ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Primidone: Drug information

Primidone: Drug information
(For additional information see "Primidone: Patient drug information" and see "Primidone: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Mysoline
Pharmacologic Category
  • Antiseizure Agent, Miscellaneous;
  • Barbiturate
Dosing: Adult
Seizure disorder

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maintenance dose as other drug is gradually decreased, continue until desired level obtained or other drug completely withdrawn.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.

Essential tremor

Essential tremor (off-label use): Oral: Initial: 25 mg once daily; increase 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).

Dosing: Kidney Impairment: Adult

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).

Dosing: Hepatic Impairment: Adult

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.

Dosing: Older Adult

Avoid use (Ref).

Dosing: Pediatric

(For additional information see "Primidone: Pediatric drug information")

Seizure disorder

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.

Dosing: Kidney Impairment: Pediatric

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.

Dosing: Hepatic Impairment: Pediatric

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.

Adverse Reactions (Significant): Considerations
CNS effects

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)

Hypersensitivity reactions (delayed)

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).

Adverse Reactions

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 (Pollack 1979), Stevens-Johnson syndrome (Ordonez 2015), toxic epidermal necrolysis (Ordonez 2015)

Gastrointestinal: Anorexia (Sciarra 1954), nausea (Mattson 1995), vomiting (Mattson 1995)

Genitourinary: Impotence (Mattson 1995)

Hematologic & oncologic: Megaloblastic anemia (Chanarin 1958, Kahn 1963)

Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms (Handfield-Jones 1993)

Nervous system: Ataxia (Lenka 2021), behavioral changes (Gaitatzis 2013, Wolf 1978), cognitive dysfunction (Calendre 1990, Farwell 1990, Gaitatzis 2013), drowsiness (Lenka 2021), fatigue (Sciarra 1954), hyperirritability (Herranz 1984), vertigo (Lenka 2021)

Ophthalmic: Eyelid edema (Sciarra 1954), nystagmus disorder (Lenka 2021)

Contraindications

Hypersensitivity to phenobarbital; porphyria

Warnings/Precautions

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.

Warnings: Additional Pediatric Considerations

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).

Dosage Forms: US

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

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Mysoline Oral)

50 mg (per each): $22.73

250 mg (per each): $78.24

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.

Dosage Forms: Canada

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

Tablet, Oral:

Generic: 125 mg, 250 mg

Administration: Pediatric

Oral: Administer without regard to food.

Medication Guide and/or Vaccine Information Statement (VIS)

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.

Use: Labeled Indications

Management of grand mal, psychomotor, and focal seizures

Use: Off-Label: Adult

Essential tremor

Medication Safety Issues
Sound-alike/look-alike issues:

Primidone may be confused with predniSONE, primaquine, pyridoxine

Older Adult: High-Risk Medication:

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]).

Metabolism/Transport Effects

Substrate of CYP2C19 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP1A2 (weak), CYP2A6 (weak), CYP2B6 (weak), CYP2C9 (weak), CYP3A4 (strong), UGT1A1

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 (Strong) may decrease the serum concentration of Abemaciclib. Risk X: Avoid combination

Abiraterone Acetate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abiraterone Acetate. Management: Avoid when possible. If the combination cannot be avoided, increase abiraterone acetate dosing frequency from once daily to twice daily during combined use. Reduce abiraterone dose back to the prior dose and frequency once strong inducer is discontinued. Risk D: Consider therapy modification

Acalabrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Acalabrutinib. Management: Avoid co-administration of strong CYP3A inducers in patients taking acalabrutinib. If strong CYP3A inducers cannot be avoided, increase the dose of acalabrutinib to 200 mg twice daily. Risk D: Consider therapy modification

Acetaminophen: Primidone may increase the metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor therapy

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

Afatinib: Primidone may decrease the 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

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

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

ALfentanil: CYP3A4 Inducers (Strong) may decrease the serum concentration of ALfentanil. Management: If concomitant use of alfentanil and strong CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Risk D: Consider therapy modification

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

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

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

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

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

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

Apixaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apixaban. Management: Avoid concurrent use of apixaban with strong CYP3A4 inducers whenever possible. Use of a strong CYP3A4 inducer with apixaban should be strictly avoided in any patient who is using an agent (either the CYP3A4 inducer or a third drug) that induces P-gp. Risk D: Consider therapy modification

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

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

ARIPiprazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of ARIPiprazole. Management: For indications other than major depressive disorder: double the oral aripiprazole dose over 1 to 2 weeks and closely monitor. Avoid use of strong CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Risk D: Consider therapy modification

ARIPiprazole Lauroxil: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Patients taking the 441 mg dose of aripiprazole lauroxil increase their dose to 662 mg if used with a strong CYP3A4 inducer for more than 14 days. No dose adjustment is necessary for patients using the higher doses of aripiprazole lauroxil. Risk D: Consider therapy modification

Artemether and Lumefantrine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. CYP3A4 Inducers (Strong) may decrease the serum concentration of Artemether and Lumefantrine. Risk X: Avoid combination

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

Atazanavir: Primidone may decrease the serum concentration of Atazanavir. Atazanavir may decrease the serum concentration of Primidone. Risk X: Avoid combination

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

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

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

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

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

Axitinib: CYP3A4 Inducers (Strong) 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

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

Bazedoxifene: Primidone may decrease the 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 therapy

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

Belumosudil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Belumosudil. Management: Increase the dose of belumosudil to 200 mg twice daily when coadministered with strong CYP3A4 inducers. Risk D: Consider therapy modification

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

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

Benzhydrocodone: Primidone may enhance the CNS depressant effect of Benzhydrocodone. Primidone may decrease serum concentrations of the active metabolite(s) 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 strong CYP3A4 inducer, monitor for decreased benzhydrocodone efficacy and withdrawal if combined. Risk D: Consider therapy modification

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

Bictegravir: Primidone may decrease the 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

Bisoprolol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bisoprolol. 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

Blood Pressure Lowering Agents: Barbiturates may enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

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

Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor therapy

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

Brexpiprazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brexpiprazole. Management: If brexpiprazole is used together with a strong CYP3A4 inducer, the brexpiprazole dose should gradually be doubled over the course of 1 to 2 weeks. Decrease brexpiprazole to original dose over 1 to 2 weeks if the strong CYP3A4 inducer is discontinued. Risk D: Consider therapy modification

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

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

Brivaracetam: Primidone may decrease the serum concentration of Brivaracetam. Risk C: Monitor therapy

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

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

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

Buprenorphine: Primidone may enhance the CNS depressant effect of Buprenorphine. Primidone may decrease the serum concentration of Buprenorphine. Management: Avoid use of buprenorphine and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased buprenorphine efficacy and withdrawal if combined. Risk D: Consider therapy modification

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

BusPIRone: CYP3A4 Inducers (Strong) may decrease the serum concentration of BusPIRone. Management: Consider alternatives to this combination. If coadministration of these agents is deemed necessary, monitor patients for reduced buspirone effects and increase buspirone doses as needed. Risk D: Consider therapy modification

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

Cabotegravir: UGT1A1 Inducers may decrease the serum concentration of Cabotegravir. Risk X: Avoid combination

Cabozantinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, increase cabozantinib capsules (Cometriq) by 40 mg from previous dose, max 180 mg daily. Increase cabozantinib tablets (Cabometyx) by 20 mg from previous dose, max 80 mg daily Risk D: Consider therapy modification

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

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

Canagliflozin: Primidone may decrease the 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: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Cannabidiol. CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabidiol. Risk C: Monitor therapy

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

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

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

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

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

Carmustine: Primidone may decrease the serum concentration of Carmustine. Management: Consider alternatives to primidone when using carmustine. If combined, monitor for reduced carmustine efficacy. Risk D: Consider therapy modification

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

Chloramphenicol (Systemic): May increase serum concentrations of the active metabolite(s) of Primidone. Specifically, the concentrations of phenobarbital may be increased. Primidone may decrease the serum concentration of Chloramphenicol (Systemic). 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

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

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

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

Clarithromycin: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Strong) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A4 inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and may impair clarithromycin efficacy. Risk D: Consider therapy modification

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

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

CloZAPine: CYP3A4 Inducers (Strong) may decrease the serum concentration of CloZAPine. Management: Avoid use with strong CYP3A4 inducers when possible. If combined, monitor patients closely and consider clozapine dose increases. Clozapine dose reduction and further monitoring may be required when strong CYP3A4 inducers are discontinued. Risk D: Consider therapy modification

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

Cobicistat: Primidone may decrease the serum concentration of Cobicistat. Risk X: Avoid combination

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

Codeine: Primidone may enhance the CNS depressant effect of Codeine. Primidone may decrease the 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

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

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

Cosyntropin: May enhance the hepatotoxic effect of Primidone. Risk C: Monitor therapy

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

CycloSPORINE (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of CycloSPORINE (Systemic). Management: Monitor closely for reduced cyclosporine concentrations when combined with strong CYP3A4 inducers. Cyclosporine dose increases will likely be required to maintain adequate serum concentrations. Risk D: Consider therapy modification

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

Dabigatran Etexilate: Primidone may decrease the serum concentration of Dabigatran Etexilate. Risk C: Monitor therapy

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

Dapsone (Systemic): May enhance the adverse/toxic effect of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease the serum concentration of Dapsone (Systemic). Risk C: Monitor therapy

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

Darunavir: May decrease the serum concentration of Primidone. Risk C: Monitor therapy

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

Dasatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib. Management: Avoid concurrent use of dasatinib with strong CYP3A4 inducers when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Risk D: Consider therapy modification

Deferasirox: UGT1A1 Inducers may decrease the 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 (Strong) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Risk X: Avoid combination

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

Delavirdine: Primidone may decrease the serum concentration of Delavirdine. Risk X: Avoid combination

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

DexAMETHasone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of DexAMETHasone (Systemic). Management: Consider dexamethasone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced dexamethasone efficacy. Consider avoiding this combination when treating life threatening conditions (ie, multiple myeloma). Risk D: Consider therapy modification

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

Dexmethylphenidate: May increase serum concentrations of the active metabolite(s) of Primidone. Specifically, phenobarbital concentrations could become elevated. Dexmethylphenidate may increase the serum concentration of Primidone. Risk C: Monitor therapy

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

Dienogest: CYP3A4 Inducers (Strong) 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 (Strong) may decrease the serum concentration of DilTIAZem. Management: Consider alternatives to this combination when possible. If combined, monitor for decreased diltiazem efficacy. Risk D: Consider therapy modification

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

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

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

Dolutegravir: Primidone may decrease the serum concentration of Dolutegravir. Specifically, the Primidone metabolite phenobarbital may decrease Dolutegravir serum concentrations. Risk X: Avoid combination

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

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

Doxercalciferol: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Doxercalciferol. Risk C: Monitor therapy

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

Doxycycline: Barbiturates may decrease the serum concentration of Doxycycline. Risk C: Monitor therapy

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

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

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

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 (Strong) may decrease the serum concentration of Duvelisib. Risk X: Avoid combination

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

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

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

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

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

Elagolix, Estradiol, and Norethindrone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elagolix, Estradiol, and Norethindrone. Risk C: Monitor therapy

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

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk X: Avoid combination

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

Elvitegravir: Primidone may decrease the serum concentration of Elvitegravir. Risk X: Avoid combination

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

Enfortumab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor therapy

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

Enzalutamide: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Enzalutamide. CYP3A4 Inducers (Strong) may decrease the serum concentration of Enzalutamide. Management: Consider using an alternative agent that has no or minimal CYP3A4 induction potential when possible. If this combination cannot be avoided, increase the dose of enzalutamide from 160 mg daily to 240 mg daily. Risk D: Consider therapy modification

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

Eravacycline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eravacycline. Management: Increase the eravacycline dose to 1.5 mg/kg every 12 hours when combined with strong CYP3A4 inducers. Risk D: Consider therapy modification

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

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

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

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

Eslicarbazepine: Primidone may decrease the serum concentration of Eslicarbazepine. (based on studies with phenobarbital) Risk C: Monitor therapy

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

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

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

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

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

Etoposide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide. If combined, monitor patients closely for diminished etoposide response and need for etoposide dose increases. Risk D: Consider therapy modification

Etoposide Phosphate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide Phosphate. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide phosphate. If these combinations cannot be avoided, monitor patients closely for diminished etoposide phosphate response. Risk D: Consider therapy modification

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

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

Everolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus. Management: Concomitant use of everolimus and strong CYP3A4 inducers is generally not recommended. However, if combined, monitor for decreased everolimus concentrations and effects, and adjust everolimus dose as needed. Risk D: Consider therapy modification

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

Exemestane: CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane. Management: Increase the exemestane dose to 50 mg once daily in patients receiving concurrent strong CYP3A4 inducers. Monitor patients closely for evidence of toxicity or inadequate clinical response. Risk D: Consider therapy modification

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

Felbamate: May increase serum concentrations of the active metabolite(s) of Primidone. Specifically, phenobarbital concentrations may increase. Primidone may decrease the 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: CYP3A4 Inducers (Strong) may decrease the serum concentration of Felodipine. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced felodipine efficacy and the need for felodipine dose increases. Risk D: Consider therapy modification

Fenfluramine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fenfluramine. Management: Avoid concurrent use of strong CYP3A4 inducers with fenfluramine when possible. If combined use cannot be avoided, consider increasing the fenfluramine dose, but do not exceed the fenfluramine maximum daily dose. Risk D: Consider therapy modification

FentaNYL: Primidone may enhance the CNS depressant effect of FentaNYL. Primidone may decrease the serum concentration of FentaNYL. Management: Avoid use of fentanyl and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased fentanyl efficacy and withdrawal if combined. Risk D: Consider therapy modification

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

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

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

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

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

Folic Acid: May decrease the serum concentration of Primidone. Additionally, folic acid may decrease concentrations of active metabolites of primidone (e.g., phenobarbital). Risk C: Monitor therapy

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

Fosaprepitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite aprepitant. Risk X: Avoid combination

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

Fosphenytoin-Phenytoin: Primidone may enhance the adverse/toxic effect of Fosphenytoin-Phenytoin. Specifically, the risk for agranulocytosis may be increased. Fosphenytoin-Phenytoin may increase serum concentrations of the active metabolite(s) of Primidone. Risk C: Monitor therapy

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

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

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

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

Ganaxolone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and strong CYP3A4 inducers whenever possible. If combined, consider increasing the dose of ganaxolone, but do not exceed the maximum recommended daily dose. Risk D: Consider therapy modification

Gefitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase the gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers; resume 250 mg dose 7 days after discontinuation of the strong inducer. Carefully monitor clinical response. Risk D: Consider therapy modification

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

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

Gestrinone: Primidone may decrease the serum concentration of Gestrinone. Risk C: Monitor therapy

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

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

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

Griseofulvin: Barbiturates may decrease the serum concentration of Griseofulvin. Risk C: Monitor therapy

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

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

Hemin: Barbiturates may diminish the therapeutic effect of Hemin. Risk X: Avoid combination

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

HYDROcodone: Primidone may enhance the CNS depressant effect of HYDROcodone. Primidone may decrease the 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 (Strong) 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 (Strong) may decrease the serum concentration of Ibrexafungerp. Risk X: Avoid combination

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

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

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

Imatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib. Management: Avoid use of imatinib and strong CYP3A4 inducers when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Doses up to 1200 mg/day (600 mg twice daily) have been used. Risk D: Consider therapy modification

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

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

Irinotecan Products: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan Products. Management: Avoid administration of strong CYP3A4 inducers during irinotecan treatment, and substitute non-CYP3A4 inducing agents at least 2 weeks prior to irinotecan initiation, whenever possible. If combined, monitor for reduced irinotecan efficacy. Risk D: Consider therapy modification

Isavuconazonium Sulfate: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Risk X: Avoid combination

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

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

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

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

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

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

Ixabepilone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixabepilone. Management: Avoid this combination whenever possible. If this combination must be used, a gradual increase in ixabepilone dose from 40 mg/m2 to 60 mg/m2 (given as a 4-hour infusion), as tolerated, should be considered. Risk D: Consider therapy modification

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

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

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

Ketoconazole (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Ketoconazole (Systemic). Management: The use of ketoconazole concurrently with or within 2 weeks of a strong CYP3A4 inducer is not recommended. If such a combination cannot be avoided, monitor patients closely for evidence of diminished clinical response to ketoconazole. Risk D: Consider therapy modification

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

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

LamoTRIgine: May enhance the adverse/toxic effect of Primidone. Specifically, the risk for hematologic toxicities may be increased. Primidone may decrease the serum concentration of LamoTRIgine. Management: For patients taking primidone 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 (Strong) may decrease the serum concentration of Lapatinib. Management: If concomitant use cannot be avoided, titrate lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Risk D: Consider therapy modification

Larotrectinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inducers with larotrectinib. If this combination cannot be avoided, double the larotrectinib dose. Reduced to previous dose after stopping the inducer after a period of 3 to 5 times the inducer's half-life. Risk D: Consider therapy modification

Ledipasvir: Primidone may decrease the serum concentration of Ledipasvir. Risk X: Avoid combination

Lefamulin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with strong CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider therapy modification

Lefamulin (Intravenous): CYP3A4 Inducers (Strong) may decrease the serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin intravenous infusion with strong CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider therapy modification

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

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

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

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

Letermovir: UGT1A1 Inducers may decrease the serum concentration of Letermovir. Risk X: Avoid combination

Leucovorin Calcium-Levoleucovorin: May decrease the serum concentration of Primidone. Additionally, leucovorin/levoleucovorin may decrease concentrations of active metabolites of primidone (e.g., phenobarbital). Risk C: Monitor therapy

Leuprolide and Norethindrone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Leuprolide and Norethindrone. Specifically, norethindrone concentrations may be decreased. Risk C: Monitor therapy

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

LevETIRAcetam: May enhance the CNS depressant effect of Primidone. Primidone may decrease the serum concentration of LevETIRAcetam. Risk C: Monitor therapy

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

Levomefolate: May decrease serum concentrations of the active metabolite(s) of Primidone. Levomefolate may decrease the serum concentration of Primidone. Risk C: Monitor therapy

Levomethadone: May enhance the CNS depressant effect of Primidone. Primidone may decrease the 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): CYP3A4 Inducers (Strong) may diminish the therapeutic effect of Levonorgestrel (IUD). CYP3A4 Inducers (Strong) may decrease the serum concentration of Levonorgestrel (IUD). Risk C: Monitor therapy

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

LinaGLIPtin: CYP3A4 Inducers (Strong) may decrease the serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Risk D: Consider therapy modification

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 (Strong) may decrease the serum concentration of Lonafarnib. Risk X: Avoid combination

Lopinavir: Primidone may decrease the serum concentration of Lopinavir. Management: Avoid once-daily administration of lopinavir/ritonavir if used together with phenobarbital. If lopinavir/ritonavir twice daily is combined with phenobarbital, monitor closely for decreased efficacy of lopinavir/ritonavir. Risk D: Consider therapy modification

Lorlatinib: CYP3A4 Inducers (Strong) may enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Lorlatinib. Risk X: Avoid combination

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

Lumacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk X: Avoid combination

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

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

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

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

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

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

Manidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inducers. If combined, monitor closely for decreased manidipine effects and loss of efficacy. Increased manidipine doses may be required. Risk D: Consider therapy modification

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

Maribavir: Primidone may decrease the 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 (Strong) may decrease the serum concentration of Mavacamten. Risk X: Avoid combination

Mefloquine: May diminish the therapeutic effect of Primidone. Primidone may decrease the serum concentration of Mefloquine. Mefloquine may decrease the 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 enhance the CNS depressant effect of Meperidine. Primidone may increase serum concentrations of the active metabolite(s) 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

Methadone: Primidone may enhance the CNS depressant effect of Methadone. Primidone may decrease the 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 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

Methoxyflurane: Barbiturates may enhance the nephrotoxic effect of Methoxyflurane. Barbiturates may increase the metabolism of Methoxyflurane. Risk X: Avoid combination

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

Methylfolate: May decrease the serum concentration of Primidone. Risk C: Monitor therapy

Methylphenidate: May increase serum concentrations of the active metabolite(s) of Primidone. Specifically, phenobarbital concentrations could become elevated. Methylphenidate may increase the serum concentration of Primidone. Risk C: Monitor therapy

MethylPREDNISolone: CYP3A4 Inducers (Strong) may decrease the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Risk D: Consider therapy modification

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

MetroNIDAZOLE (Systemic): Primidone may decrease the serum concentration of MetroNIDAZOLE (Systemic). 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 enhance the CNS depressant effect of Barbiturates. Mianserin may diminish the therapeutic effect of Barbiturates. Barbiturates may decrease the serum concentration of Mianserin. Risk X: Avoid combination

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

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

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

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

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

Mirodenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mirodenafil. Management: Consider avoiding the concomitant use of mirodenafil and strong CYP3A4 inducers. If combined, monitor for decreased mirodenafil effects. Mirodenafil dose increases may be required to achieve desired effects. Risk D: Consider therapy modification

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

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

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

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Barbiturates. Risk C: Monitor therapy

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

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

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

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

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

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

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

Nevirapine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nevirapine. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced nevirapine efficacy. Risk D: Consider therapy modification

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

NIFEdipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NIFEdipine. Management: Avoid coadministration of nifedipine with strong CYP3A4 inducers when possible and if combined, monitor patients closely for clinical signs of diminished nifedipine response. Risk D: Consider therapy modification

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

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

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

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

Nirmatrelvir and Ritonavir: Primidone may decrease serum concentrations of the active metabolite(s) of Nirmatrelvir and Ritonavir. Nirmatrelvir and Ritonavir may decrease the serum concentration of Primidone. Risk X: Avoid combination

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

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

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

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

OLANZapine: CYP1A2 Inducers (Weak) may decrease the serum concentration of OLANZapine. Risk C: Monitor therapy

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

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

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

Ondansetron: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ondansetron. 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 (Strong) 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

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

Osimertinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Osimertinib. Management: Avoid coadministration of osimertinib and strong CYP3A4 inducers if possible. If coadministration is unavoidable, increase osimertinib to 160 mg daily. Reduce osimertinib to 80 mg daily 3 weeks after discontinuation of the strong CYP3A4 inducer. Risk D: Consider therapy modification

OXcarbazepine: CYP3A4 Inducers (Strong) may decrease the serum concentration of OXcarbazepine. Specifically, the concentrations of the 10-monohydroxy active metabolite of oxcarbazepine may be decreased. Risk C: Monitor therapy

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: Primidone may enhance the CNS depressant effect of OxyCODONE. Primidone may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

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

Perampanel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with strong CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider therapy modification

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

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

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

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

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

Pitolisant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pitolisant. Management: If on a stable pitolisant dose of 8.9 mg or 17.8 mg/day and starting a strong CYP3A4 inducer, double the pitolisant dose over 7 days (ie, to either 17.8 mg/day or 35.6 mg/day, respectively). Reduce pitolisant dose by 50% when the inducer is discontinued. Risk D: Consider therapy modification

Polatuzumab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be decreased. Risk C: Monitor therapy

PONATinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of PONATinib. Management: Avoid coadministration of ponatinib with strong CYP3A4 inducers unless the potential benefit of concomitant treatment outweighs the risk of reduced ponatinib exposure. Monitor patients for reduced ponatinib efficacy if combined. Risk D: Consider therapy modification

Ponesimod: UGT1A1 Inducers may decrease the serum concentration of Ponesimod. Risk X: Avoid combination

Pralsetinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pralsetinib. Management: Avoid concomitant use of pralsetinib with strong CYP3A4 inducers when possible. If combined, increase the starting dose of pralsetinib to double the current pralsetinib dosage starting on day 7 of coadministration. Risk D: Consider therapy modification

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

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

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

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

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

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

Propacetamol: Primidone may increase the metabolism of Propacetamol. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor therapy

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

Pyridoxine: May decrease serum concentrations of the active metabolite(s) of Primidone. Specifically, concentrations of phenobarbital may be reduced. Risk C: Monitor therapy

QUEtiapine: CYP3A4 Inducers (Strong) may decrease the serum concentration of QUEtiapine. Management: An increase in quetiapine dose (as much as 5 times the regular dose) may be required to maintain therapeutic benefit. Reduce the quetiapine dose back to the previous/regular dose within 7 to 14 days of discontinuing the inducer. Risk D: Consider therapy modification

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

QuiNINE: May increase the serum concentration of Primidone. Primidone may decrease the 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 (Strong) may decrease the serum concentration of Quizartinib. Risk X: Avoid combination

Radotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Radotinib. Management: Consider alternatives to this combination when possible as the risk of radotinib treatment failure may be increased. Risk D: Consider therapy modification

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

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

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

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

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

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

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

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

Rilpivirine: Primidone may decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

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

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

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

RisperiDONE: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of RisperiDONE. CYP3A4 Inducers (Strong) may decrease the serum concentration of RisperiDONE. Management: Careful monitoring for reduced risperidone efficacy and possible dose adjustment are recommended when combined with strong CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider therapy modification

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

Ritonavir: May decrease the serum concentration of Primidone. Primidone may decrease the 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 phenobarbital and ritonavir concentrations and effects during coadministration. Risk D: Consider therapy modification

Rivaroxaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban. Management: Consider alternatives to use of rivaroxaban with strong CYP3A4 inducers. Use of a strong CYP3A4 inducer with rivaroxaban should be strictly avoided in any patient who is using an agent (either the CYP3A4 inducer or a third drug) that induces P-gp. Risk D: Consider therapy modification

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

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

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

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 increase serum concentrations of the active metabolite(s) of Primidone. Specifically, phenobarbital concentrations may be increased. Primidone may decrease the serum concentration of Rufinamide. Risk C: Monitor therapy

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

Sacituzumab Govitecan: UGT1A1 Inducers may decrease serum concentrations of the active metabolite(s) of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be decreased. Risk X: Avoid combination

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

Sapropterin: Primidone may decrease the serum concentration of Sapropterin. Risk C: Monitor therapy

Saquinavir: Primidone may decrease the serum concentration of Saquinavir. Risk X: Avoid combination

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

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

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

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

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

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

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

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

Sirolimus (Conventional): CYP3A4 Inducers (Strong) may decrease the serum concentration of Sirolimus (Conventional). Management: Avoid concomitant use of strong CYP3A4 inducers and sirolimus if possible. If combined, monitor for reduced serum sirolimus concentrations. Sirolimus dose increases will likely be necessary to prevent subtherapeutic sirolimus levels. Risk D: Consider therapy modification

Sirolimus (Protein Bound): CYP3A4 Inducers (Strong) may decrease the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination

Sofosbuvir: Primidone may decrease the serum concentration of Sofosbuvir. Risk X: Avoid combination

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

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

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

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

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

Stiripentol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Stiripentol. Management: Avoid concomitant use of stiripentol and strong CYP3A4 inducers when possible. If combined, monitor for reduced stiripentol efficacy and increase the stiripentol dose as needed. Risk D: Consider therapy modification

SUFentanil: Primidone may enhance the CNS depressant effect of SUFentanil. Primidone may decrease the serum concentration of SUFentanil. Management: Avoid use of sufentanil and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased sufentanil efficacy and withdrawal if combined. Risk D: Consider therapy modification

Sulthiame: Primidone may enhance the adverse/toxic effect of Sulthiame. Risk C: Monitor therapy

SUNItinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SUNItinib. Management: Avoid when possible. If combined, increase sunitinib dose to a max of 87.5 mg daily when treating GIST or RCC. Increase sunitinib dose to a max of 62.5 mg daily when treating PNET. Monitor patients for both reduced efficacy and increased toxicities. Risk D: Consider therapy modification

Suvorexant: 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 (Strong) may decrease the serum concentration of Tacrolimus (Systemic). Management: Monitor for decreased tacrolimus concentrations and effects when combined with strong CYP3A4 inducers. Tacrolimus dose increases will likely be needed during concomitant use. Risk D: Consider therapy modification

Tadalafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil. Management: Erectile dysfunction or benign prostatic hypertrophy: monitor for decreased effectiveness - no standard dose adjustment is recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Risk D: Consider therapy modification

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

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

Taurursodiol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Taurursodiol. Specifically, the concentrations of phenylbutyrate may be decreased. Risk C: Monitor therapy

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

Temsirolimus: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be decreased. CYP3A4 Inducers (Strong) may decrease the serum concentration of Temsirolimus. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inducers. If coadministration is unavoidable, increase temsirolimus dose to 50 mg per week. Resume previous temsirolimus dose after discontinuation of the strong CYP3A4 inducer. Risk D: Consider therapy modification

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

Tenofovir Alafenamide: Primidone may decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination

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

Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol. Management: Avoid use of the tetrahydrocannabinol/cannabidiol oromucosal spray and strong CYP3A4 inducers when possible. If combined use is necessary, careful titration is recommended, notably within the two weeks following discontinuation of the inducer. Risk D: Consider therapy modification

Tezacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tezacaftor and Ivacaftor. Risk X: Avoid combination

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

Theophylline Derivatives: Barbiturates may decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

Thiotepa: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inducers (Strong) may decrease the serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inducers. If concomitant use is unavoidable, monitor for adverse effects. Risk D: Consider therapy modification

Thiothixene: Primidone may decrease the serum concentration of Thiothixene. Risk C: Monitor therapy

Thyroid Products: Primidone may decrease the serum concentration of Thyroid Products. Risk C: Monitor therapy

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

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

Tipranavir: Primidone may decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Primidone. Risk C: Monitor therapy

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

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

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

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

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

TraMADol: Primidone may enhance the CNS depressant effect of TraMADol. Primidone may decrease the serum concentration of TraMADol. Management: Avoid use of tramadol and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased tramadol efficacy and withdrawal if combined. Risk D: Consider therapy modification

TraZODone: CYP3A4 Inducers (Strong) may decrease the serum concentration of TraZODone. Management: Consider increasing the trazodone dose during coadministration with strong CYP3A4 inducers. Risk D: Consider therapy modification

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

Triazolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Triazolam. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced triazolam efficacy. Substantial triazolam dose increases will likely be required. Risk D: Consider therapy modification

Tricyclic Antidepressants: Barbiturates may increase the 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

Valproate Products: May increase the serum concentration of Primidone. More specifically, the serum concentration of phenobarbital, primidone's primary active metabolite, may be increased. Primidone may decrease the serum concentration of Valproate Products. Risk C: Monitor therapy

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

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

Vemurafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib. Management: Avoid coadministration of vemurafenib and strong CYP3A4 inducers if possible. If coadministration is unavoidable, increase the vemurafenib dose by 240 mg as tolerated. Resume prior vemurafenib dose 2 weeks after discontinuation of strong CYP3A4 inducer. Risk D: Consider therapy modification

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

Verapamil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Verapamil. Management: Consider alternatives to this combination. If combined, monitor for reduced verapamil efficacy. Verapamil dose increases may be necessary. Risk D: Consider therapy modification

Vilazodone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vilazodone. Management: Consider increasing vilazodone dose by as much as 2-fold (do not exceed 80 mg/day), based on response, in patients receiving strong CYP3A4 inducers for > 14 days. Reduce to the original vilazodone dose over 1 to 2 weeks after inducer discontinuation. Risk D: Consider therapy modification

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

VinCRIStine (Liposomal): CYP3A4 Inducers (Strong) may decrease the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination

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

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

Vitamin K Antagonists (eg, warfarin): Barbiturates may increase the 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 (Strong) may decrease the serum concentration of Voclosporin. Risk X: Avoid combination

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

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

Voriconazole: Primidone may decrease the serum concentration of Voriconazole. Risk X: Avoid combination

Vortioxetine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vortioxetine. Management: Consider increasing the vortioxetine dose to no more than 3 times the original dose when used with a strong drug metabolism inducer for more than 14 days. The vortioxetine dose should be returned to normal within 14 days of stopping the strong inducer. Risk D: Consider therapy modification

Voxelotor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and strong CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,500 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider therapy modification

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

Zaleplon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zaleplon. Management: Consider the use of an alternative hypnotic that is not metabolized by CYP3A4 in patients receiving strong CYP3A4 inducers. If zaleplon is combined with a strong CYP3A4 inducer, monitor for decreased effectiveness of zaleplon. Risk D: Consider therapy modification

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

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

Zolpidem: 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

Zonisamide: May enhance the CNS depressant effect of Primidone. Primidone may decrease the serum concentration of Zonisamide. Risk C: Monitor therapy

Zopiclone: Primidone may enhance the CNS depressant effect of Zopiclone. Primidone may decrease the serum concentration of Zopiclone. Risk C: Monitor therapy

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

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

Food Interactions

Protein-deficient diets increase duration of action of primidone.

Pregnancy Considerations

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.

Breastfeeding Considerations

Primidone and its metabolites (PEMA, phenobarbital, and p-hydroxyphenobarbital) are found in breast milk (variable concentrations). The manufacturer recommends discontinuing breast-feeding if undue drowsiness and somnolence occur in the newborn.

Dietary Considerations

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).

Monitoring Parameters

Serum primidone and phenobarbital concentration, neurological status. Monitor CBC and comprehensive metabolic panel at 6-month intervals to compare with baseline obtained at start of therapy. Monitor for suicidality and depression.

Reference Range

Therapeutic: Children <5 years: 7-10 mcg/mL (SI: 32-46 micromole/L); Adults: 5-12 mcg/mL (SI: 23-55 micromole/L); toxic effects rarely present with levels <10 mcg/mL (SI: 46 micromole/L) if phenobarbital concentrations are low. Dosage of primidone is adjusted with reference mostly to the phenobarbital level; Toxic: >15 mcg/mL (SI: >69 micromole/L). There is no clear correlation between serum level and clinical benefit when used for essential tremor (Hedera 2013).

Mechanism of Action

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

Pharmacokinetics (Adult Data Unless Noted)

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)

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

  • (AE) United Arab Emirates: Mysoline;
  • (AR) Argentina: Mysodone | Mysoline;
  • (AT) Austria: Cyral | Mysoline;
  • (AU) Australia: Apo primidone | Mysoline;
  • (BD) Bangladesh: Rimidon;
  • (BE) Belgium: Mysoline;
  • (BG) Bulgaria: Liskantin;
  • (BR) Brazil: Primid | Primidon | Primidona;
  • (CH) Switzerland: Mysoline;
  • (CL) Chile: Primidona;
  • (CN) China: Mysolin;
  • (CO) Colombia: Mysoline | Primidol | Primidona;
  • (CZ) Czech Republic: Lepsiral | Liskantin | Mysoline | Sertan;
  • (DE) Germany: Liskantin | Mylepsinum | Primidon | Resimatil;
  • (DK) Denmark: Primidon era;
  • (DO) Dominican Republic: Mysoline;
  • (EC) Ecuador: Mysoline;
  • (EE) Estonia: Liskantin | Mysoline;
  • (ES) Spain: Mysoline;
  • (FI) Finland: Mysedon | Mysoline;
  • (FR) France: Mysoline;
  • (GB) United Kingdom: Mysoline | Primidone aspire | Primidone auden;
  • (GR) Greece: Liskantin | Mysoline;
  • (HK) Hong Kong: Mysoline;
  • (HU) Hungary: Mysoline | Sertan;
  • (ID) Indonesia: Mysoline;
  • (IE) Ireland: Mysoline;
  • (IL) Israel: Prysoline;
  • (IN) India: Mysoline | Prolet | Tremidon;
  • (IT) Italy: Mysoline;
  • (JO) Jordan: Mysoline;
  • (JP) Japan: Primidone dainippon | Primron;
  • (KR) Korea, Republic of: Daewoong primidone;
  • (LB) Lebanon: Mysoline;
  • (LT) Lithuania: Hexamidin | Lepsiral | Liskantin | Majsolin | Mylepsinum | Mysoline | Primidon | Sertan;
  • (LU) Luxembourg: Mysoline;
  • (LV) Latvia: Hexamidin | Lepsiral | Liskantin | Majsolin | Mysoline | Sertan;
  • (MX) Mexico: Mysoline | Pridona | Primidona | Stabin;
  • (MY) Malaysia: Apo primidone | Mysoline;
  • (NL) Netherlands: Mysoline;
  • (NO) Norway: Liskantin | Mysoline | Primidon | Primidone amneal;
  • (NZ) New Zealand: Apo primidone | Mysoline;
  • (PE) Peru: Mysoline;
  • (PL) Poland: Lepsiral | Liskantin | Mizodin | Mysoline | Sertan;
  • (PR) Puerto Rico: Mysoline;
  • (PT) Portugal: Mysoline | Primidona | Primidone serb;
  • (RU) Russian Federation: Hexamidin;
  • (SA) Saudi Arabia: Mysoline;
  • (SE) Sweden: Mysoline;
  • (SG) Singapore: Mysoline;
  • (SI) Slovenia: Liskantin | Primidon | Primidon Holsten;
  • (SK) Slovakia: Liskantin | Mysoline;
  • (TH) Thailand: Mysoline;
  • (TN) Tunisia: Mysoline;
  • (TR) Turkey: Mysoline;
  • (TW) Taiwan: Mysoline;
  • (UA) Ukraine: Hexamidin;
  • (UY) Uruguay: Mysoline | Primidona;
  • (VE) Venezuela, Bolivarian Republic of: Mysoline;
  • (ZA) South Africa: Mysoline
  1. 2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372 [PubMed 37139824]
  2. Abboud H, Ahmed A, Fernandez HH. Essential tremor: choosing the right management plan for your patient. Cleve Clin J Med. 2011;78(12):821-828. doi:10.3949/ccjm.78a.10178 [PubMed 22135272]
  3. Apeland T, Mansoor MA, Pentieva K, McNulty H, Strandjord RE. Fasting and post-methionine loading concentrations of homocysteine, vitamin B2, and vitamin B6 in patients on antiepileptic drugs. Clin Chem. 2003;49(6 pt 1):1005-1008. doi:10.1373/49.6.1005 [PubMed 12766014]
  4. Apeland T, Frøyland ES, Kristensen O, Strandjord RE, Mansoor MA. Drug-induced pertubation of the aminothiol redox-status in patients with epilepsy: improvement by B-vitamins. Epilepsy Res. 2008;82(1):1-6. doi:10.1016/j.eplepsyres.2008.06.003 [PubMed 18644700]
  5. Arana A, Wentworth CE, Ayuso-Mateos JL, Arellano FM. Suicide-related events in patients treated with antiepileptic drugs. N Engl J Med. 2010;363(6):542-551. doi:10.1056/NEJMoa0909801 [PubMed 20818889]
  6. Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007, p 91.
  7. Asconapé JJ. Use of antiepileptic drugs in hepatic and renal disease. Handb Clin Neurol. 2014;119:417-432. doi:10.1016/B978-0-7020-4086-3.00027-8 [PubMed 24365310]
  8. Belcastro V, Striano P. Antiepileptic drugs, hyperhomocysteinemia and B-vitamins supplementation in patients with epilepsy. Epilepsy Res. 2012;102(1-2):1-7. doi:10.1016/j.eplepsyres.2012.07.003 [PubMed 22824326]
  9. Bell GS, Gaitatzis A, Bell CL, Johnson AL, Sander JW. Suicide in people with epilepsy: how great is the risk? Epilepsia. 2009;50(8):1933-42. doi:10.1111/j.1528-1167.2009.02106.x [PubMed 19453718]
  10. 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
  11. Błaszczyk B, Lasoń W, Czuczwar SJ. Antiepileptic drugs and adverse skin reactions: An update. Pharmacol Rep. 2015;67(3):426-434. doi:10.1016/j.pharep.2014.11.009 [PubMed 25933949]
  12. Bochyńska A, Lipczyńska-Łojkowska W, Gugała-Iwaniuk M, et al. The effect of vitamin B supplementation on homocysteine metabolism and clinical state of patients with chronic epilepsy treated with carbamazepine and valproic acid. Seizure. 2012;21(4):276-281. doi:10.1016/j.seizure.2012.01.013 [PubMed 22360846]
  13. Bourdet SV, Gidal BE, Alldredge BK. Pharmacologic management of epilepsy in the elderly. J Am Pharm Assoc (Wash). 2001;41(3):421-436. doi:10.1016/s1086-5802(16)31256-6 [PubMed 11372907]
  14. Bourgeois BF. Antiepileptic drugs in pediatric practice. Epilepsia. 1995; 36(Suppl 2):S34-45. doi:10.1111/j.1528-1157.1995.tb05998.x [PubMed 8784213]
  15. Bourgeois BF. Pharmacokinetic properties of current antiepileptic drugs: what improvements are needed? Neurology. 2000;55(11 suppl 3):S11-S16. [PubMed 11147563]
  16. Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]
  17. Calandre EP, Dominguez-Granados R, Gomez-Rubio M, Molina-Font JA. Cognitive effects of long-term treatment with phenobarbital and valproic acid in school children. Acta Neurol Scand. 1990;81(6):504-506. doi:10.1111/j.1600-0404.1990.tb01008.x [PubMed 2220307]
  18. Chanarin I, Elmes PC, Mollin DL. Folic-acid studies in megaloblastic anaemia due to primidone. Br Med J. 1958;2(5088):80-82. doi:10.1136/bmj.2.5088.80 [PubMed 13546653]
  19. Chen JJ, Swope DM. Essential tremor: diagnosis and treatment. Pharmacotherapy. 2003;23(9):1105-1122. doi:10.1592/phco.23.10.1105.32750 [PubMed 14524643]
  20. Deik A, Tarsy D. Post TW, ed. Essential tremor: treatment and prognosis. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 4, 2023.
  21. Deuschl G, Raethjen J, Hellriegel H, Elble R. Treatment of patients with essential tremor. Lancet Neurol. 2011;10(2):148-161. doi:10.1016/S1474-4422(10)70322-7 [PubMed 21256454]
  22. Duncan KO, Tigelaar RE, Bolognia JL. Stevens-Johnson syndrome limited to multiple sites of radiation therapy in a patient receiving phenobarbital. J Am Acad Dermatol. 1999;40(3):493-496. doi:10.1016/s0190-9622(99)70508-6 [PubMed 10071329]
  23. El-Masri HA, Portier CJ. Physiologically based pharmacokinetics model of primidone and its metabolites phenobarbital and phenylethylmalonamide in humans, rats, and mice. Drug Metab Dispos. 1998;26(6):585-594. [PubMed 9616196]
  24. Errani A, Reggiani M, Schianchi S, Staffa M. Toxic epidermal necrolysis induced by barbiturates and radiotherapy. Br J Dermatol. 1994;131(4):586-587. doi:10.1111/j.1365-2133.1994.tb08571.x [PubMed 7947221]
  25. Fabbrocini G, Panariello L, Pensabene M, et al. EMPACT syndrome associated with phenobarbital. Dermatitis. 2013;24(1):37-39. doi:10.1097/DER.0b013e31827ede32 [PubMed 23340399]
  26. Farwell JR, Lee YJ, Hirtz DG, Sulzbacher SI, Ellenberg JH, Nelson KB. Phenobarbital for febrile seizures--effects on intelligence and on seizure recurrence. N Engl J Med. 1990;322(6):364-369. doi:10.1056/NEJM199002083220604 [PubMed 2242106]
  27. Ferreira JJ, Mestre TA, Lyons KE, et al; MDS Task Force on Tremor and the MDS Evidence Based Medicine Committee. MDS evidence-based review of treatments for essential tremor. Mov Disord. 2019;34(7):950-958. doi:10.1002/mds.27700 [PubMed 31046186]
  28. Findley LJ, Cleeves L, Calzetti S. Primidone in essential tremor of the hands and head: a double blind controlled clinical study. J Neurol Neurosurg Psychiatry. 1985;48(9):911-915. doi:10.1136/jnnp.48.9.911 [PubMed 3900296]
  29. Fowler T, Bansal AS, Lozsádi D. Risks and management of antiepileptic drug induced skin reactions in the adult out-patient setting. Seizure. 2019;72:61-70. doi:10.1016/j.seizure.2019.07.003 [PubMed 31708349]
  30. Fujino Y, Nakajima M, Inoue H, Kusuhara T, Yamada T. Human herpesvirus 6 encephalitis associated with hypersensitivity syndrome. Ann Neurol. 2002;51(6):771-774. doi:10.1002/ana.10194 [PubMed 12112085]
  31. Gaitatzis A, Sander JW. The long-term safety of antiepileptic drugs. CNS Drugs. 2013;27(6):435-455. doi:10.1007/s40263-013-0063-0 [PubMed 23673774]
  32. Guvenir H, Dibek Misirlioglu E, et al. The frequency and clinical features of hypersensitivity reactions to antiepileptic drugs in children: A prospective study. J Allergy Clin Immunol Pract. 2018;6(6):2043-2050. doi:10.1016/j.jaip.2018.02.018 [PubMed 29501520]
  33. Handfield-Jones SE, Jenkins RE, Whittaker SJ, Besse CP, McGibbon DH. The anticonvulsant hypersensitivity syndrome. Br J Dermatol. 1993;129(2):175-177. doi:10.1111/j.1365-2133.1993.tb03523.x [PubMed 7654579]
  34. Hedera P, Cibulčik, Davis TL. Pharmacotherapy of essential tremor. J Cent Nerv Syst Dis. 2013;22(5):43-55. doi:10.4137/JCNSD.S6561 [PubMed 24385718]
  35. Herranz JL, Armijo JA, Arteaga R. Effectiveness and toxicity of phenobarbital, primidone, and sodium valproate in the prevention of febrile convulsions, controlled by plasma levels. Epilepsia. 1984;25(1):89-95. doi:10.1111/j.1528-1157.1984.tb04160.x [PubMed 6420147]
  36. Hesdorffer DC, Kanner AM. The FDA alert on suicidality and antiepileptic drugs: Fire or false alarm? Epilepsia. 2009;50(5):978-86. doi:10.1111/j.1528-1167.2009.02012.x [PubMed 19496806]
  37. Hosohata K, Inada A, Oyama S, Niinomi I, Wakabayashi T, Iwanaga K. Adverse cutaneous drug reactions associated with old- and new- generation antiepileptic drugs using the Japanese Pharmacovigilance Database. Clin Drug Investig. 2019;39(4):363-368. doi:10.1007/s40261-019-00754-z [PubMed 30689189]
  38. Kahn SB, Lischner H, Baker L, Williams WJ. Megaloblastic anemia associated with the ingestion of phenobarbital and primidone. report of a case in a six-year-old child. Pediatrics. 1963;32:376-383. [PubMed 14063515]
  39. Kennedy GM, Lhatoo SD. CNS adverse events associated with antiepileptic drugs. CNS Drugs. 2008;22(9):739-760. doi:10.2165/00023210-200822090-00003 [PubMed 18698874]
  40. Kim HK, Kim DY, Bae EK, Kim DW. Adverse skin reactions with antiepileptic drugs using Korea adverse event reporting system database, 2008-2017. J Korean Med Sci. 2020;35(4):e17. doi:10.3346/jkms.2020.35.e17 [PubMed 31997613]
  41. Knowles SR, Dewhurst N, Shear NH. Anticonvulsant hypersensitivity syndrome: an update. Expert Opin Drug Saf. 2012;11(5):767-778. doi:10.1517/14740338.2012.705828 [PubMed 22794330]
  42. Lee CS, Marbury TC, Perchalski RT, Wilder BJ. Pharmacokinetics of primidone elimination by uremic patients. J Clin Pharmacol. 1982;22(7):301-308. doi:10.1002/j.1552-4604.1982.tb02679.x [PubMed 7107978]
  43. Lenka A, Louis ED. Primidone intolerance in essential tremor: Is it more than just age? Tremor Other Hyperkinet Mov (N Y). 2021;11:57. doi:10.5334/tohm.672 [PubMed 35070493]
  44. Louis ED. Clinical practice. Essential tremor. N Engl J Med. 2001;345(12):887-891. doi: 10.1056/NEJMcp010928 [PubMed 11565522]
  45. Maitre NL, Smolinsky C, Slaughter JC, Stark AR. Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures. J Perinatol. 2013;33(11):841-846. doi:10.1038/jp.2013.116 [PubMed 24051577]
  46. Mattson RH. Efficacy and adverse effects of established and new antiepileptic drugs. Epilepsia. 1995;36(suppl 2):S13-S26. doi:10.1111/j.1528-1157.1995.tb05995.x [PubMed 8784211]
  47. McNamara JO. Drugs effective in the therapy of the epilepsies. Gardman JG, Limbird LE, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill; 2001:532.
  48. Mikati MA, Tchapyjnikov D. Treatment of seizures and epilepsy. In: Kliegman RM, St. Geme J, eds. Nelson Textbook of Pediatrics. 21st ed. Elsevier; 2020:chap. 611.6.
  49. 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]
  50. Mysoline (primidone) [prescribing information]. Bridgewater, NJ: Bausch Health US, LLC; July 2020.
  51. Nau H, Rating D, Häuser I, Jäger E, Koch S, Helge H. Placental transfer and pharmacokinetics of primidone and its metabolites phenobarbital, PEMA and hydroxyphenobarbital in neonates and infants of epileptic mothers. Eur J Clin Pharmacol. 1980;18(1):31-42. doi:10.1007/BF00561476 [PubMed 7398746]
  52. Neels HM, Sierens AC, Naelaerts K, Scharpé SL, Hatfield GM, Lambert WE. Therapeutic drug monitoring of old and newer anti-epileptic drugs. Clin Chem Lab Med. 2004;42(11):1228-1255. doi:10.1515/CCLM.2004.245 [PubMed 15576287]
  53. Newell BD, Moinfar M, Mancini AJ, Nopper AJ. Retrospective analysis of 32 pediatric patients with anticonvulsant hypersensitivity syndrome (ACHSS). Pediatr Dermatol. 2009;26(5):536-546. doi:10.1111/j.1525-1470.2009.00870.x [PubMed 19840307]
  54. National Institute for Health and Care Excellence (NICE). Drug allergy: Diagnosis and management. Clinical Guideline 183 (CG183). Published September 3, 2014. www.nice.org.uk/guidance/cg183.
  55. O'Brien MD, Upton AR, Toseland PA. Benign familial tremor treated with primidone. Br Med J (Clin Res Ed). 1981;282(6259):178-180. doi:10.1136/bmj.282.6259.178 [PubMed 6779938]
  56. Ordoñez L, Salgueiro E, Jimeno FJ, Manso G. Spontaneous reporting of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with antiepileptic drugs. Eur Rev Med Pharmacol Sci. 2015;19(14):2732-2737. [PubMed 26221907]
  57. Pahwa R, Lyons KE. Essential tremor: differential diagnosis and current therapy. Am J Med. 2003;115(2):134-42. doi:10.1016/s0002-9343(03)00259-6 [PubMed 12893400]
  58. Porter RJ, Meldrum BD. Antiepileptic Drugs. Katzung BG, ed. Basic & Clinical Pharmacology. 6th ed. East Norwalk, CT: Appleton & Lange; 1995:369.
  59. Patorno E, Bohn RL, Wahl PM, Avorn J, Patrick AR, Liu J, Schneeweiss S. Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death. JAMA. 2010;303(14):1401-1409. doi:10.1001/jama.2010.410. Erratum in: JAMA. 2010;303(22):2252. Dosage error in article text. [PubMed 20388896]
  60. Patsalos PN, Spencer EP, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: a 2018 update. Ther Drug Monit. 2018;40(5):526-548. doi:10.1097/FTD.0000000000000546 [PubMed 29957667]
  61. Pollack MA, Burk PG, Nathanson G. Mucocutaneous eruptions due to antiepileptic drug therapy in children. Ann Neurol. 1979;5(3):262-267. doi:10.1002/ana.410050308 [PubMed 443758]
  62. Primidone tablets [prescribing information]. Vaughan, Ontario, Canada: AA Pharma Inc; June 2015.
  63. Refer to manufacturer's labeling.
  64. Ruggiero A, Buonuomo PS, Maurizi P, Cefalo MG, Corsello M, Riccardi R. Stevens-Johnson syndrome in children receiving phenobarbital therapy and cranial radiotherapy [published correction appearing in J Neurooncol. 2008;87(3):367]. J Neurooncol. 2007;85(2):213-215. doi:10.1007/s11060-007-9399-y [PubMed 17589805]
  65. 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]
  66. Schwankhaus JD, Kattah JC, Lux WE, Masucci EF, Kurtzke JF. Primidone/phenobarbital-induced periodic alternating nystagmus. Ann Ophthalmol. 1989;21(6):230-232. [PubMed 2764437]
  67. Sciarra D, Carter S, Vicale CT, Merritt HH. Clinical evaluation of primidone (Mysoline), new anticonvulsant drug. J Am Med Assoc. 1954;154(10):827-829. doi:10.1001/jama.1954.02940440025007 [PubMed 13129047]
  68. Serrano-Dueñas M. Use of primidone in low doses (250 mg/day) versus high doses (750 mg/day) in the management of essential tremor. Double-blind comparative study with one-year follow-up. Parkinsonism Relat Disord. 2003;10(1):29-33. doi:10.1016/s1353-8020(03)00070-1 [PubMed 14499204]
  69. Shanker V. Essential tremor: diagnosis and management. BMJ. 2019;366:l4485. doi:10.1136/bmj.l4485 [PubMed 31383632]
  70. Tensini TS, Von Glehn CQ, Bettinotti MP, et al. Cutaneous adverse reactions associated with antiseizure medication: clinical characteristics and implications in epilepsy treatment. Epileptic Disord. 2021;23(3):466-475. doi:10.1684/epd.2021.1288 [PubMed 34080983]
  71. Tohyama M, Hashimoto K, Yasukawa M, et al. Association of human herpesvirus 6 reactivation with the flaring and severity of drug-induced hypersensitivity syndrome. Br J Dermatol. 2007;157(5):934-940. doi:10.1111/j.1365-2133.2007.08167.x [PubMed 17854362]
  72. Wolf SM, Forsythe A. Behavior disturbance, phenobarbital, and febrile seizures. Pediatrics. 1978;61(5):728-731. [PubMed 662511]
  73. Zappia M, Albanese A, Bruno E, et al. Treatment of essential tremor: a systematic review of evidence and recommendations from the Italian Movement Disorders Association. J Neurol. 2013;260(3):714-740. doi:10.1007/s00415-012-6628-x [PubMed 22886006]
  74. Zesiewicz TA, Elble RJ, Louis ED, et al. Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards subcommittee of the American Academy of Neurology. Neurology. 2011;77(19):1752-1755. doi:10.1212/WNL.0b013e318236f0fd [PubMed 22013182]
  75. Zesiewicz TA, Elble R, Louis ED, et al; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2005;64(12):2008-2020. doi:10.1212/01.WNL.0000163769.28552.CD [PubMed 15972843]
Topic 9811 Version 485.0

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟