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All about: Primidone

Big Image Pronouncation: (PRIM-ih-dohn)
Class: Anticonvulsant

Trade Names:
- Tablets 50 mg
- Tablets 250 mg

Apo-Primidone (Canada)
Sertan (Canada)

Mechanism of Action


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



Readily absorbed from the GI tract. T max is 3 hr (primidone) and 7 to 8 hr (phenobarbital and phenylethylmalonamide [PEMA] metabolites). Bioavailability is 90% to 100%.


Protein binding is negligible for primidone and PEMA; approximately 50% (phenobarbital). Distributes into breast milk. Vd is 0.64 to 0.86 L/kg.


Hepatic, 2 active metabolites: phenobarbital (15% to 25%) and PEMA. PEMA is the major metabolite and is less active than phenobarbital.


Excreted in the urine (40% as unchanged and remainder excreted as metabolites). Plasma t ½ is 5 to 15 hr (primidone), 10 to 18 hr (PEMA), and 53 to 140 hr (phenobarbital).

Indications and Usage

Control of grand mal, psychomotor, or focal epileptic seizures; may control grand mal seizures refractory to other anticonvulsants.

Unlabeled Uses

Treatment of benign familial tremor (essential tremor).


Hypersensitivity to barbiturates; porphyria.

Dosage and Administration

Adults and Children over 8 yr of age

If no previous treatment, initiate as follows: PO For days 1 to 3, give 100 to 125 mg at bedtime; days 4 to 6, give 100 to 125 mg bid; days 7 to 9, give 100 to 125 mg tid; and day 10 through maintenance dose, give 250 mg tid or qid. May increase to 250 mg 5 to 6 times/day, but do not exceed 500 mg qid (2 g/day).

Children under 8 yr of age

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

Patients Already Taking Anticonvulsants

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

General Advice

Administer without regard to meals. Administer with food if GI upset occurs.


Store tablets at controlled room temperature (59° to 86°F).

Drug Interactions


Decreased anticoagulant effects.


Effects of beta-blockers may be reduced.


Decreased primidone levels; increased concentrations of carbamazepine.


Decreased effect of corticosteroids.


Decreased doxycycline serum levels.

Estrogens, oral contraceptives

Contraceptive failure has been reported.


Additive CNS suppression.


Decreased effect of felodipine.


Decreased serum griseofulvin levels.

Hydantoins, valproic acid

Increased primidone serum levels.


Plasma concentrations may be reduced by primidone, leading to opiate withdrawal.


Enhanced renal toxicity may occur.


Therapeutic failure of metronidazole.


Decreased nifedipine levels.


Decreased quinidine serum levels.


Decreased primidone levels.


Decreased theophylline levels.

Laboratory Test Interactions

None well documented.

Adverse Reactions


Ataxia; vertigo; fatigue; hyperirritability; emotional disturbances; drowsiness; personality deterioration; mood changes; paranoia.


Morbilliform or maculopapular skin eruptions.


Diplopia; nystagmus.


Nausea; anorexia; vomiting.


Impotence; crystalluria.


Megaloblastic anemia; granulocytopenia, agranulocytosis, red-cell hypoplasia, aplasia (rarely).



Category D . Consult health care provider regarding anticonvulsant use during pregnancy.


Excreted in breast milk.

Status epilepticus

May be precipitated by abrupt withdrawal.

Patient Information

  • Explain name, dose, action, and potential side effects of drug.
  • Advise patient to read the Patient Information leaflet before starting therapy and with each refill.
  • Instruct patient, family, or caregiver to continue to take other medications for seizures unless advised by health care provider.
  • Instruct patient to take exactly as prescribed and to not change the dose or discontinue unless advised by health care provider.
  • Advise patient that medication will be started at a low dose and then gradually increased until max benefit has been obtained.
  • Advise patient that each dose may be taken without regard to meals but to take with food if stomach upset occurs.
  • Advise patient that the most common side effects of therapy are dizziness, drowsiness, feeling of whirling motion, and incoordination and that they generally occur early in therapy or after a dose increase and tend to disappear with continued therapy.
  • Advise patient 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.
  • Caution patient that drug may cause dizziness, drowsiness, or coordination problems and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
  • Advise women to notify health care provider if pregnant, planning to become pregnant, or breastfeeding.
  • Instruct patient to contact health care provider immediately if rash or fever occur.
  • Instruct patient to inform health care provider if seizures get worse of if new types of seizures occur.
  • Advise patient to avoid alcoholic beverages and other depressants while taking this medication.
  • Advise patient to carry identification (eg, Medic Alert ) indicating medication usage and epilepsy.
  • Advise patient not to take any prescription or OTC medications, dietary supplements, or herbal preparations unless advised by health care provider.

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