Lithium Carbonate

Lithium Carbonate in Kenya

Lithium Carbonate Mode of Action:

The precise mechanism of action of lithium as a mood-stabilising agent remains unknown, although many cellular actions of lithium have been characterised.

Drug Label Information | Brands:

Lithium Carbonate in Kenya

LITHIUM INDICATIONS

The treatment and prophylaxis of mania, manic-depressive illness and recurrent depression, and the treatment of aggressive or self mutilating behaviour.

DOSAGE:

Lithium 400 mg is usually administered according to a twice daily regimen.

When lithium levels have stabilised, a once daily regimen may be preferred

Lithium carbonate has a narrow therapeutic window. The dose required for treatment must be titrated and adjusted on the basis of regular monitoring of the serum concentration .

Lithium therapy should not be initiated unless adequate facilities for routine monitoring of plasma concentrations are available. On initiation of treatment, 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.

Toxic symptoms are usually associated with concentrations exceeding 1.5 mmol/l and levels above 1.5mmol/l should be avoided. In the event of toxicity, lithium should be withdrawn immediately.

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.

Aggressive and self-mutilating behaviour:

Adults: Dosage is at the lower end of the range for the treatment for manic

depressive illness.

CONTRAINDICATIONS:

  • Hypersensitivity to the active substance or to any of the excipients.
  • Severely impaired renal function
  • Untreated or untreatable hypothyroidism.
  • Cardiac disease associated with rhythm disorder.
  • Brugada syndrome or family history of Brugada syndrome
  • Low body sodium levels for example dehydrated patients, those on low sodium diets, or those with Addison’s disease.
  • Breast-feeding.

ADVERSE EFFECTS:

Side effects are usually related to serum lithium concentrations and are less common in patients with plasma lithium concentrations below 1.0 mmol/l.

Initial Therapy: fine tremor of the hands, polyuria and thirst may occur.

Blood and lymphatic system disorders: leucocytosis.

Immune system disorders: increase in antinuclear antibodies.

Endocrine disorders: disturbances of thyroid function including (euthyroid) goitre, hypothyroidism and hyperthyroidism, hyperparathyroidism, parathyroid adenoma.

Metabolism and nutrition disorders: hypercalcaemia, hypermagnesaemia, hyperglycaemia, anorexia, weight gain.

Nervous system disorders: coma, benign intracranial hypertension, syndrome of irreversible lithium effectuated neurotoxicity (SILENT), encephalopathy, stupor, seizures, neuroleptic malignant syndrome, myasthenia gravis, serotonin syndrome, parkinsonism, extrapyramidal symptoms, ataxia, dizziness, memory impairment, mild cognitive impairment may occur during long term use, giddiness, nystagmus, slurred speech, vertigo, hyperactive deep tendon reflexes, dazed feeling, fine hand tremors.

Eye Disorders: scotomata and blurred vision.

Cardiac disorders: cardiac arrest, ventricular fibrillation, ventricular tachycardia, ventricular arrhythmias, Torsade de pointes, QT interval prolongation, cardiomyopathy, arrhythmia, bradycardia, sinus node dysfunction, ECG changes.

Vascular disorders: peripheral circulatory collapse, hypotension.

Gastrointestinal disorders: gastritis, nausea, diarrhoea, vomiting, dry mouth,

excessive salivation. Lithium salts have been implicated in dysgeusia.

Skin and subcutaneous tissue disorders: Allergic rash, exacerbation of psoriasis, acneiform eruptions, alopecia, acne, papular skin disorder, folliculitis, pruritus, rash.

Frequency not known: lichenoid drug reaction

Musculoskeletal and connective tissue disorders: muscle weakness.

Renal and urinary disorders: symptoms of nephrogenic diabetes insipidus, impairment of renal function, permanent changes in the kidney, nephrotic syndrome, histological renal changes with interstitial fibrosis after long term treatment, polyuria, polydipsia.

Frequency unknown: Microcysts, oncocytoma and collecting duct renal carcinoma (in long-term therapy)
Reproductive system and breast disorders: sexual dysfunction.

General disorders and administration site conditions: sudden unexplained death, oedema, asthenia, lethargy, thirst, fatigue, and malaise can occur due to lithium toxicity.

Some adverse events will be seen when Lithium levels are raised

DRUG INTERACTIONS:

Interactions which increase lithium concentrations

Co-administration of the following drugs with lithium may lead to increased lithium concentrations and a risk of toxicity:

  • Any drug which may cause renal impairment has the potential to cause lithium levels to rise, thereby causing toxicity. If the use of the drug is unavoidable, carefully monitor lithium blood level and adapt dosage as necessary.
  • Antibiotics (metronidazole, tetracyclines, co-trimoxazole, trimethoprim), N.B. Toxic symptoms may also occur at low or normal levels when used in conjunction with co-trimoxazole or trimethoprim. Lithium toxicity has been reported on isolated occasions in patients receiving spectinomycin.
  • Non-steroidal anti-inflammatory drugs (including selective cyclooxygenase (COX) II inhibitors); monitor serum lithium concentrations more frequently if NSAID therapy is initiated or discontinued.
  • Drugs affecting the renin angiotensin system (ACE inhibitors, Angiotensin II receptor antagonists).
  • Diuretics (including herbal preparations). In addition to the effects noted above, thiazide diuretics show a paradoxical antidiuretic effect resulting in possible water retention and lithium intoxication. Loop diuretics (furosemide and bumetanide, and etacrynic acid) seem less likely to cause lithium retention, although caution is warranted.
  • Other drugs affecting electrolyte balance, e.g. steroids, may alter lithium excretion and should therefore be avoided.

Interactions which decrease serum lithium concentrations:

Co-administration of the following drugs with lithium may lead to decreased lithium concentrations and a risk of loss of efficacy:

  • xanthine derivatives (e.g. theophylline, caffeine).
  • products containing large quantities of sodium e.g. sodium bicarbonate.
  • carbonic anhydrase inhibitors.
  • Urea.

Interactions which may not be associated with increased or reduced lithium levels:

Concomitant use of the following drugs may precipitate symptoms of toxicity when the lithium level is within the normal range:

  • antipsychotics, including the atypical antipsychotics olanzapine,
  • clozapine and haloperidol at high doses
  • carbamazepine
  • phenytoin
  • methyldopa
  • clonazepam
  • tricyclic and tetracyclic antidepressants
  • calcium channel blockers.

These drugs may cause neurotoxic reactions at therapeutic levels

  • neuromuscular blocking agents. Lithium may cause neurotoxic reactions at therapeutic lithium levels.
  • Selective serotonin re-uptake inhibitors (SSRIs): Concurrent use with lithium may precipitate a serotonergic syndrome.
  • Non-steroidal anti-inflammatory drugs including COX II inhibitors: monitor serum lithium concentrations more frequently if NSAID therapy is initiated or discontinued
  • Triptans: lithium toxicity reported suggestive of serotonin syndrome.
  • Neuromuscular blockers: Lithium may prolong the effects of neuromuscular blocking agents.

Drugs which lower seizure threshold

Caution is advised if lithium is co-administered with drugs that lower the epileptic threshold e.g. antidepressants, antipsychotics, anaesthetics and theophylline.

Drugs which prolong the QT interval

Lithium can cause an increase in the QTc interval, particularly at higher blood levels. Therefore, concurrent use of drugs which have a risk of prolonging the QTc interval should be avoided , and consideration be made of other potential risk factors such as increasing age, female sex, congenital long QT syndrome, cardiac and thyroid disease and the following metabolic disturbances: hypocalcaemia, hypokalaemia, hypomagnesaemia.

The following products have a high risk of causing QT prolongation and torsade de pointes:

  • Class Ia antiarrhythmics, (ajmaline, cibenzoline, disopyramide, hydroquinidine, procainamide, quinidine),
  • Class III antiarrhythmics (amiodarone, azimilide, cibenzoline, dofetilidem, ibutilide, sotalol),
  • Antipsychotics (amisulpride, haloperidol, droperidol, mesoridazine, pimozide, sertindole, thioridazine and clozaril),
  • Antibiotics (intravenous erythromycin, sparfloxacin),
  • Serotonin antagonists (ketanserin, dolasetron mesylate),
  • Antihistamines (astemizole, terfenadine),
  • Antimalarials (artemisinin derivatives, mefloquine, halofantrine),
  • Other: arsenic trioxide, cisapride and ranolazine.

ECG should be performed after initiation of treatment and at any point where the patient becomes symptomatic or when there are changes in disease or treatment which may increase the risk of interaction or arrhythmia.

Non-Drug Interactions:

  • Low sodium diet. Rapid reduction of sodium intake may cause raised lithium levels.
  • Intercurrent illness may cause lithium toxicity.

Prescription Category:
DDA Schedule:
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Routes of Administration:
Protein Binding:
Metabolosim:
Bioavailability:
Elimination Half life:
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References/ Citation:

Prescription Category:
DDA Schedule:
Dosage Forms:
Routes of Administration:
Protein Binding:
Metabolosim:
Bioavailability:
Elimination Half life:
Drug Indentifiers:

References/ Citation: