Primidone oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of primidone.
Drugs List
Therapeutic Indications
Uses
Epilepsy - except absence seizures
Management of essential tremor
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.
Dosage
Treatment should be always be managed on an individual basis. In many patients it will be possible to use primidone alone, but in some it may need to be combined with other anticonvulsants or with supporting therapy.
Adults
Primidone should be started at the lowest possible dose in the evening and thereafter the dose should be increased in a stepwise manner to minimise adverse reactions.
Epilepsy
The average daily maintenance dose is 750 to 1500mg.
Treatment should be started with 125mg once daily, late in the evening. The daily dosage should be increased by 125mg every 3 days until the patient is receiving 500mg daily. Thereafter, increase the daily dosage by 250mg every 3 days until control is obtained or the maximum tolerated dose is being given. This may be as much as 1500mg per day.
The total daily dose is usually best administered in two equal amounts, one in the morning and one in the evening. In certain patients it may be considered advisable to give a larger dose when seizures are more frequent. For instance, if the attacks are nocturnal then all or most of the daily dose should be given in the evening or if the attacks are associated with some particular event such as menstruation, a slight increase in the appropriate dose is often beneficial.
Essential tremor
Initially a dose of 50mg daily should be introduced in a single intake late afternoon. The daily dose (given in two divided doses) should be increased gradually over a 2 to 3 week period until remission of symptoms or the highest tolerated dose up to a maximum of 750mg daily is obtained.
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 nausea, vertigo and unsteadiness. It is therefore essential to start such patients at a low dose and titrate the dosage slowly.
Elderly
It is advisable to monitor elderly patients with reduced renal function during treatment, and consider a reduced dose.
Children
Epilepsy
The average daily dose for children over 9 years
750 to 1500mg
The average daily dose for children 6 to 9 years
750 to 1000mg
The average daily dose for children 2 to 5 years
500 to 750mg
The average daily dose for children up to 2 years
250 to 500mg
Treatment should be started with 125mg once daily, late in the evening. The daily dosage should be increased by 125mg every 3 days until the patient is receiving 500mg daily. Thereafter, increase the daily dosage by 250mg in children over the age of 9 and by 125mg in children under 9 years every 3 days until control is obtained or the maximum tolerated dose is being given.
Patients with Renal Impairment
The Renal Drug Handbook recommends no change in dose at a glomerular filtration rate (GFR) above 20ml/min. For GFR less than 20ml/min the following dose changes are suggested:
GFR 10 to 20ml/min: Dose as in normal renal function, but avoid large doses.
GFR less than 10ml/min: Reduce the dose by 25 to 50% initially, and avoid large single doses in patients.
Additional Dosage Information
Concomitant use/switch from other anticonvulsant treatments
In the 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. Initially, primidone should be added to the previous treatment following a method of progressive dose increase. When an 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. The dose adjustment is to be performed for 2 weeks during which it may be necessary to increase primidone doses to maintain a good control.
Contraindications
Acute porphyria
Pregnancy
Severe respiratory depression
Precautions and Warnings
Children under 18 years
Debilitation
Elderly
Females of childbearing potential
Breastfeeding
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of alcohol abuse
History of drug misuse
Lactose intolerance
Renal impairment
Respiratory impairment
Advise ability to drive/operate machinery may be affected by side effects
Increased risk of osteomalacia; consider vitamin D supplement
Prescribe by manufacturer's product to ensure seizure control maintenance
Some formulations contain lactose
Monitor closely for skin reactions
Monitor for signs of suicide ideation or behaviour
Neonate exposed in utero: Monitor for neonatal withdrawal syndrome
Tolerance and dependence may occur
Potential for withdrawal symptoms
Avoid abrupt withdrawal
Discontinue and do not restart if severe cutaneous adverse reactions occur
Discontinue if megaloblastic anaemia develops
Consider dose reduction in renal impairment
Consider dose reduction in severe hepatic impairment
Start treatment at lowest recommended dose
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Female: Ensure adequate contraception during treatment
Neonate exposed in utero: Administer vitamin K at birth
Pregnancy: Administer vitamin K in the last few weeks of pregnancy
Pregnancy: Advise taking folate supplement as risk of neural tube defects
Advise patient/carers to report signs of suicide ideation or behaviour
Introduction of an anti-epileptic drug may be rarely followed by recrudescence of the crises of by occurrence of a new type of crisis for the patient. For primidone, causes of theses aggravations may be: a choice of 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.
Antiepileptic treatment is associated with a increased risk of suicidal thoughts and behaviour. Patients should be alert to any mood changes, distressing thoughts, or feelings about suicide or harming themselves at any point during treatment.
Pregnancy and Lactation
Pregnancy
Primidone is contraindicated during pregnancy.
The manufacturer does not recommend using primidone during pregnancy unless clearly necessary. Available reports indicate teratogenic effects including congenital heart disease, cleft palate, spina bifida, microencephaly and anencephaly. If primidone is used during pregnancy, the minimal effective dose should be used.
Pregnant patients should be given vitamin K1 through the last month of pregnancy up to the time of delivery as anticonvulsant therapy in pregnancy has been associated with coagulation disorders in the neonates. In the absence of such pre-treatment, 10mg vitamin K1 may be given to the mother at the time of delivery and 1mg should be given immediately to the neonate at risk.
Lactation
Use primidone with caution during breastfeeding.
The manufacturer does not recommend primidone during breastfeeding. There is a risk of sedation during the neonatal immediate period which can cause difficulties in suckling, and therefore poor weight gain.
If primidone is required by the mother, it is not a reason to discontinue breastfeeding. However, the infant must be monitored for drowsiness, adequate nursing and weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsant drugs. Measurement of an infant serum level might help rule out of toxicity if there is a concern (LactMed, 2022).
Side Effects
Allergic reaction
Arthralgia
Ataxia
Blood dyscrasias
Cardiovascular depression
Decrease in bone mineral density
Dizziness
Drowsiness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dupuytren's contracture
Exfoliative dermatitis
Folate deficiency
Gamma glutamyl transferase (GGT) increased
Headache
Hypersensitivity syndrome
Increase in alkaline phosphatase
Increased risk of fractures
Increases in hepatic enzymes
Listlessness
Lupus erythematosus
Maculopapular rash
Megaloblastic anaemia
Morbilliform eruption
Nausea
Nystagmus
Osteomalacia
Osteopenia
Osteoporosis
Personality change
Psychotic symptoms
Respiratory depression
Scarlatiniform rash
Severe cutaneous adverse reactions
Stevens-Johnson syndrome
Suicidal tendencies
Toxic epidermal necrolysis
Visual disturbances
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: November 2019
Reference Sources
Summary of Product Characteristics: Primidone Aspire 50mg tablets. Aspire Pharma Ltd. Revised August 2022.
Summary of Product Characteristics: Primidone Aspire 250mg tablets. Aspire Pharma Ltd. Revised August 2022.
Summary of Product Characteristics: Primidone Auden 50mg tablets. Teva UK Ltd. Revised November 2018.
Summary of Product Characteristics: Primidone Auden 250mg tablets. Teva UK Ltd. Revised November 2018.
The Renal Drug Handbook. Fifth Edition (2019) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
MHRA Drug Safety Update Vol 2, Issue 9, April 2009
Antiepileptics: adverse effects on bone
Available at: www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/index.htm
Last accessed: 15/10/10
MHRA Drug Safety Update Vol 2, Issue 1, August 2008
Antiepileptics: risk of suicidal thoughts and behaviour
Available at: www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON023078
Last accessed: 15/10/10
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 07 November 2019
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Primidone Last revised: 18 January 2022.
Last accessed: 17 January 2023.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.