HSA would like to share with healthcare professionals a recent advisory issued by Health Canada regarding the risk of hypercalcaemia associated with lithium therapy, which may or may not be accompanied with hyperparathyroidism. Lithium has been registered locally since 1988 as Camcolit-400® (Apex Pharma Marketing Pte Ltd) for the treatment and prophylaxis of mania, manic-depressive illness and recurrent depression.
Background
Rates of lithium-induced hypercalcaemia have been estimated to be between 5% to 40%.1 While the effects of high blood calcium and/or parathyroid hormone (PTH) may be unnoticeable or mild in many cases, they can be life threatening in severe cases, leading to medical emergencies such as coma and cardiac arrest.2, 3
In a published systematic review and meta-analysis of studies investigating the association between lithium and all reported major adverse effects, the authors found a 10% increase in blood calcium (+0.09mmol/L; 95% CI 0.02, 0.17; p=0.009) and PTH (+7.32pg/mL; 95% CI 3.42, 11.23; p<0.0001) values when compared with normal values, in patients given lithium compared with controls.4 The increase was postulated to be attributed to lithium’s inactivation of the calcium-sensing receptor and interference with intracellular second messenger signalling. This effect leads to an increased release of PTH, which raises blood calcium concentration.
Review by Health Canada
Based on its review, Health Canada has reaffirmed that the benefits of lithium therapy in the treatment of bipolar disorder continue to outweigh the known risks of this drug. The agency had recommended reviewing patient calcium blood levels at the following times: before the start of lithium treatment, six months after initiation of lithium and subsequently on an annual basis for patients on long-term treatment. Healthcare professionals were also advised to consider measuring the PTH blood levels, if necessary, to identify or rule out hyperparathyroidism.
Local situation and HSA's advisory
To date, HSA has received one adverse drug reaction report of hyperparathyroidism with lithium use. There were no reports relating to hypercalcaemia suspected to be associated with lithium use. Hypercalcaemia and hyperparathyroidism are both known risks associated with lithium therapy, which have already been highlighted in the local package insert of Camcolit-400®. Healthcare professionals may wish to consider the above information in the management of their patients and be vigilant to possible signs and symptoms of hypercalcaemia and hyperparathyroidism in patients prescribed lithium.
References
- Prim Care Companion J Clin Psychiatry 2010; 12: PCC.09l00917
- http://emedicine.medscape.com/article/240681-overview#a0104
- http://circ.ahajournals.org/content/112/24_suppl/IV-121.full
- Lancet 2012; 379: 721-8