OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO	MOLECULAR FORMULA	STRUCTURE
Nisoldipine	63675-72-9	C20-H24-N2-O6

ANNOTATED BIBLIOGRAPHY

References updated: 11 January 2017

• Zimmerman HJ. Calcium channel blockers. Drugs used in cardiovascular disease. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 646-7.

  (Expert review of hepatotoxicity published in 1999; among calcium channel blockers, diltiazem, nifedipine, bepridil and verapamil have been incriminated in instances of hepatic injury; nisoldipine is not mentioned).
• De Marzio DH, Navarro VJ. Calcium channel blockers. Hepatotoxicity of cardiovascular and antidiabetic drugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 524.

  (Review of hepatotoxicity of calcium channel blockers mentions that diliazem, nifedipine and verapamil have been implicated in causing cholestatic liver injury; nisoldipine is not mentioned).
• Michel T, Hoffman BB. Calcium channel antagonists. Treatment of myocardial ischemia. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 755-60.

  (Textbook of pharmacology and therapeutics).
• Knorr A. The pharmacology of nisoldipine. Cardiovasc Drugs Ther 1987; 1: 393-402. (Review of pharmacology of nisoldipine). [PubMed: 3154674]
• Friedel HA, Sorkin EM. Nisoldipine. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of angina pectoris, hypertension and related cardiovascular disorders. Drugs 1988; 36: 682-731. (Review of pharmacology, efficacy and safety of nisoldipine; [PubMed: 3065058]

  side effects are largely due to the vasodilating activty of nisoldipine, and in clinical trials no "clinically important" biochemical laboratory changes occurred).
• Frishman WH, Heiman M. Usefulness of oral nisoldipine for stable angina pectoris. The Nisoldipine Multicenter Angina Study Group. Am J Cardiol 1991; 68: 1004-9. [PubMed: 1927911]

  (Controlled trial of 5 week course of one of 3 doses of nisoldipine vs placebo in 178 patients with angina pectoris, only minor side effects occurred and no mention is made of liver injury or ALT elevations).
• Mitchell J, Frishman W, Heiman M. Nisoldipine: a new dihydropyridine calcium-channel blocker. J Clin Pharmacol 1993; 33: 46-52. [PubMed: 8429113]

  (Review of structure, pharmacodynamics, clinical efficacy and safety of nisoldipine, "Side effects... appear to be dose-related, mild in severity and transient"; no mention is made of ALT elevations or liver injury).
• DEFIANT-II Research Group. Doppler flow and echocardiography in functional cardiac insufficiency: assessment of nisoldipine therapy. Results of the DEFIANT-II Study. Eur Heart J 1997; 18: 31-40. [PubMed: 9049513]

  (Trial of 6 month course of nisoldipine in 542 patients reported no hepatic adverse events or withdrawals due to liver complications).
• Fodor JG. Nisoldipine CC: efficacy and tolerability in hypertension and ischemic heart disease. Cardiovasc Drugs Ther 1997; 10: (Suppl 3): 873-9. [PubMed: 9126676]

  (Nisoldipine is available in an extended release formulation that has favorable pharmokinetics allowing once daily administration, with tolerability that is similar to other calcium channel blockers and "no significant changes in laboratory parameters").
• Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug-induced liver injury in the United States. Liver Transpl 2004; 10: 1018-23. [PubMed: 15390328]

  (Among ~50,000 liver transplants reported to UNOS between 1990 and 2002, 270 [0.5%] were done for drug induced acute liver failure, but none were attributed to a calcium channel blocker).
• Björnsson E, Jerlstad P, Bergqvist A, Olsson R. Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden. Scand J Gastroenterol 2005; 40: 1095-101. [PubMed: 16165719]

  (Summary of 25 years of adverse drug reaction reporting in Sweden identified 103 cases of drug induced acute liver failure; only one case was possibly linked to a calcium channel blocker: felodipine).
• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US collected from 2004 to 2008, calcium channel blockers were implicated as a sole agent in 2 cases [1 amlodipine, 1 verapamil] and as one of several agents in 2 cases [both amlodipine]).
• Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, but no case was attributed to nisoldipine or other calcium channel blockers).
• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013; 144: 1419-25. [PubMed: 23419359]

  (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, none of which were attributed to a calcium channel blocker or other antihypertensive medication).
• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America. An analysis of published reports. Ann Hepatol 2014; 13: 231-9. [PubMed: 24552865]

  (Systematic review of literature of drug induced liver injury in Latin American countries published from 1996 to 2012 identified 176 cases; one case was attributed to verapamil, but none were linked to nisoldipine or other calcium channel blockers).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 39 [4%] were due to antihypertensive agents including 4 due to calcium channel blockers [amlodipine in 1 and verapamil in 3 instances], but none to nisoldipine).