Primidone
Barbiturates and Derivatives
Sold as ENODAMA
- Drug class
- Barbiturates and Derivatives
- Availability
- Prescription only
- Routes
- Oral
- Markets covered
- 3
- Products on record
- 45
- FDA reports (12 mo)
- 481
Overview
Plain-language summary, compiled from the cited regulatory records
Primidone is a medication classified as a barbiturate and derivative [1]. It is approved for use in managing certain types of epileptic seizures, including grand mal, psychomotor, and focal seizures [1]. Primidone can be used as a standalone treatment or in combination with other anticonvulsant medications [1]. It may also be effective in controlling grand mal seizures that have not responded to other anticonvulsant therapies [1].
In the past 12 months, there have been 481 adverse event reports associated with primidone [2]. The most frequently reported adverse events include off-label use, reports of the drug being ineffective, drug interactions, diarrhea, and fatigue [2].
This is not medical advice. Consult a qualified healthcare professional.
Regulatory status by market
| Market | Regulator | Products | Last revision |
|---|---|---|---|
| GB United Kingdom | MHRA | 40 | April 10, 2026 |
| US United States | FDA | 3 | June 10, 2025 |
| CA Canada | Health Canada | 2 | November 17, 2025 |
GBUnited Kingdom· MHRA
40 products
Uses
'Primidone' is indicated in the management of grand mal and psychomotor (temporal lobe) epilepsy. It is also of value in the management of focal or Jacksonian seizures, myoclonic jerks and akinetic attacks. Management of essential tremor.
How to take
Posology Primidone should be started at the lowest possible dose in the evening and thereafter the dose should be increase in a stepwise manner to minimise adverse reactions. Epilepsy Treatment must always be planned on an individual basis.
In many patients primidone treatment may be given as monotherapy, but in some, Primidone will need to be combined with other anticonvulsants or with supporting therapy. In certain patients, it may be advisable to give a larger dose when the seizures are more frequent.
For instance: 1) If the attacks are nocturnal then all or most of the daily dose may be given in the evening; 2) If the attacks are associated with some particular event such as menstruation, a slight increase in the appropriate dose is often beneficial.
In adults:
Initial dose: it is usually 125 mg in a single intake in the evening. Then every 3 days, the daily dose is increased in a stepwise approach by 125 mg until the patient is receiving 500 mg daily. 5 g daily.
Maintenance dose:
Milligrams Adults 750 - 1500 Paediatric population: Initial dose: it is usually 125 mg in a single intake in the evening. Then every 3 days, the daily dose is increased in a stepwise approach by 125 mg until the patient is receiving 500 mg daily.
Thereafter, every 3 days, the daily dose (given in 2 divided doses) is increased by 250 mg in children over the age of 9 and by 125 mg in children under 9 years until control is obtained or until the maximum tolerated dose in children.
Maintenance doses:
Milligrams Children over 9 years 750 to 1500 Children 6 to 9 years 750 to 1000 Children 2 to 5 years 500 to 750 Children up to 2 years 250 to 500 Concomitant use / switch from other anticonvulsant treatments In case of lack of efficacy of other anticonvulsant treatments or in case of adverse reactions induced by these drugs, primidone may be used to increase the efficacy of the existing/underlying treatment or to replace it.
At first, primidone should be added to the previous treatment following a method of progressive dose increase as previously described. When an appreciable/acceptable therapeutic effect is reached and primidone dose has reached at least half of the previous dose, the discontinuation of the previous treatment can be attempted.
This dose adjustment is to be performed progressively for a period of 2 weeks during which it could be necessary to increase primidone doses to maintain a good control. Withdrawal of previous treatment should not be too rapid or status epilepticus may occur.
Where phenobarbital formed the major part of the previous treatment, however, both its withdrawal and Primidone substitution should be made earlier, so as to prevent excessive drowsiness from interfering with accurate assessment of the optimum dosage of Primidone.
Essential tremor Initially a dose of 50 mg daily should be introduced in a single intake late afternoon, using, when available, the 50 mg tablet. The daily dose (given in 2 divided doses) should be increased gradually over a 2 to 3-week period until remission of symptoms or the highest dose tolerated up to a maximum of 750 mg daily.
Patients not previously treated with anticonvulsants Patients with essential tremor who have not previously been exposed to anticonvulsants, or other drugs known to induce increased hepatic enzyme activity, may experience acute symptoms of intolerance to Primidone, frequently characterised by vertigo, unsteadiness and nausea.
It is, therefore, essential to respect initial dose therapeutic regimen. Special population Patients with renal impairment Due to decrease renal elimination of primidone in patients with renal insufficiency, the dose should be adjusted according to clinical response and biological monitoring.
Patients with hepatic impairment Due to the possible altered conversion of primidone to its metabolites and reduced elimination of phenobarbital in patients with severe hepatic impairment, the dose should be adjusted according to clinical response and biological monitoring.
Elderly patients It is advisable to monitor elderly patients with reduced renal function who are receiving primidone. Method of administration Oral use. The tablets should be swallowed whole with a glass of water.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
At treatment initiation, the most common side effects are drowsiness, dizziness and ataxia; they may disappear with treatment continuation and/or posology reduction. On occasions an idiosyncratic reaction may occur which involves visual disturbances, nausea, headache, dizziness, vomiting, nystagmus and ataxia; these symptoms are usually transient even when pronounced.
In an acute and severe form, withdrawal of treatment is required.
Other adverse reactions, observed during post-marketing setting, may include:
Frequencies are defined as: very rare (< 1/10,000), not known (cannot be estimated from the available data). Frequency System Organe Class Adverse reactions Common ( >1/100, <1/10) Eye disorders Visual disturbances Nervous system disorders Apathy, ataxia, nystagmus Gastrointestinal disorders Nausea Uncommon (>1/1000, <1/100) Nervous system disorders Headache, dizziness Gastrointestinal disorders Vomiting Skin and subcutaneous tissue disorders Allergic reactions particularly affecting the skin which can include maculopapular, morbilliform or scarlatiniform rashes.
Rare (>1/10000, <1/1000) Blood and lymphatic system disorders Megaloblastic anemia*, leucopenia, thrombocytopenia, lymphadenopathy Psychiatric disorders Psychotic reactions Musculoskeletal and connective tissue disorders Arthralgia, osteomalacia**.
As with phenobarbital, Dupuytren’s contracture Skin and subcutaneous tissue disorders Exfoliative dermatitis, lupus erythematosus. 4) pruritus. * Exceptionally, as with phenytoin and phenobarbital, primidone can cause megaloblastic anaemia requiring discontinuation of primidone.
This condition may respond to treatment with folic acid and/or Vitamin B12. ** Vitamin D supplementation may be needed during long-term Primidone therapy, since vitamin D catabolism may be increased. 4 Special warnings and precautions for use.
**** The mechanism by which affect bone metabolism has not been identified. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
uk/yellowcard) or search for MHRA Yellow Card in the Google Play or Apple App Store.
Special warnings Primidone is not efficient for the treatment of absences and myoclonic fits which may be sometimes aggravated. 2). Primidone should be given with caution and may be required in reduced dosage in children, the elderly, debilitated patients or those with impaired renal, hepatic or respiratory function.
6). Crisis aggravation Introduction of an anti-epileptic drug may be rarely followed by recrudescence of the crises or by occurrence of new type of crisis for the patient, independently of the fluctuations observed in some epilepsy.
For primidone, causes of these aggravations may be: a choice of a treatment inadequate for the crises or the epileptic syndrome in this patient, a change of the concomitant anti-epileptic treatment or a pharmacokinetic interaction, a toxicity or overdose.
There could be no other explanation than a paradoxal reaction. Treatment cessation Sudden withdrawal of a treatment at efficient anti-epileptic doses may induce convulsive fits and epilepticus status, mainly in case of alcoholism added.
Primidone is a potent CNS depressant and is partially metabolised into phenobarbital. After prolonged administration there is a potential for tolerance, dependence and a withdrawal reaction on abrupt cessation of treatment. Prevention of vitamin deficiencies Primidone is an enzymatic inducer (CYP450) which may increase the catabolism of vitamin D.
A dose-dependent increase in the risk of osteomalacia has been observed during therapy with primidone, which may predispose to the development of bone disease. 8). Exceptionally, as with phenytoin and phenobarbital, megaloblastic anaemia may develop requiring discontinuation of primidone.
8). Suicidal behaviour Suicidal ideation and behaviour have been reported in patients treated with anti- epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour.
The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for primidone. Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered.
Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. Severe skin reactions Life-threatening cutaneous reactions Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with the use of primidone.
Patients should be advised of the signs and symptoms and monitored closely for skin reactions. The highest risk for occurrence of SJS, TEN or DRESS is within the first weeks of treatment. g. progressive skin rash often with blisters or mucosal lesions) are present, primidone treatment should be discontinued.
The best results in managing SJS, TEN and DRESS come from early diagnosis and immediate discontinuation of any suspect drug. Early withdrawal is associated with a better prognosis. If the patient has developed SJS, TEN or DRESS with the use of primidone (or phenobarbital), primidone must not be re-started in this patient at any time.
8). Women of childbearing potential Primidone is extensively metabolised to phenobarbital. Thus information on phenobarbital must be taken into account. Phenobarbital may cause foetal harm when administered to a pregnant woman. 6). Primidone should not be used in women of childbearing potential unless the potential benefit is judged to outweigh the risks following consideration of other suitable treatment options.
Women of childbearing potential should be fully informed of the potential risk to the foetus if they take primidone during pregnancy. A pregnancy test to rule out pregnancy should be considered prior to commencing treatment with primidone in women of childbearing potential.
Women of childbearing potential should use highly effective contraception during treatment and for 2 months after the last dose. Due to enzyme induction, phenobarbital may result in a failure of the therapeutic effect of oral contraceptive drugs containing oestrogen and/or progesterone.
6). Women planning a pregnancy should be advised to consult in advance with her physician so that adequate counselling can be provided and appropriate other treatment options can be discussed prior to conception and before contraception is discontinued.
Women of childbearing potential should be counselled to contact her doctor immediately if she becomes pregnant or thinks she may be pregnant while on treatment with primidone. 5). Concomitant intake of this medicinal product with alcoholic beverages or with medicinal products containing alcohol is not recommended.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
5)
This is not medical advice. Consult a qualified healthcare professional.
Brands in United Kingdom (1)
USUnited States· FDA
3 products
Uses
INDICATIONS AND USAGE
Primidone, used alone or concomitantly with other anticonvulsants, is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy.
How to take
DOSAGE AND ADMINISTRATION
d. ). d. Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations of primidone may be necessary for optimal dosage adjustment. The clinically effective serum level for primidone is between 5 to 12 µg/mL.
INITIAL:
ADULTS AND CHILDREN OVER 8 KEY: •=50 mg tablet; ●=250 mg tablet Day 1 2 3 4 5 6 AM •• •• •• NOON PM •• •• •• •• •• •• DAY 7 8 9 10 11 12 AM •• •• •• ● Adjust to Maintenance NOON •• •• •• ● PM •• •• •• ● Patients Already Receiving Other Anticonvulsants Primidone should be started at 100 to 125 mg at bedtime and gradually increased to maintenance level as the other drug is gradually decreased.
This regimen should be continued until satisfactory dosage level is achieved for the combination, or the other medication is completely withdrawn. When therapy with primidone alone is the objective, the transition from concomitant therapy should not be completed in less than two weeks.
Pediatric Dosage For children under 8 years of age, the following regimen may be used: Days 1 to 3: 50 mg at bedtime. Days 4 to 6: 50 mg twice a day Days 7 to 9: 100 mg twice a day Day 10 to maintenance: 125 mg three times a day to 250 mg three times a day For children under 8 years of age, the usual maintenance dosage is 125 to 250 mg three times daily or, 10 to 25 mg/kg/day in divided doses.
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 481 reports total. [4]
- Off Label Use 40
- Drug Ineffective 33
- Drug Interaction 32
- Diarrhoea 30
- Fatigue 27
- Cough 25
- Product Dose Omission Issue 23
- Tremor 23
- Fall 22
- Product Use Issue 22
- Seizure 22
- Dyspnoea 21
Side effects & warnings
ADVERSE REACTIONS
The most frequently occurring early side effects are ataxia and vertigo. These tend to disappear with continued therapy, or with reduction of initial dosage. Occasionally, the following have been reported: nausea, anorexia, vomiting, fatigue, hyperirritability, emotional disturbances, sexual impotency, diplopia, nystagmus, drowsiness and morbilliform skin eruptions.
Granulocytopenia, agranulocytosis, and red-cell hypoplasia and aplasia, have been reported rarely. These and, occasionally, other persistent or severe side effects may necessitate withdrawal of the drug. Megaloblastic anemia may occur as a rare idiosyncrasy to primidone and to other anticonvulsants.
The anemia responds to folic acid without necessity of discontinuing medication. gov/medwatch.
WARNINGS
The abrupt withdrawal of antiepileptic medication may precipitate status epilepticus. The therapeutic efficacy of a dosage regimen takes several weeks before it can be assessed. 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.
Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. 7) of suicidal thinking or behavior compared to patients randomized to placebo.
24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication.
The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Table 1 shows absolute and relative risk by indication for all evaluated AEDs. 9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing primidone or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior.
Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm.
Behaviors of concern should be reported immediately to healthcare providers. Pregnancy To provide information regarding the effects of in utero exposure to primidone, physicians are advised to recommend that pregnant patients taking primidone enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry.
This can be done by calling the toll-free number 1-888-233-2334, and must be done by patients themselves. org/ . The effects of primidone in human pregnancy and nursing infants are unknown. Recent reports suggest an association between the use of anticonvulsant drugs by women with epilepsy and an elevated incidence of birth defects in children born to these women.
Data are more extensive with respect to diphenylhydantoin and phenobarbital, but these are also the most commonly prescribed anticonvulsants; less systematic or anecdotal reports suggest a possible similar association with the use of all known anticonvulsant drugs.
The reports suggesting an elevated incidence of birth defects in children of drug-treated epileptic women cannot be regarded as adequate to prove a definite cause and effect relationship. , genetic factors or the epileptic condition itself, may be more important than drug therapy.
The great majority of mothers on anticonvulsant medication deliver normal infants. It is important to note that anticonvulsant drugs should not be discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life.
In individual cases where the severity and frequency of the seizure disorders are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus.
The prescribing physician will wish to weigh these considerations in treating or counseling epileptic women of childbearing potential. Neonatal hemorrhage, with a coagulation defect resembling vitamin K deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants.
Pregnant women under anticonvulsant therapy should receive prophylactic vitamin K1 therapy for one month prior to, and during, delivery.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CONTRAINDICATIONS
Primidone is contraindicated in: 1) patients with porphyria and 2) patients who are hypersensitive to phenobarbital (see ACTIONS ).
This is not medical advice. Consult a qualified healthcare professional.
CACanada· Health Canada
2 products
2 products on record with this regulator. Detailed label text (uses, dosage, side effects) is being ingested — the original document is linked under Sources [3].
Drug interactions
Known interactions involving Primidone. Select one for details. This list is informational and not a complete interaction checker.
Showing 240 of 600. Type above to find a specific drug.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
Sources & citations
- [1]MHRA (UK) · PL488360025 · revised April 10, 2026
- [2]FDA DailyMed · 0193c0a4-f593-60… · revised June 10, 2025 [PDF]
- [3]Health Canada (DPD) · 00396761 · revised November 17, 2025
- [4]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.