Source: Health Products Regulatory Authority (IE) Revision Year: 2021 Publisher: Essential Pharma Limited, Vision Exchange Building, Triq it-Territorjals, Zone 1, Central Business District, Birkirkara, CBD 1070, Malta
When considering Priadel therapy, it is necessary to ascertain whether patients are receiving lithium in any other form. If so, check serum levels before proceeding.The minimum clinically effective dose of lithium should always be used (see also section 4.2). Clear instructions regarding the symptoms of impending toxicity should be given by the physician to patients receiving long term lithium therapy (see 4.9 Overdose – Toxic effects). At the first sign of toxicity, the patient should consult a physician and lithium levels should be checked.
Before starting treatment with lithium renal function, cardiac function and thyroid function should be evaluated. Patients should be euthyroid before initiation of lithium therapy. Lithium therapy is contraindicated in patients with severe renal insufficiency or cardiac insufficiency (see section 4.3). Renal, cardiac and thyroid functions should be re-assessed regularly during treatment with lithium.For monitoring recommendations of lithium serum levels see section 4.2.
Since lithium is primarily excreted via the renal route, significant accumulation of lithium may occur in patients with renal insufficiency. Therefore, if patients with mild or moderate renal impairment are being treated with lithium, serum lithium levels should be closely monitored (see section 4.2) and the dose should be adjusted accordingly. If very regular and close monitoring of serum lithium levels and plasma creatinine levels is not possible, lithium should not be prescribed in this population. Lithium is contraindicated in patients with severe renal insufficiency, (see section 4.3). Patients should also be warned to report if polyuria or polydipsia develop. In patients who develop polyuria and/or polydipsia (see section 4.8), renal function should be monitored in addition to the routine serum lithium assessment. 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).
If episodes of nausea, vomiting, diarrhoea, excessive sweating and/or other conditions leading to salt/water depletion (including severe dieting) occur, lithium dosage should be closely monitored and dosage adjustments made as necessary.Caution should be exercised to ensure that diet and fluid intake are normal in order to maintain a stable electrolyte balance. This may be of special importance in very hot weather or work environment. Infectious diseases including colds, influenza, gastro-enteritis and urinary infection may alter fluid balance and thus affect serum lithium levels. Treatment discontinuation should be considered during any intercurrent infection.
The risk of convulsions may be increased in case of co-administration of lithium with drugs that lower the epileptic threshold, or in epileptic patients (see section 4.5 & section 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 caution should be exercised in patients with risk factors for QT interval prolongation (e.g. uncorrected hypokalemia, bradycardia), and in patients concomitantly treated with drugs that are known to prolong the QT interval (see section 4.5 & section 4.8).
Lithium may unmask or aggravate Brugada syndrome, a hereditary disease of the cardiac sodium channel with characteristic electrocardiographic 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.
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.
Elderly patients are particularly liable to lithium toxicity and may exhibit adverse reactions at serum levels ordinarily tolerated by younger patients. Caution is also advised since lithium excretion may be reduced in the elderly due to age related decrease in renal function (see also section 4.2 & section 5.2).
The use in children is not recommended.
Use in patients requiring a low sodium intake is not normally recommended.
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.
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:
Co-administration of the following drugs may increase the risk of neurotoxicity:
Seritonin syndrome: The Serotonin Syndrome is a potentially life-threatening adverse drug reaction, which is caused by an excess in serotonin (e.g. from overdose or concomitant use of serotonergic drugs), necessitating hospitalisation or even causing death. Symptoms may include:
Strict adherence to the recommended doses is an essential factor for the prevention of the occurrence of this syndrome.
Lithium therapy should not be used during pregnancy, especially during the first trimester, unless considered essential. It may be harmful to the foetus in human pregnancy. Cardiac, especially Ebstein anomaly, and other malformations have been reported. Therefore, a pre-natal diagnosis such as ultrasound examination is strongly recommended.
If it is considered essential to maintain lithium treatment during pregnancy, serum lithium levels should be closely monitored 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, 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.
Women of childbearing potential should use effective contraceptive methods during treatment with lithium.
Lithium is secreted in breast milk, and there have been reports of neonates showing signs of lithium toxicity (see section 4.6.1). Therefore lithium should not be used during breast feeding (see section 4.3). 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.
Published studies in rats exposed to lithium have reported spermatogenesis abnormalities that may lead to impairment of fertility. This risk may also potentially apply to humans.
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.
Since lithium may slow reaction time, and considering the adverse reactions profile of lithium (see section 4.8), patients should be warned of the possible hazards when driving or operating machinery.
Side effects are usually related to serum lithium concentration and are infrequent at levels below 1.0 mmol/l. The adverse reactions usually subside with a temporary reduction or discontinuation of lithium treatment. Mild gastrointestinal effects such as nausea, a general discomfort and vertigo, may occur initially, but frequently disappear after the first few days of lithium administration. Fine hand tremors, polyuria and mild thirst may persist.
Skin and subcutaneous tissue disorders: acne, aggravation or occurrence of psoriasis, allergic rashes, alopecia, cutaneous ulcers.
Frequency unknown: Lichenoid drug reaction.
Musculoskeletal and connective tissue disorders: muscle weakness, rhabdomyolysis.
Nervous system disorders: tremor especially fine hand tremors, dysarthria, myoclonus, benign intracranial hypertension (see section 4.4).
Vertigo, impaired consciousness, abnormal reflexes, convulsions (see section 4.4 & section 4.5), extrapyramidal disorders, encephalopathy, cerebellar syndrome (usually reversible), nystagmus. The above symptoms may result in fall (frequency not known).
Peripheral neuropathy may occur on long-term treatment and is usually reversible at cessation of lithium.
Memory impairment may occur during long term use.
Serotonin syndrome.
Neuroleptic malignant syndrome.
Gastrointestinal disorders: abdominal discomfort, taste disorder, nausea, vomiting, diarrhoea, salivary hypersecretion, dry mouth.
Endocrine disorders: long term adverse effects may include thyroid function disturbances such as euthyroid goitre and/or hypothyroidism. Rarely hyperthyroidism may also occur. Hypercalcaemia, hypermagnesaemia, hyperparathyroidism have been reported.
Metabolic and Nutrition disorders: Weight increase.
Cardiac disorders: QT prolongation, sometimes associated with ventricular tachycardia or torsades de points, which may result in ventricular fibrillation or cardiac arrest and sudden death. Othercardiac arrhythmia mainly bradycardia, sinus node dysfunction, ECG changes such as reversible flattening or inversion of T-waves, AV block, cardiomyopathy.
Eye disorders: eye irritation (reversible in most cases); optic disc swelling, in some cases without increased intracranial pressure; papilloedema leading to possible visual impairment (generally reversible); exophthalmos (not always associated with thyroid disorders)
Blood and lymphatic disorders: leucocytosis
Renal and urinary disorders: polydipsia and/or polyuria and nephrogenic diabetes insipidus have been reported (see section 4.4). This is usually reversible on lithium withdrawal.
Long term treatment with lithium may result in permanent changes in kidney histology, formation of renal microcysts, oncocytoma and collecting duct renal carcinoma (in long-term therapy) (see Section 4.4) and impairment of renal function.
High serum concentrations of lithium including episodes of acute lithium toxicity may aggravate these changes.
Cases of nephrotic syndrome have been reported.
Psychiatric disorders: Confusion, delirium (frequency not known).
General disorders and administration site conditions: Peripheral oedema. Urticaria and angioedema, attributed to some excipients.
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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.
Not applicable.
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