Basic Information
ID DDInter1915 and DDInter1081
Interaction Concomitant use of angiotensin II receptor antagonists may increase the serum concentrations of lithium. The exact mechanism of interaction is unknown, but thought to be related to the natriuresis induced by angiotensin II receptor antagonists secondary to the inhibition of aldosterone secretion.
Management Given the narrow therapeutic index of lithium, caution is advised during coadministration with angiotensin II receptor antagonists, particularly in the elderly or patients with other risk factors (e.g., sodium restriction, renal impairment, congestive heart failure, dehydration, concomitant use of diuretics or NSAIDs). Pharmacologic response and serum lithium levels should be monitored more closely whenever an angiotensin II receptor antagonist is added to or withdrawn from therapy, and the lithium dosage adjusted as necessary. Empiric reductions of both drugs may be appropriate during initial therapy. Renal function should also be monitored regularly. Patients should be advised to seek medical attention if they experience potential signs and symptoms of lithium toxicity such as drowsiness, dizziness, confusion, muscle weakness, vomiting, diarrhea, polydipsia, polyuria, tinnitus, tremor, ataxia, and blurred vision.
References [1] Blanche P, Raynaud E, Kerob D, Galezowski N "Lithium intoxication in an elderly patient after combined treatment with losartan." Eur J Clin Pharmacol 52 (1997): 501 [2] "Product Information. Cozaar (losartan)." Merck & Co, Inc, West Point, PA. [3] Spinewine A, Schoevaerdts D, Mwenge GB, Swine C, Dive A "Drug-induced lithium intoxication: a case report." J Am Geriatr Soc 53 (2005): 360-1 [4] "Product Information. Benicar (olmesartan)." Sankyo Parke Davis, Parsippany, NJ. [5] "Product Information. Benicar HCT (hydrochlorothiazide-olmesartan)." Sankyo Parke Davis, Parsippany, NJ. [6] "Product Information. Eskalith (lithium)." SmithKline Beecham, Philadelphia, PA. [7] Su YP, Chang CJ, Hwang TJ "Lithium intoxication after valsartan treatment." Psychiatry Clin Neurosci 61 (2007): 204 [8] Leung M, Remick RA "Potential drug interaction between lithium and valsartan." J Clin Psychopharmacol 20 (2000): 392-3 [9] "Product Information. Atacand (candesartan)." Astra Pharmaceuticals, Wayne, PA. [10] "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim, Ridgefield, CT. [11] Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7 [12] "Product Information. Fycompa (perampanel)." Eisai Inc, Teaneck, NJ. [13] 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): [14] "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc, Rockville, MD. [15] Ray K, Dorman S, Watson R "Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction." J Hum Hypertens 13 (1999): 717-20 [16] "Product Information. Cozaar (losartan)." Merck & Co, Inc, West Point, PA. [17] Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit 23 (2001): 369-73
Alternative for Valsartan C09D
Sacubitril Aliskiren

C10B
Atorvastatin Simvastatin Lovastatin Rosuvastatin Niacin Pravastatin
Ezetimibe Bempedoic acid Fenofibrate

C09C
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.