irinotecan by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- lapatinib
darolutamide will increase the level or effect of lapatinib by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- lasmiditan
lasmiditan increases levels of darolutamide by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- ledipasvir/sofosbuvir
darolutamide will increase the level or effect of ledipasvir/sofosbuvir by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- leflunomide
darolutamide will increase the level or effect of leflunomide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- lenvatinib
darolutamide will increase the level or effect of lenvatinib by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- lonafarnib
lonafarnib will increase the level or effect of darolutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
- methotrexate
darolutamide will increase the level or effect of methotrexate by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- mitoxantrone
darolutamide will increase the level or effect of mitoxantrone by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- nitrofurantoin
darolutamide will increase the level or effect of nitrofurantoin by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- osimertinib
darolutamide will increase the level or effect of osimertinib by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- ozanimod
darolutamide increases toxicity of ozanimod by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of ozanimod (a BCRP substrate) with BCRP inhibitors increases the exposure of the minor (RP101988, RP101075) and major active metabolites (CC112273, CC1084037) of ozanimod, which may increase the risk of ozanimod adverse reactions. .
- pantoprazole
darolutamide will increase the level or effect of pantoprazole by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- pazopanib
darolutamide will increase the level or effect of pazopanib by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- phenobarbital
phenobarbital will increase the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.
- phenytoin
phenytoin will decrease the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.
- pitavastatin
darolutamide will increase the level or effect of pitavastatin by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- primidone
primidone will decrease the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.
- rifabutin
rifabutin will decrease the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.
- rifampin
rifampin will decrease the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.
- rifapentine
rifapentine will decrease the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.
- rimegepant
darolutamide will increase the level or effect of rimegepant by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of rimegepant (a BCRP substrate) with inhibitors of BCRP.
- riociguat
darolutamide will increase the level or effect of riociguat by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- rosuvastatin
darolutamide will increase the level or effect of rosuvastatin by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions; dose of rosuvastatin should not exceed 5 mg once daily (refer BCRP substrate prescribing information).
- selexipag
darolutamide will increase the level or effect of selexipag by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- simvastatin
darolutamide will increase the level or effect of simvastatin by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- sotorasib
sotorasib will decrease the level or effect of darolutamide by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.
- St John's Wort
St John's Wort will decrease the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.
- tepotinib
tepotinib will increase the level or effect of darolutamide by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.
- topotecan
darolutamide will increase the level or effect of topotecan by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- tucatinib
tucatinib will increase the level or effect of darolutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
- velpatasvir
darolutamide will increase the level or effect of velpatasvir by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- vemurafenib
darolutamide will increase the level or effect of vemurafenib by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- voxelotor
voxelotor will increase the level or effect of darolutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
Monitor Closely (38)
- belzutifan
belzutifan will decrease the level or effect of darolutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
- berotralstat
darolutamide increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.
berotralstat will increase the level or effect of darolutamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered. - cenobamate
cenobamate will decrease the level or effect of darolutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
- clarithromycin
clarithromycin will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- cobicistat
cobicistat will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- conivaptan
conivaptan will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- cyclosporine
cyclosporine will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- dronedarone
dronedarone will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- elagolix
elagolix will increase the level or effect of darolutamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
elagolix will decrease the level or effect of darolutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed. - erythromycin base
erythromycin base will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- etravirine
etravirine will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- fedratinib
fedratinib will increase the level or effect of darolutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- gallium Ga 68 PSMA-11
darolutamide will decrease the level or effect of gallium Ga 68 PSMA-11 by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Androgen deprivation therapy and other therapies targeting the androgen pathway may result in changes in the uptake of gallium Ga 68 PSMA-11 in prostate cancer. The effect of ADT on the performance of gallium Ga 68 PSMA-11 is unknown.
- grapefruit
grapefruit will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- indinavir
indinavir will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- istradefylline
istradefylline will increase the level or effect of darolutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
istradefylline will increase the level or effect of darolutamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates. - itraconazole
itraconazole will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- ketoconazole
ketoconazole will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- lapatinib
lapatinib will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- lenacapavir
lenacapavir will increase the level or effect of darolutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- levoketoconazole
levoketoconazole will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- lonafarnib
lonafarnib will increase the level or effect of darolutamide by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.
- lopinavir
lopinavir will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- nelfinavir
nelfinavir will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- posaconazole
posaconazole will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- ritonavir
ritonavir will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- rucaparib
rucaparib will increase the level or effect of darolutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- saquinavir
saquinavir will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- sofosbuvir
darolutamide will increase the level or effect of sofosbuvir by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- stiripentol
stiripentol will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- sulfasalazine
darolutamide will increase the level or effect of sulfasalazine by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- talazoparib
darolutamide will increase the level or effect of talazoparib by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- tazemetostat
tazemetostat will decrease the level or effect of darolutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tenofovir AF
darolutamide will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- tenofovir DF
darolutamide will increase the level or effect of tenofovir DF by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- tipranavir
tipranavir will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
- tucatinib
tucatinib will increase the level or effect of darolutamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.
Minor (1)
- verapamil
verapamil will increase the level or effect of darolutamide by Other (see comment). Minor/Significance Unknown. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
Adverse Effects
All grades of severity are listed unless otherwise indicated
>10%
nmCRPC
- AST increased (23%)
- Neutrophil count decreased (20%)
- Fatigue (16%)
- Bilirubin increased (16%)
mHSPC
- Constipation (23%)
- Decreased appetite (19%)
- Rash (19%)
- Hemorrhage (18%)
- Weight increased (18%)
- Hypertension (14%)
1-10%
nmCRPC
- Pain in extremity (6%)
- Rash (4%)
- Neutrophil count decreased, Grade 3 or 4 (4%)
mHSPC
- Hypertension, Grade 3 or 4 (7%)
- Weight increased, Grade 3 or 4 (2.1%)
- Rash, Grade 3 or 4 (1.8%)
- Hemorrhage, Grade 3 or 4 (1.4%)
<1%
nmCRPC
- Fatigue, Grade 3 or 4 (0.6%)
- AST increased, Grade 3 or 4 (0.5%)
- Rash, Grade 3 or 4 (0.1%)
- Bilirubin increased, Grade 3 or 4 (0.1%)
mHSPC
- Constipation, Grade 3 or 4 (0.3%)
- Decreased appetite, Grade 3 or 4 (0.2%)
Warnings
Contraindications
None
Cautions
Based on its mechanism of action, fetal harm and loss of pregnancy may occur when administered to a pregnant females
Ischemic heart disease
- Ischemic heart disease, including fatal cases, reported
- Monitor for signs and symptoms of ischemic heart disease
- Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia
- Discontinue therapy for Grade 3-4 ischemic heart disease
- Inform patients that therapy has been associated with increased risk of ischemic heart disease; advise patients to seek immediate medical attention if any symptoms suggestive of ischemic heart disease event occur
Seizures
- Seizures may occur
- Unknown if antiepileptic medications will prevent darolutamide-related seizures
- Advise patients of the risk of developing a seizure during therapy and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others
- Consider discontinuing therapy in patients who develop a seizure during treatment
- Inform patients to contact their healthcare provider right away if they have loss of consciousness or seizure
Drug interaction overview
- P-gp and CYP3A4 substrate
- BCRP transporter inhibitor; OATP1B1 and OATP1B3 inhibitor
-
Combined P-gp and strong or moderate CYP3A4 inducers
- Avoid coadministration
- Combined P-gp and strong or moderate CYP3A4 inducer decreases darolutamide exposure, which may decrease darolutamide activity
-
Combined P-gp and strong CYP3A4 inhibitors
- Combined P-gp and strong CYP3A4 inhibitor increases darolutamide exposure which may increase the risk of darolutamide adverse reactions
- Monitor more frequently for darolutamide adverse reactions and modify darolutamide dosage as needed
-
Breast cancer resistance protein (BCRP) substrates
- Darolutamide increases the AUC and peak plasma concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities
- Avoid use with drugs that are BCRP substrates where possible
- If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate drug; refer to the prescribing information of the BCRP substrate when used concomitantly with darolutamide
Pregnancy & Lactation
Pregnancy
Safety and efficacy have not been established in females
Based on its mechanism of action, fetal harm and loss of pregnancy may occur
Animal embryofetal developmental toxicology studies were not conducted with darolutamide
There are no human data on the use in pregnant females
Contraception
- Males: Based on the mechanism of action, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose
Infertility
- Males: Based on animal studies, fertility may be impaired in males of reproductive potential
Lactation
Safety and efficacy have not been established in females
There are no data on the presence of darolutamide or its metabolites in human milk, the effect on the breastfed child, or the effect on milk production
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Androgen receptor (AR) inhibitor; competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription
Keto-darolutamide (major metabolite) exhibited similar in vitro activity
In addition, darolutamide functioned as a progesterone receptor (PR) antagonist in vitro
Also, decreases prostate cancer cell proliferation in vitro and tumor volume in mouse xenograft models of prostate cancer
Absorption
Steady-state peak plasma concentration: 4.79 mg/L
Peak plasma time: ~4 hr (after single 600-mg dose)
Absolute bioavailability: ~30% (after 300-mg dose under fasted conditions)
AUC: 52.82 mcg⋅hr/mL
Steady-state is reached 2-5 days after repeated dosing with food, with a ~2-fold accumulation
Effect of food
- Bioavailability of darolutamide increased by 2- to 2.5-fold when administered with food
- Similar increase of exposure was observed for the active metabolite keto-darolutamide
Distribution
Vd: 119 L (IV)
Protein bound: 92% (darolutamide); 99.8% (active metabolite, keto-darolutamide)
Serum albumin is main binding protein for darolutamide and keto-darolutamide
Metabolism
Primarily metabolized CYP3A4, as well as by UGT1A9 and UGT1A1
Keto-darolutamide total exposure in plasma is 1.7-fold higher compared with darolutamide
Elimination
Half-life: ~20 hr
Clearance: 116 mL/min
Excretion
- Urine: 63.4%, ~7% unchanged
- Feces 32.4%; ~30% unchanged
- >95% of dose recovered within 7 days after administration
Administration
Oral Administration
Take with food
Swallow tablets whole
Missed dose: Take any missed dose as soon as possible before the next scheduled dose; do NOT double dose to make up for missed dose
Storage
Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
Keep bottle tightly closed after opening
Images
Formulary
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- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
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