Drugs List

Therapeutic Indications

Uses

Aggressive or self mutilating behaviour
Hypomania
Mania
Manic depression - prophylaxis
Manic-depressive illness - treatment
Prevention of relapse or recurrence of depressive illness

Contraindications

Family history of Brugada syndrome
Restricted sodium intake
Addison's disease
Breastfeeding
Brugada syndrome
Cardiac impairment
Cardiovascular disorder
Dehydration
Hyponatraemia
Long QT syndrome
Severe renal impairment
Torsade de pointes
Uncontrolled hypothyroidism

Precautions and Warnings

Children under 18 years
Diarrhoea
Elderly
Family history of long QT syndrome
Family history of sudden death
Females of childbearing potential
Hot climates
Infection
Major surgery
Predisposition to epileptic disorder
Predisposition to prolongation of QT interval
Severe dieting
Suicidal ideation
Vomiting
Electrolyte imbalance
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
History of torsade de pointes
Mild renal impairment
Myasthenia gravis
Pregnancy
Psoriasis
Reduced seizure threshold

Advise ability to drive/operate machinery may be affected by side effects
Renal impairment: Risk of renal tumour if treated for more than 10 years
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some brands contain Sunset Yellow (E110) - can trigger allergic reactions
Some formulations contain glucose
Some formulations contain hydroxybenzoate
Some formulations contain propylene glycol
Some formulations may contain alcohol
Evaluate renal function before and during treatment
Monitor cardiac function before and regularly during treatment
Monitor thyroid function prior to and periodically during treatment
Perform urine analysis before and periodically during treatment
Evaluate benefit/risk in long term use ( > 5 years)
Monitor lithium levels every three months when stabilized
Monitor lithium levels weekly after initiation or dose change until stable
Monitor renal function if polyuria or polydipsia occurs
Monitor serum electrolytes
Advise patient of signs of toxicity
Advise patients/carers to seek medical advice if suicidal intent develops
Discontinue if active infection develops
Discontinue immediately on the first signs of toxicity
Hypothyroidism may occur
Patient to report nausea, vomiting or situations leading to salt/water loss
Discontinue treatment 24 hours prior to surgery
To discontinue, reduce dose gradually
Bioavailability differs with preparations;caution on changing formulations
Maintain treatment at the lowest effective dose
Reduce dose in elderly
Female: Ensure adequate contraception during treatment
Advise patient to avoid strict low salt diet
Lithium therapy record book to be issued

Advise patient to report a persistent headache and/or visual disturbances.

Pregnancy and Lactation

Pregnancy

Use lithium with caution in pregnancy.

Lithium crosses the placenta. Animal studies have shown some teratogenic effects in foetal development including Ebstein's anomaly as well as some interference with gestation and fertility. Briggs (2015) states that if lithium is used within the first trimester, adequate screening tests such as an ultrasound and electrocardiogram of the foetus should be strongly advised.

Lithium should be discontinued before a planned pregnancy, however if treatment is considered essential to maintain during pregnancy, Schaefer (2015) suggests serum levels should be monitored frequently due to the risk of foetal polyuria and toxicity and a daily intake of folic acid should be administered.

Schaefer (2015) also recommends that treatment should be discontinued within the onset of labour, before delivery, and recommenced a few days after birth to avoid toxicity. The manufacturer suggests to avoid the use of lithium during pregnancy, especially in the first trimester, unless considered essential then serum levels should be monitored as necessary.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Lithium is contraindicated in breastfeeding.

Lithium is excreted in breast milk. Studies have shown it is excreted in doses of up to 30% (Briggs et al, 2015). There have been some reports of toxicity in neonates, however Briggs (2015) states that there have been no adverse reactions found in infants when lithium has been administered during breastfeeding. Schaefer (2015) also states lithium can be administered during breastfeeding as long as the infant is closely monitored and the doses are as low as possible.

There is limited published information on the long term use of lithium during breastfeeding. The manufacturer states lithium is contraindicated in breastfeeding, suggesting to analyse the importance of lithium treatment for the mother and the potential benefit of breastfeeding for the infant, and to discontinue either lithium treatment or breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal discomfort
Acne
Acneform changes
Alopecia
Anorexia
Arthralgia
Ataxia
Atrioventricular block
Benign raised intracranial pressure
Blurred vision
Bradycardia
Cardiac arrest
Cardiac arrhythmias
Cardiomyopathy
Circulatory collapse
Collecting duct renal carcinoma
Coma
Confusion
Cutaneous ulcer
Dazed feeling
Decreased reflexes
Diabetes insipidus
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Dysarthria
Dysgeusia
ECG changes
Exacerbation of psoriasis
Extrapyramidal effects
Folliculitis
Gastritis
Giddiness
Goitre
Histological renal changes
Hyperactive deep tendon reflexes
Hypercalcaemia
Hyperglycaemia
Hypermagnesaemia
Hyperparathyroidism
Hyperreflexia
Hypersalivation
Hyperthyroidism
Hypotension
Hypothyroidism
Impaired consciousness
Impaired memory
Inco-ordination
Interstitial fibrosis
Leucocytosis
Maculopapular rash
Muscle weakness
Myalgia
Myasthenia gravis-like syndrome
Myoclonus
Nausea
Nephrotic syndrome
Nystagmus
Oedema
Papular eruption
Polydipsia
Polyuria
Prolongation of QT interval
Pruritus
Pseudotumour cerebri
Rash (allergic)
Raynaud's phenomenon
Reflex disorders
Renal impairment
Renal microcysts
Renal oncocytoma
Scotoma
Seizures
Sensorimotor disorder
Sexual dysfunction
Sinus node dysfunction
Slurred speech
Speech disturbances
Stupor
T-wave changes
Thirst
Thyrotoxicosis
Tinnitus
Tremor
Urinary dysfunction
Ventricular fibrillation
Ventricular tachycardia
Vertigo
Vomiting
Weight gain

Presentation

Oral formulations of lithium citrate

Drugs List

Therapeutic Indications

Uses

Aggressive or self mutilating behaviour
Hypomania
Mania
Manic depression - prophylaxis
Manic-depressive illness - treatment
Prevention of relapse or recurrence of depressive illness

Dosage

Lithium levels should be checked before changing between lithium preparations.

Adults

Elderly

Therapeutic Drug Monitoring

Lithium has a narrow therapeutic/toxic ratio and therefore regular monitoring of serum lithium concentration is obligatory when lithium is used. Lithium therapy should not be initiated unless adequate facilities for routine monitoring of serum concentrations are available.

On initiation of therapy, plasma concentrations should be measured after 4 to 7 days of treatment then weekly until dosage has remained constant for 4 weeks and every 3 months thereafter. Doses are adjusted to achieve serum lithium concentration of 0.5 to 1.5 mmol/L (lower end of the range for maintenance therapy and elderly patients).

Additional measurements should be made if signs of lithium toxicity occur, on dosage alteration, development of significant intercurrent disease, signs of manic or depressive relapse and if significant changes 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 NSAIDs.

As bioavailability may vary between formulations, should a change of preparation be made, blood levels should be monitored weekly until restabilisation is achieved.

Blood samples for measurement of serum lithium concentration should be taken 12 hours after the preceding dose, concentration should be 0.5 to 0.8 mmol/L.

Serum lithium concentration of over 1.5 mmol/L may be fatal and toxic effects include tremor, ataxia, dysarthria, nystagmus, renal impairment and convulsions. If these potentially hazardous signs occur, treatment should be stopped, serum lithium concentrations redetermined, and steps taken to reverse lithium toxicity. Serum lithium concentration in excess of 2 mmol/L require urgent treatment.

Contraindications

Family history of Brugada syndrome
Restricted sodium intake
Addison's disease
Breastfeeding
Brugada syndrome
Cardiac impairment
Cardiovascular disorder
Dehydration
Hyponatraemia
Long QT syndrome
Severe renal impairment
Torsade de pointes
Uncontrolled hypothyroidism

Precautions and Warnings

Children under 18 years
Diarrhoea
Elderly
Family history of long QT syndrome
Family history of sudden death
Females of childbearing potential
Hot climates
Infection
Major surgery
Predisposition to epileptic disorder
Predisposition to prolongation of QT interval
Severe dieting
Suicidal ideation
Vomiting
Electrolyte imbalance
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
History of torsade de pointes
Mild renal impairment
Myasthenia gravis
Pregnancy
Psoriasis
Reduced seizure threshold

Advise ability to drive/operate machinery may be affected by side effects
Renal impairment: Risk of renal tumour if treated for more than 10 years
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some brands contain Sunset Yellow (E110) - can trigger allergic reactions
Some formulations contain glucose
Some formulations contain hydroxybenzoate
Some formulations contain propylene glycol
Some formulations may contain alcohol
Evaluate renal function before and during treatment
Monitor cardiac function before and regularly during treatment
Monitor thyroid function prior to and periodically during treatment
Perform urine analysis before and periodically during treatment
Evaluate benefit/risk in long term use ( > 5 years)
Monitor lithium levels every three months when stabilized
Monitor lithium levels weekly after initiation or dose change until stable
Monitor renal function if polyuria or polydipsia occurs
Monitor serum electrolytes
Advise patient of signs of toxicity
Advise patients/carers to seek medical advice if suicidal intent develops
Discontinue if active infection develops
Discontinue immediately on the first signs of toxicity
Hypothyroidism may occur
Patient to report nausea, vomiting or situations leading to salt/water loss
Discontinue treatment 24 hours prior to surgery
To discontinue, reduce dose gradually
Bioavailability differs with preparations;caution on changing formulations
Maintain treatment at the lowest effective dose
Reduce dose in elderly
Female: Ensure adequate contraception during treatment
Advise patient to avoid strict low salt diet
Lithium therapy record book to be issued

Advise patient to report a persistent headache and/or visual disturbances.

Pregnancy and Lactation

Pregnancy

Use lithium with caution in pregnancy.

Lithium crosses the placenta. Animal studies have shown some teratogenic effects in foetal development including Ebstein's anomaly as well as some interference with gestation and fertility. Briggs (2015) states that if lithium is used within the first trimester, adequate screening tests such as an ultrasound and electrocardiogram of the foetus should be strongly advised.

Lithium should be discontinued before a planned pregnancy, however if treatment is considered essential to maintain during pregnancy, Schaefer (2015) suggests serum levels should be monitored frequently due to the risk of foetal polyuria and toxicity and a daily intake of folic acid should be administered.

Schaefer (2015) also recommends that treatment should be discontinued within the onset of labour, before delivery, and recommenced a few days after birth to avoid toxicity. The manufacturer suggests to avoid the use of lithium during pregnancy, especially in the first trimester, unless considered essential then serum levels should be monitored as necessary.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Lithium is contraindicated in breastfeeding.

Lithium is excreted in breast milk. Studies have shown it is excreted in doses of up to 30% (Briggs et al, 2015). There have been some reports of toxicity in neonates, however Briggs (2015) states that there have been no adverse reactions found in infants when lithium has been administered during breastfeeding. Schaefer (2015) also states lithium can be administered during breastfeeding as long as the infant is closely monitored and the doses are as low as possible.

There is limited published information on the long term use of lithium during breastfeeding. The manufacturer states lithium is contraindicated in breastfeeding, suggesting to analyse the importance of lithium treatment for the mother and the potential benefit of breastfeeding for the infant, and to discontinue either lithium treatment or breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal discomfort
Acne
Acneform changes
Alopecia
Anorexia
Arthralgia
Ataxia
Atrioventricular block
Benign raised intracranial pressure
Blurred vision
Bradycardia
Cardiac arrest
Cardiac arrhythmias
Cardiomyopathy
Circulatory collapse
Collecting duct renal carcinoma
Coma
Confusion
Cutaneous ulcer
Dazed feeling
Decreased reflexes
Diabetes insipidus
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Dysarthria
Dysgeusia
ECG changes
Exacerbation of psoriasis
Extrapyramidal effects
Folliculitis
Gastritis
Giddiness
Goitre
Histological renal changes
Hyperactive deep tendon reflexes
Hypercalcaemia
Hyperglycaemia
Hypermagnesaemia
Hyperparathyroidism
Hyperreflexia
Hypersalivation
Hyperthyroidism
Hypotension
Hypothyroidism
Impaired consciousness
Impaired memory
Inco-ordination
Interstitial fibrosis
Leucocytosis
Maculopapular rash
Muscle weakness
Myalgia
Myasthenia gravis-like syndrome
Myoclonus
Nausea
Nephrotic syndrome
Nystagmus
Oedema
Papular eruption
Polydipsia
Polyuria
Prolongation of QT interval
Pruritus
Pseudotumour cerebri
Rash (allergic)
Raynaud's phenomenon
Reflex disorders
Renal impairment
Renal microcysts
Renal oncocytoma
Scotoma
Seizures
Sensorimotor disorder
Sexual dysfunction
Sinus node dysfunction
Slurred speech
Speech disturbances
Stupor
T-wave changes
Thirst
Thyrotoxicosis
Tinnitus
Tremor
Urinary dysfunction
Ventricular fibrillation
Ventricular tachycardia
Vertigo
Vomiting
Weight gain

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

The MHRA have produced 'generic' overdose sections for the top ten drugs for which the NPIS received the greatest number of queries about management of overdose in 2002. This information is attached below:

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. The fatal dose, in a single overdose, is probably over 5 g.

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.

Lithium toxicity can also occur in chronic accumulation for the following reasons:
Acute or chronic overdosage
Dehydration e.g. due to intercurrent illness
Deteriorating renal function
Drug interactions, most commonly involving a thiazide diuretic or a non-steroidal anti-inflammatory drug (NSAID)

In patients with a raised lithium concentration, the risk of toxicity is greater in those with the following underlying medical conditions: hypertension; diabetes; congestive heart failure; chronic renal failure; schizophrenia; Addison's disease.

Signs and 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, blurred vision, polyuria, light headedness, fine resting tremor, muscular weakness and drowsiness.
Moderate: Increasing confusion, blackouts, fasciculation and 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 including sino-atrial block, sinus and junctional bradycardia and first degree heart block. Hypotension or rarely hypertension, circulatory collapse and renal failure.

Treatment

Consider gastric lavage for non-sustained-release preparations if more than 4 g has been ingested by an adult within one hour or definite ingestion of a significant amount by a child. Slow-release tablets do not disintegrate in the stomach and most are too large to pass up a lavage tube. Gut decontamination is not useful for chronic accumulation. Whole bowel irrigation may be helpful in patients ingesting large quantities of a 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 overdose if the serum lithium concentration is >7.5 mmol/L. In cases of acute on chronic overdose or in cases of chronic lithium toxicity if the lithium concentration is >4.0 mmol/L, discuss with your local poisons service.

Note: Clinical improvement generally takes longer than reduction of serum lithium concentrations regardless of the method used.

Further Information

Last Full Review Date: May 2017

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 23 September 2017

Summary of Product Characteristics: Priadel liquid. Sanofi-Aventis. Revised June 2015.

Summary of Product Characteristics: Li-Liquid 509 mg/5 ml oral syrup. Rosemont Pharmaceuticals. Revised March 2017.

Summary of Product Characteristics: Li-Liquid 1018 mg/5 ml oral syrup. Rosemont Pharmaceuticals. Revised March 2017.