Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Essential Pharma, 7 Egham Business Village, Crabtree Road, Egham, Surrey, TW20 8RB, United Kingdom
Lithium carbonate has a narrow therapeutic window. The dose required for treatment must be titrated and adjusted on the basis of regular monitoring of serum concentration of lithium. Lithium therapy should not be initiated unless adequate facilities for routine monitoring of plasma concentrations are available.
Elderly patients are particularly liable to lithium toxicity. Use with care as lithium excretion may also be reduced. They may also exhibit adverse reactions at serum levels ordinarily tolerated by younger patients (see section 4.2).
Before beginning a lithium treatment:
Renal, cardiac and thyroid functions should be re-assessed periodically.
The risk of convulsions may be increased when lithium is co-administered with drugs that lower the epileptic threshold, or in epileptic patients (see sections 4.5 and 4.8).
There have been case reports of benign intracranial hypertension (see section 4.8). Patients should be warned to report persistent headache and/or visual disturbances.
As a precautionary measure, lithium should be avoided in patients with congenital long QT syndrome, and in patients concomitantly treated with drugs that are known to prolong the QT interval (see sections 4.5 and 4.8). Caution should be exercised in patients with risk factors for QT interval prolongation (which include cardiac disease, bradycardia, thyroid disease, hypokalaemia, hypomagnesaemia, hypocalcaemia, female sex and advanced age.
Lithium may unmask or aggravate Brugada syndrome, a hereditary disease of the cardiac sodium channel with characteristic ECG changes (right bundle branch block and ST segment elevation in right precordial leads), which may lead to cardiac arrest or sudden death. Lithium should not be administered to patients with Brugada syndrome or a family history of Brugada syndrome (see section 4.3) Caution is advised in patients with a family history of cardiac arrest or sudden death.
Concomitant administration of antipsychotics should be avoided.
A lower maintenance dosage of Lithium may be required for patients, who have undergone a bariatric surgery because of decreased glomerular filtration following marked weight loss. Also, drug levels should be monitored closely in connection with bariatric surgery due to the risk of lithium toxicity.
Serum concentration of lithium should be measured on a sample taken just prior to the time when a dose of lithium is due to be taken (i.e. at trough level 12 hours following the last dose).
Toxic effects may be expected at serum-lithium concentrations of about 1.5 mmol/litre, although they can appear at lower concentrations. They call for immediate withdrawal of treatment and should always be considered very seriously
Serum concentration of lithium should be measured every 5 to 7 days from initiation until stabilisation is achieved and at regular intervals for the duration of treatment.
Serum lithium concentrations should be monitored more frequently (revert to weekly monitoring) in the following circumstances:
Patients should also be warned to report if polyuria or polydipsia develops. 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.
Lithium should be stopped 24 hours before major surgery, but the normal dose can be continued for minor surgery if fluids and electrolytes are carefully monitored
Lithium excretion is reduced in the presence of renal impairment. This increases the risk of toxicity. Lithium is contra-indicated in patients with severe renal impairment (see section 4.3). If patients with mild or moderate renal impairment are being treated with lithium, serum levels should be closely monitored.
Renal function should be monitored in patients with renal impairment, and in patients with polyuria and polydipsia.
Clear instructions regarding the symptoms of impending toxicity should be given by the doctor to all patients receiving long-term lithium therapy (see Section 4.9 for symptoms of intoxication) and advice given for the need for urgency in seeking medical assistance if these symptoms appear.
Renal tumours: cases of microcysts, oncocytomas and collecting duct renal carcinoma have been reported in patients with severe renal impairment who received lithium for more than 10 years (see section 4.8).
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.
Interactions may occur as a result of increased or decreased lithium levels, or may act through other mechanisms, the most important being neurotoxicity which may occur at therapeutic levels when other drugs which act centrally on the CNS are taken concurrently.
Co-administration of the following drugs with lithium may lead to increased lithium concentrations and a risk of toxicity:
Co-administration of the following drugs with lithium may lead to decreased lithium concentrations and a risk of loss of efficacy:
Concomitant use of the following drugs may precipitate symptoms of toxicity when the lithium level is within the normal range:
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.
Caution is advised if lithium is co-administered with drugs that lower the epileptic threshold (see section 4.4). e.g. antidepressants, antipsychotics, anaesthetics and theophylline.
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 (see section 4.4), 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:
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.
Lithium therapy should not be used during pregnancy, especially during the first trimester, unless considered essential. There is epidemiological evidence that it may be harmful to the foetus in human pregnancy.
Lithium crosses the placental barrier. An increase in cardiac and other abnormalities, especially Ebstein anomaly, are 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. Studies in animals have shown reproductive toxicity (see section 5.3).
If it is considered essential to maintain lithium treatment during pregnancy, serum lithium levels should be closely monitored and measured frequently since renal function changes gradually during pregnancy and suddenly at parturition. Dosage adjustments are required. It is recommended that lithium be discontinued shortly before delivery and reinitiated a few days post-partum.
Neonates may show signs of lithium toxicity necessitating fluid therapy in the neonatal period. Neonates born with low serum lithium concentrations may have a flaccid appearance that returns to normal without any treatment.
It is advisable that women treated with lithium should adopt adequate contraceptive methods. In case of a planned pregnancy, it is strongly recommended to discontinue lithium therapy.
Since adequate human data on use during lactation and adequate human reproduction studies are not available and as lithium is secreted in breast milk, bottle-feeding is recommended (see section 4.3 Contraindications).
Studies in animals have shown adverse effects on male fertility (see section 5.3).
Camcolit has minor to moderate influence on the ability to drive and use machines.
As lithium may cause disturbances of the CNS, patients should be warned of the possible hazards when driving or operating machinery.
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.
Psychiatric disorders: Delirium
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, rhabdomyolysis.
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) (see Section 4.4).
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 – for symptoms see section 4.9 Overdose.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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