Lithium Other names: Lithium salts

Monitor serum lithium concentrations more frequently if NSAID therapy is initiated or discontinued.

Interaction causing neurotoxicity.

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.

Steroids may alter lithium excretion and therefore should be avoided.

Serum lithium levels may be decreased due to an increase in lithium renal clearance in case of concomitant administration of sodium bicarbonate.

Thiazides show a paradoxical antidiuretic effect resulting in possible water retention and lithium intoxication. Should be prescribed with extreme caution and careful monitoring. Similar precautions should be exercised on diuretic withdrawal. Note that thiazides show a paradoxical antidiuretic effect resulting in possible water retention and lithium intoxication. If a thiazide diuretic has to be prescribed for a lithium-treated patient, lithium dosage should first be reduced and the patient re-stabilised with frequent monitoring. Similar precautions should be exercised on diuretic withdrawal. Loop diuretics seem less likely to increase lithium levels.

Calcium channel blockers may lead to a risk of neurotoxicity in the form of ataxia, confusion and somnolence, reversible after discontinuation of the drug. Lithium concentrations may be increased.

If ACE inhibitor is initiated, lithium dosage should either be adjusted or concomitant treatment stopped, as appropriate.

If angiotensin II receptor antagonist is initiated, lithium dosage should either be adjusted or concomitant treatment stopped, as appropriate.

If tetracycline is initiated, lithium dosage should either be adjusted or concomitant treatment stopped, as appropriate.

Lithium may prolong the effects of neuromuscular blocking agents.

Triptan derivatives and/or serotonergic antidepressants such as Selective Serotonin Re-uptake Inhibitors (e.g. fluvoxamine and fluoxetine) as this combination may precipitate a serotonergic syndrome, which justifies immediate discontinuation of treatment.

Serum lithium levels may be decreased due to an increase in lithium renal clearance in case of concomitant administration of xanthines.

Serum lithium levels may be decreased due to an increase in lithium renal clearance in case of concomitant administration of calcitonin.

Carbamazepine may lead to dizziness, somnolence, confusion and cerebellar symptoms such as ataxia.

Neuroleptics (particularly haloperidol at higher dosages), flupentixol, risperidone, diazepam, thioridazine, fluphenazin, chlorpromazine and clozapine may lead in rare cases to neurotoxicity in the form of confusion, disorientation, lethargy, tremor, extrapyramidal symptoms and myoclonus. Co-administration of lithium with neuroleptics increases the risk of Neuroleptic Malignant Syndrome (NMS), which may be fatal. Discontinuation of both drugs is recommended at the first signs of neurotoxicity.

Interaction causing neurotoxicity.

Metronidazole may reduce lithium renal clearance.

Serum lithium levels may be decreased due to an increase in lithium renal clearance in case of concomitant administration of urea.

As a precautionary measure, lithium should be avoided in patients with congenital long QT syndrome, and caution should be exercised in patients with risk factors such as QT interval prolongation (e.g. uncorrected hypokalaemia, bradycardia), and in patients concomitantly treated with drugs that are known to prolong the QT interval.

Serotonin syndrome is a potentially life-threatening adverse reaction, which is caused by an excess of serotonin (e.g. from overdose or concomitant use of serotonergic drugs), necessitating hospitalisation and even causing death.

Symptoms may include:

• Mental status changes (agitation, confusion, hypomania, eventually coma)
• Neuromuscular abnormalities (myoclonus, tremor, hyperreflexia, rigidity, akathisia)
• Autonomic hyperactivity (hypo or hypertonia, tachycardia, shivering, hyperthermia, diaphoresis)
• Gastrointestinal symptoms (diarrhoea)

Strict adherence to the recommended doses is an essential factor for the prevention of the occurrence of this syndrome.

There have been case reports of benign intracranial hypertension. Patients should be warned to report persistent headache and/or visual disturbances.

Lithium therapy should not be used during pregnancy, especially during the first trimester, unless considered essential. There is epidemiological evidence that lithium may be harmful to the foetus in human pregnancy. Lithium crosses the placental barrier. In animal studies lithium has been reported to interfere with fertility, gestation and foetal development. An increase in cardiac and other abnormalities, especially Ebstein anomaly, have been reported. Therefore, a pre-natal diagnosis such as ultrasound and electrocardiogram examination is strongly recommended. In certain cases where a severe risk to the patient could exist if treatment were stopped, lithium has been continued during pregnancy.

It is strongly recommended that lithium be discontinued before a planned pregnancy. If it is considered essential to maintain treatment with lithium during pregnancy, serum lithium levels should be monitored closely since renal function changes gradually during pregnancy and suddenly at parturition, requiring dosage adjustments. It is recommended that administration of lithium be discontinued shortly before delivery and recommenced a few days post-partum.

Neonates may show signs of lithium toxicity including symptoms such as lethargy, flaccid muscle tone, or hypotonia. Careful clinical observation of the neonate exposed to lithium during pregnancy is recommended and lithium levels may need to be monitored as necessary.

Lithium is secreted in breast milk therefore bottle feeding is recommended.

There have been case reports of neonates showing signs of lithium toxicity. Therefore lithium should not be used during breast-feeding. A decision should be made whether to discontinue lithium therapy or to discontinue breast-feeding, taking into account the importance of the drug to the mother and the importance of breast-feeding to the infant.

Women of child-bearing potential

It is advisable that women treated with lithium should adopt adequate contraceptive methods.

Lithium may cause disturbances of the CNS. Since lithium may slow reaction time, and considering the adverse reactions profile of lithium, patients should be warned of the possible hazards when driving or operating machinery.