Lithium

Generic name
Lithium
Brand name
ATC Code
N05AN01
Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

The kinetic parameters of lithium carbonate (normal preparation) were determined using a population pharmacokinetics model [Landersdorfer 2017]; the Cl and Vd are based on the lean body mass (LBM):

t½ (h) 28.5
Cl (l/h/53 kg LBM)*0.75 1.64 (SE 3%)
Vd (l/53 kg LBM) 23.6 (SE 5.1%)

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

General Dose Info

IMPORTANT NOTE: The lithium preparations differ in bioavailability (and salt form) and are therefore not interchangeable. The dosage recommendations below already take these differences into account. Conversion is not necessary unless one switches to a preparation with a different salt form.

  • Titrate dosage based on blood levels:
    • acute phase 0.8-1.2 mmol/l;
    • maintenance 0.6-0.8 mmol/l, in children > 12 years to max 1.2 mmol/l)
  • The dose should be determined individually and the lowest possible dose should be applied.
  • After stabilization of blood levels, once-daily dosing is preferred.
  • On discontinuation, the dose should be gradually reduced, especially at high doses.
  • Lithium should be prescribed by a specialist in child and adolescent psychiatry.

Dosages

LITHIUM CITRATE: Acute manic episodes and as maintenance treatment in bipolar disorders
  • Oral
    • Tablet with regulated release
      • 6 years up to 12 years
        • 25 - 76 mg/kg/day in 1 - 2 doses.
      • 12 years up to 18 years
        • 1.527 - 4.580 mg/day in 1 - 2 doses.
    • 6 years up to 12 years
      [1] [2] [3] [6] [8]
      • 25 - 76 mg/kg/day in 1 - 2 doses.
    • 12 years up to 18 years
      [1] [2] [3] [6] [8]
      • 1.527 - 4.580 mg/day in 1 - 2 doses.
LITHIUM CARBONATE: Acute manic episodes and as maintenance treatment in bipolar disorders
Li+ ION: Acute manic episodes and as maintenance treatment in bipolar disorders

Renal impaiment in children > 3 months

• GFR 10-50 ml/min/1.73m²
Preferably do not use; if lithium used nevertheless:
- Start at 50% of the normal dose each time and do not adjust the interval between two doses.
- Check the trough lithium concentration and adjust the dose as necessary; after reaching a stable concentration, check every 3-6 months and check the kidney function twice a year.
• GFR <10 ml/min/1.73m²:
- contraindicated

Clinical consequences

The renal clearance of lithium is less when the renal function is reduced. The risk of side effects is elevated as a result.

Symptoms of excessively high lithium levels include vomiting, diarrhoea, drunk-sounding speech and gait, muscle shocks and muscle weakness, sleepiness and drowsiness. Prolonged high concentrations can have an irreversible harmful effect on the kidneys.
Chronic intoxication can occur in people who are treated chronically with lithium, due to either increased dosages or reduced clearance. In these cases, there is already a balance that has been found between the amount of lithium in the blood and in the organs and there is a degree of correlation between serum lithium concentration and clinical symptoms. Lithium takes a long time to disappear from the organs and so the elimination half-life can be as long as approximately 60 hours.
More information about the side effects of chronic lithium use can be found in the guideline of the Dutch Federation for Nephrology

Lithium has a narrow therapeutic range. The prophylactic concentration is 0.4-0.8 mmol/l, the therapeutic concentration is 0.8-1.2 mmol/l. Toxic symptoms can occur from 1.5 mmol/l, and also at therapeutic levels.

Other comments
Risk factors are cardiac failure and changes in the water/sodium intake.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

At therapeutic levels: nausea, vomiting, diarrhoea, tremor, concentration problems, weight gain, psoriasis, acne, alopecia, polyuria, polydipsia, enlarged thyroid, hypothyroidism, cognitive impairment.

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications in children

Renal function disorders, severe heart diseases or brain damage.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Summary:
Leads to reduced reaction and concentration, needs regular monitoring of plasma levels and creatinine levels, risk of intoxication in cases of reduced absorption and/or loss of NaCl and fluid, heart function and thyroid function should also be monitored.

Using it can result in reduced capacity to react and concentrate. This can hinder numerous day-to-day activities.    
 
As the therapeutic width is limited and accumulation may occur, the lithium plasma level should be monitored once or twice a week at the start of treatment and after every dose change (in the case of an acute attack of mania every second day at the same time); thereafter once a month, in properly adjusted patients every 2-3 months. For the normal preparation, a trough level is determined; for a preparation with controlled release, the plasma level is determined 12 hours after the last dose taken. The plasma level must also be determined again when converting from an ordinary tablet to a tablet with delayed release.  
 
 
Circumstances in which reduced absorption or excessive loss of NaCl and fluid occur (e.g. vomiting, prolonged diarrhoea, flu, diuretic treatment and excessive perspiration) can lead to an increase in lithium plasma levels and to lithium intoxication arising.

Long-term administration of lithium at high doses can have a harmful effect on the kidneys. Creatinine levels should therefore be regularly monitored during lithium therapy. The heart function should be checked at the start of treatment and periodically thereafter. The thyroid function should also be checked three months after the start of therapy and every six to twelve months thereafter.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

ANTIPSYCHOTICS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Phenothiazines with aliphatic side-chain
N05AA02
Butyrophenone derivatives
N05AD01
N05AD05
Indole derivatives
N05AE05
N05AE04
Diphenylbutylpiperidine derivatives
N05AG02
Diazepines, oxazepines, thiazepines and oxepines
N05AH02
N05AH03
N05AH04
Other antipsychotics
N05AX12
N05AX13
N05AX08

References

  1. Alessi N, et al, Update on lithium carbonate therapy in children and adolescents., J Am Acad Child Adolesc Psychiatry, 1994, 33, 291-304
  2. Lopez-Larson M, et al, Empirical evidence for the use of lithium and anticonvulsants in children with psychiatric disorders., Harv Rev Psychiatry, 2006, 14, 285-304
  3. Scahill L, et al., Lithium in children and adolescents, J Child Adolesc Psychiatr Nurs, 2001, 14, 89-93
  4. Vitiello B, et al, Pharmacokinetics of lithium carbonate in children., J Clin Psychopharmacol., 1988, 8, 355-9
  5. Teva Nederland BV. , SPC lithiumcarbonaat tablet (RVG 52076, 55991-2) 23-8-2016. , www.geneesmiddeleninformatiebank.nl
  6. Geller B et al, A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents., Arch Gen Psychiatry., 2012, May;69(5), 515-28
  7. Landersdorfer CB et al., Lithium in Paediatric Patients with Bipolar Disorder: Implications for Selection of Dosage Regimens via Population Pharmacokinetics/Pharmacodynamics, Clin Pharmacokinet, 2017, Jan;56(1), 77-90
  8. Walkup JT et al, Treatment of Early-Age Mania: Outcomes for Partial and Nonresponders to Initial Treatment, J Am Acad Child Adolesc Psychiatry, 2015, Dec;54(12), 1008-19
  9. Teva Nederland BV., SPC lithiumcarbonaat tablet (RVG 52076, 55991-2) 23-8-2016., www.geneesmiddeleninformatiebank.nl

Changes

Therapeutic Drug Monitoring


Overdose