Drug Description
Each tablet contains 50mg primidone.
Presentation
TabletWhite or virtually white, round, biconvex, uncoated tablets intagliated with a single M on one side and plain on the reverse.
Indications
Mysoline 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.
Adult Dosage
Epilepsy: Treatment must always be planned on an individual basis. In many patients it will be possible to use Mysoline alone, but in some, Mysoline will need to be combined with other anticonvulsants or with supporting therapy.Mysoline is usually given twice daily and may be administered using either the 50 mg or 250 mg strength tablets.Begin with 125 mg once daily late in the evening. Every 3 days increase the daily dosage by 125 mg until the patient is receiving 500 mg daily. Thereafter, every 3 days increase the daily dosage by 250 mg in adults or 125 mg in children under 9 years - until control is obtained or the maximum tolerated dosage is being given. This may be as much as 1.5 g a day in adults; 1 g a day in children.Average daily maintenance doses:MilligramsAdults and children over 9 years750 to 1500Children 6 to 9 years750 to 1000Children 2 to 5 years500 to 750Children up to 2 years250 to 500The total daily dose is usually best divided and given in two equal amounts, one in the morning and the other in the evening. In certain patients, it may be considered 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 day's 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.Elderly patients: It is advisable to monitor elderly patients with reduced renal function who are receiving primidone.Patients on other anticonvulsants: Where a patient's attacks are not sufficiently well controlled with other anticonvulsants, or disturbing side effects have arisen, Mysoline may be used to augment or replace existing treatment. First add Mysoline to the current anticonvulsant treatment by the method of gradual introduction described previously. When a worthwhile effect has been achieved and the amount of Mysoline being given has been built up to at least half the estimated requirement, withdrawal of the previous treatment can then be attempted. This should be done gradually over a period of 2 weeks, during which time it may be necessary to increase the Mysoline dosage to maintain control.Withdrawal of previous treatment should not be too rapid or status epilepticus may occur. Where phenobarbitone formed the major part of the previous treatment, however, both its withdrawal and Mysoline substitution should be made earlier, so as to prevent excessive drowsiness from interfering with accurate assessment of the optimum dosage of Mysoline.Essential tremor: Initially a dose of 50 mg daily should be introduced. The daily dose 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 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 tolerance to Mysoline, frequently characterised by vertigo, unsteadiness and nausea. It is, therefore, essential to start such patients at a low dosage (initially 50 mg daily) increasing very slowly up to the maximum tolerated dose or that which produces remission of tremor (up to 750mg daily).
Contra Indications
Patients who exhibit hypersensitivity or an allergic reaction to primidone, to a constituent of the formulation or to phenobarbitone, should not receive the drug. Primidone should not be administered to patients with acute intermittent porphyria.
Special Precautions
Mysoline 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.Primidone is a potent CNS depressant and is partially metabolised to phenobarbitone. After prolonged administration there is a potential for tolerance, dependence and a withdrawal reaction on abrupt cessation of treatment.Exceptionally, as with phenytoin and phenobarbitone, megaloblastic anaemia may develop requiring discontinuation of primidone. This condition may respond to treatment with folic acid and/or vitamin B12. There have been isolated reports of other blood dyscrasias.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.
Interactions
Both primidone and its major metabolite phenobarbitone are metabolized by, and also induce, liver enzyme activity, principally the CYP 450 3A4 enzyme system..Agents which inhibit the CYP 450 3A4 enzyme system, such as chloramphenicol, felbamate, nelfinavir*, metronidazole and sodium valproate may result in increased plasma levels of concomitantly administered primidone and its metabolite phenobarbitone.In addition, St. John's Wort* induces the CYP450 enzyme system and may result in a reduction of plasma levels of concomitantly administered primidone and of its major metabolite phenobarbitone.Theophylline protein binding may affect phenobarbitone binding, affecting free phenobarbitone levels.Primidone therapy may also lead to altered pharmacokinetics in concomitantly administered drugs, whose metabolism may be increased and lead to lowered plasma levels and/or a shorter half-life. These drugs include androgens*, beta-antagonists, carbamazepine, cyclosporin, cloazepine, chloramphenicol, corticosteroids/glucocorticosteroids, cyclophosphamide, dicoumarins, digitoxin*, doxycycline, ethosuxamide, etoposide, felbamate, granisetron, lamotrigine, losartan, methadone*, metronidazole, mainserin, montelukast*, nelfinavir*, nimodipine, oral-contraceptives, oxcarbazepine, phenytoin, quinidine, rocuronium, sodium valproate, tiagabine, theophyllines, topiramate, tricyclic antidepressants, vecuronium, warfarin and zonisamide.Primidone inhibits the glucoronidation of paracetamol* and may increase the hepatotoxicity of paracetamol.The CNS depressant effect of primidone is additive to those of other CNS depressants such as alcohol, opiates and barbiturates.The above interactions are potentially clinically significant.* No formal interaction studies have been performed. The inclusion of the drug is based on reports of their influence or dependence upon enzyme systems influenced by, or of relevance to the metabolic pathways of primidone or its major metabolite, phenobarbitone.
Adverse Reactions
If adverse effects do appear, the most common side effects are drowsiness and listlessness but these generally occur only in the beginning of treatment.Visual disturbances, nausea, headache, dizziness, vomiting, nystagmus and ataxia have been reported but are usually transient even when pronounced. On occasions an idiosyncratic reaction may occur which involves these symptoms in an acute and severe form necessitating withdrawal of treatment.Common( >1/100)GeneralDrowsinessCentral and peripheral nervous systemListlessness, ataxia, visual disturbances, nystagmusGastrointestinalNauseaLess common(1/100 - 1/1000)GeneralHeadache, dizzinessGastrointestinalVomitingDermatologicalAllergic reactions particularly affecting the skin can include maculopapular, morbilliform or scarlatiniform rashes.Rare(< 1/1000)Central and peripheral nervous systemPersonality changes, which may include psychotic reactions.HaematologicalMegaloblastic anaemia, blood dyscrasiasHepaticElevations in hepatic enzymes, including gamma-glutamyl transferase (gamma GT) and alkaline phosphatase.MusculoskeletalArthralgia, osteomalacia.As with phenobarbitone, Dupuytren's contracture has been reportedDermatologicalSevere reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis and lupus erythematosus.Vitamin D supplementation may be needed during long-term primidone therapy, since vitamin D catabolism may be increased.Exceptionally, as with phenytoin and phenobarbitone, megaloblastic anaemia may develop requiring discontinuation of primidone. This condition may respond to treatment with folic acid and/or Vitamin B12.
Manufacturer
Acorus Therapeutics Limited
Drug Availability
POM-Prescription Only Medicine
Updated
21 September 2010
