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Pronunciation: prim-I-done
Class: Anticonvulsant

Trade Names

- Tablets, oral 50 mg
- Tablets, oral 250 mg

Apo-Primidone (Canada)


Primidone and its metabolites (phenobarbital and phenylethylmalonamide [PEMA]) have anticonvulsant activity, raising seizure threshold and altering seizure patterns.

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Readily absorbed from the GI tract. T max is 3 h (primidone).


Protein binding is variable up to 20% to plasma proteins. It crosses the placenta and is distributed into breast milk.


Converted to 2 actives metabolites, phenobarbital and PEMA.


Excreted in the urine (40% as unchanged and the remainder excreted as metabolites). Plasma half-life is 5 to 15 h (primidone) and 16 h (PEMA).

Indications and Usage

As monotherapy or adjunct therapy for control of generalized tonic-clonic, psychomotor, or focal epileptic seizures; it may control generalized tonic-clonic seizures refractory to other anticonvulsants.

Unlabeled Uses

Treatment of benign familial tremor (essential tremor).


Hypersensitivity to phenobarbital; porphyria.

Dosage and Administration

Adults and Children 8 y and older

PO If no previous treatment, initiate as follows: For days 1 to 3, give 100 to 125 mg at bedtime; for days 4 to 6, give 100 to 125 mg twice daily; for days 7 to 9, give 100 to 125 mg 3 times daily; and for day 10 through maintenance dose, give 250 mg 3 times daily or 4 times daily. May increase to 1,250 to 1,500 mg/day in 3 to 4 divided doses, but do not exceed 500 mg 4 times daily (2 g/day).

Children younger than 8 y

PO For days 1 to 3, give 50 mg at bedtime; for days 4 to 6, give 50 mg twice daily; for days 7 to 9, give 100 mg twice daily; and for day 10 through maintenance dose, give 125 to 250 mg 3 times daily or 10 to 25 mg/kg/day in divided doses.

Concomitant therapy with other anticonvulsants

PO Initiate at 100 to 125 mg at bedtime, gradually increasing the dose to maintenance level as the other drug is gradually decreased. Complete switch to primidone should occur over 2 wk or more.


Store between 68° and 77°F.

Drug Interactions

Anticoagulants (eg, warfarin)

Anticoagulation effects may be decreased. Monitor closely and adjust dosage as needed.

Aromatase inhibitors (eg, exemestane), beta-blockers (eg, propranolol), brentuximab, clozapine, corticosteroids (eg, prednisone), doxycycline, felodipine, ixabepilone, maraviroc, methadone, metronidazole, mTOR inhibitors (eg, everolimus, temsirolimus), quinidine, tacrolimus, teniposide, theophyllines, ulipristal, verapamil

Primidone may decrease the concentration and/or pharmacologic effects of the coadministered drug. Use with caution. Increase the dosage of exemestane to 50 mg once daily when coadministered with primidone.

Cabazitaxel, bortezomib, dronedarone, etravirine, hepatitis C virus protease inhibitors (eg, boceprevir, telaprevir), HIV protease inhibitors (eg, darunavir, lopinavir, ritonavir), ivacaftor, lurasidone, nifedipine, rilpivirine, roflumilast, ticagrelor, tolvaptan, tyrosine kinase receptor inhibitors (eg, dasatinib)

Primidone may decrease the concentration and/or pharmacologic effects of the coadministered drug. Coadministration should be avoided and may be contraindicated.


Concomitant use may decrease primidone, its metabolite phenobarbital, and carbamazepine serum concentrations.

Estrogens, hormonal contraceptives (eg, ethinyl estradiol/dienogest)

Concomitant use may decrease the estrogen/hormonal contraceptive concentrations. Contraceptive failure has been reported. Alternate contraception methods are recommended.


Additive CNS and respiratory depression have been noted upon acute ethanol ingestion. Chronic ethanol ingestion may manifest as drug tolerance. Avoid concomitant use.

Hydantoins (eg, phenytoin), valproic acid

Primidone (and its metabolite phenobarbital) plasma concentrations may increase. Monitor serum concentrations and adjust dosage as indicated.

Sodium oxybate

Concurrent use may increase sleep duration and CNS depression. Coadministration is contraindicated.

Succinimides (eg, ethosuximide)

Primidone (and its metabolite phenobarbital) plasma concentrations may decrease. Monitor serum concentrations and adjust dosage as indicated.

Adverse Reactions


Ataxia; drowsiness; emotional disturbances; fatigue; hyperirritability; vertigo.


Morbilliform skin eruptions.


Diplopia; nystagmus.


Anorexia; nausea; vomiting.




Agranulocytosis; aplasia; granulocytopenia; megaloblastic anemia; red-cell hypoplasia.



Monitor CBC and a sequential multiple analysis-12 (SMA-12) every 6 mo. Monitor for suicidality (eg, suicidal thoughts, depression, changes in behavior). In some cases, serum blood levels of primidone may be necessary for optimal dosage adjustment.


Category undetermined . Advise patients to consult their health care provider regarding anticonvulsant use during pregnancy.


Excreted in breast milk.

Suicidal behavior and ideation

Antiepileptic drugs (AEDs), including primidone, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Increased risk has been observed as early as 1 wk after starting treatment with AEDs.

Withdrawal seizures

Status epilepticus may be precipitated by abrupt withdrawal.



No data reported.

Patient Information

  • Instruct patients, families, or caregivers that other medications for seizures should continue to be taken unless advised by their health care provider.
  • Instruct patients to take exactly as prescribed and not to change the dose or discontinue unless advised by their health care provider.
  • Advise patients that medication will be started at a low dose and then gradually increased until max benefit has been obtained.
  • Advise patients that the most common side effects of therapy are dizziness, drowsiness, vertigo, and incoordination; these generally occur early in therapy or after a dose increase and tend to disappear with continued therapy.
  • Advise patients that, if medication needs to be discontinued, it will be slowly withdrawn over a period of several weeks unless safety concerns (eg, rash) require a more rapid withdrawal.
  • Counsel patients, their caregivers, and families that AEDs, including primidone, may increase the risk of suicidal thoughts and behavior and advise them of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts of self-harm. Behaviors of concern should be reported immediately to their health care provider.
  • Encourage female patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll-free number 1-888-233-2334.

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