P.I. Pharma


JF Draf
Full Prescribing Info
Lithium carbonate.
Each tablet contains 450 mg of lithium carbonate in sustained release form.
Pharmacology: Pharmacodynamics: Lithium is an alkali metal available for medical use as lithium carbonate or lithium citrate. The exact mechanism of action of lithium in the treatment of bipolar disorders is not known. Mode of action of lithium is still not fully understood. However, lithium modifies the production and turnover of certain neurotransmitters, particularly serotonin, and it may also block dopamine receptors. It modifies concentrations of some electrolytes, particularly calcium and magnesium and it may reduce thyroid activity.
Pharmacokinetics: Lithium ions are rapidly absorbed from the gastrointestinal tract and plasma lithium peaks are reached 2 to 4 hours after lithium administration. The distribution of lithium in the body approximates that of total body water, but its passage across the blood-brain barrier is slow and at equilibration the CSF lithium level reaches only approximately half the plasma concentration.
The elimination half-life of lithium averages 20-24 hours. Half-life in geriatric patients and patients with impaired renal function is increased, 36 and 40 to 50 hours have been reported respectively.
Lithium is excreted primarily in urine with less than 1% being eliminated with feces. Lithium is filtered by the glomeruli and 80% of the filtered lithium is reabsorbed in the tubules, probably by the same mechanism responsible for sodium reabsorption. The renal clearance of lithium is proportional to its plasma concentration. About 50% of a single dose of lithium is excreted in 24 hours. A low salt intake resulting in low tubular concentration of sodium will increase lithium reabsorption and might result in retention or intoxication.
Lithium carbonate is indicated in the treatment of manic episodes of manic-depressive illness. Maintenance therapy prevents or diminishes the intensity of subsequent episodes in those manic-depressive patients with a history of mania.
Dosage/Direction for Use
In acute treatment of mania and hypomania up to the equivalent of 1.5 to 2 g of lithium carbonate daily may be given for the first 5 to 7 days, together with close checks of serum-lithium concentrations since concentrations close to the toxic level may be required. The dose may be reduced rapidly once the acute phased has passed.
Treatment of mania, Treatment of bipolar disorder, Treatment of recurrent depression, Treatment of aggressive or self-harming behaviour: Adult: Initially 450-675 mg twice daily, dose adjusted to achieve a serum-lithium concentration of 0.4-1 mmol/litre 12 hours after a dose on days 4-7 of treatment, then every week until dosage has remained constant for 4 weeks and every 3 months thereafter, doses are initially divided throughout the day, but once daily administration is preferred when serum lithium concentration stabilised.
Prophylaxis of mania, Prophylaxis of bipolar disorder, Prophylaxis of recurrent depression, Prophylaxis of aggressive or self-harming behaviour: Adult: Initially 450 mg twice daily, dose adjusted to achieve a serum-lithium concentration of 0.4-1 mmol/litre 12 hours after a dose on days 4-7 of treatment, then every week until dosage has remained constant for 4 weeks and every 3 months thereafter, doses are initially divided throughout the day, but once daily administration is preferred when serum lithium concentration stabilised.
Symptoms: Sluggishness, drowsiness, lethargy, coarse hand tremor or muscle twitchings, loss of appetite, vomiting and diarrhea. Others signs and symptoms of lithium intoxication have been described under adverse effects.
Treatment: Discontinue lithium therapy. Support respiratory and cardiovascular functions. Depending on mental status, use ipecac syrup or gastric lavage. Follow with activated charcoal and saline cathartic if multiple ingestion is suspected (charcoal does not absorb lithium effectively). Restore fluid and electrolyte balance. Phenytoin may be needed for seizures.
Contraindicated in patients with severe cardiovascular or renal disease and those with evidence of severe debilitation or dehydration, sodium depletion, brain damage.
Special Precautions
Lithium decreases sodium reabsorption by the renal tubules which could lead to sodium depletion. Lithium is excreted primarily by the kidney; adequate renal function and adequate salt and fluid intake are essential in order to avoid lithium accumulation and intoxication. Diminished intake of excessive loss of salt and fluids, as a result of vomiting, diarrhea, perspiration or use of diuretics will also increase lithium retention. If diuretics are used during lithium therapy the serum lithium concentration must be closely monitored.
Use In Pregnancy & Lactation
Lithium should not be given during pregnancy and without careful weighing of risk versus benefit. Lithium should be used during pregnancy only in severe disease for which safer drugs cannot be used or are ineffective. When possible, lithium should be withdrawn for at least the first trimester unless it is determined that this would seriously endanger the mother. Serum lithium concentrations should be carefully monitored and dosage adjusted if necessary since renal clearance of the drug and distribution of the drug erythrocytes may be increased during pregnancy.
Lithium passes into milk and its use should be avoided during lactation.
Adverse Reactions
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, thirst, dryness of mouth, abdominal pain.
Neurologic: General muscle weakness, ataxia, tremor, muscle hyperirritability.
CNS: Slurred speech, blurring of vision, headache, seizures, psychomotor retardation, somnolence, restlessness.
Cardiovascular: Arrhythmia, hypotension, cardiac collapse.
Genitourinary: Albuminuria, polyuria, glycosuria.
Dermatologic: Dryness and thinning of the hair, leg ulcers, skin rash.
Hematologic: Anemia, leucopenia, leucocytosis.
Drug Interactions
Interactions which increase lithium concentrations: Serum lithium levels may be increased if one of the following drugs is co-administered. When appropriate, either lithium dosage should be adjusted or concomitant treatment stopped.
Metronidazole may reduce lithium renal clearance.
Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase (COX) 2 inhibitors (monitor serum lithium concentrations more frequently if NSAID therapy is initiated or discontinued).
Angiotensin-converting enzyme (ACE) inhibitors.
Angiotensin II receptor antagonists.
Diuretics (thiazides show a paradoxical antidiuretics effect resulting in possible water retention and lithium intoxication). If a thiazide diuretic has to be prescribed for 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.
Other drugs affecting electrolyte balance, eg, steroids, may alter lithium excretion and should therefore be avoided.
Interactions which decrease serum lithium concentrations: Serum lithium levels may be decreased due to an increase in lithium renal clearance in case of concomitant administration of one of the following drugs: Xanthines (theophylline, caffeine); Sodium bicarbonate containing products; Diuretics (osmotic and carbonic anhydrase inhibitors); Urea; Calcitonin.
Interactions causing neurotoxicity: Co-administration of the following drugs may increase the risk of neurotoxicity: Antipsychotics (particularly Haloperidol at higher dosages), Flupentixol, Diazepam, Thioridazine, Fluphenazine, Chlorpromazine and Clozapine may lead in rare cases to severe neurotoxicity with symptoms, such as confusion, disorientation, lethargy, tremor, extra-pyramidal symptoms, and myoclonus. Increased lithium levels were present in some of the reported cases. Co-administration of Antipsychotics and Lithium may increase risk of Neuroleptic Malignant Syndrome, which may be fatal. Discontinuation of both drugs is recommended at the first signs of neurotoxicity.
Triptan derivatives and/or serotonergic Antidepressants such as Selective Serotonin Re-uptake Inhibitors (eg, Fluvoxamine and Fluoxetine) as this combination may precipitate a serotoninergic syndrome, which justifies immediate discontinuation of treatment.
Calcium channel blockers may lead to neurotoxicity with symptoms such as ataxia, confusion and somnolence. Lithium concentrations may be increased.
Carbamazepine may lead to dizziness, somnolence, confusion and cerebellar symptoms such as ataxia.
Other: Caution is advised if lithium is co-administered with other drugs that prolong the QT interval, eg, Class IA (eg, Quinidine, Disopyramide), or Class III (eg, Amiodarone) Antiarrhythmic agents, Cisapride, Antibiotics such as Erythromycin, Antipsychotics such as Thioridazine or Amisulpride. Caution is advised if lithium is co-administered with drugs that lower the epileptic threshold, eg, Antidepressants such as SSRIs, Tricyclic antidepressants, Antipsychotic, Anaesthetics, Theophylline.
Lithium may prolong the effects of neuromuscular blocking agents. There have been reports of interaction between lithium and phenytoin, indomethacin and other prostaglandin-synthetase inhibitors.
Serotonin Syndrome: Serotonin syndrome is a potentially life-threatening adverse reaction, with is caused by an excess of serotonin (eg, 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.
Store at temperatures not exceeding 30°C. Protect from light.
MIMS Class
ATC Classification
N05AN01 - lithium ; Belongs to the class of lithium antipsychotics.
SR tab 450 mg (off white, round, flat, scored on one side and plain on the other side, uncoated) x 100's.
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