Source: Health Products Regulatory Authority (ZA) Publisher: Ruby Pharmaceuticals (PTY) LTD, P.O. Box 431, Pinetown 3600
In the treatment of generalised epilepsy, particularly with the following patterns of seizures:
as well as, for partial epilepsy:
RUBILIM CR for the treatment and prevention of mania associated with bipolar disorders.
RUBILIM CR is a controlled release formulation, which reduces peak concentration and ensures a more even plasma concentration throughout the day. RUBILIM CR may be given once or twice daily.
Daily dosage requirements vary according to age and body weight.
In patients where adequate control has been achieved, RUBILIM CR formulations are interchangeable with other conventional or prolonged release formulations on an equivalent daily dosage basis.
Dosage should start at 600 mg/day, where applicable in divided doses, increasing by 200 mg/day at three day intervals until control is achieved; this is generally within the range of 1 000 to 2 000 mg/day (i.e. 20–30 mg/kg body mass). If adequate control has not been achieved after two weeks, the dose may be further increased, in stages, to a maximum of 2 500 mg/day, or one other anti-epileptic medicine may be added at a low dosage. In patients already receiving other therapy, the same pattern should be followed. If increased sedation is observed, dosage of barbiturates or benzodiazepines (e.g. lorazepam) should be reduced as that of RUBILIM CR is increased; dosage of both RUBILIM CR and other medicines should be adjusted, during the stabilization period, to give optimum control at the lowest possible combined dosage level, and it may be found possible to maintain optimum control with RUBILIM CR alone.
Initial dosage should be 400 mg/day irrespective of mass, where applicable in divided doses, with spaced increases until control is achieved. This is usually within the range of 20 to 30 mg/kg of body mass per day. Where adequate control is not achieved within this range, the dose may be increased to 35 mg/kg body mass per day.
20 mg/kg of body mass per day; in severe cases, this may be increased but only in patients in whom plasma valproic acid levels can be monitored. Above 40 mg/kg/day, clinical chemistry and haematological parameters should be monitored.
The recommended initial dose is 1 000 mg/day. The dose should be increased as rapidly as possible to achieve the lowest therapeutic dose, which produces the desired clinical effect.
Doses should be adjusted according to individual clinical response.
Prophylactic treatment should be established individually with the lowest effective dose.
Although the pharmacokinetics of RUBILIM CR is modified in the elderly, this is of limited clinical significance and dosage should be determined by seizure control. The volume of distribution is increased in the elderly, and, because of decreased binding to serum albumin, the proportion of free drug is increased. This will affect the clinical interpretation of plasma valproic acid levels.
It may be necessary to decrease dosage. Dosage should be adjusted according to clinical monitoring since monitoring of plasma concentrations may be misleading. (see section 5.2)
The safety and efficacy of RUBILIM CR for the treatment of manic episodes in bipolar disorder have not been established in studies in patients aged less than 18 year (see section 4.4).
When starting RUBILIM CR in patients already on other anticonvulsants, these should be tapered slowly; initiation of RUBILIM CR therapy should then be gradual, with target dose being reached after about 2 weeks. In certain cases it may be necessary to raise the dose by 5 to 10 mg/kg/day when used in combination with anticonvulsants, which induce liver enzyme activity, e.g. phenytoin, phenobarbitone and carbamazepine. Once known enzyme inducers have been withdrawn, or if side-effects, such as tremor, are experienced, it may be possible to maintain seizure control on a reduced dose of RUBILIM CR. When barbiturates are being administered concomitantly and particularly if sedation is observed (particularly in children) the dosage of barbiturate should be reduced.
The concentration of valproate in plasma that appears to be associated with therapeutic effects is approximately 30-100 μg/ml. Optimum dosage is mainly determined by seizure control and routine measurement of plasma levels is unnecessary. However, a method for measurement of plasma levels is available and may be helpful where there is poor control or side-effects are suspected (see section 5.2)
For oral use.
RUBILIM CR should be taken with or without food. The tablets should be swallowed whole, if necessary, with a little water (but not aerated mineral water) and not crushed or chewed.
Clinical signs of acute massive overdose usually include a coma, with muscular hypotonia, hyporeflexia, miosis and impaired respiratory function.
Symptoms may however be variable and seizures have been reported in the presence of very high plasma levels. Cases of intracranial hypertension related to cerebral oedema have been reported.
Hospital management of overdose should be symptomatic: cardio-respiratory monitoring, assisted ventilation and other supportive measures are recommended. Haemodialysis and haemoperfusion have been used successfully.
Naloxone has been successfully used in a few isolated cases.
Deaths have occurred following massive overdose.
3 years.
Store at or below 25°C.
Store in the original package in order to protect from light and moisture.
Keep out of reach of children.
RUBILIM CR is packed in cold form ALU-ALU blister packs in cartons of 56, 60, 100 or 120 or 140 tablets.
Not all pack sizes may be marketed.
No special requirements.
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