Version July 2025
Seizure disorder (generalized tonic-clonic, psychomotor, and focal):
Weight-directed: Limited data available: Infants and Children <8 years: Oral: Usual maintenance range: 10 to 25 mg/kg/day in 2 to 3 divided doses; start with lower dosage and titrate upward; usual maximum dose: 500 mg/dose (Ref).
Fixed dosing:
Children <8 years:
Initial: Days 1 to 3: Oral: 50 mg at bedtime; Days 4 to 6: 50 mg twice daily; Days 7 to 9: 100 mg twice daily.
Maintenance (starting Day 10 of therapy): Oral: 125 to 250 mg 3 times daily.
Patients already receiving other antiseizure medications: Specific recommendations in this age group are not available. However, in older pediatric patients (≥8 years of age), the usual initial starting dose is recommended, and then gradually increase primidone to maintenance dose as other drug is gradually decreased; continue until desired level obtained or other drug completely withdrawn. If goal is monotherapy, conversion should be completed over ≥2 weeks.
Children ≥8 years and Adolescents:
Initial: Days 1 to 3: Oral: 100 to 125 mg at bedtime; Days 4 to 6: 100 to 125 mg twice daily; Days 7 to 9: 100 to 125 mg 3 times daily.
Maintenance (starting Day 10 of therapy): Oral: 250 mg 3 times daily; adjust dose to usual daily maintenance range: 750 to 1,000 mg/day in divided doses 3 to 4 times daily; higher doses may be needed up to 500 mg 4 times daily; maximum daily dose: 2,000 mg/day.
Patients already receiving other antiseizure medications: Oral: Initial: 100 to 125 mg at bedtime; gradually increase to maintenance dose as other drug is gradually decreased, continue until desired level obtained or other drug completely withdrawn. If goal is monotherapy, conversion should be completed over ≥2 weeks.
Infants, Children, and Adolescents: Limited data available: Oral:
Altered kidney function: There are no dosage adjustments provided in manufacturer's labeling; however, based on adult information, it is recommended to avoid use in renal failure due to complex pharmacokinetics and active metabolites with long half-lives (Ref). If used, monitor serum concentrations to determine dosing adjustments.
CRRT: Based on experience with phenobarbital, monitor serum concentrations to determine dosing adjustments; a case report suggests that clearance and volume of distribution of phenobarbital is increased in patients receiving CVVH.
Infants, Children, and Adolescents: Limited data available: Oral: There are no dosage adjustments provided in manufacturer's labeling. Phenobarbital exposure is increased with hepatic impairment; reduced doses are recommended; use with caution; monitor plasma levels and adjust dose accordingly.
(For additional information see "Primidone: Drug information")
Essential tremor (off-label use):
Note: For patients with inadequate response, may add or switch to another agent (Ref).
Oral: Initial: 25 to 50 mg once daily at bedtime; consider 25 mg in patients at greater risk of adverse effects (eg, patients who are frail or taking other sedating medications). Increase total daily dose gradually (eg, every 3 to 7 days) based on response and tolerability in increments of 25 mg. Usual dosage: 150 to 250 mg/day in 1 or 2 divided doses. Maximum: 750 mg/day (Ref).
Seizure disorder (grand mal, psychomotor, and focal): Oral: Days 1 to 3: 100 to 125 mg/day at bedtime; days 4 to 6: 100 to 125 twice daily; days 7 to 9: 100 to 125 mg 3 times daily; usual dose: 750 to 1,500 mg/day in divided doses 3 to 4 times/day with maximum dosage of 2 g/day
Patients already receiving other antiseizure medications: Initial: 100 to 125 mg at bedtime; gradually increase to maintenance dose as other drug is gradually decreased, continue until desired level obtained or other drug completely withdrawn. If goal is monotherapy, conversion should be completed over ≥2 weeks.
No dosage adjustment provided in manufacturer's labeling. However, the following recommendations (based on a maximum of 750 mg twice daily in normal kidney function) have been used by some clinicians: Note: Avoid in renal failure if possible; due to active metabolites with long half-lives and complex kinetics (Ref):
GFR ≥50 mL/minute: No dosage adjustment necessary.
GFR 10 to 50 mL/minute: Administer no more frequently than every 12 to 24 hours (Ref).
GFR <10 mL/minute: Administer no more frequently than every 24 hours (Ref).
Hemodialysis: Dialyzable (Ref). Administer dose after dialysis due to high extraction during hemodialysis or may administer a supplemental dose prior to dialysis session that is 30% of the patient's usual dose (Ref).
No dosage adjustment provided in manufacturer’s labeling. However, increased side effects may occur in severe liver disease; monitor plasma levels and adjust dose accordingly.
Primidone may cause CNS effects, including drowsiness/sedation, ataxia, nystagmus disorder, cognitive dysfunction, and vertigo with initiation of therapy (Ref). CNS “first-dose" effects (predominantly sedation and nystagmus) resolve within a few days, as tolerance develops (Ref). In pediatric patients, the active metabolite of primidone (phenobarbital) has been shown to decrease cognitive performance, increase behavioral changes (including ADHD), and has long-term negative effects on learning ability (Ref).
Mechanism: Dose-related; related to the pharmacologic activity. Primidone is metabolized to phenobarbital and phenylethylmalonamide (PEMA); PEMA may enhance the activity of phenobarbital. Phenobarbital decreases neuronal excitability by activating the GABA-A receptor (Ref).
Onset: Varied; CNS effects (predominantly sedation and nystagmus) may appear as “first-dose” effects within the first day or as chronic effects, developing with continued use (Ref).
Risk factors :
• High doses (especially at initiation of therapy); however, can also occur at lower doses (Ref)
• Older adults (Ref)
Primidone is associated with a variety of delayed hypersensitivity reactions, ranging from mild reactions (eg, maculopapular rash) to severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) (often referred to as a hypersensitivity syndrome) (Ref). Although there are limited case reports in the literature documenting reactions to primidone, primidone is metabolized to phenobarbital and similar adverse reactions would be expected (Ref).
Mechanism: Non–dose-related; immunologic. Delayed hypersensitivity reactions, including maculopapular eruptions and SCARs, are T-cell-mediated (Ref).
Onset: Delayed hypersensitivity reactions: Varied; maculopapular rash usually occurs 3 to 20 days after start of therapy (Ref). SCARs usually occur 1 to 8 weeks after initiation (Ref); re-exposure may lead to more rapid onset (usually with 1 to 4 days) (Ref).
Risk factors:
• An increased risk of DRESS in first-degree relatives of patients with a history of DRESS to an aromatic antiseizure medications (eg, phenytoin, carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, primidone, zonisamide) (Ref)
• Reactivation of viruses: Viral reactivation, in particular human herpesvirus 6 (HHV-6) reactivation may be associated with a prolonged and more severe course of DRESS (Ref)
• Cross-reactivity: High degree of cross-reactivity exists between aromatic antiseizure medications, including phenytoin, carbamazepine, phenobarbital, primidone, and oxcarbazepine (Ref)
• Age: Younger pediatric patients <12 years of age and older adult patients may be at risk for severe SCARs associated with aromatic antiseizure medications, including primidone (Ref)
• Radiation therapy (especially cranial irradiation): Phenobarbital may increase the risk of cutaneous reactions, including erythema multiforme and TEN/SJS (Ref).
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Frequency not defined.
Dermatologic: Morbilliform rash
Hematologic & oncologic: Agranulocytosis, granulocytopenia, pure red cell aplasia, red cell hypoplasia
Nervous system: Emotional disturbance
Ophthalmic: Diplopia
Postmarketing:
Dermatologic: Maculopapular rash (Ref), Stevens-Johnson syndrome (Ref), toxic epidermal necrolysis (Ref)
Gastrointestinal: Anorexia (Ref), nausea (Ref), vomiting (Ref)
Genitourinary: Impotence (Ref)
Hematologic & oncologic: Megaloblastic anemia (Ref)
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms (Ref)
Nervous system: Ataxia (Ref), behavioral changes (Ref), cognitive dysfunction (Ref), drowsiness (Ref), fatigue (Ref), hyperirritability (Ref), vertigo (Ref)
Hypersensitivity to phenobarbital; porphyria
Concerns related to adverse effects:
• Suicidal ideation: Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur.
Disease-related concerns:
• Depression: Use with caution in patients with depression or suicidal tendencies.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Hypoadrenalism: Use with caution in patients with hypoadrenalism.
• Renal impairment: Use with caution in patients with renal impairment.
• Respiratory disease: Use with caution in patients with respiratory disease.
• Substance abuse: Use with caution in patients with a history of drug abuse; potential for drug dependency exists. Tolerance or psychological and physical dependence may occur with prolonged use.
Concurrent drug therapy issues:
• Sedatives: Effects with other sedative drugs or ethanol may be potentiated.
Special populations:
• Debilitated patients: Use with caution in patients who are debilitated; may cause paradoxical responses.
• Older adult: Use with caution in elderly patients due to cognitive function declines. Primidone may cause paradoxical responses.
• Pediatric: Primidone's active metabolite, phenobarbital, has been associated with cognitive deficits in children receiving chronic therapy for febrile seizures.
Other warnings/precautions:
• Acute pain: Do not administer to patients in acute pain.
• 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.
One of the active metabolites of primidone is phenobarbital. Phenobarbital may cause CNS depression and effects with other sedative drugs may be potentiated. Phenobarbital has been associated with cognitive deficits in children receiving therapy for complicated febrile seizures (Maitre 2013).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Mysoline: 50 mg, 250 mg [scored]
Generic: 50 mg, 125 mg, 250 mg
Yes
Tablets (Mysoline Oral)
50 mg (per each): $23.87
250 mg (per each): $82.15
Tablets (Primidone Oral)
50 mg (per each): $0.24 - $0.50
125 mg (per each): $1.98
250 mg (per each): $0.45 - $1.00
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 125 mg, 250 mg
Oral: Administer without regard to food.
Store at 20°C to 25°C (68°F to 77°F).
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM222370.pdf, must be dispensed with this medication.
Treatment of generalized tonic-clonic (grand mal), psychomotor, and focal seizures as monotherapy or in combination with other antiseizure agents (FDA approved in children and adults).
Primidone may be confused with predniSONE, primaquine, pyridoxine
Beers Criteria: Primidone is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its high rate of physical dependence, tolerance to sleep benefits, and increased risk of overdose at low dosages (Beers Criteria [AGS 2023]).
Substrate of CYP2C19 (Major with inhibitors), CYP2C19 (Minor with inducers), CYP2C9 (Minor), CYP2E1 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP1A2 (Weak), CYP2A6 (Weak), CYP2B6 (Weak), CYP3A4 (Moderate), UGT1A1;
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.
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
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
Acalabrutinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Acalabrutinib. Risk C: Monitor
Acetaminophen: Primidone may increase metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor
Acoramidis: UGT1A1 Inducers may decrease serum concentration of Acoramidis. Risk X: Avoid
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Afatinib: Primidone may decrease serum concentration of Afatinib. Management: Consider increasing the afatinib dose by 10 mg as tolerated in patients requiring chronic coadministration of phenobarbital with afatinib. Reduce afatinib dose back to the original afatinib dose 2 to 3 days after discontinuation of phenobarbital. Risk D: Consider Therapy Modification
Ajmaline: Phenobarbital-Primidone may decrease serum concentration of Ajmaline. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alfacalcidol: Phenobarbital-Primidone may decrease serum concentration of Alfacalcidol. 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
Apixaban: Phenobarbital-Primidone may decrease serum concentration of Apixaban. Risk C: Monitor
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: Primidone may decrease serum concentration of Atazanavir. Atazanavir may decrease serum concentration of Primidone. Risk X: Avoid
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: Phenobarbital-Primidone may decrease serum concentration of Axitinib. Management: Concurrent use of axitinib with phenobarbital or primidone, which is metabolized to phenobarbital, 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
Bazedoxifene: Primidone may decrease serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. Risk C: Monitor
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
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Benzhydrocodone: Primidone may increase CNS depressant effects of Benzhydrocodone. Primidone may decrease active metabolite exposure of Benzhydrocodone. Specifically, serum concentrations of hydrocodone may be decreased. Management: Avoid use of benzhydrocodone and primidonel when possible. Monitor for respiratory depression/sedation. Because primidone is also a moderate CYP3A4 inducer, monitor for decreased benzhydrocodone efficacy and withdrawal if combined. Risk D: Consider Therapy Modification
Bictegravir: Primidone may decrease serum concentration of Bictegravir. Management: When possible consider using an alternative antiseizure drug with concurrent bictegravir, emtricitabine, and tenofovir alafenamide. If the combination must be used, monitor closely for evidence of reduced antiviral effectiveness. Risk D: Consider Therapy Modification
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
Blood Pressure Lowering Agents: Barbiturates may increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
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: Primidone may decrease 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: Primidone may increase CNS depressant effects of Buprenorphine. Primidone may decrease serum concentration of Buprenorphine. Management: Avoid use of buprenorphine and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a moderate CYP3A4 inducer, monitor for decreased buprenorphine efficacy and withdrawal if combined. 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
Cabotegravir: UGT1A1 Inducers may decrease serum concentration of Cabotegravir. Risk X: Avoid
Cabozantinib: Phenobarbital-Primidone 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: Phenobarbital-Primidone may decrease serum concentration of Calcifediol. Risk X: Avoid
Calcitriol (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of Calcitriol (Systemic). Risk C: Monitor
Canagliflozin: Primidone may decrease serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 200 mg/day in patients tolerating 100 mg/day. A further increase to 300 mg/day can be considered in patients with an estimated glomerular filtration rate (GFR) of 60 mL/min/1.73 m2 or greater. Risk D: Consider Therapy Modification
Cannabidiol: Phenobarbital-Primidone may decrease serum concentration of Cannabidiol. Cannabidiol may increase serum concentration of Phenobarbital-Primidone. 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: CYP3A4 Inducers (Moderate) may decrease serum concentration of CarBAMazepine. Risk C: Monitor
Cariprazine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cariprazine. Risk X: Avoid
Carmustine: Primidone may decrease serum concentration of Carmustine. Management: Consider alternatives to primidone when using carmustine. If combined, monitor for reduced carmustine efficacy. Risk D: Consider Therapy Modification
Cenobamate: May increase CNS depressant effects of Phenobarbital-Primidone. Cenobamate may increase serum concentration of Phenobarbital-Primidone. 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
Chloramphenicol (Systemic): May increase active metabolite exposure of Primidone. Specifically, the concentrations of phenobarbital may be increased. Primidone may decrease serum concentration of Chloramphenicol (Systemic). Risk C: Monitor
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
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: Phenobarbital-Primidone may increase CNS depressant effects of CloBAZam. Phenobarbital-Primidone may decrease serum concentration of CloBAZam. Risk C: Monitor
CloZAPine: CYP1A2 Inducers (Weak) may decrease serum concentration of CloZAPine. 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: Primidone may decrease serum concentration of Cobicistat. Risk X: Avoid
Cobimetinib: CYP3A4 Inducers (Moderate) may decrease serum concentration of Cobimetinib. Risk X: Avoid
Codeine: Primidone may increase CNS depressant effects of Codeine. Primidone may decrease serum concentration of Codeine. Management: Avoid use of codeine and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased codeine efficacy and withdrawal if combined. Risk D: Consider Therapy Modification
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
CycloPHOSphamide: Primidone may decrease serum concentration of CycloPHOSphamide. Primidone may increase active metabolite exposure of CycloPHOSphamide. More specifically, primidone may increase the rate of cyclophosphamide conversion to its primary active metabolite, 4-hydroxycyclophosphamide. Risk C: Monitor
CycloSPORINE (Systemic): CYP3A4 Inducers (Moderate) may decrease serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP2C19 Inhibitors (Moderate): May increase active metabolite exposure of Primidone. Specifically, concentrations of phenobarbital may be increased. Risk C: Monitor
CYP2C19 Inhibitors (Strong): May increase active metabolite exposure of Primidone. Specifically, concentrations of phenobarbital may be increased. Risk C: Monitor
Dabigatran Etexilate: Primidone may decrease serum concentration of Dabigatran Etexilate. 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
Darunavir: May decrease serum concentration of Primidone. Risk C: Monitor
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
Deferasirox: UGT1A1 Inducers may decrease serum concentration of Deferasirox. Management: Avoid concomitant use of deferasirox and UGT1A1 inducers when possible. If combined, consider a 50% increase in the initial deferasirox dose, with monitoring of serum ferritin concentrations and clinical response to guide further dosing. Risk D: Consider Therapy Modification
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
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
Dexmethylphenidate: May increase serum concentration of Primidone. Dexmethylphenidate may increase active metabolite exposure of Primidone. Specifically, phenobarbital concentrations could become elevated. 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
Dolutegravir: Primidone may decrease serum concentration of Dolutegravir. Specifically, the Primidone metabolite phenobarbital may decrease Dolutegravir serum concentrations. Risk X: Avoid
Doravirine: Phenobarbital-Primidone may decrease serum concentration of Doravirine. Risk X: Avoid
Doxercalciferol: Phenobarbital-Primidone may increase active metabolite exposure of Doxercalciferol. Risk C: Monitor
DOXOrubicin (Conventional): CYP3A4 Inducers (Moderate) may decrease serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
Doxycycline: Barbiturates may decrease serum concentration of Doxycycline. Risk C: Monitor
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: Phenobarbital-Primidone 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
Elexacaftor, Tezacaftor, and Ivacaftor: Phenobarbital-Primidone 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
Esketamine (Injection): Phenobarbital-Primidone may decrease serum concentration of Esketamine (Injection). Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Eslicarbazepine: Primidone may decrease serum concentration of Eslicarbazepine. (based on studies with phenobarbital) Risk C: Monitor
Estrogen Derivatives: CYP3A4 Inducers (Moderate) may decrease serum concentration of Estrogen Derivatives. Risk C: Monitor
Ethosuximide: Phenobarbital-Primidone may decrease serum concentration of Ethosuximide. 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: Phenobarbital-Primidone may decrease serum concentration of Etravirine. Risk X: Avoid
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
Felbamate: May increase active metabolite exposure of Primidone. Specifically, phenobarbital concentrations may increase. Primidone may decrease serum concentration of Felbamate. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the primidone dose by 20%. Risk D: Consider Therapy Modification
Felodipine: Phenobarbital-Primidone may decrease serum concentration of Felodipine. Risk C: Monitor
FentaNYL: Primidone may increase CNS depressant effects of FentaNYL. Primidone may decrease serum concentration of FentaNYL. Management: Avoid use of fentanyl and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a moderate CYP3A4 inducer, monitor for decreased fentanyl efficacy and withdrawal if combined. Risk D: Consider Therapy Modification
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
Fludrocortisone: Phenobarbital-Primidone may decrease serum concentration of Fludrocortisone. Risk C: Monitor
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
Folic Acid: May decrease serum concentration of Primidone. Additionally, folic acid may decrease concentrations of active metabolites of primidone (e.g., phenobarbital). Risk C: Monitor
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 increase CNS depressant effects of Phenobarbital-Primidone. Phenobarbital-Primidone may decrease serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may increase serum concentration of Phenobarbital-Primidone. Risk C: Monitor
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: May increase CNS depressant effects of Phenobarbital-Primidone. Phenobarbital-Primidone may decrease serum concentration of Ganaxolone. Management: Avoid this combination if possible. In patients stabilized on ganaxolone who initiate or dose escalate phenobarbital or primidone the ganaxolone dose may need to be increased, but should 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
Gestrinone: Primidone may decrease serum concentration of Gestrinone. 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
Griseofulvin: Barbiturates may decrease serum concentration of Griseofulvin. 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
Haloperidol: Phenobarbital-Primidone may decrease serum concentration of Haloperidol. Risk C: Monitor
Hemin: Barbiturates may decrease therapeutic effects of Hemin. Risk X: Avoid
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
HYDROcodone: Primidone may increase CNS depressant effects of HYDROcodone. Primidone may decrease serum concentration of HYDROcodone. Management: Avoid use of hydrocodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased hydrocodone efficacy and withdrawal if combined. 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: Phenobarbital-Primidone may decrease serum concentration of Irinotecan Products. Management: Avoid administration of phenobarbital or primidone during irinotecan treatment, and substitute non-CYP3A4 inducing agents at least 2 weeks prior to irinotecan initiation, whenever possible. If combined, monitor closely for reduced irinotecan efficacy. Risk D: Consider Therapy Modification
Isavuconazonium Sulfate: Phenobarbital-Primidone may decrease active metabolite exposure of Isavuconazonium Sulfate. Specifically, isavuconazole serum concentrations may be reduced. Risk X: Avoid
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: Phenobarbital-Primidone 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
LamoTRIgine: May increase adverse/toxic effects of Phenobarbital-Primidone. Specifically, the risk for hematologic toxicities may be increased. Phenobarbital-Primidone may decrease serum concentration of LamoTRIgine. Management: For patients taking primidone or phenobarbital without valproate, lamotrigine dose adjustments are recommended for lamotrigine initiation. Recommendations vary based on lamotrigine indication and age. See full interact monograph for details. Risk D: Consider Therapy Modification
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
Ledipasvir: Primidone may decrease serum concentration of Ledipasvir. 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
Letermovir: UGT1A1 Inducers may decrease serum concentration of Letermovir. Risk X: Avoid
Leucovorin Calcium-Levoleucovorin: May decrease serum concentration of Primidone. Additionally, leucovorin/levoleucovorin may decrease concentrations of active metabolites of primidone (e.g., phenobarbital). Risk C: Monitor
Levamlodipine: CYP3A4 Inducers (Moderate) may decrease serum concentration of Levamlodipine. Risk C: Monitor
LevETIRAcetam: May increase CNS depressant effects of Primidone. Primidone may decrease serum concentration of LevETIRAcetam. 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
Levomethadone: May increase CNS depressant effects of Primidone. Primidone may decrease serum concentration of Levomethadone. Management: Avoid concomitant use of levomethadone and primidone 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
Levonorgestrel (IUD): Phenobarbital-Primidone may decrease therapeutic effects of Levonorgestrel (IUD). Phenobarbital-Primidone may decrease serum concentration of Levonorgestrel (IUD). Risk C: Monitor
Lidocaine (Systemic): Phenobarbital-Primidone may decrease serum concentration of Lidocaine (Systemic). 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
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: Primidone may decrease serum concentration of Lopinavir. Management: Avoid once-daily administration of lopinavir/ritonavir if used together with primidone. If lopinavir/ritonavir twice daily is combined with primidone, monitor closely for decreased efficacy of lopinavir/ritonavir. Risk D: Consider Therapy Modification
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: Phenobarbital-Primidone 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: Primidone may decrease serum concentration of Maribavir. Management: Increase the dose of maribavir to 1,200 mg twice daily with concomitant use of primidone. Risk D: Consider Therapy Modification
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 Primidone. Primidone may decrease serum concentration of Mefloquine. Mefloquine may decrease serum concentration of Primidone. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If primidone is being used for another indication, monitor for decreased concentrations and efficacy of both primidone/phenobarbital and mefloquine. Risk D: Consider Therapy Modification
Meperidine: Primidone may increase CNS depressant effects of Meperidine. Primidone may increase active metabolite exposure of Meperidine. Management: Avoid concomitant use of meperidine and primidone 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
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methadone: Primidone may increase CNS depressant effects of Methadone. Primidone may decrease serum concentration of Methadone. Management: Avoid concomitant use of methadone and primidone 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
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: Barbiturates may increase nephrotoxic effects of Methoxyflurane. Barbiturates may increase metabolism of Methoxyflurane. Risk X: Avoid
Methylphenidate: May increase serum concentration of Primidone. Methylphenidate may increase active metabolite exposure of Primidone. Specifically, phenobarbital concentrations could become elevated. 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
MetroNIDAZOLE (Systemic): Primidone may decrease serum concentration of MetroNIDAZOLE (Systemic). 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: May increase CNS depressant effects of Barbiturates. Mianserin may decrease therapeutic effects of Barbiturates. Barbiturates may decrease serum concentration of Mianserin. Risk X: Avoid
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
Montelukast: Phenobarbital-Primidone may decrease serum concentration of Montelukast. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease serum concentration of Barbiturates. 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: Phenobarbital-Primidone may decrease serum concentration of NiMODipine. Risk X: Avoid
Nirmatrelvir and Ritonavir: May decrease serum concentration of Primidone. Primidone may decrease active metabolite exposure of Nirmatrelvir and Ritonavir. Risk X: Avoid
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
OLANZapine: CYP1A2 Inducers (Weak) may decrease serum concentration of OLANZapine. Risk C: Monitor
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
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: Antiseizure Agents may decrease serum concentration of Opipramol. 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
OXcarbazepine: Phenobarbital-Primidone may decrease serum concentration of OXcarbazepine. Risk C: Monitor
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: Barbiturates may increase CNS depressant effects of Oxybate Salt Products. Risk X: Avoid
OxyCODONE: Primidone may increase CNS depressant effects of OxyCODONE. Primidone may decrease serum concentration of OxyCODONE. Management: Avoid use of oxycodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a moderate CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. 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
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
Propacetamol: Primidone may increase metabolism of Propacetamol. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor
Pyridoxine: May decrease active metabolite exposure of Primidone. Specifically, concentrations of phenobarbital may be reduced. Risk C: Monitor
Pyrimethamine: Phenobarbital-Primidone may decrease serum concentration of Pyrimethamine. 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: May increase serum concentration of Primidone. Primidone may decrease serum concentration of QuiNINE. Management: Consider alternatives to this combination when possible. If coadministration of primidone and quinine cannot be avoided, monitor for reduced quinine efficacy and for increased phenobarbital (active metabolite) serum concentrations and toxicities. Risk D: Consider Therapy Modification
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
Reboxetine: Phenobarbital-Primidone may decrease serum concentration of Reboxetine. Risk C: Monitor
Regorafenib: Phenobarbital-Primidone may decrease serum concentration of Regorafenib. Phenobarbital-Primidone 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: Primidone may decrease serum concentration of Rilpivirine. Risk X: Avoid
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: May decrease serum concentration of Primidone. Primidone may decrease serum concentration of Ritonavir. Management: Consider avoiding this combination due to the potential for decreased ritonavir concentrations and the possible development of resistance. If combined, monitor for decreased primidone and ritonavir concentrations and effects during coadministration. Risk D: Consider Therapy Modification
Rivaroxaban: Phenobarbital-Primidone may decrease serum concentration of Rivaroxaban. 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
Roflumilast (Systemic): Phenobarbital-Primidone may decrease serum concentration 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
Rufinamide: Primidone may decrease serum concentration of Rufinamide. Rufinamide may increase active metabolite exposure of Primidone. Specifically, phenobarbital concentrations may be increased. Risk C: Monitor
Sacituzumab Govitecan: UGT1A1 Inducers may decrease active metabolite exposure of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be decreased. Risk X: Avoid
Samidorphan: CYP3A4 Inducers (Moderate) may decrease serum concentration of Samidorphan. Risk C: Monitor
Sapropterin: Primidone may decrease serum concentration of Sapropterin. Risk C: Monitor
Saquinavir: Primidone may decrease serum concentration of Saquinavir. Risk X: Avoid
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
Sofosbuvir: Primidone may decrease serum concentration of Sofosbuvir. Risk X: Avoid
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
Stiripentol: Phenobarbital-Primidone may decrease serum concentration of Stiripentol. Stiripentol may increase serum concentration of Phenobarbital-Primidone. Risk C: Monitor
SUFentanil: Primidone may increase CNS depressant effects of SUFentanil. Primidone may decrease serum concentration of SUFentanil. Management: Avoid use of sufentanil and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a moderate CYP3A4 inducer, monitor for decreased sufentanil efficacy and withdrawal if combined. Risk D: Consider Therapy Modification
Sulthiame: Primidone may increase adverse/toxic effects of Sulthiame. 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): Phenobarbital-Primidone 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
Tenofovir Alafenamide: Primidone may decrease serum concentration of Tenofovir Alafenamide. Risk X: Avoid
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: Phenobarbital-Primidone may decrease serum concentration of Tezacaftor and Ivacaftor. Risk C: Monitor
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Theophylline Derivatives: Barbiturates may decrease serum concentration of Theophylline Derivatives. Risk C: Monitor
Thiotepa: CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Thiotepa. CYP3A4 Inducers (Moderate) may decrease serum concentration of Thiotepa. Risk C: Monitor
Thiothixene: Primidone may decrease serum concentration of Thiothixene. Risk C: Monitor
Thyroid Products: Primidone may decrease serum concentration of Thyroid Products. Risk C: Monitor
TiaGABine: Phenobarbital-Primidone may decrease serum concentration of TiaGABine. Risk C: Monitor
Ticagrelor: Phenobarbital-Primidone may decrease serum concentration of Ticagrelor. Risk C: Monitor
Tipranavir: Primidone may decrease serum concentration of Tipranavir. Tipranavir may decrease serum concentration of Primidone. 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: Phenobarbital-Primidone may decrease serum concentration of Toremifene. Risk C: Monitor
Trabectedin: Phenobarbital-Primidone may decrease serum concentration of Trabectedin. Risk C: Monitor
TraMADol: Primidone may increase CNS depressant effects of TraMADol. Primidone may decrease serum concentration of TraMADol. Management: Avoid use of tramadol and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a moderate CYP3A4 inducer, monitor for decreased tramadol efficacy and withdrawal if combined. Risk D: Consider Therapy Modification
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
Tricyclic Antidepressants: Barbiturates may increase metabolism of Tricyclic Antidepressants. Management: Monitor for decreased efficacy of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. Tricyclic antidepressant dose adjustments are likely required. Risk D: Consider Therapy Modification
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Tropisetron: Phenobarbital-Primidone may decrease serum concentration of Tropisetron. 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
Valproic Acid and Derivatives: May increase serum concentration of Primidone. More specifically, the serum concentration of phenobarbital, primidone's primary active metabolite, may be increased. Primidone may decrease serum concentration of Valproic Acid and Derivatives. 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
Vitamin K Antagonists: Barbiturates may increase metabolism of Vitamin K Antagonists. Management: Monitor INR more closely. Anticoagulant dose increases of 30% to 60% may be needed after a barbiturate is initiated or given at an increased dose. Anticoagulant dose decreases may be needed following barbiturate discontinuation or dose reduction. Risk D: Consider Therapy Modification
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: Primidone may decrease serum concentration of Voriconazole. Risk X: Avoid
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: Phenobarbital-Primidone 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
Zonisamide: May increase CNS depressant effects of Primidone. Primidone may decrease serum concentration of Zonisamide. Risk C: Monitor
Zopiclone: Primidone may increase CNS depressant effects of Zopiclone. Primidone may decrease serum concentration of Zopiclone. Risk C: Monitor
Zuranolone: CYP3A4 Inducers (Moderate) may decrease serum concentration of Zuranolone. Risk X: Avoid
Protein-deficient diets increase duration of action of primidone.
Folic acid: Low erythrocyte and CSF folate concentrations. Megaloblastic anemia has been reported. To avoid folic acid deficiency and megaloblastic anemia, some clinicians recommend giving patients on antiseizure medications prophylactic doses of folic acid and cyanocobalamin.
Vitamin B: Primidone use has been associated with low serum concentrations of vitamin B2 (riboflavin), B6 (pyridoxine), and B12 (cyanocobalamin), which may contribute to hyperhomocysteinemia. Hyperhomocysteinemia may contribute to cardiovascular disease, venous thromboembolic disease, dementia, neuropsychiatric symptoms, and poor seizure control. Some clinicians recommend administering riboflavin, pyridoxine, and cyanocobalamin supplements in patients taking primidone (Apeland 2003; Apeland 2008; Belcastro 2010; Bochyńska 2012).
Primidone and its metabolites (PEMA, phenobarbital, and p-hydroxyphenobarbital) cross the placenta; neonatal serum concentrations at birth are similar to those in the mother. Withdrawal symptoms may occur in the neonate and may be delayed due to the long half-life of primidone and its metabolites. Use may be associated with birth defects and adverse events; the use of folic acid throughout pregnancy and vitamin K during the last month of pregnancy is recommended. Epilepsy itself, number of medications, genetic factors, or a combination of these probably influence the teratogenicity of antiseizure therapy.
Patients exposed to primidone during pregnancy are encouraged to enroll themselves into the NAAED Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.
CNS status, seizure activity, liver enzymes, CBC with differential, renal function, serum concentrations; signs and symptoms of suicidality (eg, anxiety, depression, behavior changes).
Monitor both phenylethylmalonamide (PEMA) and phenobarbital serum concentrations.
PEMA: 4 to 13 mg/L (Mikati 2021; Patsalos 2018).
Phenobarbital: Refer to Phenobarbital monograph for additional information.
Decreases neuron excitability, raises seizure threshold similar to phenobarbital; primidone has two active metabolites, phenobarbital and phenylethylmalonamide (PEMA); PEMA may enhance the activity of phenobarbital
Absorption: Well absorbed (Neels 2004)
Distribution: Vd: 0.6 to 0.75 L/kg (Bourgeois 2000; Neels 2004)
Protein binding: <20% (Bourgeois 2000; Neels 2004)
Metabolism: Hepatic to phenobarbital (active) by oxidation and to phenylethylmalonamide (PEMA; active) by ring cleavage at the second carbon position (El-Masri 1998)
Bioavailability: >90% (Bourgeois 2000)
Half-life elimination (age dependent): Primidone: 5 to16 hours (variable); PEMA: 16 to 50 hours (variable); Phenobarbital: 50 to 150 hours (Bourgeois 2000; Neels 2004)
Time to peak, serum: 0.5 to 9 hours (variable) (Neels 2004)
Excretion: Urine (15% to 65% as unchanged drug; the remainder is unconjugated PEMA, phenobarbital and its metabolites) (Neels 2004)
