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Indications

Adult Dosage

Regular monitoring of plasma lithium concentration is always obligatory when Lithium is used; lithium therapy should not be initiated unless adequate facilities for routine monitoring of plasma concentrations are available. On initiation of plasma therapy concentrations should be measured weekly until stabilisation is achieved, then weekly for one month and at monthly intervals thereafter.

Additional measurements should be made if signs of lithium toxicity occur, on dosage alteration, development of significant intercurrent disease, signs of manic depressions or depressive relapse and if significant change in sodium or fluid intake occurs. More frequent monitoring is required if patients are receiving any drug treatment that affects renal clearance of lithium e.g. diuretics and NSAID. As bioavailability may vary between formulations, should a change of preparations be made, blood levels should be monitored weekly until restabilisation is achieved.

Acute mania:

Adults: Treatment should be initiated in hospital where regular monitoring of plasma lithium levels can be conducted. The dosage of Camcolit should be adjusted to produce a plasma lithium level between 0.6 and 1.0 mmol/l 12 hours after the last dose. The required plasma lithium level may be achieved in one of two ways but, whichever is adopted, regular estimations must be carried out to ensure maintenance of levels within the therapeutic range. For consistent results it is essential that the blood samples for plasma lithium estimations are taken 12 hours after the last dose of lithium.

1. 1,000-1,500 mg of lithium carbonate are administered daily for the first five days. A blood sample for plasma lithium estimation is taken 12 hours after the last dose on the fifth day, and the dosage of Camcolit is adjusted to keep the plasma lithium level within the therapeutic range. Subsequently, regular plasma lithium estimations must be carried out and, where necessary, the dosage of Camcolit adjusted accordingly. The precise initial dose of lithium should be decided in the light of the age and weight of the patient; young patients often require a dose higher than average and older patients a lower dose.

2. A lithium clearance test is carried out and the initial dosage calculated from the results. Even when the initial dosage is calculated in this way, it is still desirable that plasma lithium levels should be determined at weekly intervals during the first three weeks of treatment, and any necessary adjustments to dosage made as a result of the levels actually obtained.

Most of the above applies in the treatment of hypomania as well as mania, but the patient (if not too ill) can be started on treatment as an outpatient provided that facilities for regular plasma lithium monitoring are available, and assays are initiated within one week.

Prophylaxis of recurrent affective disorders:

Adults: (Including unipolar mania & unipolar depressions and bipolar manic-depressive illness): A low dose of 300-400 mg of lithium carbonate can be administered daily for the first seven days. A blood sample for plasma lithium estimation is then taken 12 hours after the last dose, and the dosage of Camcolit is adjusted to keep the plasma lithium level within the range of 0.4-0.8 mmol/l. Toxic symptoms are usually associated with concentrations exceeding 1.5 mmol/l.

Child Dosage

Elderly Dosage

As for prophylaxis above, but 12 hour lithium levels should be kept in the range of 0.4-0.7 mmol/l as toxic symptoms are likely with plasma concentrations above 1.0 mmol/l.

Contra Indications

Patients with renal disease, cardiovascular Addison's disease or those breast feeding.

Special Precautions

Pre-treatment and periodic routine clinical monitoring is essential. This should include assessment of renal function, urine analysis, assessment of thyroid function and cardiac function, especially in patients with cardiovascular disease.

Patients should be euthyroid before initiation of lithium therapy.

Clear instructions regarding the symptoms of impending toxicity should be given by the doctor to all patients receiving long-term lithium therapy. Patients should also be warned to report if polyuria or polydipsia develop. Episodes of nausea and vomiting or other conditions leading to salt/water depletion (including severe dieting) should also be reported. Patients should be advised to maintain their usual salt and fluid intake.

Elderly patients are particularly liable to lithium toxicity.

Caution is advised in patients with cardiovascular disease or family history of QT prolongation.

Concomitant administration of antipsychotics should be avoided.

Interactions

Lower doses of lithium may be required during diuretic therapy as lithium clearance is reduced.

Serum lithium concentrations may increase during concomitant therapy with non-steroidal anti-inflammatory drugs, or tetracycline, possibly resulting in lithium toxicity. Serum lithium concentrations therefore should be monitored more frequently if NSAID or tetracycline therapy is initiated or discontinued.

Raised plasma levels of ADH may occur during treatment.

Symptoms of nephrogenic diabetes insipidus are particularly prevalent in patients receiving concurrent treatment with tricyclic or tetracyclic antidepressants

Use with concomitant QT prolonging drugs (e.g. Class IA and III antiarrhythmics, arsenic trioxide, dolasetron mesylate, mefloquine, IV erythromycin) is not recommended.

Use with drugs causing electrolyte imbalance is not recommended.

Adverse Reactions

Long term treatment with lithium may result in permanent changes in the kidney and impairment of renal function. High serum concentrations of lithium, including episodes of acute lithium toxicity may enhance these changes. The minimum clinically effective dose of lithium should always be used. Patients should only be maintained on lithium after 3-5 years if, on assessment, benefit persists.

Renal function should be routinely monitored in patients with polyuria and polydipsia.

Side effects are usually related to serum lithium concentrations and are infrequent at levels below 1.0 mmol/l.

Mild gastro-intestinal effects, nausea, vertigo, muscle weakness and a dazed feeling may occur, but frequently disappear after stabilisation. Fine hand tremors, polyuria and mild thirst may persist. Some studies suggest that the tremor can be controlled by relatively small doses of propranolol.

Long term treatment with lithium is frequently associated with disturbances of thyroid function including goitre and hypothyroidism. These can be controlled by administration of small doses of thyroxine (0.05-0.2 mg daily) concomitantly with lithium. Thyrotoxicosis has also been reported.

Mild cognitive impairment may occur during long term use.

Hypercalcaemia, hypermagnesaemia, hyperparathyroidism and an increase in antinuclear antibodies have also been reported.

Exacerbation of psoriasis may occur.

Cardiovascular effects of lithium are rare and often benign. Reported effects are arrhythmia, oedema and sinus node dysfunction. QT interval prolongation, ventricular arrhythmias – ventricular fibrillation, ventricular tachycardia (rare), sudden unexplained death, cardiac arrest and Torsade de pointes have been reported, Any signs of cardiac disturbance e.g. syncope, heart rhythm or rate disturbances should be investigated further.

Oedema with weight gain can occur and may lead to an increased risk of lithium toxicity if treated incautiously with diuretic drugs.

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