Medically Reviewed on 5/24/2022

Generic Name: primidone

Brand Name: Mysoline

Drug Class: Anticonvulsants, Barbiturates; CYP3A4 Inducer, Strong

What is primidone, and what is it used for?

Primidone is an anticonvulsant medication used alone or in combination with other antiepileptic drugs to control certain types of epileptic seizures.

Primidone is a first generation barbiturate anticonvulsant medication, and with the development of many newer antiepileptic drugs, primidone use is generally limited to the treatment of seizure forms that are resistant to other therapies. Primidone has high efficacy in controlling grand mal, focal and psychomotor (temporal lobe epilepsy) seizures. Primidone is also used off-label to treat essential tremors.

Primidone raises seizure threshold and reduces the frequency and intensity of seizures by reducing abnormal electrical activity in the brain. Primidone’s exact mechanism of action is not clear, but it appears to bind to sodium channels on the nerve cell (neuron) membranes, inhibiting the repeated firing of neurons that cause convulsions or tremors.

In addition to primidone’s anticonvulsant activity, primidone is also metabolized in the liver into two active metabolites, phenobarbital and phenylethylmalonamide (PEMA). Although primidone does not directly interact with gamma aminobutyric acid (GABA), the natural inhibitory chemical (neurotransmitter) in the brain, its metabolite phenobarbital does.

Phenobarbital interacts with GABA-A receptors on neuronal membranes and increases the influx of chloride ions, which results in enhanced GABA neurotransmission. GABA reduces neuronal excitability, their electrical activity and nerve signals that propagate seizure activity. PEMA has weak anticonvulsant activity, but it potentiates the effects of phenobarbital.

Primidone is FDA-approved for the treatment of:

  • Grand mal seizures, which cause violent muscle contractions and loss of consciousness
  • Psychomotor seizures or temporal lobe epilepsy, a form of seizure that is limited to the temporal lobes of the brain and causes a disruption in awareness of one's surroundings and responsiveness
  • Focal seizures or partial seizures which begin in one area of the brain, but may spread to other parts of the brain and become generalized
  • Primidone is used off-label to treat essential tremors.


  • Do not use primidone to treat patients who have:
    • Hypersensitivity to phenobarbital
    • Porphyria, a group of disorders that mainly affect the skin or nervous system due to excessive accumulation of porphyrin, a substance that is essential for production of heme, the compound in hemoglobin that carries oxygen
  • Primidone increases the risk for suicidal thoughts, particularly in patients with depression. Patients, their caregivers and families should be counseled to monitor for behavior that indicates onset or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
  • Use primidone with caution in patients with:
  • Use with caution in patients with a history of substance abuse or alcoholism. There is a potential for drug dependency, and tolerance or psychological and physical dependence may occur with prolonged use.
  • Do not administer primidone to patients with acute pain.
  • Primidone may depress the central nervous system (CNS) and may impair mental and physical abilities. Advice patients appropriately.
  • Avoid concurrent use with other CNS depressants and advise patients to avoid alcohol.
  • May cause paradoxical responses in the elderly and debilitated patients, use with caution.
  • May render oral hormonal contraceptives ineffective.
  • Inhibits transplacental vitamin K transport, leading to increased risk of fetal hemorrhage.
  • Primidone’s active metabolite phenobarbital is associated with cognitive deficits in children receiving chronic therapy for febrile seizures.
  • Pediatric patients may be at an increased risk for vitamin D deficiency with chronic therapy, and must be monitored.
  • Some formulations of primidone may contain benzyl alcohol, which is associated with potentially fatal toxicity (gasping syndrome) in newborn. Do not use these formulations in newborn infants.
  • When replacing another antiseizure drug with primidone, gradually increase dosage of primidone while gradually decreasing dosage of the other drug over at least 2 weeks.
  • Withdraw primidone gradually, abrupt withdrawal may precipitate status epilepticus, a state of prolonged seizure lasting for longer than five minutes.


What Is Epilepsy? Symptoms, Causes, and Treatments See Slideshow

What are the side effects of primidone?

Common side effects of primidone include:

Less common side effects of primidone include:

Rare side effects of primidone include:

  • Acute psychosis
  • Softening of bones (osteomalacia)
  • Rickets, a bone disorder caused by vitamin D, calcium or phosphate deficiency
  • Stevens-Johnson syndrome, a severe life-threatening hypersensitivity skin reaction

Side effects that decrease with continued treatment include:

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

What are the dosages of primidone?


  • 50 mg
  • 250 mg


Seizures (Psychomotor, Focal, and Grand Mal)

  • Initial: 100-125 mg orally at bedtime for 3 days, THEN
  • 100-125 mg twice daily for 3 days, THEN
  • 100-125 mg three times daily for 3 days, THEN
  • 250 mg three to four times daily; not to exceed 2 g/day

Partial Seizures

  • 125 mg orally at bedtime
  • Increase dose every 3 days by 125 mg if needed to 250 mg every 12 hours; do not exceed 500 mg/day

Essential Tremor

  • 12.5-25 mg/day orally at bedtime
  • Increase dose over 2-3 weeks to 250 mg orally once/day or divided twice daily; do not exceed 750 mg/day

Seizures (Psychomotor, Focal, and Grand Mal)


  • Initial: 50 mg orally at bedtime for 3 days, THEN
  • 50 mg twice daily for 3 days, THEN
  • 100 mg twice daily for 3 days, THEN
  • After 9th day: 125-250 mg orally three times daily, OR 10-25 mg/kg/day divided every 8 hours orally

Dosing considerations

  • May take with food
  • Monitor: Complete blood count (CBC), SMA-12 every 6 months
  • Do not exceed 2 g/day
  • May control grand mal seizures refractory to other anticonvulsants
  • Do not abruptly discontinue, due to the risk of precipitation of status epilepticus
  • Therapeutic efficacy of dosage regimen may take several weeks to assess


  • Primidone overdose may cause
  • Overdose is treated with symptomatic and supportive care.
  • Undigested drug may be eliminated with gastric lavage, and urine alkalinization and forced diuresis may increase drug excretion in the urine.
  • Hemodialysis may be necessary in serious overdose.

What drugs interact with primidone?

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

  • Severe interactions of primidone include:
    • artemether/lumefantrine
    • cabotegravir
    • cariprazine
    • cobimetinib
    • dienogest/estradiol valerate
    • doravirine
    • elbasvir/grazoprevir
    • elvitegravir/cobicistat/emtricitabine/tenofovir DF
    • fostemsavir
    • isavuconazonium sulfate
    • lonafarnib
    • lorlatinib
    • lumacaftor/ivacaftor
    • lumefantrine
    • nirmatrelvir/ritonavir
    • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
    • panobinostat
    • roflumilast
    • vandetanib
  • Primidone has serious interactions with at least 169 different drugs.
  • Primidone has moderate interactions with at least 390 different drugs.
  • Primidone has mild interactions with at least 140 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

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Pregnancy and breastfeeding

  • Primidone and its metabolites can cause fetal harm, use only for life-threatening emergencies during pregnancy.
  • Primidone may cause withdrawal symptoms in the newborn.
  • Primidone should not be discontinued in pregnant women, because it can precipitate major seizures and status epilepticus that can result in maternal and fetal hypoxia and threat to life. Even minor seizures may pose some hazard to the fetus.
  • Discontinuation of primidone may be considered prior to and during pregnancy in individual cases if the seizure disorder severity and frequency do not pose a serious threat to the patient.
  • A coagulation defect resembling vitamin K deficiency has been reported in newborns whose mothers have been on primidone and other anticonvulsants. Pregnant women under anticonvulsant therapy should have supplemental vitamin K1 during the last month of pregnancy, and delivery.
  • Pregnant patients are recommended to take supplemental folic acid throughout pregnancy.
  • Primidone is present in breastmilk in substantial quantities. Nursing mothers should discontinue breastfeeding if there is undue drowsiness or somnolence in the newborn.
  • A registry is available for women exposed to primidone during pregnancy: Pregnant women may enroll themselves into the North American Antiepileptic Drug (AED) Pregnancy Registry (1-888-233-2334 or 

What else should I know about primidone?

  • Primidone has a potential for dependency, exercise caution.
  • Take primidone exactly as prescribed; do not take larger or more frequent doses.
  • Store primidone safely out of reach of children.
  • In case of overdose, seek medical help immediately or contact Poison Control.
  • Primidone can impair mental and physical abilities, do not engage in hazardous activities such as driving and operating heavy machinery.
  • Do not drink alcohol or take drugs that depress the central nervous system while on primidone therapy.
  • Primidone may affect the reliability of oral hormonal contraceptives, consider alternate methods of contraception.
  • Primidone can precipitate onset or worsening of depression and can cause suicidal thoughts and behavior. Caregivers and family should be watchful for unusual behavior and signs indicative of depression and self-harm, and contact the healthcare provider immediately if any such symptoms are apparent in the patient.


Primidone is an anticonvulsant medication used alone or in combination with other antiepileptic drugs to control certain types of epileptic seizures by reducing the frequency and intensity of seizures. Common side effects of primidone include vertigo, impaired coordination/balance/speech (ataxia), abnormal skin sensations (paresthesia), and difficulty with speech or slurred speech (dysarthria). Consult your doctor before taking primidone if pregnant or breastfeeding.

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Medically Reviewed on 5/24/2022