Lithium

CLINICAL USE

Treatment and prophylaxis of mania, manic depressive illness, and recurrent depressionAggressive or self-mutilating behaviour

DOSE IN NORMAL RENAL FUNCTION

See individual preparations. Adjust according to lithium plasma concentration

PHARMACOKINETICS

Molecular weight :73.9

%Protein binding :0

%Excreted unchanged in urine : 95

Volume of distribution (L/kg) :0.5–0.9

half-life – normal/ESRD (hrs) :12–24/40–50

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Avoid if possible, or reduce dose and monitor plasma concentration carefully

10 to 20 : Avoid if possible, or reduce dose and monitor plasma concentration carefully

<10 : Avoid if possible, or reduce dose and monitor plasma concentration carefully

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Dialysed in lithium intoxication. Dose as in GFR <10 mL/min

HD :Dialysed in lithium intoxication. Dose as in GFR <10 mL/min

HDF/high flux :Dialysed in lithium intoxication. Dose as in GFR <10 mL/min

CAV/VVHD :Dialysed. Dose as in GFR=10–20 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugsACE inhibitors and angiotensin-II antagonists: lithium excretion reduced

Analgesics: NSAIDs and ketorolac reduce excretion of lithium

Anti-arrhythmics: increased risk of ventricular arrhythmias with amiodarone – avoid concomitant use

Antidepressants: increased risk of CNS effects with SSRIs; risk of toxicity with tricyclics; possible increased serotonergic effects with venlafaxine

Antipsychotics: increased risk of extrapyramidal side effects and possibly neurotoxicity with clozapine, haloperidol and phenothiazines; increased risk of ventricular arrhythmias with sertindole – avoid concomitant use; increased risk of extrapyramidal side effects with sulpiride

Diuretics: lithium excretion reduced by loop diuretics, potassium-sparing diuretics, aldosterone antagonists and thiazides; lithium excretion increased by acetazolamideMethyldopa: neurotoxicity may occur without increased lithium levels

ADMINISTRATION

Reconstition

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Route

Oral

Rate of Administration

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Comments

Different preparations vary widely in bioavailability; a change in the preparation used requires the same precautions as initiation of treatment

OTHER INFORMATION

Doses are adjusted to achieve lithium plasma concentrations of 0.4–1.0 mmol/L (lower end of range for maintenance therapy in elderly patients) in samples taken 12 hours after the preceding dose. It takes 4–7 days to reach steady stateLong-term treatment may result in permanent changes in kidney histology and impairment of renal function. High serum concentration of lithium, including episodes of acute lithium toxicity, may aggravate these changes. The minimum clinically effective dose of lithium should always be usedLithium carbonate.440 LiThiUM CArBonATEBennett (4th ed.) suggests 25–50% of normal dose if GFR <10 mL/min, and 50–75% of normal dose if GFR between 10–50 mL/min – monitor lithium plasma concentrations closelyLithium generally should not be used in patients with severe renal disease because of increased risk of toxicityDialysability: serum lithium concentrations rebound within 5–8 hours post haemodialysis because of redistribution of the drug, often necessitating repeated courses of haemodialysis. Peritoneal dialysis is less effective at removing lithium and is only used if haemodialysis is not possibleUp to one-third of patients on lithium may develop polyuria, usually due to lithium blocking the effect of ADH. This reaction is reversible on withdrawal of lithium therapy.

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