Version May 2024
Prostate cancer, castration resistant: Note: Patients receiving enzalutamide for castration-resistant prostate cancer should also receive a gonadotropin-releasing hormone analog concurrently (or have had a bilateral orchiectomy).
Oral: 160 mg once daily; continue until disease progression or unacceptable toxicity (Ref).
Prostate cancer, metastatic, castration resistant, HRR gene-mutated (off-label combination): Oral: 160 mg once daily (in combination with talazoparib); continue until disease progression or unacceptable toxicity (Ref).
Prostate cancer, metastatic, castration sensitive: Note: Patients receiving enzalutamide for metastatic, castration-sensitive prostate cancer should also receive a gonadotropin-releasing hormone analog concurrently (or have had a bilateral orchiectomy).
Oral: 160 mg once daily; continue until disease progression or unacceptable toxicity (Ref).
Prostate cancer, non metastatic, castration sensitive, with biochemical recurrence at high risk for metastasis (high-risk biochemical recurrence): Note: Patients receiving enzalutamide for nonmetastatic, castration-sensitive prostate cancer with high-risk biochemical recurrence may be treated with or without a concurrent gonadotropin-releasing hormone analog.
Oral: 160 mg once daily; continue until disease progression or unacceptable toxicity. Treatment with enzalutamide (with or without a gonadotropin-releasing hormone analog) can be suspended for undetectable PSA (<0.2 ng/mL) after 36 weeks of therapy. Reinitiate treatment when PSA ≥2 ng/mL in patients with prior radical prostatectomy or PSA ≥5 ng/mL in patients with prior primary radiation therapy (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: No initial dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
End-stage kidney disease: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Hepatic impairment prior to treatment initiation: Mild, moderate, or severe impairment (Child-Turcotte-Pugh class A, B, or C): No dosage adjustment necessary.
If ≥ grade 3 toxicity or intolerable side effects occur, withhold treatment for 1 week or until symptom(s) improve to ≤ grade 2, then resume at same dose, or reduce dose to 120 mg or 80 mg once daily, if necessary.
Hypersensitivity reaction, serious: Permanently discontinue treatment.
Ischemic heart disease, grade 3 or 4: Discontinue treatment.
Posterior reversible encephalopathy syndrome: Discontinue treatment.
Seizures: Permanently discontinue treatment.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Hypertension (6% to 14%), peripheral edema (12% to 15%)
Endocrine & metabolic: Hot flash (13% to 27%), hyperglycemia (86%), hypermagnesemia (17%), hyponatremia (14%), weight loss (6% to 12%)
Gastrointestinal: Constipation (9% to 23%), decreased appetite (5% to 19%), diarrhea (12% to 22%; grades 3/4: ≤1%), nausea (11% to 14%; grades 3/4: <1%)
Hematologic & oncologic: Decreased hemoglobin (50%; grades 3/4: 2%), decreased neutrophils (20%; grades 3/4: 1%), decreased white blood cell count (18%; grades 3/4: <1%)
Nervous system: Asthenia (24% to 51%, including fatigue), dizziness (9% to 12%), falling (5% to 13%), headache (9% to 12%)
Neuromuscular & skeletal: Arthralgia (21%), back pain (19% to 29%), bone fracture (4% to 13%), musculoskeletal pain (6% to 16%)
Respiratory: Dyspnea (11%), upper respiratory tract infection (11% to 16%)
1% to 10%:
Cardiovascular: Ischemic heart disease (4%)
Dermatologic: Pruritus (4%), xeroderma (4%)
Endocrine & metabolic: Gynecomastia (3%), hypercalcemia (8%), hypophosphatemia (10%)
Gastrointestinal: Dysgeusia (8%)
Genitourinary: Hematuria (7% to 9%), pollakiuria (5%)
Nervous system: Altered mental status (4% to 6%, including cognitive dysfunction, disturbance in attention, memory impairment), anxiety (3% to 6%), cauda equina syndrome (≤7%), hypoesthesia (4%), insomnia (8% to 9%), myasthenia (10%), paresthesia (7%), restless leg syndrome (2%), spinal cord compression (≤7%)
Neuromuscular & skeletal: Muscle rigidity (3%)
Respiratory: Epistaxis (3%), pulmonary infection (≤8%, including bronchitis, lower respiratory tract infection, pneumonia)
<1%:
Hypersensitivity: Facial edema, lip edema, tongue edema
Nervous system: Seizure
Frequency not defined:
Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase
Hypersensitivity: Hypersensitivity reaction
Postmarketing:
Dermatologic: Acute generalized exanthematous pustulosis, erythema multiforme, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis
Gastrointestinal: Vomiting
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms
Nervous system: Reversible posterior leukoencephalopathy syndrome
Respiratory: Pharyngeal edema
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to enzalutamide or any component of the formulation; women who are or may become pregnant or are lactating
Concerns related to adverse effects:
• Cardiovascular effects: Ischemic heart disease (including grades 3 or 4 ischemic events) occurred more commonly in patients receiving enzalutamide (compared to placebo); some events were fatal. Androgen-deprivation therapy may increase the risk for cardiovascular disease (Levine 2010). An increase in systolic and diastolic blood pressures has been observed (Scher 2012); may worsen preexisting hypertension. Optimize management of cardiovascular risk factors (including hypertension, diabetes, and/or dyslipidemia).
• Fractures: Falls and fractures have occurred in patients receiving enzalutamide; in clinical trials, the incidence of falls and fractures was higher in patients who received enzalutamide (vs placebo); grades 3/4 fractures have occurred. The median time to fracture onset was ~11 months (range: 2 days to ~5 years). Routine assessment of bone density and osteoporosis treatment with bone-modifying agents were not performed in studies. Evaluate fall and fracture risk. Manage fracture risk according to established treatment guidelines; consider the use of bone-modifying agents.
• Hypersensitivity: Hypersensitivity reactions, including facial, tongue, or lip edema, have been observed with enzalutamide; pharyngeal edema has also been reported. If hypersensitivity symptoms occur, advise patients to temporarily discontinue enzalutamide and obtain prompt medical care.
• Posterior reversible encephalopathy syndrome: Posterior reversible encephalopathy syndrome (PRES) has been reported in patients receiving enzalutamide. PRES is a neurological disorder which may present with rapidly evolving symptoms (headache, seizure, lethargy, confusion, blindness, and other visual/neurologic disturbances) with or without associated hypertension. PRES diagnosis may be confirmed with MRI.
• Seizures: Seizures were observed in enzalutamide clinical trials; patients with predisposing risk factors for seizures were generally excluded from these studies. The onset of seizure ranged from 13 days to ~60 months after enzalutamide treatment initiation. Enzalutamide was permanently discontinued in patients experiencing seizures; seizures resolved upon therapy cessation. In a study designed to assess seizure risk in patients with predisposing factors, 2.2% of patients who received enzalutamide experienced a seizure; after the first seizure resolved, a few of those patients experienced a second seizure with continued enzalutamide treatment. It is not known if antiseizure medications can prevent enzalutamide-related seizures. Patients in the study had one or more predisposing factors, including the use of concomitant medications that may lower the seizure threshold, history of traumatic brain or head injury, history of cerebrovascular accident/transient ischemic attack, and Alzheimer disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, prior seizure history, presence of a space occupying brain lesion, history of arteriovenous malformation, or history of brain infection; some patients had more than one risk factor. Advise patients of the risk of seizures during enzalutamide treatment and of the risk of engaging in activities where sudden loss of consciousness could cause serious harm to themselves or others.
Dosage forms specific issues:
• Sorbitol: Capsules contain sorbitol.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Xtandi: 40 mg
Tablet, Oral:
Xtandi: 40 mg, 80 mg
No
Capsules (Xtandi Oral)
40 mg (per each): $143.32
Tablets (Xtandi Oral)
40 mg (per each): $143.32
80 mg (per each): $286.65
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Xtandi: 40 mg
Oral: Administer at the same time each day, either with or without food. Swallow capsules or tablets whole; do not chew, dissolve, or open the capsules; do not cut, crush, or chew the tablets.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Prostate cancer:
Treatment of castration-resistant prostate cancer.
Treatment of metastatic castration-sensitive prostate cancer.
Treatment of nonmetastatic castration-sensitive prostate cancer with biochemical recurrence (BCR) at high risk for metastasis (high-risk BCR).
Enzalutamide may be confused with apalutamide, bicalutamide, darolutamide, estramustine, flutamide, nilutamide.
Xtandi may be confused with Jevtana, Xgeva, Xofigo, Xpovia, Zejula, Zometa, Zydelig, Zytiga.
Substrate of CYP2C8 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits MRP2, P-glycoprotein/ABCB1; Induces CYP2C19 (moderate), CYP2C9 (moderate), CYP3A4 (strong)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abemaciclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abemaciclib. Risk X: Avoid combination
Abiraterone Acetate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abiraterone Acetate. Management: Avoid when possible. If the combination cannot be avoided, increase abiraterone acetate dosing frequency from once daily to twice daily during combined use. Reduce abiraterone dose back to the prior dose and frequency once strong inducer is discontinued. Risk D: Consider therapy modification
Abrocitinib: CYP2C19 Inducers (Moderate) may decrease the serum concentration of Abrocitinib. Risk C: Monitor therapy
Abrocitinib: CYP2C9 Inducers (Moderate) may decrease the serum concentration of Abrocitinib. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Adagrasib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Adagrasib. Risk X: Avoid combination
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification
Alfacalcidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Alfacalcidol. Risk C: Monitor therapy
ALfentanil: CYP3A4 Inducers (Strong) may decrease the serum concentration of ALfentanil. Management: If concomitant use of alfentanil and strong CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Risk D: Consider therapy modification
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Alpelisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Alpelisib. Risk X: Avoid combination
ALPRAZolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Amiodarone: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Amiodarone. CYP3A4 Inducers (Strong) may decrease the serum concentration of Amiodarone. Risk C: Monitor therapy
AmLODIPine: CYP3A4 Inducers (Strong) may decrease the serum concentration of AmLODIPine. Risk C: Monitor therapy
Antihepaciviral Combination Products: CYP3A4 Inducers (Strong) may decrease the serum concentration of Antihepaciviral Combination Products. Risk X: Avoid combination
Apixaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apixaban. Management: Avoid concurrent use of apixaban with strong CYP3A4 inducers whenever possible. Use of a strong CYP3A4 inducer with apixaban should be strictly avoided in any patient who is using an agent (either the CYP3A4 inducer or a third drug) that induces P-gp. Risk D: Consider therapy modification
Apremilast: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apremilast. Risk X: Avoid combination
Aprepitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Aprepitant. Risk X: Avoid combination
ARIPiprazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of ARIPiprazole. Management: For indications other than major depressive disorder: double the oral aripiprazole dose over 1 to 2 weeks and closely monitor. Avoid use of strong CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Artemether and Lumefantrine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. CYP3A4 Inducers (Strong) may decrease the serum concentration of Artemether and Lumefantrine. Risk X: Avoid combination
Asunaprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Asunaprevir. Risk X: Avoid combination
Atazanavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Atazanavir. Risk C: Monitor therapy
Atogepant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider therapy modification
Atorvastatin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Atorvastatin. Risk C: Monitor therapy
Avacopan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Avacopan. Risk X: Avoid combination
Avanafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Avanafil. Risk X: Avoid combination
Avapritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Avapritinib. Risk X: Avoid combination
Avatrombopag: Enzalutamide may decrease the serum concentration of Avatrombopag. Management: For chronic immune thrombocytopenia, increase initial avatrombopag dose to 40 mg daily. No dosage adjustment needed for patients with chronic liver disease-associated thrombocytopenia using altrombopag prior to a procedure. Risk D: Consider therapy modification
Axitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib. Risk X: Avoid combination
Barnidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Barnidipine. Risk C: Monitor therapy
Bedaquiline: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inducers (Strong) may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination
Belumosudil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Belumosudil. Management: Increase the dose of belumosudil to 200 mg twice daily when coadministered with strong CYP3A4 inducers. Risk D: Consider therapy modification
Benidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Benidipine. Risk C: Monitor therapy
Benperidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Benperidol. Risk C: Monitor therapy
Benzhydrocodone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor therapy
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Betamethasone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Betamethasone (Systemic). Risk C: Monitor therapy
Bictegravir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bictegravir. Risk C: Monitor therapy
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
Bisoprolol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bisoprolol. Risk C: Monitor therapy
Blonanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Blonanserin. Risk C: Monitor therapy
Bortezomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib. Risk X: Avoid combination
Bosutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bosutinib. Risk X: 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. Risk C: 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. Decrease brexpiprazole to original dose over 1 to 2 weeks if the strong CYP3A4 inducer is discontinued. Risk D: Consider therapy modification
Brigatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brigatinib. Risk X: Avoid combination
Brivaracetam: CYP2C19 Inducers (Moderate) may decrease the serum concentration of Brivaracetam. Risk C: Monitor therapy
Bromocriptine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bromocriptine. Risk C: Monitor therapy
Bromperidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bromperidol. Risk C: Monitor therapy
Brotizolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brotizolam. Risk C: Monitor therapy
Buprenorphine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Buprenorphine. Risk C: 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. Risk D: Consider therapy modification
Butorphanol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Butorphanol. Risk C: Monitor therapy
Cabazitaxel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabazitaxel. Risk C: Monitor therapy
Cabozantinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, increase cabozantinib capsules (Cometriq) by 40 mg from previous dose, max 180 mg daily. Increase cabozantinib tablets (Cabometyx) by 20 mg from previous dose, max 80 mg daily Risk D: Consider therapy modification
Calcifediol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Calcifediol. Risk C: Monitor therapy
Calcitriol (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Calcitriol (Systemic). Risk C: Monitor therapy
Cannabidiol: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Cannabidiol. CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabidiol. Risk C: Monitor therapy
Cannabis: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor therapy
Capivasertib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Capivasertib. Risk X: Avoid combination
Capmatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Capmatinib. Risk X: Avoid combination
Cariprazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cariprazine. Risk X: Avoid combination
Carisoprodol: CYP2C19 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Carisoprodol. CYP2C19 Inducers (Moderate) may decrease the serum concentration of Carisoprodol. Risk C: Monitor therapy
Celecoxib: CYP2C9 Inducers (Moderate) may decrease the serum concentration of Celecoxib. Risk C: Monitor therapy
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy
Ceritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ceritinib. Risk X: Avoid combination
ChlorproPAMIDE: CYP3A4 Inducers (Strong) may decrease the serum concentration of ChlorproPAMIDE. Risk C: Monitor therapy
Choline C 11: Antiandrogens may diminish the therapeutic effect of Choline C 11. Risk C: Monitor therapy
Cilnidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cilnidipine. Risk C: Monitor therapy
Citalopram: CYP3A4 Inducers (Strong) may decrease the serum concentration of Citalopram. Risk C: Monitor therapy
Clarithromycin: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Strong) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A4 inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and may impair clarithromycin efficacy. Risk D: Consider therapy modification
Clindamycin (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy
ClonazePAM: CYP3A4 Inducers (Strong) may decrease the serum concentration of ClonazePAM. Risk C: Monitor therapy
CloZAPine: CYP3A4 Inducers (Strong) may decrease the serum concentration of CloZAPine. Management: Avoid use with strong CYP3A4 inducers when possible. If combined, monitor patients closely and consider clozapine dose increases. Clozapine dose reduction and further monitoring may be required when strong CYP3A4 inducers are discontinued. Risk D: Consider therapy modification
Cobicistat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cobicistat. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced cobicistat efficacy. Risk D: Consider therapy modification
Cobimetinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cobimetinib. Risk X: Avoid combination
Codeine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider therapy modification
Copanlisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Copanlisib. Risk X: Avoid combination
Crizotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib. Risk X: Avoid combination
CycloSPORINE (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of CycloSPORINE (Systemic). Management: Monitor closely for reduced cyclosporine concentrations when combined with strong CYP3A4 inducers. Cyclosporine dose increases will likely be required to maintain adequate serum concentrations. Risk D: Consider therapy modification
CYP2C8 Inhibitors (Moderate): May increase serum concentrations of the active metabolite(s) of Enzalutamide. CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Enzalutamide. Risk C: Monitor therapy
CYP2C8 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Enzalutamide. CYP2C8 Inhibitors (Strong) may increase the serum concentration of Enzalutamide. Management: Avoid concurrent use of strong CYP2C8 inhibitors and enzalutamide if possible. If the combination must be used, reduce enzalutamide to 80 mg once daily. Once the inhibitor is discontinued, return enzalutamide to the dose used prior to inhibitor initiation Risk D: Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Enzalutamide. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Enzalutamide. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of 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. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Enzalutamide. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Enzalutamide. Risk C: Monitor therapy
Cyproterone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cyproterone. Risk C: Monitor therapy
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Daclatasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Daclatasvir. Risk X: Avoid combination
Dapsone (Systemic): May enhance the adverse/toxic effect of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease the serum concentration of Dapsone (Systemic). Risk C: Monitor therapy
Daridorexant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Daridorexant. Risk X: Avoid combination
Darunavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Darunavir. Risk C: Monitor therapy
Dasabuvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasabuvir. Risk X: Avoid combination
Dasatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib. Management: Avoid concurrent use of dasatinib with strong CYP3A4 inducers when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Risk D: Consider therapy modification
Deflazacort: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Risk X: Avoid combination
Delamanid: CYP3A4 Inducers (Strong) may decrease the serum concentration of Delamanid. Risk X: Avoid combination
Delavirdine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Delavirdine. Management: Consider avoiding this combination if possible. If concomitant use is necessary, monitor for decreased delavirdine concentrations and effects if coadministered with strong CYP3A4 inducers. Risk D: Consider therapy modification
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). Risk D: Consider therapy modification
DiazePAM: CYP3A4 Inducers (Strong) may decrease the serum concentration of DiazePAM. Risk C: Monitor therapy
Diclofenac (Systemic): CYP2C9 Inducers (Moderate) may decrease the serum concentration of Diclofenac (Systemic). Risk C: Monitor therapy
Dienogest: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dienogest. Risk C: Monitor therapy
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider therapy modification
DilTIAZem: CYP3A4 Inducers (Strong) may decrease the serum concentration of DilTIAZem. Management: Consider alternatives to this combination when possible. If combined, monitor for decreased diltiazem efficacy. Risk D: Consider therapy modification
Disopyramide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Disopyramide. Risk C: Monitor therapy
DOCEtaxel: CYP3A4 Inducers (Strong) may decrease the serum concentration of DOCEtaxel. Risk C: Monitor therapy
Domperidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Domperidone. Risk C: Monitor therapy
Doravirine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Doravirine. Risk X: Avoid combination
Doxercalciferol: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Doxercalciferol. Risk C: Monitor therapy
DOXOrubicin (Conventional): CYP3A4 Inducers (Strong) may decrease the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy
DroNABinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of DroNABinol. Risk C: Monitor therapy
Dronedarone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone. Risk X: Avoid combination
Duvelisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Duvelisib. Risk X: Avoid combination
Dydrogesterone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dydrogesterone. Risk C: Monitor therapy
Ebastine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ebastine. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ebastine. Risk C: Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy
Efavirenz: CYP3A4 Inducers (Strong) may decrease the serum concentration of Efavirenz. Risk C: Monitor therapy
Elacestrant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elacestrant. Risk X: Avoid combination
Elagolix: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elagolix. Risk C: Monitor therapy
Elagolix, Estradiol, and Norethindrone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elagolix, Estradiol, and Norethindrone. Risk C: Monitor therapy
Elbasvir and Grazoprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk X: Avoid combination
Eliglustat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eliglustat. Risk X: Avoid combination
Elvitegravir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elvitegravir. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced elvitegravir efficacy. Risk D: Consider therapy modification
Encorafenib: May decrease the serum concentration of Enzalutamide. Enzalutamide may decrease the serum concentration of Encorafenib. Risk X: 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. Risk C: Monitor therapy
Entrectinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Entrectinib. Risk X: Avoid combination
Eplerenone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eplerenone. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Erdafitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Erdafitinib. Risk X: Avoid combination
Erlotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Erlotinib. Management: Avoid the combination of erlotinib and strong CYP3A4 inducers whenever possible. If this combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Risk D: Consider therapy modification
Escitalopram: CYP3A4 Inducers (Strong) may decrease the serum concentration of Escitalopram. Risk C: Monitor therapy
Estazolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Estazolam. Risk C: Monitor therapy
Estrogen Derivatives: CYP3A4 Inducers (Strong) may decrease the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
Eszopiclone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eszopiclone. Risk C: Monitor therapy
Ethosuximide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ethosuximide. Risk C: Monitor therapy
Etizolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etizolam. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification
Etoricoxib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoricoxib. Risk C: Monitor therapy
Etravirine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etravirine. Risk X: Avoid combination
Everolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus. Management: Concomitant use of everolimus and strong CYP3A4 inducers is generally not recommended. However, if combined, monitor for decreased everolimus concentrations and effects, and adjust everolimus dose as needed. Risk D: Consider therapy modification
Evogliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Evogliptin. Risk C: Monitor therapy
Exemestane: CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane. Management: Increase the exemestane dose to 50 mg once daily in patients receiving concurrent strong CYP3A4 inducers. Monitor patients closely for evidence of toxicity or inadequate clinical response. Risk D: Consider therapy modification
Fedratinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fedratinib. Risk X: Avoid combination
Felbamate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Felbamate. Risk C: Monitor therapy
Felodipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Felodipine. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced felodipine efficacy and the need for felodipine dose increases. Risk D: Consider therapy modification
Fenfluramine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fenfluramine. Management: Avoid concurrent use of strong CYP3A4 inducers with fenfluramine when possible. If combined use cannot be avoided, consider increasing the fenfluramine dose, but do not exceed the fenfluramine maximum daily dose. Risk D: Consider therapy modification
FentaNYL: CYP3A4 Inducers (Strong) may decrease the serum concentration of FentaNYL. Risk C: Monitor therapy
Fesoterodine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Fexinidazole: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Fexinidazole. Risk X: Avoid combination
Finerenone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Finerenone. Risk X: Avoid combination
Flibanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Flibanserin. Risk X: Avoid combination
Flotufolastat F18: Antiandrogens may diminish the diagnostic effect of Flotufolastat F18. Management: Therapies targeting the androgen pathway may result in changes in the uptake of flotufolastat F18 in prostate cancer. The impact of these therapies on the performance of flotufolastat F18 is unknown; consider use of alternative agents. Risk D: Consider therapy modification
Fluvastatin: CYP2C9 Inducers (Moderate) may decrease the serum concentration of Fluvastatin. Risk C: Monitor therapy
Fosamprenavir: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Risk C: Monitor therapy
Fosaprepitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite aprepitant. Risk X: Avoid combination
Fosnetupitant: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fosnetupitant. Risk X: Avoid combination
Fosphenytoin-Phenytoin: Enzalutamide may decrease the serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease the serum concentration of Enzalutamide. Management: Avoid concurrent use of phenytoin/fosphenytoin and enzalutamide whenever possible. If combined, increase enzalutamide dose to 240 mg daily. Additionally, monitor for reduced phenytoin serum concentrations and effects. Risk D: Consider therapy modification
Fostamatinib: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fostamatinib. Risk X: Avoid combination
Fostemsavir: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fostemsavir. Risk X: Avoid combination
Fruquintinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fruquintinib. Risk X: Avoid combination
Futibatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Futibatinib. Risk C: Monitor therapy
Gallium Ga 68 PSMA-11: Antiandrogens may diminish the therapeutic effect of Gallium Ga 68 PSMA-11. Management: Therapies targeting the androgen pathway may result in changes in the uptake of gallium Ga 68 PSMA-11 (gozetotide) in prostate cancer. The impact on the performance of gallium Ga 68 PSMA-11 (gozetotide) is unknown; consider use of alternative agents. Risk D: Consider therapy modification
Ganaxolone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and strong CYP3A4 inducers whenever possible. If combined, consider increasing the dose of ganaxolone, but do not exceed the maximum recommended daily dose. Risk D: Consider therapy modification
Gefitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase the gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers; resume 250 mg dose 7 days after discontinuation of the strong inducer. Carefully monitor clinical response. Risk D: Consider therapy modification
Gemigliptin: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Gemigliptin. CYP3A4 Inducers (Strong) may decrease the serum concentration of Gemigliptin. Risk X: Avoid combination
Gepirone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gepirone. Risk X: Avoid combination
Gilteritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gilteritinib. Risk C: Monitor therapy
Glasdegib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Glasdegib. Risk X: Avoid combination
Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
GuanFACINE: CYP3A4 Inducers (Strong) may decrease the serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Risk D: Consider therapy modification
Haloperidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Haloperidol. Risk C: Monitor therapy
Hormonal Contraceptives: CYP3A4 Inducers (Strong) may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a strong CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification
HYDROcodone: CYP3A4 Inducers (Strong) may decrease the serum concentration of HYDROcodone. Risk C: Monitor therapy
Hydrocortisone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
Ibrexafungerp: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrexafungerp. Risk X: Avoid combination
Ibrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrutinib. Risk X: Avoid combination
Idelalisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Idelalisib. Risk X: 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. Risk C: Monitor therapy
Imatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib. Management: Avoid use of imatinib and strong CYP3A4 inducers when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Doses up to 1200 mg/day (600 mg twice daily) have been used. Risk D: Consider therapy modification
Indinavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Indinavir. Management: Consider avoiding the combination of indinavir and strong CYP3A4 inducers whenever possible due to the risk for decreased indinavir concentrations, reduced efficacy, and development of resistance. If combined, monitor for indinavir treatment failure Risk D: Consider therapy modification
Indium 111 Capromab Pendetide: Antiandrogens may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination
Infigratinib: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Infigratinib. Risk X: 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. Management: Avoid administration of strong CYP3A4 inducers during irinotecan treatment, and substitute non-CYP3A4 inducing agents at least 2 weeks prior to irinotecan initiation, whenever possible. If combined, monitor for reduced irinotecan efficacy. Risk D: Consider therapy modification
Isavuconazonium Sulfate: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Risk X: Avoid combination
Isradipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Isradipine. Risk C: Monitor therapy
Istradefylline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Istradefylline. Risk X: Avoid combination
Itraconazole: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Itraconazole. CYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole. Risk X: Avoid combination
Ivabradine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivabradine. Risk X: Avoid combination
Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor. Risk X: Avoid combination
Ivosidenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivosidenib. Risk X: 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. Risk D: Consider therapy modification
Ixazomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixazomib. Risk X: Avoid combination
Ketamine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ketamine. Risk C: Monitor therapy
Ketoconazole (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Ketoconazole (Systemic). Management: The use of ketoconazole concurrently with or within 2 weeks of a strong CYP3A4 inducer is not recommended. If such a combination cannot be avoided, monitor patients closely for evidence of diminished clinical response to ketoconazole. Risk D: Consider therapy modification
Lacidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lacidipine. Risk C: Monitor therapy
Lapatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib. Management: If concomitant use cannot be avoided, titrate lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Risk D: Consider therapy modification
Larotrectinib: CYP3A4 Inducers (Strong) may decrease 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's half-life. Risk D: Consider therapy modification
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. Risk D: 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. Risk D: Consider therapy modification
Lemborexant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lemborexant. Risk X: Avoid combination
Lenacapavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lenacapavir. Risk X: Avoid combination
Leniolisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Leniolisib. Risk X: Avoid combination
Lercanidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lercanidipine. Risk C: Monitor therapy
Leuprolide and Norethindrone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Leuprolide and Norethindrone. Specifically, norethindrone concentrations may be decreased. Risk C: Monitor therapy
Levamlodipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Levamlodipine. Risk C: Monitor therapy
Levoketoconazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Levoketoconazole. Risk X: Avoid combination
Levomethadone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Levomethadone. Risk C: Monitor therapy
Levonorgestrel (IUD): CYP3A4 Inducers (Strong) may diminish the therapeutic effect of Levonorgestrel (IUD). CYP3A4 Inducers (Strong) may decrease the serum concentration of Levonorgestrel (IUD). Risk C: Monitor therapy
Lidocaine (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Lonafarnib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lonafarnib. Risk X: Avoid combination
Lopinavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lopinavir. Risk C: Monitor therapy
Lorlatinib: CYP3A4 Inducers (Strong) may enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Lorlatinib. Risk X: Avoid combination
Lornoxicam: CYP2C9 Inducers (Moderate) may decrease the serum concentration of Lornoxicam. Risk C: Monitor therapy
Lovastatin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lovastatin. Risk C: Monitor therapy
Lumacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk X: Avoid combination
Lumateperone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumateperone. Risk X: Avoid combination
Lurasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone. Risk X: Avoid combination
Lurbinectedin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurbinectedin. Risk X: Avoid combination
Macimorelin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Macimorelin. Risk X: Avoid combination
Macitentan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Macitentan. Risk X: 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. Risk D: Consider therapy modification
Maraviroc: CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice/day, but only if not receiving a strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Contraindicated in patients with CrCl less than 30 mL/min. Risk D: Consider therapy modification
Maribavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Maribavir. Risk X: Avoid combination
Mavacamten: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mavacamten. Risk X: Avoid combination
Mefloquine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mefloquine. Risk C: Monitor therapy
Meperidine: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Meperidine. Specifically, concentrations of normeperidine, the CNS stimulating metabolite, may be increased. CYP3A4 Inducers (Strong) may decrease the serum concentration of Meperidine. Risk C: Monitor therapy
Methadone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Methadone. Risk C: Monitor therapy
Methylergonovine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Methylergonovine. Risk C: 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. Risk D: Consider therapy modification
Mianserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mianserin. Risk C: Monitor therapy
Midazolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Midazolam. Risk C: Monitor therapy
Midostaurin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Midostaurin. Risk X: Avoid combination
MiFEPRIStone: CYP3A4 Inducers (Strong) may decrease the serum concentration of MiFEPRIStone. Management: Avoid combined use in patients treated for Cushing's disease. When used for pregnancy termination, mifepristone efficacy may be reduced and an alternative pregnancy termination procedure may be warranted. Ensure a follow-up assessment after combined use. Risk D: Consider therapy modification
Mirabegron: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mirabegron. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Mirtazapine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mirtazapine. Risk C: Monitor therapy
Mitapivat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mitapivat. Risk X: Avoid combination
Mobocertinib: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Mobocertinib. Risk X: Avoid combination
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy
Naldemedine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naldemedine. Risk X: Avoid combination
Naloxegol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naloxegol. Risk X: Avoid combination
Nateglinide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nateglinide. Risk C: Monitor therapy
Nelfinavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nelfinavir. Risk C: Monitor therapy
Neratinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Neratinib. Risk X: Avoid combination
Netupitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Netupitant. Risk X: Avoid combination
Nevirapine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nevirapine. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced nevirapine efficacy. Risk D: Consider therapy modification
NiCARdipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NiCARdipine. Risk C: Monitor therapy
NIFEdipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NIFEdipine. Management: Avoid coadministration of nifedipine with strong CYP3A4 inducers when possible and if combined, monitor patients closely for clinical signs of diminished nifedipine response. Risk D: Consider therapy modification
Nilotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib. Risk X: Avoid combination
Nilvadipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilvadipine. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NiMODipine. Risk X: Avoid combination
Nintedanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nintedanib. Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nirmatrelvir and Ritonavir. Risk X: Avoid combination
Nirogacestat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nirogacestat. Risk X: Avoid combination
Nisoldipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine. Risk X: Avoid combination
Nitrazepam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nitrazepam. Risk C: Monitor therapy
Nitrendipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nitrendipine. Risk C: Monitor therapy
Olaparib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Olaparib. Risk X: Avoid combination
Oliceridine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Oliceridine. Risk C: Monitor therapy
Olmutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Olmutinib. Risk C: Monitor therapy
Olutasidenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Olutasidenib. Risk X: Avoid combination
Omaveloxolone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Omaveloxolone. Risk X: Avoid combination
Omeprazole: CYP2C19 Inducers (Moderate) may decrease the serum concentration of Omeprazole. Risk C: Monitor therapy
Ondansetron: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ondansetron. Risk C: Monitor therapy
Orelabrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Orelabrutinib. Risk X: Avoid combination
Osilodrostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Osilodrostat. Risk C: Monitor therapy
Osimertinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Osimertinib. Management: Avoid coadministration of osimertinib and strong CYP3A4 inducers if possible. If coadministration is unavoidable, increase osimertinib to 160 mg daily. Reduce osimertinib to 80 mg daily 3 weeks after discontinuation of the strong CYP3A4 inducer. Risk D: Consider therapy modification
Ospemifene: Enzalutamide may decrease the serum concentration of Ospemifene. Risk C: Monitor therapy
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. Risk C: Monitor therapy
OxyCODONE: CYP3A4 Inducers (Strong) may decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy
PACLitaxel (Conventional): CYP3A4 Inducers (Strong) may decrease the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP3A4 Inducers (Strong) may decrease the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy
Pacritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pacritinib. Risk X: Avoid combination
Palbociclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Palbociclib. Risk X: Avoid combination
Palovarotene: CYP3A4 Inducers (Strong) may decrease the serum concentration of Palovarotene. Risk X: Avoid combination
Panobinostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Panobinostat. Risk X: Avoid combination
PAZOPanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of PAZOPanib. Risk X: Avoid combination
Pemigatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pemigatinib. Risk X: Avoid combination
Perampanel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with strong CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider therapy modification
Pexidartinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pexidartinib. Risk X: Avoid combination
Piflufolastat F18: Antiandrogens may diminish the diagnostic effect of Piflufolastat F18. Management: Therapies targeting the androgen pathway may result in changes in the uptake of piflufolastat F18 in prostate cancer. The impact of these therapies on the performance of piflufolastat F18 is unknown; consider use of alternative agents. Risk D: Consider therapy modification
Pimavanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pimavanserin. Risk X: Avoid combination
Piperaquine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Piperaquine. Risk X: Avoid combination
Pirtobrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pirtobrutinib. Risk X: Avoid combination
Pitolisant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pitolisant. Management: If on a stable pitolisant dose of 8.9 mg or 17.8 mg/day and starting a strong CYP3A4 inducer, double the pitolisant dose over 7 days (ie, to either 17.8 mg/day or 35.6 mg/day, respectively). Reduce pitolisant dose by 50% when the inducer is discontinued. Risk D: Consider therapy modification
Polatuzumab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be decreased. Risk C: Monitor therapy
PONATinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of PONATinib. Management: Avoid coadministration of ponatinib with strong CYP3A4 inducers unless the potential benefit of concomitant treatment outweighs the risk of reduced ponatinib exposure. Monitor patients for reduced ponatinib efficacy if combined. Risk D: Consider therapy modification
Pralsetinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pralsetinib. Management: Avoid concomitant use of pralsetinib with strong CYP3A4 inducers when possible. If combined, increase the starting dose of pralsetinib to double the current pralsetinib dosage starting on day 7 of coadministration. Risk D: Consider therapy modification
Praziquantel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel. Risk X: Avoid combination
PrednisoLONE (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of PrednisoLONE (Systemic). Risk C: Monitor therapy
PredniSONE: CYP3A4 Inducers (Strong) may decrease the serum concentration of PredniSONE. Risk C: Monitor therapy
Pretomanid: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pretomanid. Risk X: Avoid combination
Propafenone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Propafenone. Risk C: 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 to 14 days of discontinuing the inducer. Risk D: Consider therapy modification
QuiNIDine: CYP3A4 Inducers (Strong) may decrease the serum concentration of QuiNIDine. Risk C: Monitor therapy
QuiNINE: CYP3A4 Inducers (Strong) may decrease the serum concentration of QuiNINE. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced quinine efficacy and treatment failure. Risk D: Consider therapy modification
Quizartinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Quizartinib. Risk X: Avoid combination
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. Risk D: Consider therapy modification
Ramelteon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ramelteon. Risk C: Monitor therapy
Ranolazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine. Risk X: Avoid combination
Reboxetine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Reboxetine. Risk C: Monitor therapy
Regorafenib: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib. Risk X: Avoid combination
Repaglinide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Repaglinide. Risk C: Monitor therapy
Repotrectinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Repotrectinib. Risk X: Avoid combination
Ribociclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ribociclib. Risk X: Avoid combination
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
Rilpivirine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rilpivirine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced rilpivirine efficacy (eg, loss of virologic response or resistance). Risk X: Avoid combination
Rimegepant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rimegepant. Risk X: Avoid combination
Riociguat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Riociguat. Risk C: Monitor therapy
Ripretinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ripretinib. Risk X: Avoid combination
RisperiDONE: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of RisperiDONE. CYP3A4 Inducers (Strong) may decrease the serum concentration of RisperiDONE. Management: Careful monitoring for reduced risperidone efficacy and possible dose adjustment are recommended when combined with strong CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider therapy modification
Ritlecitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ritlecitinib. Risk X: Avoid combination
Ritonavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ritonavir. Risk X: Avoid combination
Rivaroxaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban. Management: Consider alternatives to use of rivaroxaban with strong CYP3A4 inducers. Use of a strong CYP3A4 inducer with rivaroxaban should be strictly avoided in any patient who is using an agent (either the CYP3A4 inducer or a third drug) that induces P-gp. Risk D: Consider therapy modification
Roflumilast (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Roflumilast (Systemic). CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast (Systemic). Risk X: Avoid combination
Rolapitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rolapitant. Risk X: Avoid combination
RomiDEPsin: CYP3A4 Inducers (Strong) may decrease the serum concentration of RomiDEPsin. Risk X: Avoid combination
Ruxolitinib (Systemic): CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Ruxolitinib (Systemic). CYP3A4 Inducers (Strong) may decrease the serum concentration of Ruxolitinib (Systemic). Risk C: Monitor therapy
Samidorphan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Samidorphan. Risk X: Avoid combination
Saquinavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Saquinavir. Management: Consider alternatives to strong CYP3A4 inducers in patients treated with saquinavir. If combined, monitor closely for signs of decreased saquinavir concentrations and effects. Risk D: Consider therapy modification
SAXagliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of SAXagliptin. Risk C: Monitor therapy
Selpercatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Selpercatinib. Risk X: Avoid combination
Selumetinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Selumetinib. Risk X: Avoid combination
Sertindole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sertindole. Risk C: Monitor therapy
Sertraline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sertraline. Risk C: Monitor therapy
Sildenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sildenafil. Risk C: Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy
Simeprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir. Risk X: Avoid combination
Simvastatin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Simvastatin. Risk C: Monitor therapy
Siponimod: Enzalutamide may decrease the serum concentration of Siponimod. Risk X: Avoid combination
Sirolimus (Conventional): CYP3A4 Inducers (Strong) may decrease the serum concentration of Sirolimus (Conventional). Management: Avoid concomitant use of strong CYP3A4 inducers and sirolimus if possible. If combined, monitor for reduced serum sirolimus concentrations. Sirolimus dose increases will likely be necessary to prevent subtherapeutic sirolimus levels. Risk D: Consider therapy modification
Sirolimus (Protein Bound): CYP3A4 Inducers (Strong) may decrease the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Solifenacin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Solifenacin. Risk C: Monitor therapy
Sonidegib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sonidegib. Risk X: Avoid combination
SORAfenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SORAfenib. Risk X: Avoid combination
Sotorasib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sotorasib. Risk X: Avoid combination
Sparsentan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sparsentan. Risk X: Avoid combination
Stiripentol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Stiripentol. Management: Avoid concomitant use of stiripentol and strong CYP3A4 inducers when possible. If combined, monitor for reduced stiripentol efficacy and increase the stiripentol dose as needed. Risk D: Consider therapy modification
SUFentanil: CYP3A4 Inducers (Strong) may decrease the serum concentration of SUFentanil. Management: If a strong CYP3A4 inducer is initiated in a patient on sufentanil, consider a sufentanil dose increase and monitor for decreased sufentanil effects and opioid withdrawal symptoms. Risk D: Consider therapy modification
Sulfonylureas: CYP2C9 Inducers (Moderate) may decrease the serum concentration of Sulfonylureas. Risk C: Monitor therapy
SUNItinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SUNItinib. Management: Avoid when possible. If combined, increase sunitinib dose to a max of 87.5 mg daily when treating GIST or RCC. Increase sunitinib dose to a max of 62.5 mg daily when treating PNET. Monitor patients for both reduced efficacy and increased toxicities. Risk D: Consider therapy modification
Suvorexant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Suvorexant. Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Tacrolimus (Systemic). Management: Monitor for decreased tacrolimus concentrations and effects when combined with strong CYP3A4 inducers. Tacrolimus dose increases will likely be needed during concomitant use. Risk D: Consider therapy modification
Tadalafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil. Management: Erectile dysfunction or benign prostatic hypertrophy: monitor for decreased effectiveness - no standard dose adjustment is recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Risk D: Consider therapy modification
Tamoxifen: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. CYP3A4 Inducers (Strong) may decrease the serum concentration of Tamoxifen. Risk X: Avoid combination
Tasimelteon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tasimelteon. Risk X: Avoid combination
Tazemetostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tazemetostat. Risk X: Avoid combination
Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy
Temsirolimus: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be decreased. CYP3A4 Inducers (Strong) may decrease the serum concentration of Temsirolimus. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inducers. If coadministration is unavoidable, increase temsirolimus dose to 50 mg per week. Resume previous temsirolimus dose after discontinuation of the strong CYP3A4 inducer. Risk D: Consider therapy modification
Teniposide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Tetrahydrocannabinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol. Management: Avoid use of the tetrahydrocannabinol/cannabidiol oromucosal spray and strong CYP3A4 inducers when possible. If combined use is necessary, careful titration is recommended, notably within the two weeks following discontinuation of the inducer. Risk D: Consider therapy modification
Tezacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tezacaftor and Ivacaftor. Risk X: 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. Risk D: Consider therapy modification
TiaGABine: CYP3A4 Inducers (Strong) may decrease the serum concentration of TiaGABine. Risk C: Monitor therapy
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. Risk X: Avoid combination
Tipranavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tipranavir. Risk C: Monitor therapy
Tivozanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tivozanib. Risk X: Avoid combination
Tofacitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tofacitinib. Risk X: Avoid combination
Tolvaptan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Risk X: Avoid combination
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Toremifene: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Toremifene. CYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene. Risk X: Avoid combination
Torsemide: CYP2C9 Inducers (Moderate) may decrease the serum concentration of Torsemide. Risk C: Monitor therapy
Trabectedin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Trabectedin. Risk X: Avoid combination
TraMADol: CYP3A4 Inducers (Strong) may decrease the serum concentration of TraMADol. Risk C: Monitor therapy
TraZODone: CYP3A4 Inducers (Strong) may decrease the serum concentration of TraZODone. Management: Consider increasing the trazodone dose during coadministration with strong CYP3A4 inducers. Risk D: Consider therapy modification
Triamcinolone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Triamcinolone (Systemic). Risk C: Monitor therapy
Triazolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Triazolam. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced triazolam efficacy. Substantial triazolam dose increases will likely be required. Risk D: Consider therapy modification
Tropisetron: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tropisetron. Risk C: Monitor therapy
Tucatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tucatinib. Risk X: Avoid combination
Ubrogepant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ubrogepant. Risk X: Avoid combination
Udenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Udenafil. Risk C: Monitor therapy
Ulipristal: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal. Risk X: Avoid combination
Upadacitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Upadacitinib. Risk X: Avoid combination
Valbenazine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inducers (Strong) may decrease the serum concentration of Valbenazine. Risk X: Avoid combination
Vandetanib: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Vandetanib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib. Risk X: Avoid combination
Velpatasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Velpatasvir. Risk X: Avoid combination
Vemurafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib. Management: Avoid coadministration of vemurafenib and strong CYP3A4 inducers if possible. If coadministration is unavoidable, increase the vemurafenib dose by 240 mg as tolerated. Resume prior vemurafenib dose 2 weeks after discontinuation of strong CYP3A4 inducer. Risk D: Consider therapy modification
Venetoclax: CYP3A4 Inducers (Strong) may decrease the serum concentration of Venetoclax. Risk X: Avoid combination
Verapamil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Verapamil. Management: Consider alternatives to this combination. If combined, monitor for reduced verapamil efficacy. Verapamil dose increases may be necessary. Risk D: Consider therapy modification
Vilazodone: CYP3A4 Inducers (Strong) may decrease 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 to 2 weeks after inducer discontinuation. Risk D: Consider therapy modification
VinCRIStine: CYP3A4 Inducers (Strong) may decrease the serum concentration of VinCRIStine. Risk C: Monitor therapy
VinCRIStine (Liposomal): CYP3A4 Inducers (Strong) may decrease the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Vinflunine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vinflunine. Risk X: Avoid combination
Vinorelbine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vinorelbine. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): CYP2C9 Inducers (Moderate) may decrease the serum concentration of Vitamin K Antagonists. Management: Monitor for decreased effects of vitamin K antagonists (eg, decreased INR, thrombosis) if combined with moderate CYP2C9 inducers. Vitamin K antagonist dose adjustments will likely be required. Risk D: Consider therapy modification
Voclosporin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Voclosporin. Risk X: Avoid combination
Vonoprazan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vonoprazan. Risk X: Avoid combination
Vorapaxar: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vorapaxar. Risk X: Avoid combination
Voriconazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Voriconazole. Management: Consider alternatives to this combination when possible. If combined, monitor for decreased voriconazole concentrations and effects. Risk D: Consider therapy modification
Vortioxetine: CYP3A4 Inducers (Strong) may decrease 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. Risk D: 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 unavoidable, increase the voxelotor dose to 2,500 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider therapy modification
Voxilaprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Voxilaprevir. Risk X: Avoid combination
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 zaleplon is combined with a strong CYP3A4 inducer, monitor for decreased effectiveness of zaleplon. Risk D: Consider therapy modification
Zanubrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zanubrutinib. Risk X: Avoid combination
Ziprasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ziprasidone. Risk C: Monitor therapy
Zolpidem: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zolpidem. Risk C: Monitor therapy
Zonisamide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zonisamide. Risk C: Monitor therapy
Zopiclone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zopiclone. Risk C: Monitor therapy
Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol. Risk C: Monitor therapy
Zuranolone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuranolone. Risk X: Avoid combination
Patients with partners who could become pregnant should use effective contraception during treatment and for 3 months after the last enzalutamide dose.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to enzalutamide may cause fetal harm and loss of pregnancy.
It is not known if enzalutamide is present in breast milk.
PSA levels (when indicated). CBC with differential and liver function tests (baseline and periodic); additional INR monitoring (if on warfarin); blood pressure (baseline and periodic). Monitor for signs/symptoms of ischemic heart disease, posterior reversible encephalopathy syndrome, and seizure; evaluate fall and fracture risk. Monitor adherence.
Cardiovascular monitoring for patients with prostate cancer: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; baseline and serial ECGs are recommended in patients at risk of QTc prolongation during androgen deprivation therapy (ADT); estimate 10-year cardiovascular disease risk in patients without cardiovascular disease at baseline; assess cardiovascular risk annually during ADT (ASCO [Armenian 2017]; ESC [Lyon 2022]).
Enzalutamide is a pure androgen receptor signaling inhibitor; unlike other antiandrogen therapies, it has no known agonistic properties. It inhibits androgen receptor nuclear translocation, DNA binding, and coactivator mobilization, leading to cellular apoptosis and decreased prostate tumor volume.
Note: The steady-state AUC and Cmax of enzalutamide and N-desmethyl enzalutamide are similar for tablet and capsule formulations.
Distribution: 110 L.
Protein binding: Parent drug: 97% to 98% to primarily albumin; active metabolite: 95% to plasma proteins.
Metabolism: Primarily hepatic via CYP2C8 (responsible for formation of active metabolite N-desmethyl enzalutamide) and CYP3A4; carboxylesterase 1 metabolizes N-desmethyl enzalutamide and enzalutamide to the inactive carboxylic acid metabolite.
Half-life elimination: Parent drug: 5.8 days (range: 2.8 to 10.2 days); N-desmethyl enzalutamide: 7.8 to 8.6 days.
Time to peak: Capsule: 1 hour (range: 0.5 to 3 hours); Tablet: 2 hours (range 0.5 to 6 hours).
Excretion: Hepatic metabolism.
Clearance: 0.56 L/hour (range: 0.33 to 1.02 L/hour).
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