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Cenobamate: Drug information

Cenobamate: Drug information
(For additional information see "Cenobamate: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Xcopri;
  • Xcopri (250 MG Daily Dose);
  • Xcopri (350 MG Daily Dose)
Brand Names: Canada
  • Xcopri
Pharmacologic Category
  • Antiseizure Agent, Miscellaneous
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: Hepatic Impairment: Adult

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

Severe impairment (Child-Pugh class C): Use is not recommended (has not been studied).

Dosing: Older Adult

Refer to adult dosing; use with caution.

Adverse Reactions (Significant): Considerations
CNS effects

The most common adverse reactions secondary to cenobamate are dose-dependent CNS-related adverse reactions, including 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). The majority of cases in clinical trials were mild or 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 GABAA ion channels).

Onset: Varied; timing may be impacted by high doses, dose titration, or accumulation.

Risk factors:

• Concurrent use of other CNS depressants

• Rapid titration (Ref)

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

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 commonly associated with dose-dependent 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), drowsiness (19% to 37%) (table 3), fatigue (12% to 24%) (table 4), 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

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), asthenia (3%), ataxia (2% to 6%) (table 8), balance impairment (3% to 9%) (table 9), bradyphrenia, confusion (2% to 3%) (table 10), 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), 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 (Lattanzi 2020)

Nervous system: Suicidal tendencies (Sperling 2020)

Postmarketing:

Dermatologic: Maculopapular rash (Krauss 2020; Sperling 2020)

Gastrointestinal: Appendicitis (Sperling 2020)

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: 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): $25.29

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

150 & 200 mg (per each): $50.57

Tablet Therapy Pack (Xcopri Oral)

14 x 12.5 MG &14 x 25 MG (per each): $4.62

14 x 50 MG &14 x100 MG (per each): $50.57

14 x 150 MG &14 x200 MG (per each): $50.57

Tablets (Xcopri Oral)

50 mg (per each): $47.20

100 mg (per each): $47.20

150 mg (per each): $47.20

200 mg (per each): $47.20

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

Oral: Administer with or without food. Swallow tablets whole with liquid; do not crush or chew.

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#page=25

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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

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

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

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

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

ALfentanil: CYP3A4 Inducers (Moderate) may decrease the 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

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

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

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

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

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

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

Artemether and Lumefantrine: CYP3A4 Inducers (Moderate) 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 (Moderate) may decrease the serum concentration of Artemether and Lumefantrine. Risk C: Monitor therapy

Asunaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir. Risk X: Avoid combination

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

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

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

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

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

Axitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib. Risk X: Avoid combination

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Bedaquiline: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination

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

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

Blonanserin: CNS Depressants may enhance the CNS depressant effect 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 the serum concentration of Bortezomib. Risk C: Monitor therapy

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

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

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

Brigatinib: CYP3A4 Inducers (Moderate) may decrease the 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect 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 the serum concentration of BuPROPion. Risk C: Monitor therapy

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

Cabozantinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cabozantinib. Risk C: Monitor therapy

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

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

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

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

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

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

Carisoprodol: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Carisoprodol. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Carisoprodol. Risk C: Monitor therapy

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

Chlormethiazole: May enhance the CNS depressant effect 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 enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Cilostazol: CYP2C19 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Cilostazol. CYP2C19 Inhibitors (Moderate) may increase the serum concentration 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 the 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 increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Moderate) 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 impair its efficacy. Risk D: Consider therapy modification

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

CloBAZam: CYP2C19 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of CloBAZam. Risk C: Monitor therapy

Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk C: Monitor therapy

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

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

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

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

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

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

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

Daclatasvir: CYP3A4 Inducers (Moderate) may decrease the 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

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

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

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

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

Deflazacort: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Risk X: Avoid combination

Delavirdine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Delavirdine. Risk C: Monitor therapy

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

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

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

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect 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 the serum concentration of DiazePAM. Risk C: Monitor therapy

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

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

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

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

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

Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy

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

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

DroPERidol: May enhance the CNS depressant effect 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 the 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 the serum concentration of Dydrogesterone. Risk C: Monitor therapy

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

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

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

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

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

Elvitegravir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elvitegravir. Risk C: Monitor therapy

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

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

Enzalutamide: 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

Erdafitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erdafitinib. Management: Dose modifications of erdafitinib may be required. See full monograph for details. Risk D: Consider therapy modification

Erlotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erlotinib. Risk C: Monitor therapy

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

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

Fexinidazole: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Fexinidazole. Risk X: Avoid combination

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

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

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect 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 serum concentrations of the active metabolite(s) of Fosamprenavir. Risk C: Monitor therapy

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

Fosnetupitant: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Fosnetupitant. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: May decrease the serum concentration of Cenobamate. Cenobamate may increase the 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 serum concentrations of the active metabolite(s) of Fostamatinib. Risk C: Monitor therapy

Fruquintinib: CYP3A4 Inducers (Moderate) may decrease the 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 the 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 the serum concentration of Gefitinib. Risk C: Monitor therapy

Gemigliptin: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Gemigliptin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Gemigliptin. Risk C: Monitor therapy

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

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

GuanFACINE: CYP3A4 Inducers (Moderate) 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

Hormonal Contraceptives: CYP3A4 Inducers (Moderate) 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 moderate CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification

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

HydrOXYzine: May enhance the CNS depressant effect 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 the serum concentration of Ibrexafungerp. Risk X: Avoid combination

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

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

Ifosfamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy

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

Indinavir: CYP3A4 Inducers (Moderate) may decrease the 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

Infigratinib: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Infigratinib. Risk X: Avoid combination

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

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

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

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

Itraconazole: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Itraconazole. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Itraconazole. Risk C: Monitor therapy

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

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

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

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

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

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

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lacosamide: Antiseizure Agents (Sodium Channel Blockers) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy

LamoTRIgine: Cenobamate may enhance the arrhythmogenic effect of LamoTRIgine. Cenobamate may decrease the 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 the serum concentration of Lansoprazole. Risk C: Monitor therapy

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

Larotrectinib: CYP3A4 Inducers (Moderate) may decrease the 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

Lefamulin: CYP3A4 Inducers (Moderate) may decrease the 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

Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease the 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

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

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

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

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

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

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

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

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

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

Lorlatinib: CYP3A4 Inducers (Moderate) may enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Lovastatin. Risk C: Monitor therapy

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

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

Lurasidone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurasidone. Management: Monitor for decreased lurasidone effects if combined with moderate CYP3A4 inducers and consider increasing the lurasidone dose if coadministered with a moderate CYP3A4 inducer for 7 or more days. Risk D: Consider therapy modification

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

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Mavacamten: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Mavacamten. Risk X: Avoid combination

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

Mefloquine: May diminish the therapeutic effect of Antiseizure Agents. Mefloquine may decrease the 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

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect 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

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

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyraPONE: Antiseizure Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May diminish the therapeutic effect of Antiseizure Agents. Risk C: Monitor therapy

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

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

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

MiFEPRIStone: CYP3A4 Inducers (Moderate) 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

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Mitapivat: CYP3A4 Inducers (Moderate) may decrease the 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 concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mobocertinib. Risk X: Avoid combination

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

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

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

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

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

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect 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

Orelabrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Orelabrutinib. Risk X: Avoid combination

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

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

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

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect 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 the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy

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

Pacritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pacritinib. Risk X: Avoid combination

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

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

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

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

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

Perampanel: CYP3A4 Inducers (Moderate) may decrease the 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

PHENobarbital: Cenobamate may increase the serum concentration of PHENobarbital. Risk C: Monitor therapy

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

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

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pirtobrutinib: CYP3A4 Inducers (Moderate) may decrease the 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

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

Pralsetinib: CYP3A4 Inducers (Moderate) may decrease the 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 enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

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

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

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

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Proguanil: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Proguanil. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Proguanil. Risk C: Monitor therapy

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

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

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

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

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

Regorafenib: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Regorafenib. Risk C: Monitor therapy

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

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

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

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

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

Ripretinib: CYP3A4 Inducers (Moderate) may decrease the 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 concentrations of the active metabolite(s) of RisperiDONE. CYP3A4 Inducers (Moderate) may decrease the serum concentration of RisperiDONE. Risk C: Monitor therapy

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

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

Roflumilast (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Roflumilast (Systemic). CYP3A4 Inducers (Moderate) may decrease the serum concentration of Roflumilast (Systemic). Risk C: Monitor therapy

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

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect 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 enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Suvorexant: CNS Depressants may enhance the CNS depressant effect 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

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

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

Tamoxifen: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tamoxifen. Risk C: Monitor therapy

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

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

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

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

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

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

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Thiotepa: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Thiotepa. Risk C: Monitor therapy

Ticagrelor: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ticagrelor. Risk C: Monitor therapy

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

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

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

Toremifene: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Toremifene. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Toremifene. Risk C: Monitor therapy

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

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

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

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

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

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

Valbenazine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Valbenazine. Risk C: Monitor therapy

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Vandetanib: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Vandetanib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vandetanib. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

Voxelotor: CYP3A4 Inducers (Moderate) may decrease the 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 the serum concentration of Voxilaprevir. Risk X: Avoid combination

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

Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease the 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 enhance the CNS depressant effect 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 the serum concentration of Zopiclone. Risk C: Monitor therapy

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

Reproductive Considerations

Cenobamate may decrease the efficacy of oral contraceptives. Females of childbearing potential 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 females 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 GABAA ion channels.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: ≥88%.

Distribution: Vd: ~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: 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 2.1-fold to 2.3-fold in patients with mild to moderate hepatic impairment (Child-Pugh class A and B).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (BE) Belgium: Ontozry;
  • (CZ) Czech Republic: Ontozry;
  • (DE) Germany: Ontozry;
  • (ES) Spain: Ontozry;
  • (FI) Finland: Ontozry;
  • (FR) France: Ontozry;
  • (GB) United Kingdom: Ontozry | Xcopri;
  • (HU) Hungary: Ontozry;
  • (IE) Ireland: Ontozry;
  • (IT) Italy: Ontozry;
  • (NL) Netherlands: Ontozry;
  • (NO) Norway: Ontozry;
  • (PL) Poland: Ontozry;
  • (PR) Puerto Rico: Xcopri;
  • (PT) Portugal: Ontozry;
  • (SE) Sweden: Ontozry;
  • (SK) Slovakia: Ontozry
  1. Bell GS, Gaitatzis A, Bell CL, Johnson AL, Sander JW. Suicide in people with epilepsy: how great is the risk? Epilepsia. 2009;50(8):1933-1942. doi:10.1111/j.1528-1167.2009.02106.x [PubMed 19453718]
  2. Bellivier F, Belzeaux R, Scott J, Courtet P, Golmard JL, Azorin JM. Anticonvulsants and suicide attempts in bipolar I disorders. Acta Psychiatr Scand. 2017;135(5):470-478. doi:10.1111/acps.12709 [PubMed 28190254]
  3. Hesdorffer DC, Kanner AM. The FDA alert on suicidality and antiepileptic drugs: fire or false alarm? Epilepsia. 2009;50(5):978-986. doi:10.1111/j.1528-1167.2009.02012.x [PubMed 19496806]
  4. Kanner AM. Are antiepileptic drugs used in the treatment of migraine associated with an increased risk of suicidality? Curr Pain Headache Rep. 2011;15(3):164-169. doi:10.1007/s11916-011-0199-x [PubMed 21479999]
  5. Krauss GL, Klein P, Brandt C, et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trial. Lancet Neurol. 2020;19(1):38-48. doi:10.1016/S1474-4422(19)30399-0 [PubMed 31734103]
  6. Lattanzi S, Trinka E, Zaccara G, et al. Adjunctive cenobamate for focal-onset seizures in adults: a systematic review and meta-analysis. CNS Drugs. 2020;34(11):1105-1120. doi:10.1007/s40263-020-00759-9 [PubMed 32851590]
  7. Medical Research Council Antiepileptic Drug Withdrawal Study Group. Randomised study of antiepileptic drug withdrawal in patients in remission. Lancet. 1991;337(8751):1175-1180. [PubMed 1673736]
  8. Mula M, Kanner AM, Schmitz B, Schachter S. Antiepileptic drugs and suicidality: an expert consensus statement from the Task Force on Therapeutic Strategies of the ILAE Commission on Neuropsychobiology. Epilepsia. 2013;54(1):199-203. doi:10.1111/j.1528-1167.2012.03688.x [PubMed 22994856]
  9. Schrijvers R, Gilissen L, Chiriac AM, Demoly P. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back. Clin Transl Allergy. 2015;5:31. doi:10.1186/s13601-015-0073-8 [PubMed 26339470]
  10. Sperling MR, Klein P, Aboumatar S, et al. Cenobamate (YKP3089) as adjunctive treatment for uncontrolled focal seizures in a large, phase 3, multicenter, open-label safety study. Epilepsia. 2020;61(6):1099-1108. doi:10.1111/epi.16525 [PubMed 32396252]
  11. Xcopri (cenobamate) [prescribing information]. Paramus, NJ: SK Life Science Inc; March 2020.
  12. Xcopri (cenobamate) [prescribing information]. Paramus, NJ: SK Life Science Inc; April 2021.
  13. Xcopri (cenobamate) [prescribing information]. Paramus, NJ: SK Life Science Inc; June 2022.
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