Primidone


Generic Medicine Info
Indications and Dosage
Oral
Essential tremor
Adult: Initially, 50 mg daily, may increase gradually over 2-3 weeks based on patient’s clinical response and tolerability. Max: 750 mg daily. Dosing recommendations may vary among countries or individual products or preparations. Refer to country- or product-specific recommendations.
Elderly: Dosage reduction may be required.

Oral
Grand mal epilepsy, Partial seizures, Psychomotor epilepsy
Adult: Dose is individualised based on patient’s clinical response and tolerability. As monotherapy or in combination with other anticonvulsants: Initially, 125 mg once daily at bedtime, may increase by 125 mg every 3 days up to a total of 500 mg daily in 2 divided doses. If needed, may further increase by 250 mg every 3 days. Maintenance: 750-1,500 mg daily to be given in 2 divided doses. Max: 1,500 mg daily. In patients on other anticonvulsants, initiating primidone and withdrawal of previous treatment should be gradually done over a period of 2 weeks. Dosing recommendations may vary among countries or individual products or preparations. Refer to country- or product-specific recommendations.
Child: Dose is individualised based on patient’s clinical response and tolerability. Initially, 125 mg once daily at bedtime, may increase by 125 mg every 3 days. Maintenance: <2 years 250-500 mg daily; 2-5 years 500-750 mg daily; 6-9 years 750-1,000 mg daily; >9 years Same as adult dose. Maintenance doses are to be given in 2 divided doses. Dosing recommendations may vary among countries or individual products or preparations. Refer to country- or product-specific recommendations.
Elderly: Dosage reduction may be required.
Special Patient Group
Debilitated patients: Dosage reduction may be required.
Renal Impairment
Dosage reduction may be required.
Hepatic Impairment
Dosage reduction may be required.
Administration
May be taken with or without food. May be taken w/ food or milk to avoid stomach upset.
Contraindications
Acute intermittent porphyria.
Special Precautions
Patients with depression, suicidal tendencies, history of drug abuse or potential for drug dependency, hypoadrenalism, respiratory disease. Debilitated patients. Avoid abrupt withdrawal. Children and elderly. Renal and hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Significant: Suicidal ideation and behaviour; rarely, megaloblastic anaemia and blood dyscrasias; decreased serum folate and vitamin D levels (long-term therapy).
Eye disorders: Visual disturbances, diplopia.
Gastrointestinal disorders: Nausea, vomiting.
General disorders and administration site conditions: Fatigue.
Immune system disorders: Rarely, exfoliative dermatitis, SLE.
Metabolism and nutrition disorders: Anorexia.
Musculoskeletal and connective tissue disorders: Arthralgia, Dupuytren’s contracture, osteomalacia.
Nervous system disorders: Drowsiness, headache, dizziness, nystagmus, ataxia, vertigo.
Psychiatric disorders: Apathy, listlessness, personality change, hyperirritability.
Reproductive system and breast disorders: Sexual impotency.
Skin and subcutaneous tissue disorders: Maculopapular, morbilliform or scarlatiniform rashes.
Potentially Fatal: Rarely, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Patient Counseling Information
This drug may cause drowsiness or reduced alertness, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor serum primidone and phenobarbital levels, CBC; signs of depression, suicidal ideation and behaviours, neurological status; serum folate levels; bone density (long-term therapy). Obtain comprehensive metabolic panel at 6-month intervals to compare with baseline at the start of therapy.
Overdosage
Symptoms: CNS depression (e.g. ataxia, loss of consciousness, respiratory depression, coma), crystalluria. Management: General supportive treatment. May perform aspiration of stomach contents, administer activated charcoal or IV fluids, forced alkaline diuresis depending on the severity of intoxication. May perform haemoperfusion (if the patient is hypotensive) or haemodialysis in a more life-threatening situation.
Drug Interactions
May have increased serum concentration with CYP3A4 inhibitors (e.g. chloramphenicol, felbamate, nelfinavir, metronidazole, Na valproate). May increase metabolism resulting in lower serum concentration and shorter half-life of androgens, β-antagonists, carbamazepine, chloramphenicol, clozapine, corticosteroids, cyclophosphamide, cyclosporin, dicoumarins, digitoxin, doxycycline, ethosuximide, etoposide, felbamate, granisetron, lamotrigine, losartan, methadone, metronidazole, mianserin, montelukast, nelfinavir, nimodipine, oral contraceptives, oxcarbazepine, phenytoin, quinidine, rocuronium, Na valproate, tiagabine, theophylline, topiramate, TCAs, vecuronium, warfarin, zonisamide. May increase the hepatotoxicity of paracetamol. Additive CNS depressant effect with other CNS depressant (e.g. barbiturates, opiates).
Food Interaction
May have decreased serum concentration with St. John’s wort. Additive CNS depressant effect with alcohol. May have increased duration of action with protein-deficient diets.
Action
Description: Primidone raises the seizure threshold and decreases the excitability of neurons. It is metabolised into 2 active metabolites namely, phenobarbital and phenylethylmalonamide (PEMA) where PEMA potentiates the activity of phenobarbital.
Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract. Bioavailability: >90%. Time to peak plasma concentration: 0.5-9 hours (variable).
Distribution: Well distributed in all organs and tissues. Crosses the placenta, enters breast milk and crosses the blood-brain barrier. Volume of distribution: 0.6-0.75 L/kg. Plasma protein binding: <20%.
Metabolism: Metabolised in the liver via oxidation into phenobarbital and via ring cleavage at the 2nd carbon position into phenylethylmalonamide (PEMA).
Excretion: Via urine (15-65% as unchanged drug; remainder is metabolites). Elimination half-life: Approx 10-15 hours.
Chemical Structure

Chemical Structure Image
Primidone

Source: National Center for Biotechnology Information. PubChem Database. Primidone, CID=4909, https://pubchem.ncbi.nlm.nih.gov/compound/Primidone (accessed on Jan. 23, 2020)

Storage
Store below 25°C. Protect from light and moisture.
MIMS Class
ATC Classification
N03AA03 - primidone ; Belongs to the class of barbiturates and derivatives antiepileptics.
References
Anon. Primidone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 10/02/2021.

Apotex NZ Ltd. Apo-Primidone 250 mg Tablets data sheet 22 August 2018. Medsafe. http://www.medsafe.govt.nz. Accessed 10/02/2021.

Buckingham R (ed). Primidone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/02/2021.

Joint Formulary Committee. Primidone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/02/2021.

Primidone Auden 50 mg Tablets (TEVA UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 10/02/2021.

Primidone Tablet (Actavis Pharma, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/02/2021.

Disclaimer: This information is independently developed by MIMS based on Primidone from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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