Basic Information
ID DDInter883 and DDInter1081
Interaction Thiazide diuretics may cause a rapid increase in serum lithium levels and potentiate the risk of lithium toxicity. The exact mechanism is unknown but may be related to the sodium loss induced by thiazide diuresis, which produces a compensatory increase in proximal tubular reabsorption of sodium along with lithium.
Management Thiazide diuretics should generally not be prescribed to patients receiving lithium unless close monitoring of serum lithium levels and electrolytes can be rendered. Lithium dose reductions may be required. Patients should be advised to notify their physician if they experience potential signs and symptoms of lithium toxicity such as drowsiness, dizziness, muscle weakness, vomiting, diarrhea, thirst, polyuria, tinnitus, tremor, ataxia, and blurred vision.
References [1] Crabtree BL, Mack JE, Johnson CD, Amyx BC "Comparison of the effects of hydrochlorothiazide and furosemide on lithium disposition." Am J Psychiatry 148 (1991): 1060-3 [2] Hanna ME, Lobao CB, Stewart JT "Severe lithium toxicity associated with indapamide therapy." J Clin Psychopharmacol 10 (1990): 379-80 [3] Finley PR, Warner MD, Peabody CA "Clinical relevance of drug interactions with lithium." Clin Pharmacokinet 29 (1995): 172-91 [4] Macfie AC "Lithium poisoning precipitated by diuretics." Br Med J 1 (1975): 516 [5] Himmelhoch JM, Poust RI, Mallinger AG, Hanin I, Neil JF "Adjustment of lithium dose during lithium-chlorothiazide therapy." Clin Pharmacol Ther 22 (1977): 225-7 [6] Kerry RJ, Ludlow JM, Owen G "Diuretics are dangerous with lithium." Br Med J 281 (1980): 371 [7] Bennett WM "Drug interactions and consequences of sodium restriction." Am J Clin Nutr 65 (1997): S678-81 [8] Gammon GD, Docherty JP "Thiazide-induced hypercalcemia in a manic-depressive patient." Am J Psychiatry 137 (1980): 1453-5 [9] Petersen V, Hvidt S, Thomsen K, Schou M "Effect of prolonged thiazide treatment on renal lithium clearance." Br Med J 3 (1974): 143-5 [10] Nurnberger JI Jr "Diuretic-induced lithium toxicity presenting as mania." J Nerv Ment Dis 173 (1985): 316-8 [11] "Product Information. Eskalith (lithium)." SmithKline Beecham, Philadelphia, PA. [12] Jefferson JW, Kalin NH "Serum lithium levels and long-term diuretic use." JAMA 241 (1979): 1134-6 [13] Aronson JK, Reynolds DJM "ABC of monitoring drug therapy. Lithium." Br Med J 305 (1992): 1273-6 [14] Boer WH, Koomans HA, Mees EJ "Acute effects of thiazides, with and without carbonic anhydrase inhibiting activity, on lithium and free water clearance in man." Clin Sci 76 (1989): 539-45 [15] MacNeil S, Hanson-Nortey E, Paschalis C, et al "Diuretics during lithium therapy." Lancet 06/07/75 (1975): 1295-6 [16] Mehta BR, Robinson BH "Lithium toxicity induced by triamterene-hydrochlorothiazide." Postgrad Med J 56 (1980): 783-4 [17] Levy ST, Forrest JN, Jr Heninger GR "Lithium-induced diabetes insipidus: manic symptoms, brain and electrolyte correlates, and chlorothiazide treatment." Am J Psychiatry 130 (1973): 1014-8 [18] Dorevitch A, Baruch E "Lithium toxicity induced by combined amiloride HCl- hydrochlorothiazide administration." Am J Psychiatry 143 (1986): 257-8 [19] Solomon JG "Lithium toxicity precipitated by a diuretic." Psychosomatics 21 (1980): 425, 429 [20] Vipond AJ, Bakewell S, Telford R, Nicholls AJ "Lithium toxicity." Anaesthesia 51 (1996): 1156-8 [21] Poust RI, Mallinger AG, Mallinger J, Himmelhoch JM, Neil JF, Hanin I "Effect of chlorothiazide on the pharmacokinetics of lithium in plasma and erythrocytes." Psychopharmacol Commun 2 (1976): 273-84 [22] Hurtig HI, Dyson WL "Lithium toxicity enhanced by diuresis." N Engl J Med 290 (1974): 748-9 [23] Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7 [24] "Product Information. Fycompa (perampanel)." Eisai Inc, Teaneck, NJ. [25] Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990): [26] "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc, Rockville, MD.
Alternative for Hydrochlorothiazide C09D
Aliskiren Sacubitril

C09X
Aliskiren

G01A
Ciclopirox Sildenafil Amphotericin B Bosentan Miconazole Diclofenamide
Sulfamethizole Clindamycin
More
Alternative for Lithium carbonate -
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.