PRIADEL Prolonged-release tablet Ref.[27675] Active ingredients: Lithium

Dosage must be individualized depending on serum lithium levels and clinical response. The dosage necessary to maintain serum lithium levels within the therapeutic range varies from patient to patient. The minimum effective dose should be sought and maintained.

A simple treatment schedule has been evolved which except for some minor variations should be followed whether using Priadel therapeutically or prophylactically. The minor variations to this schedule depend on the elements of the illness being treated and these are described later.

1. In patients of average weight (70kg) an initial dose of 400-1,200mg of Priadel may be given as a single daily dose in the morning or on retiring. Alternatively, the dose may be divided and given morning and evening. The tablets should not be crushed or chewed. When changing for other lithium preparations serum lithium levels should first be checked, then Priadel therapy started at a daily dose as close as possible to the dose of the other form of lithium. As bioavailability varies from product to product (particularly with regard to retard or slow release preparations) a change of product should be regarded as initiation of new treatment.

2. Four to a maximum of seven days after starting treatment serum lithium levels should be measured.

3. The objective is to adjust the Priadel dose so as to maintain the serum lithium level permanently within the diurnal range of 0.5-1.5mmol/l. Blood samples should be taken 12 or 24 hours after the previous dose of Priadel, just before the next dose is due, to measure the serum lithium level at its trough “Target” serum lithium concentrations at 12 and 24 hours are shown in the table below.

“Target” serum lithium concentration (mmol/L):

The tablets have breaklines, therefore they can be divided accurately to provide smaller dosage requirements. Serum lithium levels should be monitored weekly until stabilisation is achieved.

4. Lithium therapy should not be initiated unless adequate facilities for routine monitoring of serum concentrations are available. Following stabilisation of serum lithium levels, the period between subsequent estimations can be increased gradually but should not normally exceed two to three months. Additional measurements should be made following alteration of dosage, on development of intercurrent disease, signs of manic or depressive relapse, following significant change in sodium or fluid intake, or if signs of lithium toxicity occur (see section 4.9).

5. Whilst a high proportion of acutely ill patients may respond within three to seven days of the commencement of Priadel therapy, Priadel should be continued through any recurrence of the affective disturbance. This is important as the full prophylactic effect may not occur for 6 to 12 months after the initiation of therapy.

6. In patients who show a positive response to Priadel therapy, treatment is likely to be long term. Careful clinical appraisal of the patient should be exercised throughout medication (see precautions).

Prophylactic treatment of bipolar affective disorders and control of aggressive behaviour or intentional self harm

It is recommended that the described treatment schedule is followed.

Treatment of acute manic or hypomanic episodes and recurrent depressive disorders

It is likely that a higher than normal Priadel intake may be necessary during an acute phase and divided doses would be required here. Therefore as soon as control of mania or depression is achieved, the serum lithium level should be determined and it may be necessary, dependent on the results, to lower the dose of Priadel and re-stabilise serum lithium levels. In all other details the described treatment schedule is recommended.

Elderly

Elderly patients, or those below 50kg in weight, often require lower lithium dosage to achieve therapeutic serum levels (see section 4.4). Starting doses of 200mg to 400mg are recommended. Dosage increments of 200 to 400mg every 3 to 5 days are usual. Total daily doses of 800 to 1800mg may be necessary to achieve effective blood lithium levels of 0.8 to 1.0 mmol/L. For prophylaxis, the dosage necessary to reach a blood lithium level of 0.4 to 0.8 mmol/L is generally in the range of 600 to 1200 mg/day.

Children and adolescents

Not recommended.

Renal impairment

In patients with mild and moderate renal insufficiency treated with lithium, serum lithium levels must be closely monitored and the dose should be adjusted accordingly to maintain serum lithium levels within the recommended range (see section 4.4). Lithium is contraindicated in patients with severe renal insufficiency (see section 4.3).

Symptoms of lithium intoxication include:

• Gastrointestinal disorders: increasing anorexia, diarrhoea and vomiting.
• Nervous system disorders: Encephalopathy, cerebellar syndrome with symptoms such as muscle weakness, lack of coordination, drowsiness or lethargy, giddiness, ataxia, nystagmus, coarse tremor. Tinnitus, blurred vision, dysarthria, twitching, myoclonus, extrapyramidal disorders.
• Other: ECG changes (flat or inverted T waves, QT prolongation), AV block, dehydration and electrolyte disturbances.

At blood levels above 2-3 mmol/L, there may be a large output of dilute urine and renal insufficiency, with increasing confusion, convulsions, coma and death. There is no specific antidote to lithium. In the event of lithium overdose, lithium should be discontinued and lithium serum levels monitored closely. Supportive treatment should be initiated, which includes correction of fluid and electrolyte balance, if necessary.

Diuretics should not be used (see section 4.5).

Haemodialysis is the treatment of choice for severe lithium intoxication (especially in patients manifesting with severe nervous system disorders), or in cases of overdose accompanied by renal impairment. Hemodialysis should be continued until there is no lithium in the serum or dialysis fluid. Serum lithium levels should be monitored for at least another week to take account of any possible rebound in serum lithium levels as a result of delayed diffusion from body tissues.

3 years.

Tablet containers:

Do not store above 25°C. Dispense in an airtight container. Keep the container tightly closed.

Blister strips:

Do not store above 25°C. Store in the original package to protect from moisture.

Polypropylene tablet containers of 100 and 1000 tablets with a snap on low density polyethylene lid.

PVC/PVdC/aluminium blister strips, each strip containing 10 tablets. Ten strips are packed in a cardboard outer.

Hospital packs of 100 tablets.

Not all pack sizes may be marketed.

No special requirements.