Primidone is an anti-epileptic medicine that belongs to the barbiturate class and is available as different brands. It is used to treat seizures and benign essential tremors.
Indications of Primidone:
- It is indicated for the management of grand mal, psychomotor and focal seizures.
-
Off Label Use of Primidone in Adults:
- Essential tremor
Primidone Dose in Adults
Primidone treatment dose of Seizure disorders (grand mal, psychomotor, and focal):
- Days 1 to 3 per oral dose of 100 to 125 mg once a day at bedtime
- days 4 to 6 per oral dose 100 to 125 b.i.d daily
- days 7 to 9 per oral dose of 100 to 125 mg t.i.d daily
- usual dose: 750 to 1,500 mg once a day per oral in divided doses 3 to 4 times/day with a maximum dosage of 2 g/day
Patients already receiving other anticonvulsants:
- The initial dose of 100 to 125 mg per oral at bedtime followed by maintenance dose as other drugs is reduced slowly.
- The drug should be continued until the desired level obtained or other drugs completely stopped.
- If the goal is to have a single-agent therapy, the conversion should be completed over within 14 days.
Primidone treatment dose of Essential tremor (off-label):
- The initial dose of 50 to 62.5 mg per oral once daily by gradual increase depending on response and tolerance in increments of 62.5 to 125 mg every 1 to 3 days or by 250 mg every seven days and to be given in b.i.d or t.i.d divided doses.
- Usual dosage:
- 250 to 750 mg/day.
- The maximum dose:
- 750 mg/day.
Note:
- Small maintenance doses up to 250 mg daily are found to be equally /more effective in comparison to higher doses of 750 mg daily with lesser side effects.
- However, tolerance is not improved with lower initial doses (as low as 7.5 mg/day) and more gradual titration schedules.
Primidone dosage in children:
primidone for the treatment of Seizure disorder (generalized tonic-clonic, psychomotor, and focal):
-
Weight-directed dose:
-
Infants and Children <8 years:
-
Usual maintenance range:
- 10 to 25 mg/kg per oral per day in 2 to 3 divided doses Lower dosage should be started and titrated upward
-
usual maximum dose:
- 500 mg/dose.
-
-
-
Fixed dosing:
-
Children <8 years:
- Initial dose on days 1 to 3 of 50 mg per oral at bedtime
- Days 4 to 6: 50 mg per oral every 12 hourly
- Days 7 to 9: 100 mg every 12 hourly
-
Maintenance (starting Day 10 of therapy):
- 125 to 250 mg thrice a day
-
Patients already receiving other anticonvulsants:
- Limited data are available. However, in children ≥8 years of age, the initial starting dose is prescribed and gradually increased to maintenance dose as another drug is reduced slowly.
- The drug is continued until the desired level obtained or another drug completely stopped. If the goal is a single-dose agent, the conversion should be completed over ≥14 days.
-
Children ≥8 years and Adolescents:
- Initial dose on days 1 to 3 of 100 to 125 mg per oral at bedtime
- Days 4 to 6: 100 to 125 per oral b.i.d daily
- Days 7 to 9: 100 to 125 mg per oral thrice daily
-
Maintenance (starting Day 10 of therapy):
- 250 mg per oral thrice daily.
- Adjustment of dose to usual maintenance range of 750 to 1,000 mg/day in divided doses 3 to 4 times daily is done
- Some patients may need 1,500 mg per oral once a day in divided doses 4 times daily.
- The maximum daily dose: 2000mg per oral per day
-
Primidone Pregnancy Risk Category: D
- Primidone, its metabolites, including phenobarbital and phenobarbital, have the ability to cross over the placenta.
- The mother's serum levels are the same as those at birth.
- Due to the long half life of primidone, its metabolites and neonates may experience withdrawal symptoms.
- There have been reports of birth defects and other adverse events. Folic acid should be taken throughout pregnancy, and vitamin K should be taken in the last trimester.
- Anticonvulsant therapy may be considered teratogenic if it is used in combination with other medications or genetic factors.
Use of primidone while breastfeeding
- Breast milk contains variable concentrations of primidone and its metabolites, PEMA, Phenobarbital and p-hydroxyphenobarbital.
- If the infant is experiencing somnolence or drowsiness, it is best to stop breastfeeding.
Dose adjustment in renal disease:
There is no dosage adjustment in the labeling of the manufacturer. Some clinicians have used the following suggestions:
Notice:Primidone should not be used if you have renal disease.
-
Creatinine clearance >=50mL/minute
- Every 12 hours, administer.
-
Creatinine clearance 10-50 mL/minute
-
- Take a dose every 12-24 hours.
-
-
Creatinine clearance: 10mL/minute
- Every 24 hours, administer.
-
Hemodialysis
- It is dialyzable. It is dialyzable.
Primidone dose adjustment in liver disease:
- There is no dosage adjustment in the manufacturer's labeling.
- Grave liver disease may cause adverse effects.
- Therefore, plasma levels must be monitored regularly and doses should be adjusted accordingly.
Side effects of Primidone:
-
Central Nervous System:
- Ataxia
- Drowsiness
- Emotional Disturbance
- Fatigue
- Hyperirritability
- Suicidal Ideation
- Vertigo
-
Dermatologic:
- Morbilliform Rash
-
Gastrointestinal:
- Anorexia
- Nausea
- Vomiting
-
Genitourinary:
- Impotence
-
Hematologic & Oncologic:
- Agranulocytosis
- Granulocytopenia
- Megaloblastic Anemia (Idiosyncratic)
- Pure Red Cell Aplasia
- Red Cell Hypoplasia
-
Ophthalmic:
- Diplopia
- Nystagmus
Contraindication to Primidone:
This includes hypersensitivity to phenobarbital and porphyria.
Warnings and precautions
-
Depression in the CNS:
- It may cause depression of the central nervous system, which can lead to impairment of mental or physical abilities. It is important to warn patients about driving or operating machinery.
-
Suicidal thoughts:
- There was an increase in suicidal thoughts/behavior among patients who received placebo, compared with 0.224% for patients who received it.
- The risk of injury can be seen as soon as 7 days after the trial has begun and continues for the duration of the trials (most trials last less than 24 weeks).
- Patients with depression or behavior changes that suggest suicidal thoughts and/or suicide should be closely monitored. If symptoms persist, contact your health care provider immediately.
-
Depression
- Patients with depression and suicidal tendencies should be treated with caution.
-
Hepatic impairment
- Patients with liver impairment should be cautious.
-
Hypoadrenalism
- Hypoadrenal patients should be treated with caution.
-
Renal impairment
- Patients with impaired renal function should be cautious.
-
Respiratory disease
- Patients with respiratory diseases should be cautious.
-
Substance abuse
- Patients with a history or abuse of drugs should exercise caution.
- Drug dependency is possible.
- Long-term therapy can be used to treat tolerance, psychological dependence and physical dependence.
Primidone: Drug Interaction
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Acetaminophen |
Barbiturates may increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. |
|
Alcohol (Ethyl) |
CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). |
|
Alizapride |
May enhance the CNS depressant effect of CNS Depressants. |
|
Apalutamide |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Apalutamide. |
|
Barbiturates |
Primidone may enhance the adverse/toxic effect of Barbiturates. Primidone is converted to phenobarbital, and thus becomes additive with existing barbiturate 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. |
|
Benperidol |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Benperidol. |
|
Beta-Blockers |
Barbiturates may decrease the serum concentration of Beta-Blockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol. |
|
Bictegravir |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Bictegravir. Management: Rifampin is specifically contraindicated, and the use of carbamazepine, phenytoin, or phenobarbital is not recommended when alternatives are acceptable |
|
Blood Pressure Lowering Agents |
Barbiturates may enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
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. |
|
Brexanolone |
CNS Depressants may enhance the CNS depressant effect of Brexanolone. |
|
Brimonidine (Topical) |
May enhance the CNS depressant effect of CNS Depressants. |
|
Bromopride |
May enhance the CNS depressant effect of CNS Depressants. |
|
Calcifediol |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Calcifediol. |
|
Calcium Channel Blockers |
Barbiturates may increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Exceptions: Clevidipine. |
|
Cannabidiol |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabidiol. |
|
Cannabidiol |
May enhance the CNS depressant effect of CNS Depressants. |
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Cannabis |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. |
|
Cannabis |
May enhance the CNS depressant effect of CNS Depressants. |
|
CarBAMazepine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of CarBAMazepine. |
|
Carbonic Anhydrase Inhibitors |
May enhance the adverse/toxic effect of Primidone. Specifically, osteomalacia and rickets. Carbonic Anhydrase Inhibitors may decrease the serum concentration of Primidone. Exceptions: Brinzolamide; Dorzolamide. |
|
Chlorphenesin Carbamate |
May enhance the adverse/toxic effect of CNS Depressants. |
|
ChlorproPAMIDE |
CYP3A4 Inducers (Strong) may decrease the serum concentration of ChlorproPAMIDE. |
|
Clindamycin (Systemic) |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Clindamycin (Systemic). Refer to the specific clindamycin (systemic) - rifampin drug interaction monograph for information concerning that combination. |
|
CNS Depressants |
May enhance the adverse/toxic effect of other CNS Depressants. |
|
Corticosteroids (Systemic) |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Corticosteroids (Systemic). Exceptions: Hydrocortisone (Systemic); PrednisoLONE (Systemic); PredniSONE. |
|
Cosyntropin |
May enhance the hepatotoxic effect of Primidone. |
|
Dabigatran Etexilate |
Primidone may decrease the serum concentration of Dabigatran Etexilate. |
|
Dabrafenib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Dabrafenib. |
|
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. |
|
Diethylstilbestrol |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Diethylstilbestrol. |
|
Dimethindene (Topical) |
May enhance the CNS depressant effect of CNS Depressants. |
|
Doxercalciferol |
CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Doxercalciferol. |
|
Doxylamine |
May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. |
|
Dronabinol |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronabinol. |
|
Dronabinol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Elagolix |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Elagolix. |
|
Esketamine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Eslicarbazepine |
Primidone may decrease the serum concentration of Eslicarbazepine. (based on studies with phenobarbital) |
|
Estriol (Systemic) |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Estriol (Systemic). |
|
Estriol (Topical) |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Estriol (Topical). |
|
Etizolam |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Etizolam. |
|
Evogliptin |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Evogliptin. |
|
Folic Acid |
May decrease the serum concentration of Primidone. Additionally, folic acid may decrease concentrations of active metabolites of primidone (e.g., phenobarbital). |
|
Fosphenytoin |
May increase the metabolism of Primidone. The ratio of primidone:phenobarbital is thus changed. |
|
Gestrinone |
Primidone may decrease the serum concentration of Gestrinone. |
|
Glecaprevir and Pibrentasvir |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Glecaprevir and Pibrentasvir. |
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Griseofulvin |
Barbiturates may decrease the serum concentration of Griseofulvin. |
|
Hydrocortisone (Systemic) |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Hydrocortisone (Systemic). |
|
Ifosfamide |
CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Ifosfamide. |
|
Kava Kava |
May enhance the adverse/toxic effect of CNS Depressants. |
|
Leucovorin Calcium-Levoleucovorin |
May decrease the serum concentration of Primidone. Additionally, leucovorin/levoleucovorin may decrease concentrations of active metabolites of primidone (e.g., phenobarbital). |
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LevETIRAcetam |
Primidone may decrease the serum concentration of LevETIRAcetam. |
|
Levomefolate |
May decrease serum concentrations of the active metabolite(s) of Primidone. Levomefolate may decrease the serum concentration of Primidone. |
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Levomethadone |
Primidone may decrease the serum concentration of Levomethadone. |
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Lofexidine |
May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
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Magnesium Sulfate |
May enhance the CNS depressant effect of CNS Depressants. |
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Methadone |
Primidone may decrease the serum concentration of Methadone. |
|
Methylfolate |
May decrease the serum concentration of Primidone. |
|
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. |
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MetroNIDAZOLE (Systemic) |
Primidone may decrease the serum concentration of MetroNIDAZOLE (Systemic). |
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MetyroSINE |
CNS Depressants may enhance the sedative effect of MetyroSINE. |
|
Minocycline |
May enhance the CNS depressant effect of CNS Depressants. |
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Multivitamins/Minerals (with ADEK, Folate, Iron) |
May decrease the serum concentration of Barbiturates. |
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Nabilone |
May enhance the CNS depressant effect of CNS Depressants. |
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Nalmefene |
Primidone may decrease the serum concentration of Nalmefene. |
|
Orlistat |
May decrease the serum concentration of Anticonvulsants. |
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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. |
|
Phenytoin |
May increase the metabolism of Primidone. The ratio of primidone:phenobarbital is thus changed. |
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Piribedil |
CNS Depressants may enhance the CNS depressant effect of Piribedil. |
|
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. |
|
Pramipexole |
CNS Depressants may enhance the sedative effect of Pramipexole. |
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PrednisoLONE (Systemic) |
CYP3A4 Inducers (Strong) may decrease the serum concentration of PrednisoLONE (Systemic). |
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PredniSONE |
CYP3A4 Inducers (Strong) may decrease the serum concentration of PredniSONE. |
|
Propacetamol |
Barbiturates may increase the metabolism of Propacetamol. This may 1) diminish the desired effects of propacetamol; and 2) increase the risk of liver damage. |
|
Propafenone |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Propafenone. |
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Pyridoxine |
May increase the metabolism of Barbiturates. Apparent in high pyridoxine doses (eg, 200 mg/day) |
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QuiNIDine |
Primidone may decrease the serum concentration of QuiNIDine. |
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Ramelteon |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Ramelteon. |
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Reboxetine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Reboxetine. |
|
Rifamycin Derivatives |
May increase the metabolism of Barbiturates. |
|
ROPINIRole |
CNS Depressants may enhance the sedative effect of ROPINIRole. |
|
Rotigotine |
CNS Depressants may enhance the sedative effect of Rotigotine. |
|
Rufinamide |
Primidone may decrease the serum concentration of Rufinamide. |
|
Ruxolitinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Ruxolitinib. |
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SAXagliptin |
CYP3A4 Inducers (Strong) may decrease the serum concentration of SAXagliptin. |
|
Selective Serotonin Reuptake Inhibitors |
CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. |
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Sertraline |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Sertraline. |
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Sulthiame |
Primidone may enhance the adverse/toxic effect of Sulthiame. |
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Tetrahydrocannabinol |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol. |
|
Tetrahydrocannabinol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Tetrahydrocannabinol and Cannabidiol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Tetrahydrocannabinol and Cannabidiol |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol. |
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Theophylline Derivatives |
Barbiturates may decrease the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. |
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Thiazide and Thiazide-Like Diuretics |
Barbiturates may enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics. |
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Thiothixene |
Primidone may decrease the serum concentration of Thiothixene. |
|
Trimeprazine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Tropisetron |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Tropisetron. |
|
Udenafil |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Udenafil. |
|
Valproate Products |
May decrease the metabolism of Primidone. More specifically, the metabolism of phenobarbital, primidone's primary active metabolite, may be decreased. Primidone may increase the serum concentration of Valproate Products. |
|
Zuclopenthixol |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol. |
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Risk Factor D (Consider therapy modification) |
|
|
Abiraterone Acetate |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Abiraterone Acetate. Management: Avoid whenever possible. If such a combination cannot be avoided, increase abiraterone acetate dosing frequency from once daily to twice daily during concomitant use. |
|
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. |
|
Afatinib |
Primidone may decrease the serum concentration of Afatinib. Management: Per US labeling: if requiring chronic use of primidone, increase afatinib dose by 10 mg as tolerated; reduce to original afatinib dose 2-3 days after stopping primidonel. Per Canadian labeling: avoid combination if possible. |
|
ARIPiprazole |
|
|
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. |
|
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. |
|
Blonanserin |
CNS Depressants may enhance the CNS depressant effect of Blonanserin. |
|
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. |
|
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. |
|
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. |
|
Cabozantinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, cabozantinib dose adjustments are recommended and vary based on the cabozantinib product used and the indication for use. See monograph for details. |
|
Canagliflozin |
Primidone may decrease the serum concentration of Canagliflozin. Management: Consider increasing canagliflozin dose to 300 mg/day in patients with estimated GFR >60 mL/min/1.73 m2 who tolerate canagliflozin 100 mg/day and require greater glycemic control. Consider alternatives in patients with estimated GFR 45-60 mL/min/1.73 m2. |
|
Chloramphenicol (Systemic) |
May decrease the metabolism of Barbiturates. Barbiturates may increase the metabolism of Chloramphenicol (Systemic). |
|
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. |
|
Clarithromycin |
CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Clarithromycin. Clarithromycin may increase the serum concentration of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin into 14hydroxyclarithromycin may alter the clinical activity of clarithromycin and may impair clarithromycin efficacy. |
|
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. |
|
CycloSPORINE (Systemic) |
Barbiturates may increase the metabolism of CycloSPORINE (Systemic). |
|
CYP3A4 Substrates (High risk with Inducers) |
CYP3A4 Inducers (Strong) may increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Exceptions: Benzhydrocodone; Buprenorphine; CarBAMazepine; Etizolam; HYDROcodone; TraMADol; Zolpidem. |
|
Dasatinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. |
|
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 steroid efficacy. |
|
DOXOrubicin (Conventional) |
CYP3A4 Inducers (Strong) may decrease the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP3A4 inducers in patients treated with doxorubicin. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. |
|
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. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
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. |
|
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. |
|
Erlotinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Erlotinib. Management: Avoid combination if possible. If combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. |
|
Estrogen Derivatives (Contraceptive) |
Barbiturates may diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). Contraceptive failure is possible. Management: Use of a non-hormonal contraceptive is recommended. |
|
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. |
|
Etoposide Phosphate |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide Phosphate. Management: When possible, seek alternatives to strong CYP3A4inducing medications in patients receiving etoposide phosphate. If these combinations cannot be avoided, monitor patients closely for diminished etoposide phosphate response. |
|
Everolimus |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus. Management: Avoid concurrent use of strong CYP3A4 inducers if possible. If coadministration cannot be avoided, double the daily dose of everolimus using increments of 5 mg or less. Monitor everolimus serum concentrations closely when indicated. |
|
Exemestane |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane. Management: Exemestane U.S. product labeling recommends using an increased dose (50 mg/day) in patients receiving concurrent strong CYP3A4 inducers. The Canadian product labeling does not recommend a dose adjustment with concurrent use of strong CYP3A4 inducers. |
|
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: In patients receiving primidone, initiate felbamate at 1200 mg/day in divided doses 3-4 times daily and reduce primidone dose by 20%. Monitor for increased phenobarbital concentrations/effects and decreased felbamate concentrations/effects. |
|
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. |
|
Flunitrazepam |
CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. |
|
Gefitinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase 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. |
|
GuanFACINE |
CYP3A4 Inducers (Strong) may decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating guanfacine in a patient taking a strong CYP3A4 inducer. Increase guanfacine dose gradually over 1 to 2 weeks if initiating strong CYP3A4 inducer therapy in a patient already taking guanfacine. |
|
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. |
|
HydrOXYzine |
May enhance the CNS depressant effect of Barbiturates. Management: Consider a decrease in the barbiturate dose, as appropriate, when used together with hydroxyzine. With concurrent use, monitor patients closely for excessive response to the combination. |
|
Imatinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with 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. |
|
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/m to 60 mg/m (given as a 4-hour infusion), as tolerated, should be considered. |
|
LamoTRIgine |
Primidone may decrease the serum concentration of LamoTRIgine. Management: Adjust dose per lamotrigine prescribing information guidelines during primidone treatment. Monitor for decreased concentration/effect if primidone is initiated/dose increased or increased concentration/effect if primidone is discontinued/dose decreased. |
|
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 half-life. |
|
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. |
|
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. |
|
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. |
|
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. |
|
Maraviroc |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice daily when used with strong CYP3A4 inducers. This does not apply to patients also receiving strong CYP3A4 inhibitors. Do not use maraviroc with strong CYP3A4 inducers in patients with CrCl less than 30 mL/min. |
|
Mefloquine |
May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. |
|
Meperidine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Meperidine. Management: Consider increasing meperidine dose if concomitant use with strong CYP3A4 inducers is required. Monitor for signs and symptoms of opioid withdrawal. |
|
Methotrimeprazine |
CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. |
|
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. |
|
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. |
|
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. |
|
Osimertinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Osimertinib. |
|
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. |
|
Perampanel |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. |
|
Perampanel |
May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. |
|
Pitolisant |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Pitolisant. Management: For patients who are stable on pitolisant doses of 8.9 mg or 17.8 mg/day and who are also taking a strong CYP3A4 inducer, increase the pitolisant dose over 7 days to double the original dose (ie, to either 17.8 mg/day or 35.6 mg/day, respectively). |
|
Progestins (Contraceptive) |
Primidone may diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. |
|
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 7-14 days of discontinuing the inducer. |
|
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. |
|
RisperiDONE |
CYP3A4 Inducers (Strong) may decrease the serum concentration of RisperiDONE. Management: Consider increasing the dose of oral risperidone (to no more than double the original dose) if a strong CYP3A4 inducer is initiated. For patients on IM risperidone, consider an increased IM dose or supplemental doses of oral risperidone. |
|
Rolapitant |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Rolapitant. Management: Avoid rolapitant use in patients requiring chronic administration of strong CYP3A4 inducers. Monitor for reduced rolapitant response and the need for alternative or additional antiemetic therapy even with shorter-term use of such inducers. |
|
Sirolimus |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Sirolimus. 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. |
|
Sodium Oxybate |
May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. |
|
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. |
|
SUNItinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of SUNItinib. Management: Avoid when possible. If such a combination cannot be avoided, sunitinib dose increases are recommended, and vary by indication. See full monograph for details. |
|
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. |
|
Tadalafil |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil. Management: Erectile dysfunction: monitor for decreased effectiveness - no standard dose adjustments recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. |
|
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. Management: Consider alternatives to concomitant use of strong CYP3A4 inducers and tamoxifen. If the combination cannot be avoided, monitor for reduced therapeutic effects of tamoxifen. |
|
Tapentadol |
May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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. |
|
Temsirolimus |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Temsirolimus. Management: Consider increasing the dose of temsirolimus to 50 mg IV/week (from 25 mg IV/week) if a concomitant CYP3A4 strong inducer is necessary. |
|
Teniposide |
Barbiturates may decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with barbiturates and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. |
|
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. |
|
TiaGABine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of TiaGABine. Management: Approximately 2-fold higher tiagabine doses and a more rapid dose titration will likely be required in patients concomitantly taking a strong CYP3A4 inducer. |
|
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. |
|
Tricyclic Antidepressants |
Barbiturates may increase the metabolism of Tricyclic Antidepressants. |
|
Vemurafenib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib. Management: Avoid concurrent use of vemurafenib with a strong CYP3A4 inducer and replace with another agent when possible. If a strong CYP3A4 inducer is indicated and unavoidable, the dose of vemurafenib may be increased by 240 mg (1 tablet) as tolerated. |
|
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 1-2 weeks after inducer discontinuation. |
|
Vitamin K Antagonists (eg, warfarin) |
Barbiturates may increase the metabolism of Vitamin K Antagonists. Management: Monitor INR more closely. An anticoagulant dose increase 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. |
|
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. |
|
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 zalephon is combined with a strong CYP3A4 inducer, monitor for decreased effectiveness of zaleplon. |
|
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 Factor X (Avoid combination) |
|
|
Abemaciclib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Abemaciclib. |
|
Alpelisib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Alpelisib. |
|
Antihepaciviral Combination Products |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Antihepaciviral Combination Products. |
|
Apixaban |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Apixaban. |
|
Apremilast |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Apremilast. |
|
Aprepitant |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Aprepitant. |
|
Artemether |
CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Artemether. Specifically, dihydroartemisinin concentrations may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Artemether. |
|
Asunaprevir |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Asunaprevir. |
|
Axitinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib. |
|
Azelastine (Nasal) |
CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). |
|
Bedaquiline |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Bedaquiline. |
|
Bortezomib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib. |
|
Bosutinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Bosutinib. |
|
Brigatinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Brigatinib. |
|
Bromperidol |
May enhance the CNS depressant effect of CNS Depressants. |
|
Cariprazine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Cariprazine. |
|
Ceritinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Ceritinib. |
|
CloZAPine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of CloZAPine. |
|
Cobicistat |
Primidone may decrease the serum concentration of Cobicistat. |
|
Cobimetinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Cobimetinib. |
|
Copanlisib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Copanlisib. |
|
Crizotinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib. |
|
Daclatasvir |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Daclatasvir. |
|
Dasabuvir |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasabuvir. |
|
Deflazacort |
CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Deflazacort. |
|
Delamanid |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Delamanid. |
|
Dienogest |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Dienogest. Management: Avoid use of dienogest for contraception when using medications that induce CYP3A4 and for at least 28 days after discontinuation of a CYP3A4 inducer. An alternative form of contraception should be used during this time. |
|
Dolutegravir |
Primidone may decrease the serum concentration of Dolutegravir. Specifically, the Primidone metabolite phenobarbital may decrease Dolutegravir serum concentrations. |
|
Doravirine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Doravirine. |
|
Doxycycline |
Barbiturates may decrease the serum concentration of Doxycycline. |
|
Dronedarone |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone. |
|
Duvelisib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Duvelisib. |
|
Elbasvir |
Elbasvir's serum levels may drop when CYP3A4 Inducers (Strong) are taken. |
|
Eliglustat |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Eliglustat. |
|
Encorafenib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Encorafenib. |
|
Entrectinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Entrectinib. |
|
Erdafitinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Erdafitinib. |
|
Etravirine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Etravirine. |
|
Fedratinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Fedratinib. |
|
Flibanserin |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Flibanserin. |
|
Fosaprepitant |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite aprepitant. |
|
Fosnetupitant |
CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fosnetupitant. |
|
Fostamatinib |
CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fostamatinib. |
|
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. |
|
Glasdegib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Glasdegib. |
|
Grazoprevir |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Grazoprevir. |
|
Hemin |
Barbiturates may diminish the therapeutic effect of Hemin. |
|
Ibrutinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrutinib. |
|
Idelalisib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Idelalisib. |
|
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. |
|
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. |
|
Itraconazole |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole. |
|
Ivabradine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivabradine. |
|
Ivacaftor |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor. |
|
Ivosidenib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivosidenib. |
|
Ixazomib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixazomib. |
|
Lapatinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib. Management: If therapy overlap cannot be avoided, consider titrating 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. |
|
Ledipasvir |
Primidone may decrease the serum concentration of Ledipasvir. |
|
Lorlatinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Lorlatinib. |
|
Lumefantrine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumefantrine. |
|
Lurasidone |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone. |
|
Macimorelin |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Macimorelin. |
|
Macitentan |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Macitentan. |
|
Methoxyflurane |
Barbiturates may enhance the nephrotoxic effect of Methoxyflurane. Barbiturates may increase the metabolism of Methoxyflurane. |
|
Methoxyflurane |
CYP2A6 Inducers may enhance the nephrotoxic effect of Methoxyflurane. CYP2A6 Inducers may increase the metabolism of Methoxyflurane. |
|
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. |
|
Midostaurin |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Midostaurin. |
|
MiFEPRIStone |
CYP3A4 Inducers (Strong) may decrease the serum concentration of MiFEPRIStone. |
|
Naldemedine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Naldemedine. |
|
Naloxegol |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Naloxegol. |
|
Neratinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Neratinib. |
|
Netupitant |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Netupitant. |
|
NIFEdipine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of NIFEdipine. |
|
Nilotinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib. |
|
NiMODipine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of NiMODipine. |
|
Nisoldipine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine. |
|
Olaparib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Olaparib. |
|
Orphenadrine |
CNS Depressants may enhance the CNS depressant effect of Orphenadrine. |
|
Oxomemazine |
May enhance the CNS depressant effect of CNS Depressants. |
|
Palbociclib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Palbociclib. |
|
Panobinostat |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Panobinostat. |
|
Paraldehyde |
CNS Depressants may enhance the CNS depressant effect of Paraldehyde. |
|
PAZOPanib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of PAZOPanib. |
|
Pexidartinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Pexidartinib. |
|
Pimavanserin |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Pimavanserin. |
|
Piperaquine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Piperaquine. |
|
PONATinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of PONATinib. |
|
Praziquantel |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel. Management: Use of praziquantel with strong CYP3A4 inducers is contraindicated. Discontinue rifampin 4 weeks prior to initiation of praziquantel therapy. Rifampin may be resumed the day following praziquantel completion. |
|
Pretomanid |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Pretomanid. |
|
Ranolazine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine. |
|
Regorafenib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib. |
|
Ribociclib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Ribociclib. |
|
Rilpivirine |
Primidone may decrease the serum concentration of Rilpivirine. |
|
Rivaroxaban |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban. |
|
Roflumilast |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast. Management: Roflumilast U.S. prescribing information recommends against combining strong CYP3A4 inducers with roflumilast. The Canadian product monograph makes no such recommendation but notes that such agents may reduce roflumilast therapeutic effects. |
|
RomiDEPsin |
CYP3A4 Inducers (Strong) may decrease the serum concentration of RomiDEPsin. |
|
Simeprevir |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir. |
|
Sofosbuvir |
Primidone may decrease the serum concentration of Sofosbuvir. |
|
Somatostatin Acetate |
May enhance the adverse/toxic effect of Barbiturates. Specifically, Somatostatin Acetate may enhance or prolong Barbiturate effects, including sedative effects. |
|
Sonidegib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Sonidegib. |
|
SORAfenib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of SORAfenib. |
|
Tasimelteon |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Tasimelteon. |
|
Tenofovir Alafenamide |
Primidone may decrease the serum concentration of Tenofovir Alafenamide. |
|
Thalidomide |
CNS Depressants may enhance the CNS depressant effect of Thalidomide. |
|
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. |
|
Tofacitinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Tofacitinib. |
|
Tolvaptan |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Management: If concurrent use is necessary, increased doses of tolvaptan (with close monitoring for toxicity and clinical response) may be needed. |
|
Toremifene |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene. |
|
Trabectedin |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Trabectedin. |
|
Ulipristal |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal. |
|
Ulipristal |
Barbiturates may decrease the serum concentration of Ulipristal. |
|
Upadacitinib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Upadacitinib. |
|
Valbenazine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Valbenazine. |
|
Vandetanib |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib. |
|
Velpatasvir |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Velpatasvir. |
|
Venetoclax |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Venetoclax. |
|
VinCRIStine (Liposomal) |
CYP3A4 Inducers (Strong) may decrease the serum concentration of VinCRIStine (Liposomal). |
|
Vinflunine |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Vinflunine. |
|
Vorapaxar |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Vorapaxar. |
|
Voriconazole |
Barbiturates may decrease the serum concentration of Voriconazole. |
|
Voxilaprevir |
CYP3A4 Inducers (Strong) may decrease the serum concentration of Voxilaprevir. |
Monitoring parameters:
- You should examine different parameters, including the serum primidone levels and phenobarbital concentrations and your neurological status.
- To compare baseline levels at the beginning of therapy, a 6-monthly full blood count and metabolic panel should be performed. Suicidality and depression should be monitored.
How to administer Primidone?
It is prescribed orally without regard to food but may consider food to decrease gastrointestinal side effects.
Primidone mechanism of action:
Primidone causes decreased neuron excitability, and a higher seizure threshold.
It contains 2 active metabolites: phenobarbital and phenylethylmalonamide. PEMA could increase the activity of Phenobarbital
Absorption: Well absorbed. Protein binding: 20% Metabolism: The liver produces phenobarbital (active), by oxidation, and to phenylethylmalonamide [PEMA] by ring cleavage of the second carbon position. Bioavailability: >90% Eliminating half-life(age dependent) Primidone can be used for up to 16 hours (variable). PEMA: 16-50 hours (variable). Phenobarbital: 50-150 hours When to reach the peak serum concentration: 0.5- 9 hours Excretion: In urine (5% to 65%) as an unchanged drug; the rest is unconjugated PEMA and phenobarbital and its metabolites
Primidone Brand Names (International):
- Mysoline
- Apo-Primidone
- Cyral
- Liskantin
- Majsolin
- Mizodin
- Mutigan
- Mylepsinum
- Mysoline
- Pridona
- Primid
- Primidon
- Prysoline
- Sertan
Primidone Brand Names in Pakistan:
No Brands Available in Pakistan.
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