| Section 4.4 -Special Warnings and Special Precautions for Use
Vomiting, diarrhoea, intercurrent infection, fluid deprivation and drugs likely to upset electrolyte balance, such as diuretics, may all reduce lithium excretion and thereby precipitate intoxication; reduction of dosage may be required.
Use with care in elderly patients as lithium excretion may also be reduced.
The possibility of hypothyroidism and of renal dysfunction arising during
prolonged treatment should be borne in mind and periodic assessments made.
Histological changes (including tubulointerstitial nephropathy) have been reported after long-term treatment with lithium. These changes may lead to impaired renal function. It is unclear if these changes are always reversible on stopping lithium. It is advisable to monitor renal function periodically.
Patients should be warned of the symptoms of impending intoxication (see Section 4.8), of the urgency of immediate action should these symptoms appear, and also of the need to maintain a constant and adequate salt and water intake. Outpatients should be warned to take their medication at the stipulated time. If a dose is missed, the patient should wait until the next scheduled time of dosing. A double dose to make up for the dose that has been missed should not be taken. Treatment should be discontinued immediately on the first signs of toxicity, which include cardiovascular, renal, and neurological and gastrointestinal events (see Section 4.8). Acute renal failure has been reported rarely with lithium toxicity.
Patients with the rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take Liskonum.
Lithium should be used with particular care in the elderly since this group may be particularly susceptible to toxicity due to decreasing renal function and hence elimination (see Dosage and Administration).
Section 4.8- Undesirable Effects
Initial therapy: Fine tremor of the hands, polyuria and thirst and nausea may occur.
The frequency classifications for these adverse reactions cannot be accurately
estimated from the available clinical trial data.
Blood and lymphatic system disorders: Leukocytosis Endocrine disorders: Euthyroid goitre, hypothyroidism,
hyperthyroidism, hyperparathyroidism
Metabolism and nutrition disorders: Hyperglycemia, hypercalcemia,
weight gain, anorexia, polydipsia
Psychiatric disorders: Hallucinations, somnolence, memory loss Nervous system disorders: Tremor, ataxia, impaired nerve conduction, hyperactive deep tendon reflexes, extrapyramidal symptoms, seizures, slurred speech, dizziness, vertigo, giddiness, nystagmus, stupor, coma, pseudotumor cerebri, headache, dysgeusia, myasthenia gravis Eye disorders: Scotomata, blurred vision Cardiac disorders: Cardiac arrhythmia, of which bradycardia due to sinus node dysfunction is most frequent, and oedema. ECG changes: reversible flattening and inversion of T-waves. Vascular disorders: eripheral circulatory collapse, hypotension, Raynaud's phenomena Gastrointestinal disorders: Nausea, vomiting, iarrhoea,
gastritis, excessive salivation, dry mouth Skin and subcutaneous tissue disorders: Alopecia, acne, folliculitis, pruritus, psoriasis exacerbation, angioedema, rash and other signs of skin hypersensitivity, acneiform
eruptions, papular skin disorder Musculoskeletal and connective tissue
Blood and lymphatic system disorders: Leukocytosis Endocrine disorders: Euthyroid goitre, hypothyroidism, hyperthyroidism, hyperparathyroidism
Metabolism and nutrition disorders: Hyperglycemia, hypercalcemia,
weight gain, anorexia, polydipsia Psychiatric disorders: Hallucinations, somnolence, memory loss Nervous system disorders: Tremor, ataxia, impaired nerve conduction, hyperactive deep tendon reflexes, extrapyramidal symptoms, seizures, slurred speech, dizziness, vertigo, giddiness, nystagmus, stupor, coma, pseudotumor cerebri, headache,
dysgeusia, myasthenia gravis Eye disorders: Scotomata, blurred vision Cardiac disorders: Cardiac arrhythmia, of which bradycardia due to sinus node dysfunction is most frequent, and oedema.
ECG changes: reversible flattening and inversion of T-waves.
Vascular disorders: Peripheral circulatory collapse, hypotension, Raynaud's phenomena Gastrointestinal disorders: Nausea, vomiting, diarrhoea, gastritis, excessive salivation, dry mouth
Skin and subcutaneous tissue disorders: Alopecia, acne, folliculitis, pruritus, psoriasis exacerbation, angioedema, rash and other signs of skin hypersensitivity, acneiform eruptions, papular skin disorder Musculoskeletal and connective tissue disorders: Muscle weakness, arthralgia, myalgia
Renal and urinary disorders: Symptoms of nephrogenic diabetes
insipidus, urinary incontinence, and after long-term therapy, histological
renal changes (including tubulointerstitial nephropathy) and impaired renal function Reproductive system and breast disorders: Impotence, Sexual dysfunction General disorders and administration site conditions: Oedema, dazed feeling Intoxication (see 4.4): Cardiovascular events e.g. QT/QTc prolongation.
Gastrointestinal events e.g. vomiting, diarrhoea. Neurological events e.g.
drowsiness, lack of co-ordination and/or a coarse tremor of the extremities and lower jaw may occur, especially with serum levels above the therapeutic range. Ataxia, giddiness, blurred vision, dysarthria, tinnitus, muscle hyperirritability, horeoathetoid movements peripheral neuropathy,
hypoactive or absent deep tendon reflexes, and toxic psychosis have also been described.
If any of the above symptoms appear, treatment should be stopped
immediately and arrangements made for serum lithium measurement.
The toxic concentrations for lithium are close to the therapeutic concentrations. [p1] Any overdose in a patient who has been taking chronic lithium therapy should be regarded as potentially serious. A single acute overdose usually carries low risk and patients tend to show mild symptoms only, irrespective of their serum lithium concentration. However more severe symptoms may occur after a delay if lithium elimination is reduced because of renal impairment, particularly if a slow-release preparation has been taken.
If an acute overdose has been taken by a patient on chronic lithium therapy, this can lead to serious toxicity occurring even after a modest overdose as the extravascular tissues are already saturated with lithium.
Symptoms
The onset of symptoms may be delayed, with peak effects not occurring for as long as 24 hours, especially in patients who are not receiving chronic lithium therapy, or following the use of a sustained release preparation.
Mild: Nausea, diarrhoea, vomiting, blurred vision, polyuria, light headedness, fine resting tremor, first degree heart block, muscular weakness and drowsiness.
Moderate: Increasing confusion, blackouts, fasciculation and increased deep tendon reflexes, myoclonic twitches and jerks, ataxia, choreoathetoid movements, urinary and faecal incontinence, increasing restlessness followed by stupor. Hypernatraemia.
Severe: Coma, convulsions, cerebellar signs, cardiac dysrhythmias including sino-atrial block, sinus and junctional bradycardia. Hypotension or rarely hypertension, circulatory collapse and renal failure.
Management
There is no known antidote. . Supportive and symptomatic treatment should be initiated. Correction of electrolyte balance and fluid resuscitation is critical[p2]
[p3] Gut decontamination is not useful for chronic accumulation. Whole bowel irrigation may be helpful in patients ingesting large quantities of slow-release preparation.
NOTE: activated charcoal does not adsorb lithium.
Haemodialysis is the treatment of choice for severe poisoning and should be considered in all patients with marked neurological features. It is the most efficient method of lowering lithium concentrations rapidly but substantial rebound increases can be expected when dialysis is stopped, and prolonged, or repeated treatments may be required. It should be considered also in acute, acute on chronic or chronic overdose in patients with severe symptoms regardless of serum lithium concentration; discuss with your local poisons service.
NOTE: Clinical improvement generally takes longer than reduction of serum lithium concentrations regardless of the method used.
CSI - but ne reference to support this.
CSI - but from previous CSI. No referencees.
MHRA requested wording but GDS has removed this. Is this consistant with what happens in practice?
Section 4.9- Overdose
The toxic concentrations for lithium are close to the therapeutic concentrations. [p1] Any overdose in a patient who has been taking chronic lithium therapy should be regarded as potentially serious. A single acute overdose usually carries low risk and patients tend to show mild symptoms only, irrespective of their serum lithium concentration. However more severe symptoms may occur after a delay if lithium elimination is reduced because of renal impairment, particularly if a slow-release preparation has been taken.
If an acute overdose has been taken by a patient on chronic lithium therapy, this can lead to serious toxicity occurring even after a modest overdose as the extravascular tissues are already saturated with lithium.
Symptoms
The onset of symptoms may be delayed, with peak effects not occurring for as long as 24 hours, especially in patients who are not receiving chronic lithium therapy, or following the use of a sustained release preparation.
Mild: Nausea, diarrhoea, vomiting, blurred vision, polyuria, light headedness, fine resting tremor, first degree heart block, muscular weakness and drowsiness.
Moderate: Increasing confusion, blackouts, fasciculation and increased deep tendon reflexes, myoclonic twitches and jerks, ataxia, choreoathetoid movements, urinary and faecal incontinence, increasing restlessness followed by stupor. Hypernatraemia.
Severe: Coma, convulsions, cerebellar signs, cardiac dysrhythmias including sino-atrial block, sinus and junctional bradycardia. Hypotension or rarely hypertension, circulatory collapse and renal failure.
Management
There is no known antidote. . Supportive and symptomatic treatment should be initiated. Correction of electrolyte balance and fluid resuscitation is critical[p2]
[p3] Gut decontamination is not useful for chronic accumulation. Whole bowel irrigation may be helpful in patients ingesting large quantities of slow-release preparation.
CSI - but ne reference to support this.
CSI - but from previous CSI. No referencees.
MHRA requested wording but GDS has removed this. Is this consistant with what happens in practice?
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