Cenobamate: Drug information

Dosing: Adult

Note: Adhere strictly to recommended initial dose, titration schedules, and adjustments to reduce the risk of severe, including fatal, hypersensitivity reactions.

Focal onset seizures

Focal (partial) onset seizures: Oral: Initial: weeks 1 and 2: 12.5 mg once daily; increase based on response and tolerability as follows: weeks 3 and 4: 25 mg once daily; weeks 5 and 6: 50 mg once daily; weeks 7 and 8: 100 mg once daily; weeks 9 and 10: 150 mg once daily; week 11 and thereafter: 200 mg once daily. If needed, based on response and tolerability, may increase dose further in increments of 50 mg every 2 weeks to a maximum of 400 mg daily.

Discontinuation of therapy: Manufacturer labeling recommends gradual withdrawal over at least 2 weeks. In patients on chronic therapy, consider withdrawing gradually over 2 to 6 months to minimize the potential of increased seizure frequency or other withdrawal symptoms, unless safety concerns require a more rapid withdrawal (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥90 mL/minute: No dosage adjustment necessary.

CrCl <90 mL/minute: Use with caution and consider dose reduction.

End-stage renal disease on dialysis: Use is not recommended (has not been studied).

Dosing: Liver Impairment: Adult

Mild to moderate impairment (Child-Turcotte-Pugh class A and B): Use with caution and consider dose reduction. Maximum dose: 200 mg daily.

Severe impairment (Child-Turcotte-Pugh class C): Use is not recommended.

Dosing: Older Adult

Refer to adult dosing; use with caution.

Adverse Reactions (Significant): Considerations

CNS effects

CNS-related adverse reactions secondary to cenobamate include cognitive dysfunction (eg, memory impairment, confusion, aphasia, psychomotor impairment), drowsiness, fatigue, dizziness and coordination abnormalities (eg, vertigo, balance impairment, ataxia), and visual changes (eg, nystagmus, diplopia, blurred vision). Most cases in clinical trials were mild to moderate; however, some patients required discontinuation of therapy. CNS effects tend to improve with continued use (Ref). In addition, aggressive behavior, hostility, and psychosis (delusion, hallucination, paranoid ideation) have been reported.

Mechanism: Dose-related; related to pharmacologic action (ie, inhibits voltage-gated sodium channels, reducing repetitive neuronal firing; acts as a positive allosteric modulator of GABA_A ion channels).

Onset: Varied; timing may be impacted by higher doses, rapid titration, or drug accumulation.

Risk factors:

• Higher doses

• Rapid titration (Lattanzi 2020)

• Conditions which may lead to drug accumulation (eg, older adults, patients with hepatic or kidney impairment)

• Concurrent use of other CNS depressants

Hypersensitivity reactions (delayed)

Cenobamate has been associated with development of cutaneous reactions including maculopapular rash (with or without fever) (Ref) as well as cases of drug reaction with eosinophilia and systemic symptoms (DRESS). This multiorgan hypersensitivity reaction can be potentially serious and fatal (Ref).

Mechanism: Non–dose-related; exact mechanism not established for cenobamate. In general, delayed hypersensitivity reactions are T-cell mediated (Ref).

Onset: Varied; DRESS has occurred with drug initiation and titration (Ref) as well as 3 weeks into therapy (day 24 of treatment) (Ref). Cutaneous eruptions have occurred 10 to 57 days after treatment initiation (Ref).

Risk factors:

• Rapid titration rate: Cases of DRESS have been associated with starting doses of >50 mg/day and titration rates using intervals of ≤1 week. Although it has not been established that lowering the initial dose and slowing the titration rate to 2-week intervals prevent DRESS, an open-label trial using the new titration schedule did not report any cases of DRESS in 1,339 patients with a median treatment duration of 9 months (Ref).

QT interval shortening

Cenobamate use has been associated with ECG abnormality, specifically shortening of the QT interval, and less frequently palpitations. In clinical trials, the mean change in the QTc interval at recommended dosages was -11 msec (range: -13 to -8 msec); reductions of the QTc interval below 300 msec were not observed.

Mechanism: Dose-related; thought to be due to inhibition of cardiac sodium channels (Ref).

Risk factors:

• Higher doses; a higher incidence and greater degree of QT interval shortening was seen at doses 1.25 times the maximum recommended dosage (500 mg/day) as compared to recommended dosages (200 mg/day)

• Familial short QT syndrome

• Concurrent use of other therapies known to shorten the QT interval

Suicidal ideation and tendencies

Antiseizure medications (ASMs), when used across multiple indications, have been associated with suicidal ideation and suicidal tendencies. However, the FDA meta-analysis has been criticized due to several important limitations (Ref). The risk of suicide is increased in epilepsy (Ref), but the occurrence of suicidal ideation/tendencies in epilepsy is multifactorial. While some ASMs (but not all) have been associated with treatment-emergent psychiatric effects such as anxiety and depression, other factors such as postictal suicidal behavior and pertinent patient history must also be evaluated to provide an accurate assessment of risk for any individual drug (Ref). Suicide attempts have been reported with cenobamate; however, confounding variables (eg, other concomitant ASMs, history of mood disorder or prior suicide attempt) were also present (Ref).

Mechanism: Non–dose-related. Exact mechanism not established; one theory is ASMs lower the threshold for manifesting psychiatric symptoms in patients susceptible to psychiatric disorders or antiseizure-induced disinhibition and impulsiveness, thereby influencing and promoting suicidal acts (Ref).

Onset: Varied; peak incidence of suicidality across ASMs (not specific to individual agents) has been noted to occur between 1 and 12 weeks of therapy (Ref). A review of clinical trials noted that risk extended from 1 week to 24 weeks of therapy, corresponding to the duration of most trials.

Risk factors:

• Preexisting risk factors for suicidal thoughts and behaviors (including epilepsy)

• History of psychiatric disorders or aggressive behaviors

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults administered cenobamate as adjunctive therapy with concomitant antiepileptic agents.

>10%:

Cardiovascular: ECG abnormality (QT shortening >20 msec: 31%) (table 1)

**Cenobamate: Adverse Reaction: ECG Abnormality**
Drug (Cenobamate)	Placebo	Dose	Population	Number of Patients (Cenobamate)	Number of Patients (Placebo)	Comments
31%	6% to 17%	200 mg	Healthy volunteers	N/A	N/A	QT shortening >20 msec

Endocrine & metabolic: Increased serum potassium (8% to 17%)

Nervous system: Dizziness (8% to 33%) (table 2)Cenobamate: Adverse Reaction: Dizziness, drowsiness (19% to 37%) (table 3), fatigue (12% to 24%) (table 4)Cenobamate: Adverse Reaction: Fatigue, headache (10% to 12%), hypersomnia, lethargy, malaise

**Cenobamate: Adverse Reaction: Dizziness**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
33%	15%	400 mg/day	111	216
22%	15%	200 mg/day	223	216
18%	15%	100 mg/day	108	216

**Cenobamate: Adverse Reaction: Drowsiness**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
37%	11%	400 mg/day	111	216
22%	11%	200 mg/day	223	216
19%	11%	100 mg/day	108	216

**Cenobamate: Adverse Reaction: Fatigue**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
24%	7%	400 mg/day	111	216
14%	7%	200 mg/day	223	216
12%	7%	100 mg/day	108	216

Ophthalmic: Diplopia (6% to 15%) (table 5)Cenobamate: Adverse Reaction: Diplopia

**Cenobamate: Adverse Reaction: Diplopia**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
15%	2%	400 mg/day	111	216
7%	2%	200 mg/day	223	216
6%	2%	100 mg/day	108	216

1% to 10%:

Cardiovascular: Palpitations (2%) (table 6)

**Cenobamate: Adverse Reaction: Palpitations**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
2%	0%	400 mg/day	111	216

Dermatologic: Pruritus (1% to 2%), pustular rash (2%)

Endocrine & metabolic: Weight loss (1% to 2%)

Gastrointestinal: Abdominal pain (1% to 2%), constipation (2% to 8%), decreased appetite (3% to 5%), diarrhea (1% to 5%), dysgeusia (2%), dyspepsia (2%), hiccups (1%), nausea (6% to 9%), vomiting (2% to 5%), xerostomia (1% to 3%)

Genitourinary: Dysmenorrhea (1% to 2%), pollakiuria (1%), urinary tract infection (5%)

Hepatic: Increased serum alanine aminotransferase (1% to 4%), increased serum aspartate aminotransferase (1% to 3%)

Nervous system: Abnormal gait (3% to 8%), amnesia, aphasia (1% to 4%) (table 7)Cenobamate: Adverse Reaction: Aphasia, asthenia (3%), ataxia (2% to 6%) (table 8)Cenobamate: Adverse Reaction: Ataxia, balance impairment (3% to 9%) (table 9), bradyphrenia, confusion (2% to 3%) (table 10)Cenobamate: Adverse Reaction: Confusion, disorientation, disturbance in attention, dysarthria (1% to 7%), euphoria (2%), irritability (1% to 2%), memory impairment (1% to 2%) (table 11), migraine (2%), psychomotor impairment, sedated state (1% to 2%), suicidal ideation (1% to 2%) (table 12), tremor (3%), vertigo (6%) (table 13)Cenobamate: Adverse Reaction: Vertigo, voice disorder

**Cenobamate: Adverse Reaction: Aphasia**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
4%	0%	400 mg/day	111	216
2%	0%	100 mg/day	108	216
1%	0%	200 mg/day	223	216

**Cenobamate: Adverse Reaction: Ataxia**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
6%	2%	400 mg/day	111	216
3%	2%	200 mg/day	223	216
2%	2%	100 mg/day	108	216

**Cenobamate: Adverse Reaction: Balance Impairment**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
9%	1%	400 mg/day	111	216
5%	1%	200 mg/day	223	216
3%	1%	100 mg/day	108	216

**Cenobamate: Adverse Reaction: Confusion**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
3%	0%	400 mg/day	111	216
2%	0%	200 mg/day	223	216
2%	0%	100 mg/day	108	216

**Cenobamate: Adverse Reaction: Memory Impairment**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
2%	0%	400 mg/day	111	216
2%	0%	100 mg/day	108	216
1%	0%	200 mg/day	223	216

**Cenobamate: Adverse Reaction: Suicidal Ideation**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
2%	0%	100 mg/day	108	216
1%	0%	200 mg/day	223	216

**Cenobamate: Adverse Reaction: Vertigo**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
6%	1%	400 mg/day	111	216
1%	1%	200 mg/day	223	216
1%	1%	100 mg/day	108	216

Neuromuscular & skeletal: Back pain (4% to 5%), musculoskeletal chest pain (1% to 2%)

Ophthalmic: Blurred vision (2% to 4%) (table 14), nystagmus disorder (3% to 7%) (table 15)

**Cenobamate: Adverse Reaction: Blurred Vision**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
4%	0%	400 mg/day	111	216
2%	0%	200 mg/day	223	216
2%	0%	100 mg/day	108	216

**Cenobamate: Adverse Reaction: Nystagmus Disorder**
Drug (Cenobamate)	Placebo	Dose	Number of Patients (Cenobamate)	Number of Patients (Placebo)
7%	0%	200 mg/day	223	216
6%	0%	400 mg/day	111	216
3%	0%	100 mg/day	108	216

Respiratory: Dyspnea (3%), nasopharyngitis (4% to 5%), pharyngitis (1% to 2%)

Miscellaneous: Accidental injury (head injury: 1% to 2%)

<1%:

Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms

Nervous system: Suicidal tendencies

Postmarketing:

Dermatologic: Maculopapular rash (Krauss 2020; Sperling 2020)

Gastrointestinal: Appendicitis (Sperling 2020)

Hepatic: Hepatic failure

Nervous system: Aggressive behavior, hostility, psychosis (including delusion, hallucination, paranoid ideation)

Contraindications

Hypersensitivity to cenobamate or any component of the formulation; familial Short QT syndrome

Warnings/Precautions

Disease-related concerns:

• Hepatic impairment: Use is not recommended in patients with severe hepatic impairment; use with caution and consider dose reduction in mild to moderate hepatic impairment.

• Renal impairment: Use is not recommended in patients with end-stage renal disease undergoing dialysis; use with caution and consider dose reduction in patients with mild to severe renal impairment.

Other warnings/precautions:

• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Xcopri: 25 mg [contains fd&c blue #2 (indigo carm) aluminum lake]

Xcopri: 50 mg

Xcopri: 100 mg [contains fd&c blue #2 (indigo carm) aluminum lake]

Xcopri: 150 mg, 200 mg

Tablet Therapy Pack, Oral:

Xcopri: 14 x 150 MG & 14 x200 MG (28 ea)

Xcopri: 14 x 50 MG & 14 x100 MG (28 ea); 14 x 12.5 MG & 14 x 25 MG (28 ea) [contains fd&c blue #2 (indigo carm) aluminum lake]

Xcopri (250 MG Daily Dose): 50 & 200 MG (56 ea [DSC])

Xcopri (250 MG Daily Dose): 100 & 150 MG (56 ea) [contains fd&c blue #2 (indigo carm) aluminum lake]

Xcopri (350 MG Daily Dose): 150 & 200 MG (56 ea)

Generic Equivalent Available: US

No

Pricing: US

Tablet Therapy Pack (Xcopri (250 MG Daily Dose) Oral)

100 & 150 mg (per each): $26.04

Tablet Therapy Pack (Xcopri (350 MG Daily Dose) Oral)

150 & 200 mg (per each): $52.09

Tablet Therapy Pack (Xcopri Oral)

14 x 12.5 MG &14 x 25 MG (per each): $4.76

14 x 50 MG &14 x100 MG (per each): $52.09

14 x 150 MG &14 x200 MG (per each): $52.09

Tablets (Xcopri Oral)

25 mg (per each): $48.62

50 mg (per each): $48.62

100 mg (per each): $48.62

150 mg (per each): $48.62

200 mg (per each): $48.62

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Xcopri: 12.5 mg

Xcopri: 25 mg [contains fd&c blue #2 (indigo carm) aluminum lake]

Xcopri: 50 mg

Xcopri: 100 mg [contains fd&c blue #2 (indigo carm) aluminum lake]

Xcopri: 150 mg, 200 mg

Controlled Substance

C-V

Administration: Adult

Administer with or without food. Tablets may be swallowed whole or crushed and mixed to create a suspension that may be administered orally or via an NG tube.

NG tube: Crush the appropriate number of tablets for the dose and combine with 25 mL of water; swirl mixture to suspend and administer the suspension with a syringe into the NG tube (ensure no particles are left in the container). After administration, refill the catheter-tip syringe again with 10 mL of water, swirl gently, and administer; if any particles still remain, refill the catheter-tip syringe again with 10 mL of water, swirl gently, and administer.

Oral: When administering as a suspension, crush the appropriate number of tablets for the dose and combine with 25 mL of water; swirl mixture to suspend and administer immediately (do not save for later use). After administration, rinse the container with an additional 25 mL of water and drink; if any particles still remain, rinse container again with 25 mL of water and drink.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Xcopri: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212839s006s007lbl.pdf

Use: Labeled Indications

Focal (partial) onset seizures: Treatment of focal (partial) onset seizures in adult patients.

Metabolism/Transport Effects

Substrate of CYP2A6 (Minor), CYP2B6 (Minor), CYP2C19 (Minor), CYP2E1 (Minor), CYP3A4 (Minor), UGT2B4, UGT2B7; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C19 (Moderate); Induces CYP2B6 (Weak), CYP3A4 (Moderate);

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Abemaciclib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Abemaciclib. Risk X: Avoid

Abiraterone Acetate: CYP3A4 Inducers (Moderate) may decrease serum concentration of Abiraterone Acetate. Risk C: Monitor

Abrocitinib: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Abrocitinib. Risk C: Monitor

Acalabrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Acalabrutinib. Risk C: Monitor

Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor

ALfentanil: CYP3A4 Inducers (Moderate) may decrease serum concentration of ALfentanil. Management: If concomitant use of alfentanil and moderate 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

Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Alpelisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Alpelisib. Risk C: Monitor

ALPRAZolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of ALPRAZolam. Risk C: Monitor

Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

AmLODIPine: CYP3A4 Inducers (Moderate) may decrease serum concentration of AmLODIPine. Risk C: Monitor

Antihepaciviral Combination Products: CYP3A4 Inducers (Moderate) may decrease serum concentration of Antihepaciviral Combination Products. Risk X: Avoid

Apremilast: CYP3A4 Inducers (Moderate) may decrease serum concentration of Apremilast. Risk C: Monitor

Aprepitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Aprepitant. Risk C: Monitor

ARIPiprazole Lauroxil: CYP3A4 Inducers (Moderate) may decrease serum concentration of ARIPiprazole Lauroxil. Risk C: Monitor

ARIPiprazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of ARIPiprazole. Risk C: Monitor

Artemether and Lumefantrine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Artemether and Lumefantrine. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. Risk C: Monitor

Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification

Atazanavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atazanavir. Risk C: Monitor

Atogepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider Therapy Modification

Atorvastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atorvastatin. Risk C: Monitor

Atrasentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Atrasentan. Risk X: Avoid

Avacopan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avacopan. Risk X: Avoid

Avanafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avanafil. Risk X: Avoid

Avapritinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Avapritinib. Risk X: Avoid

Axitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Axitinib. Management: Concurrent use of axitinib with a moderate CYP3A4 inducer should be avoided when possible. If any such combination is necessary, monitor for reduced axitinib efficacy. Risk D: Consider Therapy Modification

Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Bedaquiline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Bedaquiline. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Bedaquiline. Risk X: Avoid

Belumosudil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Belumosudil. Risk C: Monitor

Belzutifan: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Belzutifan. Risk C: Monitor

Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification

Bortezomib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Bortezomib. Risk C: Monitor

Bosutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Bosutinib. Risk C: Monitor

Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor

Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of Brexpiprazole. Risk C: Monitor

Brigatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inducers when possible. If combined, increase the daily dose of brigatinib in 30 mg increments after 7 days of treatment with the current brigatinib dose, up to maximum of twice the dose. Risk D: Consider Therapy Modification

Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Brivaracetam: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Brivaracetam. Risk C: Monitor

Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification

BuPROPion: CYP2B6 Inducers (Weak) may decrease serum concentration of BuPROPion. Risk C: Monitor

BusPIRone: CYP3A4 Inducers (Moderate) may decrease serum concentration of BusPIRone. Risk C: Monitor

BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Cabozantinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cabozantinib. Management: For cabozantinib tablets (Cabometyx), avoid combined use if possible. If combined, increase cabozantinib by 20 mg from previous dose, max 80 mg daily. For cabozantinib capsules (Cometriq), monitor for reduced cabozantinib efficacy if combined. Risk D: Consider Therapy Modification

Calcifediol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Calcifediol. Risk C: Monitor

Calcitriol (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Calcitriol (Systemic). Risk C: Monitor

Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor

Cannabis: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor

Capivasertib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Capivasertib. Risk X: Avoid

Capmatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Capmatinib. Risk X: Avoid

CarBAMazepine: Cenobamate may decrease serum concentration of CarBAMazepine. Risk C: Monitor

Cariprazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cariprazine. Risk X: Avoid

Carisoprodol: CYP2C19 Inhibitors (Moderate) may decrease active metabolite exposure of Carisoprodol. CYP2C19 Inhibitors (Moderate) may increase serum concentration of Carisoprodol. Risk C: Monitor

Ceritinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ceritinib. Risk C: Monitor

Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification

Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification

Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification

Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Cilostazol: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Cilostazol. CYP2C19 Inhibitors (Moderate) may increase active metabolite exposure of Cilostazol. Management: Reduce the cilostazol dose to 50 mg twice daily in patients who are also receiving moderate inhibitors of CYP2C19. Monitor clinical response to cilostazol closely. Risk D: Consider Therapy Modification

Citalopram: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a moderate CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (eg, serotonin syndrome, QT prolongation). Risk D: Consider Therapy Modification

Clarithromycin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Clarithromycin. CYP3A4 Inducers (Moderate) may increase active metabolite exposure 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 impair its efficacy. Risk D: Consider Therapy Modification

Clindamycin (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Clindamycin (Systemic). Risk C: Monitor

CloBAZam: Cenobamate may increase active metabolite exposure of CloBAZam. Cenobamate may increase serum concentration of CloBAZam. Risk C: Monitor

Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease active metabolite exposure of Clopidogrel. Risk C: Monitor

CloZAPine: CYP3A4 Inducers (Moderate) may decrease serum concentration of CloZAPine. Risk C: Monitor

CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Cobicistat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cobicistat. Risk C: Monitor

Cobimetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cobimetinib. Risk X: Avoid

Copanlisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Copanlisib. Risk C: Monitor

Crinecerfont: CYP3A4 Inducers (Moderate) may decrease serum concentration of Crinecerfont. Management: Double the evening dose of crinecerfont and continue the morning dose unchanged during coadministration with moderate CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider Therapy Modification

Crizotinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Crizotinib. Risk C: Monitor

CycloSPORINE (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of CycloSPORINE (Systemic). Risk C: Monitor

Daclatasvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily if used with a moderate CYP3A4 inducer. Risk D: Consider Therapy Modification

Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dapsone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Dapsone (Systemic). Risk C: Monitor

Daridorexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Daridorexant. Risk X: Avoid

Dasabuvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dasabuvir. Risk X: Avoid

Dasatinib: CYP3A4 Inducers (Moderate) may increase serum concentration of Dasatinib. Risk C: Monitor

Deflazacort: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Deflazacort. Risk X: Avoid

Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor

DexAMETHasone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of DexAMETHasone (Systemic). Risk C: Monitor

Dexlansoprazole: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Dexlansoprazole. Risk C: Monitor

DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification

DiazePAM: CYP2C19 Inhibitors (Moderate) may increase serum concentration of DiazePAM. Risk C: Monitor

DiazePAM: CYP3A4 Inducers (Moderate) may decrease serum concentration of DiazePAM. Risk C: Monitor

Dienogest: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dienogest. Risk C: Monitor

Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor

DilTIAZem: CYP3A4 Inducers (Moderate) may decrease serum concentration of DilTIAZem. Risk C: Monitor

Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Disopyramide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Disopyramide. Risk C: Monitor

Doravirine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Doravirine. Risk C: Monitor

Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

DOXOrubicin (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of DOXOrubicin (Conventional). Risk X: Avoid

Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor

DroNABinol: CYP3A4 Inducers (Moderate) may decrease serum concentration of DroNABinol. Risk C: Monitor

Dronedarone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dronedarone. Risk C: Monitor

DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification

Duvelisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Duvelisib. Management: Avoid if possible. If used, on day 12 of combination increase duvelisib from 25 mg twice daily to 40 mg twice daily or from 15 mg twice daily to 25 mg twice daily. Resume prior duvelisib dose 14 days after stopping moderate CYP3A4 inducer. Risk D: Consider Therapy Modification

Dydrogesterone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Dydrogesterone. Risk C: Monitor

Efavirenz: CYP3A4 Inducers (Moderate) may decrease serum concentration of Efavirenz. Risk C: Monitor

Elacestrant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Elacestrant. Risk X: Avoid

Elbasvir and Grazoprevir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk C: Monitor

Eliglustat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Eliglustat. Risk C: Monitor

Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor

Encorafenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Encorafenib. Risk C: Monitor

Ensartinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ensartinib. Risk X: Avoid

Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Entrectinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Entrectinib. Risk X: Avoid

Enzalutamide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Enzalutamide. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Enzalutamide. Risk C: Monitor

Erdafitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Erdafitinib. Management: If a moderate CYP3A4 inducer must be used at the start of erdafitinib, administer erdafitinib at a dose of 9 mg daily. If a moderate CYP3A4 inducer is discontinued, continue erdafitinib at the same dose unless there is evidence of drug toxicity. Risk D: Consider Therapy Modification

Erlotinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Erlotinib. Management: Avoid the combination of erlotinib and strong CYP3A4 inducers whenever possible. If this combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Risk D: Consider Therapy Modification

Escitalopram: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Escitalopram. Risk C: Monitor

Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Estrogen Derivatives: CYP3A4 Inducers (Moderate) may decrease serum concentration of Estrogen Derivatives. Risk C: Monitor

Etoposide Phosphate: CYP3A4 Inducers (Moderate) may decrease serum concentration of Etoposide Phosphate. Risk C: Monitor

Etoposide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Etoposide. Risk C: Monitor

Etravirine: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Etravirine. Risk C: Monitor

Etravirine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Etravirine. Risk C: Monitor

Everolimus: CYP3A4 Inducers (Moderate) may decrease serum concentration of Everolimus. Risk C: Monitor

Exemestane: CYP3A4 Inducers (Moderate) may decrease serum concentration of Exemestane. Risk C: Monitor

Fedratinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fedratinib. Risk X: Avoid

Felodipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Felodipine. Risk C: Monitor

Fexinidazole: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Fexinidazole. Risk X: Avoid

Finerenone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Finerenone. Risk X: Avoid

Flibanserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Flibanserin. Risk X: Avoid

Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid

Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification

Fosamprenavir: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Fosamprenavir. Risk C: Monitor

Fosaprepitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Risk C: Monitor

Fosnetupitant: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Fosnetupitant. Risk C: Monitor

Fosphenytoin-Phenytoin: May decrease serum concentration of Cenobamate. Cenobamate may increase serum concentration of Fosphenytoin-Phenytoin. Management: Gradually reduce the dose of fosphenytoin/phenytoin by up to 50% as the dose of cenobamate is being titrated up. Monitor phenytoin levels closely; higher doses of cenobamate may be required. Risk D: Consider Therapy Modification

Fostamatinib: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Fostamatinib. Risk C: Monitor

Fruquintinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Fruquintinib. Management: Avoid this combination when possible. If combined, continue the same fruquintinib dose, but monitor for reduced fruquintinib efficacy. Risk D: Consider Therapy Modification

Ganaxolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and moderate 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 (Moderate) may decrease serum concentration of Gefitinib. Risk C: Monitor

Gemigliptin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gemigliptin. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Gemigliptin. Risk C: Monitor

Gepirone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gepirone. Risk C: Monitor

Gepotidacin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Gepotidacin. Risk C: Monitor

Glasdegib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Glasdegib. Management: Avoid use of glasdegib and moderate CYP3A4 inducers whenever possible. If combined, increase glasdegib dose from 100 mg daily to 200 mg daily or from 50 mg daily to 100 mg daily. Resume previous glasdegib dose 7 days after discontinuation of the inducer. Risk D: Consider Therapy Modification

Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor

GuanFACINE: CYP3A4 Inducers (Moderate) may decrease serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Risk D: Consider Therapy Modification

Hormonal Contraceptives: CYP3A4 Inducers (Moderate) may decrease serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a moderate CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider Therapy Modification

Hydrocortisone (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Hydrocortisone (Systemic). Risk C: Monitor

HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification

Ibrexafungerp: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ibrexafungerp. Risk X: Avoid

Ibrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ibrutinib. Risk C: Monitor

Idelalisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Idelalisib. Risk C: Monitor

Ifosfamide: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Ifosfamide. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Ifosfamide. Risk C: Monitor

Imatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Imatinib. Risk C: Monitor

Indinavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Indinavir. Management: Consider avoiding the combination of indinavir and moderate CYP3A4 inducers whenever possible due to the risk for decreased indinavir concentrations, reduced efficacy, and development of resistance. If combined, monitor for indinavir treatment failure. Risk D: Consider Therapy Modification

Irinotecan Products: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. Risk C: Monitor

Isavuconazonium Sulfate: CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Moderate) may decrease isavuconazole serum concentrations. Risk C: Monitor

Isradipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Isradipine. Risk C: Monitor

Istradefylline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Istradefylline. Risk C: Monitor

Itraconazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of Itraconazole. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Itraconazole. Risk C: Monitor

Ivabradine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ivabradine. Risk X: Avoid

Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ivacaftor. Risk C: Monitor

Ixabepilone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ixabepilone. Risk C: Monitor

Ixazomib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ixazomib. Risk C: Monitor

Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ketamine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ketamine. Risk C: Monitor

Ketoconazole (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Ketoconazole (Systemic). Risk C: Monitor

Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Lacosamide: Cenobamate may increase adverse/toxic effects of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor

LamoTRIgine: Cenobamate may increase arrhythmogenic effects of LamoTRIgine. Cenobamate may decrease serum concentration of LamoTRIgine. Management: Consider the risk of serious arrhythmias or death versus any expected benefit of lamotrigine in patients receiving concomitant sodium channel blockers. If combined, monitor for reduced lamotrigine efficacy and increase lamotrigine dose if needed. Risk D: Consider Therapy Modification

Lansoprazole: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Lansoprazole. Risk C: Monitor

Lapatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lapatinib. Risk C: Monitor

Larotrectinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Larotrectinib. Management: Double the larotrectinib dose if used together with a moderate CYP3A4 inducer. Following discontinuation of the moderate CYP3A4 inducer, resume the previous dose of larotrectinib after a period of 3 to 5 times the inducer's half-life. Risk D: Consider Therapy Modification

Lazertinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lazertinib. Risk X: Avoid

Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with moderate CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification

Lefamulin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with moderate CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification

Lemborexant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lemborexant. Risk X: Avoid

Lenacapavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lenacapavir. Risk X: Avoid

Leniolisib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Leniolisib. Risk X: Avoid

Lercanidipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lercanidipine. Risk C: Monitor

Levamlodipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Levamlodipine. Risk C: Monitor

Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Levoketoconazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of Levoketoconazole. Risk C: Monitor

LinaGLIPtin: CYP3A4 Inducers (Moderate) may decrease serum concentration of LinaGLIPtin. Risk C: Monitor

Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lonafarnib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lonafarnib. Risk X: Avoid

Lopinavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lopinavir. Risk C: Monitor

Lorlatinib: CYP3A4 Inducers (Moderate) may increase hepatotoxic effects of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with moderate CYP3A4 inducers. If such a combination must be used, increase lorlatinib to 125 mg daily. Monitor for reduced lorlatinib efficacy and consider closer monitoring of AST, ALT, and bilirubin. Risk D: Consider Therapy Modification

Lovastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lovastatin. Risk C: Monitor

Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification

Lumacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lumacaftor and Ivacaftor. Risk C: Monitor

Lumateperone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lumateperone. Risk X: Avoid

Lurasidone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Lurasidone. Management: After chronic treatment (7 days or more) with a moderate CYP3A4 inducer, lurasidone dose increases may be needed. Monitor closely for decreased lurasidone effects and increase the lurasidone dose as needed. Risk D: Consider Therapy Modification

Macitentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Macitentan. Risk C: Monitor

Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Maraviroc: CYP3A4 Inducers (Moderate) may decrease serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice/day, but only if not receiving a strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Contraindicated in patients with CrCl less than 30 mL/min. Risk D: Consider Therapy Modification

Maribavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Maribavir. Risk C: Monitor

Mavacamten: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mavacamten. Risk X: Avoid

Mavorixafor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mavorixafor. Risk C: Monitor

Mefloquine: May decrease therapeutic effects of Antiseizure Agents. Mefloquine may decrease serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider Therapy Modification

Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification

Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

MethylPREDNISolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of MethylPREDNISolone. Risk C: Monitor

Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

MetyraPONE: Coadministration of Antiseizure Agents and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider Therapy Modification

MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor

Mianserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mianserin. Risk C: Monitor

Mianserin: May decrease therapeutic effects of Antiseizure Agents. Risk C: Monitor

Midazolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of Midazolam. Risk C: Monitor

Midostaurin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Midostaurin. Risk C: Monitor

MiFEPRIStone: CYP3A4 Inducers (Moderate) may decrease serum concentration of MiFEPRIStone. Management: Avoid combined use in patients treated for Cushing's disease. When used for pregnancy termination, mifepristone efficacy may be reduced and an alternative pregnancy termination procedure may be warranted. Ensure a follow-up assessment after combined use. Risk D: Consider Therapy Modification

Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Mirodenafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mirodenafil. Risk C: Monitor

Mitapivat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mitapivat. Management: Consider alternatives to this combination when possible. If combined, monitor hemoglobin and titrate mitapivat beyond 50 mg twice daily, if needed, but do not exceed doses of 100 mg twice daily. Risk D: Consider Therapy Modification

Mobocertinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Mobocertinib. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Mobocertinib. Risk X: Avoid

Moclobemide: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Moclobemide. Risk C: Monitor

Montelukast: CYP3A4 Inducers (Moderate) may decrease serum concentration of Montelukast. Risk C: Monitor

Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Naldemedine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Naldemedine. Risk C: Monitor

Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Naloxegol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Naloxegol. Risk C: Monitor

Nelfinavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nelfinavir. Risk C: Monitor

Neratinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Neratinib. Risk X: Avoid

Netupitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Netupitant. Risk C: Monitor

Nevirapine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nevirapine. Risk C: Monitor

NIFEdipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of NIFEdipine. Risk C: Monitor

Nilotinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nilotinib. Risk C: Monitor

Nilvadipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nilvadipine. Risk C: Monitor

NiMODipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of NiMODipine. Risk C: Monitor

Nirmatrelvir and Ritonavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nirmatrelvir and Ritonavir. Risk C: Monitor

Nirogacestat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nirogacestat. Risk X: Avoid

Nisoldipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Nisoldipine. Risk X: Avoid

Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid

Olaparib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olaparib. Risk X: Avoid

Olmutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olmutinib. Risk C: Monitor

Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Olutasidenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Olutasidenib. Risk X: Avoid

Omaveloxolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Omaveloxolone. Risk X: Avoid

Omeprazole: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Omeprazole. Risk C: Monitor

Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification

Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Orlistat: May decrease serum concentration of Antiseizure Agents. Risk C: Monitor

Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid

Osimertinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Osimertinib. Risk C: Monitor

Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification

OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification

PACLitaxel (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of PACLitaxel (Conventional). Risk C: Monitor

PACLitaxel (Protein Bound): CYP3A4 Inducers (Moderate) may decrease serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor

Pacritinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pacritinib. Risk C: Monitor

Palbociclib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Palbociclib. Risk C: Monitor

Paliperidone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Paliperidone. Risk C: Monitor

Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Palovarotene: CYP3A4 Inducers (Moderate) may decrease serum concentration of Palovarotene. Risk X: Avoid

Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid

PAZOPanib: CYP3A4 Inducers (Moderate) may decrease serum concentration of PAZOPanib. Risk C: Monitor

Pemigatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pemigatinib. Risk X: Avoid

Perampanel: CYP3A4 Inducers (Moderate) may decrease serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with moderate 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

Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Phenobarbital-Primidone: Cenobamate may increase CNS depressant effects of Phenobarbital-Primidone. Cenobamate may increase serum concentration of Phenobarbital-Primidone. Risk C: Monitor

PHENobarbital: CYP2C19 Inhibitors (Moderate) may increase serum concentration of PHENobarbital. Risk C: Monitor

Pimavanserin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pimavanserin. Risk X: Avoid

Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Piperaquine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Piperaquine. Risk C: Monitor

Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor

Pirtobrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pirtobrutinib. Management: Avoid concomitant use if possible. If combined, if the current pirtobrutinib dose is 200 mg once daily, increase to 300 mg once daily. If current pirtobrutinib dose is 50 mg or 100 mg once daily, increase the dose by 50 mg. Risk D: Consider Therapy Modification

Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

PONATinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of PONATinib. Risk C: Monitor

Pralsetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pralsetinib. Management: If this combo cannot be avoided, increase pralsetinib dose from 400 mg daily to 600 mg daily; from 300 mg daily to 500 mg daily; and from 200 mg daily to 300 mg daily. Risk D: Consider Therapy Modification

Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor

Praziquantel: CYP3A4 Inducers (Moderate) may decrease serum concentration of Praziquantel. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for reduced praziquantel efficacy. If possible, stop the moderate CYP3A4 inducer 2 to 4 weeks before praziquantel initiation. Risk D: Consider Therapy Modification

PrednisoLONE (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of PrednisoLONE (Systemic). Risk C: Monitor

PredniSONE: CYP3A4 Inducers (Moderate) may decrease serum concentration of PredniSONE. Risk C: Monitor

Pretomanid: CYP3A4 Inducers (Moderate) may decrease serum concentration of Pretomanid. Risk X: Avoid

Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Proguanil: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Proguanil. CYP2C19 Inhibitors (Moderate) may decrease active metabolite exposure of Proguanil. Risk C: Monitor

QUEtiapine: CYP3A4 Inducers (Moderate) may decrease serum concentration of QUEtiapine. Risk C: Monitor

QuiNIDine: CYP3A4 Inducers (Moderate) may decrease serum concentration of QuiNIDine. Risk C: Monitor

QuiNINE: CYP3A4 Inducers (Moderate) may decrease serum concentration of QuiNINE. Risk C: Monitor

Quizartinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Quizartinib. Risk X: Avoid

Ranolazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ranolazine. Risk X: Avoid

Regorafenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Regorafenib. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Regorafenib. Risk C: Monitor

Repaglinide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Repaglinide. Risk C: Monitor

Repotrectinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Repotrectinib. Risk X: Avoid

Revumenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Revumenib. Risk X: Avoid

Ribociclib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ribociclib. Risk C: Monitor

Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Rilpivirine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Rilpivirine. Risk C: Monitor

Rimegepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Rimegepant. Risk X: Avoid

Ripretinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ripretinib. Management: Avoid this combination if possible. If concomitant use is required, increase ripretinib to 150 mg twice daily. Decrease ripretinib to 150 mg once daily 14 days after stopping a moderate CYP3A4 inducer. Monitor patients for ripretinib response and toxicity Risk D: Consider Therapy Modification

RisperiDONE: CYP3A4 Inducers (Moderate) may decrease serum concentration of RisperiDONE. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of RisperiDONE. Risk C: Monitor

Ritlecitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ritlecitinib. Risk C: Monitor

Ritonavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ritonavir. Risk C: Monitor

Roflumilast (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Roflumilast (Systemic). CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Roflumilast (Systemic). Risk C: Monitor

Rolapitant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Rolapitant. Risk C: Monitor

Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification

ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor

Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor

Samidorphan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Samidorphan. Risk C: Monitor

Saquinavir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Saquinavir. Risk C: Monitor

Selpercatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Selpercatinib. Risk X: Avoid

Selumetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Selumetinib. Risk X: Avoid

Sertraline: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sertraline. Risk C: Monitor

Sildenafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sildenafil. Risk C: Monitor

Simeprevir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Simeprevir. Risk X: Avoid

Simvastatin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Simvastatin. Risk C: Monitor

Sirolimus (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of Sirolimus (Conventional). Risk C: Monitor

Sirolimus (Protein Bound): CYP3A4 Inducers (Moderate) may decrease serum concentration of Sirolimus (Protein Bound). Risk C: Monitor

Sonidegib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sonidegib. Risk X: Avoid

SORAfenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of SORAfenib. Risk C: Monitor

Sotorasib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sotorasib. Risk C: Monitor

Sparsentan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Sparsentan. Risk C: Monitor

SUNItinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of SUNItinib. Risk C: Monitor

Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification

Suzetrigine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Suzetrigine. Risk X: Avoid

Tacrolimus (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Tacrolimus (Systemic). Risk C: Monitor

Tadalafil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tadalafil. Risk C: Monitor

Tamoxifen: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tamoxifen. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Tamoxifen. Risk C: Monitor

Tasimelteon: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tasimelteon. Risk C: Monitor

Tazemetostat: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tazemetostat. Risk X: Avoid

Temsirolimus: CYP3A4 Inducers (Moderate) may decrease serum concentration of Temsirolimus. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Temsirolimus. Specifically, sirolimus concentrations may be decreased. Risk C: Monitor

Teniposide: CYP3A4 Inducers (Moderate) may decrease serum concentration of Teniposide. Risk C: Monitor

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor

Tetrahydrocannabinol: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tetrahydrocannabinol. Risk C: Monitor

Tezacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tezacaftor and Ivacaftor. Risk C: Monitor

Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid

Thiotepa: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Thiotepa. CYP3A4 Inducers (Moderate) may decrease serum concentration of Thiotepa. Risk C: Monitor

Ticagrelor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Ticagrelor. Risk C: Monitor

Tivozanib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tivozanib. Risk C: Monitor

Tofacitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tofacitinib. Risk C: Monitor

Tolvaptan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tolvaptan. Risk C: Monitor

Toremifene: CYP3A4 Inducers (Moderate) may decrease serum concentration of Toremifene. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Toremifene. Risk C: Monitor

Trabectedin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Trabectedin. Risk C: Monitor

TraZODone: CYP3A4 Inducers (Moderate) may decrease serum concentration of TraZODone. Risk C: Monitor

Tretinoin (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Tretinoin (Systemic). Risk C: Monitor

Triazolam: CYP3A4 Inducers (Moderate) may decrease serum concentration of Triazolam. Risk C: Monitor

Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Tucatinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Tucatinib. Risk C: Monitor

Ubrogepant: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a moderate CYP3A4 inducer. Risk D: Consider Therapy Modification

Ulipristal: CYP3A4 Inducers (Moderate) may decrease serum concentration of Ulipristal. Risk X: Avoid

Upadacitinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Upadacitinib. Risk C: Monitor

Valbenazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Valbenazine. CYP3A4 Inducers (Moderate) may decrease active metabolite exposure of Valbenazine. Risk C: Monitor

Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Vandetanib: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Vandetanib. CYP3A4 Inducers (Moderate) may decrease serum concentration of Vandetanib. Risk C: Monitor

Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Risk X: Avoid

Velpatasvir: CYP3A4 Inducers (Moderate) may decrease serum concentration of Velpatasvir. Risk X: Avoid

Vemurafenib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vemurafenib. Risk C: Monitor

Venetoclax: CYP3A4 Inducers (Moderate) may decrease serum concentration of Venetoclax. Risk X: Avoid

Verapamil: CYP3A4 Inducers (Moderate) may decrease serum concentration of Verapamil. Risk C: Monitor

Vilazodone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vilazodone. Risk C: Monitor

VinCRIStine: CYP3A4 Inducers (Moderate) may decrease serum concentration of VinCRIStine. Risk C: Monitor

Voclosporin: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voclosporin. Risk X: Avoid

Vonoprazan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vonoprazan. Risk X: Avoid

Vorapaxar: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vorapaxar. Risk X: Avoid

Voriconazole: CYP2C19 Inhibitors (Moderate) may increase serum concentration of Voriconazole. Risk C: Monitor

Voriconazole: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voriconazole. Risk C: Monitor

Vortioxetine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Vortioxetine. Risk C: Monitor

Voxelotor: CYP3A4 Inducers (Moderate) may decrease serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,000 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 (Moderate) may decrease serum concentration of Voxilaprevir. Risk X: Avoid

Zaleplon: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zaleplon. Risk C: Monitor

Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zanubrutinib. Management: Avoid this combination if possible. If coadministration of zanubrutinib and a moderate CYP3A4 inducer is required, increase the zanubrutinib dose to 320 mg twice daily. Risk D: Consider Therapy Modification

Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification

Zopiclone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zopiclone. Risk C: Monitor

Zuranolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zuranolone. Risk X: Avoid

Reproductive Considerations

Cenobamate may decrease the efficacy of oral contraceptives. Patients who could become pregnant should use additional or alternative nonhormonal contraceptive measures during treatment with cenobamate.

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies.

Data collection to monitor pregnancy and infant outcomes following exposure to cenobamate is ongoing. Health care providers are encouraged to enroll patients exposed to cenobamate during pregnancy in the North American Antiepileptic Drug Pregnancy Registry (1-888-233-2334 or http://www.aedpregnancyregistry.org/).

Breastfeeding Considerations

It is not known if cenobamate is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Monitoring Parameters

Hepatic transaminases (as clinically indicated), potassium (as clinically indicated); signs or symptoms of drug reaction with eosinophilia and systemic symptoms (fever, rash, eosinophilia, lymphadenopathy, facial swelling, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis); suicidal ideation, depression, or changes in behavior; mental alertness.

Mechanism of Action

Cenobamate inhibits voltage-gated sodium channels, reducing repetitive neuronal firing. Cenobamate also acts as a positive allosteric modulator of GABA_A ion channels.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: ≥88%.

Distribution: V_d: ~40 to 50 L.

Protein binding: 60%, primarily to albumin.

Metabolism: Extensively hepatically metabolized; primarily via UGT2B7, CYP2E1, CYP2A6, and CYP2B6, metabolized to a lesser extent by UGT2B4, CYP2C19, CYP3A4/5.

Half-life elimination: Terminal: 50 to 60 hours.

Time to peak: Crushed tablets: 0.5 hours; whole tablet: 1 to 4 hours.

Excretion: Urine (87.8%); feces (5.2%).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Renal impairment: Plasma AUC increased by 1.4-fold to 1.5-fold in patients with mild to moderate renal impairment (CrCl 30 to 89 mL/minute).

Hepatic impairment: Plasma AUC increased by 1.9-fold, 2.3-fold, and 4.2-fold in patients with mild, moderate, and severe hepatic impairment (Child-Turcotte-Pugh class A, B, and C), respectively.

خرید پکیج

Cenobamate: Drug information