OralAggression, Bipolar disorder, Mania, Recurrent depression, Self-harm behaviourAdult: As lithium carbonate: Treatment: 1,000-1,500 mg daily, or 450-675 mg bid; Prophylaxis: 300-400 mg daily, or 450 mg bid. Treatment and prophylaxis: In patients weighing <50 kg: 200-400 mg daily; In patients weighing ≥50 kg: 400-1,200 mg once daily or in 2 divided doses. Doses are initially divided throughout the day; when serum lithium concentrations are stabilised, once-daily dosage may be preferred. Adjust dose according to serum lithium concentration. As lithium citrate: Treatment and prophylaxis: In patients weighing <50 kg: 509 mg daily in 2 divided doses, or 520 mg bid; In patients weighing ≥50 kg: 400-1,200 mg once daily or in 2 divided doses, adjust dose according to serum lithium concentration; or 1,018-3,054 mg daily in 2 divided doses. Doses are initially divided throughout the day; when serum lithium concentrations are stabilised, once-daily dosage may be preferred. Adjust dose according to serum lithium concentration. Dosing recommendations may vary among countries or individual products or preparations. Refer to country- or product-specific recommendations.
Elderly: Initiate at the lower end of the dosing range.
OralBipolar disorderAdult: For acute manic or mixed episode: As lithium carbonate: Initially, 600-900 mg/day in 2-3 divided doses, increase based on response and tolerability by 300-600 mg every 1-5 days to usual therapeutic dose of 900-1,800 mg daily. After 5-7 days, at a stable therapeutic dose, adjust the dose based on patient’s clinical response, tolerability and target serum lithium concentration. Alternatively, may initially be given in 1,800 mg daily in 3-4 divided doses, or in 2-3 divided doses and then titrated slowly to achieve therapeutic serum lithium concentrations. Maintenance: As lithium carbonate: 900-1,200 mg daily, given in 3-4 divided doses. Alternatively, may be given in 2-3 divided doses. Base maintenance dosage on serum lithium concentrations noted during the acute phase of therapy and on steady-state serum lithium concentrations determined 12 hours after a dose. Dosage must be individualised according to serum lithium concentration, patient’s tolerance and clinical response. Dosing recommendations may vary among countries or individual products or preparations. Refer to country- or product-specific recommendations.
Child: Dose is individualised based on patient’s clinical response, tolerability and target serum lithium concentration. As conventional tab or cap: ≥7 years weighing 20-30 kg: Initially, 300 mg bid, increase at weekly intervals in 300 mg/day increments based on response, tolerability and target serum lithium concentration. Acute therapy: Usual dose: 600-1,500 mg daily in divided doses; target serum lithium concentration: 0.8-1.2 mEq/L. Maintenance therapy: Usual dose: 600-1,200 mg daily in divided doses; target serum lithium concentration: 0.8-1 mEq/L. ≥7 years weighing >30 kg: Initially, 300 mg tid, increase in 300 mg/day increments every 3 days based on response, tolerability and target serum lithium concentration. Acute therapy: Usual dose: 600 mg bid or tid; target serum lithium concentration: 0.8-1.2 mEq/L. Maintenance therapy: 300-600 mg bid or tid; target serum lithium concentration: 0.8-1 mEq/L. As oral solution: Each 5 mL of lithium oral solution has 8 mEq of lithium ion that is equivalent to the amount of lithium in 300 mg of conventional tab or cap of lithium carbonate. ≥7 years weighing 20-30 kg: Initially, 8 mEq bid, increase at weekly intervals in 8 mEq increments based on response, tolerability and target serum lithium concentration. Acute therapy: Usual dose: 16-40 mEq daily in divided doses; target serum lithium concentration: 0.8-1.2 mEq/L. Maintenance therapy: Usual dose: 16-32 mEq daily in divided doses; target serum lithium concentration: 0.8-1 mEq/L. ≥7 years weighing >30 kg: Initially, 8 mEq tid, increase in 8 mEq increments every 3 days based on response, tolerability and target serum lithium concentration. Acute therapy: Usual dose: 16 mEq bid or tid; target serum lithium concentration: 0.8-1.2 mEq/L. Maintenance therapy: 8-16 mEq bid or tid; target serum lithium concentration: 0.8-1 mEq/L. Dosing recommendations may vary among countries or individual products or preparations. Refer to country- or product-specific recommendations.
Elderly: Initiate at the lower end of the dosing range.
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Mild to moderate: Initiate at a low dose, then increase slowly with close monitoring. Severe: Contraindicated.
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Should be taken with food.
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Severe CV disease, cardiac disease associated with rhythm disorder, cardiac insufficiency, low body Na levels (e.g. dehydrated patients, on low Na diet, or with Addison’s disease), debilitation; known, suspected or family history of Brugada syndrome; untreated or untreatable hypothyroidism. Severe renal impairment. Concomitant use with diuretics.
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Patient with risk factors for QT interval prolongation (e.g. cardiac disease, bradycardia, thyroid disease, hypokalaemia, hypomagnesaemia, hypocalcaemia, female, advanced age); myasthenia gravis, suicidal tendency, seizure, family history of cardiac arrest or sudden death. Patients undergoing electroconvulsive therapy (ECT). Avoid abrupt withdrawal. Mild to moderate renal impairment. Children and elderly. Pregnancy and lactation.
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Significant: Heart failure, hyperparathyroidism, hypercalcaemia, hypothyroidism, pseudotumor cerebri, nephrogenic diabetes insipidus, polydipsia, polyuria, unmask or aggravate Brugada Syndrome.
Blood and lymphatic system disorders: Leucocytosis.
Cardiac disorders: Cardiac arrhythmia, bradycardia. cardiac arrest, ventricular fibrillation, ventricular tachycardia, Torsade de pointes, QT interval prolongation, cardiomyopathy, sinus node dysfunction, ECG changes.
Endocrine disorders: Disturbance of thyroid function (e.g. euthyroid goitre, thyrotoxicosis).
Eye disorders: Blurred vision, scotoma.
Gastrointestinal disorders: Dysgeusia, abdominal discomfort, nausea, vomiting, diarrhoea, dry mouth, gastritis.
General disorders and administration site conditions: Peripheral oedema.
Investigations: Weight gain, ECG changes, prolonged QT interval, T-wave depression.
Metabolism and nutrition disorders: Hypermagnesaemia, hyperglycaemia, anorexia.
Musculoskeletal and connective tissue disorders: Muscle weakness, rhabdomyolysis.
Nervous system disorders: Fine hand tremors, ataxia, dizziness, slurred speech, stupor, coma, myasthenia gravis, hyperactive deep tendon reflexes, giddiness, memory impairment, vertigo, seizure, extrapyramidal disorders, encephalopathy, nystagmus, peripheral neuropathy (prolonged treatment), neuroleptic malignant syndrome.
Psychiatric disorders: Delirium, confusion.
Renal and urinary disorders: Nonspecific nephron atrophy, renal interstitial fibrosis.
Reproductive system and breast disorders: Sexual dysfunction.
Skin and subcutaneous tissue disorders: Acne, alopecia, folliculitis, pruritus, exacerbation of psoriasis, rash.
Vascular disorders: Hypotension, peripheral circulatory collapse.
Potentially Fatal: Serotonin syndrome.
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This drug may cause CNS disturbances (e.g. somnolence, dizziness, hallucination), if affected, do not drive or operate machinery.
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Monitor serum lithium levels (twice weekly until both patient's clinical status and levels are stable, then repeat every 1-3 months or as clinically indicated), renal function (at baseline, every 2-3 months during the 1st 6 months of treatment, then once a year in stable patients or as clinically indicated), serum Ca concentrations (at baseline, 2-6 weeks after initiation, then every 6-12 months thereafter as clinically indicated), thyroid (at baseline, 1-2 times within the first 6 months of treatment, then once a year in stable patients or as clinically indicated), serum electrolytes, ECG, and CBC with differential (at baseline and as clinically indicated); weight. Observe for clinical worsening, suicidality, or unusual changes in behaviour (particularly during the initial course of treatment or dose changes). Assess for signs of thyroid abnormalities, kidney changes, electrolyte imbalance, polyuria, polydipsia.
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Symptoms: Mild: nausea, diarrhoea, blurred vision, polyuria, light headedness, fine resting tremor, muscular weakness, drowsiness. Moderate: confusion, blackouts, fasciculation, increased deep tendon reflexes, myoclonic twitches and jerks, choreoathetoid movements, urinary or faecal incontinence, increasing restlessness followed by stupor, hypernatraemia. Severe: coma, convulsions, cerebellar signs, cardiac dysrhythmias (e.g. sino-atrial block, sinus and junctional bradycardia, 1st-degree heart block), hypotension, hypertension (rarely), circulatory collapse, renal failure. Management: Symptomatic and supportive treatment. Correct fluid and electrolyte imbalances. Monitor ECG in symptomatic patients. Consider performing gastric lavage (for non-sustained-release preparations) if more than 4 g has been ingested within 1 hour. Consider whole bowel irrigation in patients ingesting large amount of slow-release preparation. Consider haemodialysis for severe poisoning and in patients with marked neurological features.
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May increase serum lithium concentration and risk of toxicity with antibiotics (e.g. metronidazole, tetracycline, co-trimoxazole, trimethoprim, spectinomycin), NSAIDs (including selective cyclooxygenase [COX] II inhibitors), drugs affecting the renin-angiotensin system (e.g. ACE inhibitors, angiotensin II receptor antagonists), drugs affecting electrolyte balance (e.g. steroids). May decrease serum lithium concentration and risk of loss of efficacy with xanthine derivatives (e.g. caffeine, theophylline), Na bicarbonate, carbonic anhydrase inhibitors, urea. May increase risk of toxicity with antipsychotics (e.g. olanzapine, clozapine, haloperidol at high doses), carbamazepine, phenytoin, methyldopa, clonazepam, TCAs, tetracyclic antidepressants, neuromuscular blocking agents. May increase risk of neurotoxicity with Ca channel blockers. May precipitate serotonin syndrome with SSRIs, triptans, serotonin and norepinephrine reuptake inhibitors (SNRI), MAOIs, fentanyl, tramadol, tryptophan, buspirone. May lower seizure threshold with antidepressants, antipsychotics, anaesthetic, theophylline. Increase risk of prolonging QTc interval with antiarrhythmics (e.g. disopyramide, hydroquinidine, procainamide, quinidine, amiodarone, sotalol), antipsychotics (e.g. haloperidol, droperidol, thioridazine), antibiotics (e.g. IV erythromycin, sparfloxacin), serotonin antagonists (e.g. ketanserin, dolasetron mesylate), antihistamine (e.g. astemizole, terfenadine), antimalarials (e.g. artemisinin derivatives, mefloquine, halofantrine), arsenic trioxide, cisapride, ranolazine. May enhance hypothyroid effect with potassium iodide.
Potentially Fatal: Reduced excretion, increased serum concentration and risk of toxicity with diuretics.
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May precipitate serotonin syndrome with St. John’s wort.
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Description: The exact mechanism of lithium as a mood-stabilising agent is unknown, however it is believed to affect cation transport across cell membranes in nerve and muscle cells, influence serotonin and/or norepinephrine reuptake, and inhibit 2nd messenger systems involving the phosphatidylinositol cycle.
Pharmacokinetics:
Absorption: Rapidly and completely absorbed from the gastrointestinal tract. Bioavailability: 80-100%. Time to peak plasma concentration: Approx 0.5-3 hours (immediate-release preparations); 2-6 hours (modified-release preparations); 15-60 minutes (solution).
Distribution: Distributed throughout the body, mostly into the bones, thyroid gland and portions of the brain. Crosses the placenta and enters breast milk. Volume of distribution: Approx 0.307 L/kg.
Excretion: Mainly via urine (as unchanged drug); faeces, saliva, sweat (small amounts); 80% of the glomerulus-filtered lithium is reabsorbed in the proximal convoluted tubules thru passive diffusion. Elimination half-life: Approx 12-24 hours (normal renal function); 36 hours (elderly), 40-50 hours (renal impairment).
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N05AN01 - lithium ; Belongs to the class of lithium antipsychotics.
N05AN - Lithium ; Used in the management of psychosis.
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Anon. Lithium. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 11/06/2021. Anon. Lithium. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 14/05/2021. Buckingham R (ed). Lithium Carbonate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 14/05/2021. Camcolit 400 mg, Controlled Release Lithium Carbonate (Essential Pharma). MHRA. https://products.mhra.gov.uk. Accessed 14/05/2021. Clinect NZ Pty Limited. Priadel Prolonged Release Tablets 400 mg data sheet 25 September 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 14/05/2021. Douglas Pharmaceuticals Ltd. Lithium Carbonate 250 mg Capsule data sheet 28 March 2019. Medsafe. http://www.medsafe.govt.nz. Accessed 14/05/2021. Joint Formulary Committee. Lithium Carbonate. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 14/05/2021. Joint Formulary Committee. Lithium Citrate. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 14/05/2021. Li-Liquid 1018 mg/5 mL Oral Syrup (Rosemont Pharmaceuticals Ltd). MHRA. https://products.mhra.gov.uk. Accessed 14/05/2021. Liconate Tablet (Malaysian Pharmaceutical Industries Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 14/05/2021. Liskonum Tablets (Teofarma S.r.l.). MHRA. https://products.mhra.gov.uk. Accessed 14/05/2021. Lithium Carbonate Capsule (Alembic Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 14/05/2021. Lithium Carbonate Essential Pharma 250 mg Film-Coated Tablets (Essential Pharma). MHRA. https://products.mhra.gov.uk. Accessed 14/05/2021. Lithium Carbonate Tablet, Capsule, Gelatin Coated, Solution (West-Ward Pharmaceuticals Corp). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 14/05/2021. Lithium Carbonate Tablet, Film Coated, Extended Release (Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 14/05/2021. Priadel 200 mg Prolonged-Release Tablets (Essential Pharma Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 14/05/2021. Priadel 520 mg/5 mL Liquid (Essential Pharma Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 14/05/2021.
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