INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
MYSOLINE® Tablets

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

MYSOLINE® Tablets

COMPOSITION:
Each MYSOLINE tablet contains 250 mg primidone.

PHARMACOLOGICAL CLASSIFICATION
A 2.5 Anticonvulsants, including anti-epileptics.

PHARMACOLOGICAL ACTION
Pharmacodynamic properties
The activity of MYSOLINE is due to the anticonvulsant properties of three active moieties; namely primidone itself and its two major metabolites, phenobarbitone and phenylethylmalonamide. The relative contribution of these three moieties to the clinical anticonvulsant effect has not been firmly established. Although the precise mode of action of MYSOLINE is unknown, effects on the neuronal membrane particularly with respect to alteration of ionic fluxes are likely to play a fundamental role.
Pharmacokinetics
MYSOLINE is usually absorbed rapidly from the gastro-intestinal tract with wide individual variation. Peak plasma levels are attained approximately 3 hours after ingestion. Primidone is well distributed in all organs and tissues; it crosses the blood-brain and placental barriers and is excreted in breast milk. Primidone has a plasma half-life of 7 to 14 hours which is considerably shorter than those of its principal metabolites. Primidone and phenylethylmalonamide are bound to plasma proteins to only a small extent, whereas approximately half of phenobarbitone is bound. Approximately 40% of the drug is excreted unchanged in urine.

INDICATIONS
MYSOLINE is an anticonvulsant which is effective in grand mal. It is also effective in minor seizures: psychomotor (temporal lobe) epilepsy, focal or Jacksonian seizures and in the control of myoclonic jerks and akinetic attacks.

CONTRA-INDICATIONS
Patients who exhibit hypersensitivity or allergic reactions to primidone should not receive the medicine. Primidone should not be administered to patients with acute intermittent porphyria.
Concomitant use of MYSOLINE and phenobarbitone is contra-indicated, except when transferring treatment from one to the other (see Special precautions).
Patients with severe hepatic, renal or respiratory impaired function.

DOSAGE AND DIRECTIONS FOR USE
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.
When MYSOLINE is used with or to replace existing anticonvulsant therapy, the dosage should be increased gradually while that of the other medication is maintained or decreased gradually in order to maintain seizure control. This should be done over a period of two weeks.
MYSOLINE is usually given twice daily. Begin with half a tablet once daily late in the evening.
Every three days increase the daily dosage by half a tablet until the patient is receiving 2 tablets daily. Thereafter, every three days increase the daily dosage by one tablet in adults or half a tablet in children under 9 years - until control is obtained or the maximum tolerated dosage is being given. This may be as much as 6 tablets a day in adults; 4 tablets a day in children.
Average daily maintenance doses:

	Tablets	mg
Children up to 2 years	1 to 2	250 to 500
Children 2 to 5 years	2 to 3	500 to 750
Children 6 to 9 years	3 to 4	750 to 1 000
Adults and children over 9 years	3 to 6	750 to 1 500

The 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 at the appropriate time is often beneficial.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Side-effects
If side-effects do appear they are generally confined to the early stages of treatment when patients frequently feel drowsy and listless.
Visual disturbances, nausea, headache, dizziness, vomiting, nystagmus and ataxia have been reported but these are usually transient. Dosage reduction may be necessary. On occasions an idiosyncratic reaction may occur which involves these symptoms in an acute and severe form necessitating withdrawal of treatment.
Dermatological reactions (including severe skin eruptions) and systemic conditions such as systemic lupus erythematosus have been reported.
Occasional cases of arthralgia have been reported.
Infrequently personality changes, which may include psychotic reactions, have been reported.
There have been infrequent reports of Dupuytren's contracture in patients administered MYSOLINE.
Megaloblastic anaemia has been reported 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.
Other infrequent side effects include oedema of the legs, thirst and polyuria and impairment of sexual function.
Special precautions
MYSOLINE should be given with caution and reduced dosage may be required in children, the elderly, debilitated patients or those with impaired renal, hepatic or respiratory function.
MYSOLINE can induce liver enzymes and although there is insufficient evidence to suggest a causal relationship, there is a theoretical risk of hepatic damage.
MYSOLINE may also affect Vitamin D metabolism, which may predispose to the development of bone disease.
Primidone is a potent CNS depressant and is metabolised to phenobarbitone, therefore the combination of both agents is contra-indicated. However, if patients are to be transferred from phenobarbitone to MYSOLINE, then it is recommended that the withdrawal of phenobarbitone should be done gradually over a period of two weeks, during which time it may be necessary to increase the MYSOLINE dosage to maintain control. After prolonged administration there is a potential for tolerance, dependence and a withdrawal reaction on abrupt cessation of treatment.
Pregnancy
There is evidence of a higher than average incidence of congenital abnormalities in infants born of epileptic mothers. The factors influencing this are unknown, but the possibility that anticonvulsant therapy may be involved and the slight risk of an abnormal foetus must be weighed against the risks of withholding treatment during pregnancy.
Withdrawal symptoms may occur in the newly born whose mothers have received MYSOLINE during late pregnancy.
Long-term anticonvulsant therapy can be associated with decreased serum folate levels. As folic acid requirements are also increased during pregnancy, regular screening of patients at risk is advised, and treatment with folic acid and Vitamin B12, although controversial, should be considered.
Anticonvulsant therapy in pregnancy has occasionally been associated with coagulation disorders in the neonate. For this reason pregnant patients should be given Vitamin K1 through the last month of pregnancy up to the time of delivery. In the absence of such pre-treatment, 10 mg Vitamin K1 may be given to the mother at the time of delivery and 1 mg should be given immediately to the neonate.
Lactation
During breast feeding the baby should be monitored for sedation.
Interactions
Both primidone and its major metabolite phenobarbitone induce liver enzyme activity. This may lead to altered pharmacokinetics in concomitantly administered drugs including other anticonvulsants such as phenytoin and coumarin anticoagulants.
Breakthrough bleeding and failure of contraceptive therapy has been noted in patients taking anticonvulsant drugs and oral contraceptive steroids.
The effects of other CNS depressants such as alcohol and barbiturates may be enhanced by the administration of primidone.
Effect on ability to drive or operate machinery
Patients who drive vehicles or operate machinery should be aware of the possibility of impaired reaction time.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Primidone is metabolised to phenobarbitone and overdosage leads to various degrees of CNS depression which, depending on the dose ingested, may include ataxia, loss of consciousness, respiratory depression and coma. Treatment should include aspiration of stomach contents and general supportive measures. Forced alkaline diuresis or dialysis may be helpful. There is no specific antidote.

IDENTIFICATION
Mysoline tablets are round, white to almost white, biconvex, uncoated tablets, bisected on one side with 'M' impressed on either side of the breakline.

PRESENTATION:
Mysoline tablets: Containers of 100 and 500.

STORAGE INSTRUCTIONS:
Store below 25°C.
Protect from moisture.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
Mysoline tablets: B/2.5/572

NAME AND BUSINESS ADDRESS OF THE APPLICANT
Pharmaplan (Pty) Ltd
106 16th Road
MIDRAND

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
10 November 1993

New addition to this site: December 2006
Source: Pharmaceutical Industry

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