A narrow therapeutic index drug requiring regular level, renal and thyroid monitoring
Mnemonic
“Narrow window, and everything that dries you out raises it”:
- Therapeutic range 0.4 to 1.0 mmol/l, toxic above 1.5
- Take the level 12 hours post dose
- Check weekly after starting or a dose change until stable, then every 3 months
- Check renal and thyroid function every 6 months, and calcium
Precipitants of toxicity, all reducing renal clearance:
- Dehydration, vomiting, diarrhoea, hot weather
- Diuretics, especially thiazides
- ACE inhibitors and angiotensin receptor blockers
- NSAIDs
- Renal impairment, and a low sodium diet
“Thiazides, ACE inhibitors and NSAIDs are the three that will do it”, and each should prompt a level.
Toxicity presents as coarse tremor, ataxia, dysarthria, vomiting, diarrhoea, confusion, then seizures and renal failure. Treatment is fluids and, in severe cases, haemodialysis. Long term effects are hypothyroidism, hyperparathyroidism and nephrogenic diabetes insipidus.
Expansion
Therapeutic range: 0.4 to 1.0 mmol/l, measured 12 hours post-dose.
Monitoring
- Levels weekly after starting or a dose change until stable, then every 3 months
- Renal function and thyroid function every 6 months
- Calcium, since it causes hyperparathyroidism
Long term adverse effects
- Nephrogenic diabetes insipidus: polyuria and polydipsia
- Hypothyroidism, and less often hyperthyroidism
- Hyperparathyroidism with hypercalcaemia
- Weight gain, tremor, chronic kidney disease
- Ebstein anomaly if used in pregnancy
Toxicity (above about 1.5 mmol/l): coarse tremor, ataxia, dysarthria, vomiting and diarrhoea, confusion, seizures and coma. Treated with fluids and haemodialysis in severe cases, which works because lithium has a small volume of distribution.
Precipitants of toxicity all reduce renal clearance: dehydration, vomiting and diarrhoea, NSAIDs, ACE inhibitors and ARBs, thiazides, and any intercurrent illness. Patients need sick day rules, and lithium should be held during acute illness with dehydration.