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.
Warnings
- 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:
- Impaired liver function
- Impaired kidney function
- Adrenal insufficiency (hypoadrenalism)
- Respiratory disease
- 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.

SLIDESHOW
What Is Epilepsy? Symptoms, Causes, and Treatments See SlideshowWhat are the side effects of primidone?
Common side effects of primidone include:
- Vertigo
- Impaired coordination, balance and speech (ataxia)
- Abnormal skin sensations (paresthesia)
- Difficulty with speech or slurred speech (dysarthria)
- Adverse effects in geriatric patients include:
- Excitement
- Confusion
- Depression
- Adverse effects in pediatric patients include:
- Hyperactivity
- Paradoxical excitement
Less common side effects of primidone include:
- Rash
- Nausea
- Vomiting
- Constipation
- Diarrhea
- Liver toxicity
- Megaloblastic (folate-deficiency) anemia
- Low blood calcium (hypocalcemia)
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:
- Vertigo
- Dizziness
- Drowsiness
- Ataxia
- Repetitive uncontrolled eye movements (nystagmus)
- Headache
- Irritability
- Restlessness
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.
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What are the dosages of primidone?
Tablets
- 50 mg
- 250 mg
Adult:
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)
Pediatric:
- 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
Overdose
- Primidone overdose may cause
- low blood pressure (hypotension),
- coma,
- central nervous system depression,
- suppressed response to pain,
- suppressed reflexes,
- respiratory depression, and
- decreased urine output.
- 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 https://www.aedpregnancyregistry.org/).
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.
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Summary
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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Epilepsy and Seizures: How to Treat?
A seizure is a sudden, uncontrolled electrical disturbance in the brain. Epilepsy is a neurological disorder where brain activities are abnormal, causing more than one or recurrent episodes of seizures. Most cases of seizures can be managed conservatively with medication and supportive treatments.
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How Do You Get Rid of Vestibular Migraines? Triggers, Medications, Symptoms
Getting rid of vestibular migraines involves managing the active episode (acute treatment) and preventing further episodes (prophylactic treatment).
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What Is an Episodic Migraine? Causes, Treatment, Symptoms
Migraine attacks are said to be episodic if they occur less than 15 days in a month. Learn the causes, symptoms, and treatment of episodic migraines below.
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How Do You Get Rid of a Migraine Fast?
Migraine is a neurological condition that is characterized by recurrent episodes of intense headaches. It may be associated with symptoms such as nausea, vomiting, and other clinical features.
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How Do Seizures Differ From Epilepsy and Convulsion?
You can have a seizure without epilepsy, but you can’t have epilepsy without seizures. Convulsions are a type of seizure that causes involuntary shaking.
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Are Migraine Auras Serious?
Migraine with aura (also called classic migraine) is repeated episodes of headache that occur during or after sensory disturbances (aura or migraine aura). These disturbances may include symptoms such as flashes of light, blind spots, and other vision changes or tingling over the hand or face.
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Aneurysm vs Stroke: Which Is Worse?
What is the difference between an aneurysm and a stroke?
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What Are the Different Types of Seizures?
A seizure is a sudden change in the brain's normal electrical activity. During a seizure, brain cells fire uncontrollably than their normal rate, temporarily affecting the way a person behaves, moves, thinks, or feels. Recurrent seizures are called epilepsy. Seizures are usually categorized into three types depending on their onset.
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Are Migraines a Symptom of COVID-19?
Although the main symptoms of COVID-19 are fever, cough, and shortness of breath, migraines are also a common symptom that may persist during or after infection.
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How Can I Strengthen My Arm and Hand After a Stroke?
Strengthening your arm or hands after a stroke is helpful for both pain treatments and the prevention of further injury. There are therapies that you might help you strengthen your arm.
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What Do Seizures Feel Like?
If you have a seizure, you may feel strange, notice unusual smells, experience tingling, see flashing lights, or start hallucinating.
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What Does Migraine Do to the Brain?
A migraine is a severe headache that causes throbbing pain typically on one side of the head. Here is what happens in your brain during a migraine and why it causes pain and other symptoms.
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What Triggers Tonic Seizures?
Tonic seizures may result from a variety of health conditions, such as brain tumors and head injuries. Learn all the potential triggers for epilepsy now.
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How Do You Stop Multiple Seizures?
Seizures are a medical emergency. Whether the seizure is a first-time onset or a recurring episode, it is advisable to dial 911 and call for help. A group of drugs called benzodiazepines is usually administered to stop multiple seizures.
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What Is the Most Common Type of Migraine?
The most common type of migraine is migraine without aura (common migraine). 70-90% of people with migraine experience this type. The frequency of this type of migraine may range from once a year to several times per week.
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Which Are the Pressure Points to Relieve Migraines?
Migraines are complex disorders involving episodes of recurrent and severe headaches. They generally present as a headache on one side and may be associated with visual or sensory symptoms (such as seeing flashes of light, colorful or bright shapes, or hearing sounds of various types) collectively called “aura.”
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What Are the First Signs of a Migraine?
The first sign of a migraine is severe eye pain associated with a dull headache. Migraines gradually worsen with physical activity.
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Types of Strokes
A stroke, also called cerebrovascular accident (CVA), occurs when the blood supply is cut off or reduced to a part of the brain. There are five main types of strokes, and the causes and clinical presentation of each of them vary
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What Causes Migraines?
A migraine is a complex disorder that involves episodes of recurrent and severe headaches. An episode of a migraine can be very painful, lasting for hours, making day-to-day activities difficult until the episode is resolved. The frequency and severity of migraine attacks tend to decline with age. And women are more likely to suffer from migraines than men.
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Is Exercise a Trigger for Migraines?
Vigorous exercise can trigger migraines for some people, possibly due to changes in blood vessel caliber. Here are 8 ways to prevent exercise-induced migraines.
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Do Seizures Come in Clusters?
Yes, seizures can come in clusters. The term seizure clusters is used when three or more seizures that occur within 24 hours (or within six hours as defined in some studies).
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What Does a Vestibular Migraine Feel Like? Treatment, Triggers
Vestibular migraine is a type of migraine that causes vertigo, as well as dizziness, unsteadiness, or lack of balance.
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How Do You Prevent Migraines When Exercising?
Here are a few tips to help prevent a workout from causing a migraine, such as staying hydrated and sticking to a protein-rich diet.
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Warning Signs of a Stroke
Signs of a stroke may sometimes go unnoticed initially and gradually progress. Sometimes, the signs of a stroke may appear suddenly.
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What Does the Start of a Migraine Feel Like?
Warning signs that a migraine is coming on may include increased urination, constipation, food cravings, mood changes, tiredness, and sensitivity to light or sound.
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Why Do Certain Foods Trigger Migraines?
According to recent studies, diet can play a significant role in triggering migraine episodes. Learn about foods you should avoid if you have migraine headaches.
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What Foods Trigger Migraines?
Migraine is a chronic neurological disorder that features intense headaches on one or both sides of the head. Migraine attacks may resolve in few hours or may take as long as several days.
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How Should You Sleep to Avoid Migraines?
Migraines can be avoided by practicing good sleep hygiene. Here are 11 tips for improving your sleep habits and preventing headaches.
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Can Bad Sleeping Habits Cause Migraines?
Bad sleeping habits can cause migraines, as migraine attacks have been linked to the sleep-wake cycle or circadian rhythm. If your sleep-wake cycle is disrupted, it can trigger a migraine.
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How Is Episodic Migraine Treated? Acute, How Long It Lasts
An episodic migraine can last between four hours to three days and may require the following treatment options.
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What Is the Best Cure for Migraine?
The best cure for migraine involves preventive medications and lifestyle changes. Some newer medications and therapies are effective in controlling the symptoms of migraine. Avoiding or controlling triggers may provide considerable benefit. Migraine can be prevented mainly by using medications, avoiding triggers and implementing lifestyle changes.
Treatment & Diagnosis
- Epilepsy and Seizures FAQs
- Stroke FAQs
- Migraine Headaches FAQs
- Migraine Headache Treatment
- What Is a Massive Stroke?
- What Are the Different Types of Epilepsy?
- Senator Ted Kennedy: Seizure, Brain Cancer, and Death
- Vestibular Migraine and Janet Jackson
- Brain Cancer Symptoms: Headaches and Seizures
- Surviving a Stroke
- Seizure Symptoms: How to Assist the Victim
- Ramipril, Heart Disease, Stroke & Diabetes
- Heart Disease & Stroke - Progress
- Proven measures to prevent heart attacks and strokes?
- Heart Disease Stroke and Diabetes
- Why Remove Half A Brain?
- Cancer,Stroke & Heart Attack Risks- ReducedThrough Walking
- The Cox-2 Inhibitors Controversy: Q&A with Dr. Shiel
- Stroke: Recognizing a Stroke - Three Commands for the Victim
- Seizures: When the Computer Goes Haywire
- TIA (Mini Stroke) Symptoms: A Trip to the ER
- What Is a Jacksonian Seizure?
- Does Lupus Cause Seizures?
- How Do You Get Rid of a Migraine?
- Can Botox Cure Migraines?
- Is It a Stroke or a TIA (Mini Stroke)?
- Stroke Symptoms - Typical
- Stroke Treatment
- Migraine Symptoms
- Stroke Symptoms
- Migraines: Eat to Minimize Your Migraines
Medications & Supplements

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https://www.ncbi.nlm.nih.gov/books/NBK562297/