OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO	MOLECULAR FORMULA	STRUCTURE
Isradipine	75695-93-1	C19-H21-N3-O5

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; isradipine is not mentioned).
• De Marzio DH, Navarro VJ. Calcium channel blockers. Hepatotoxicity of cardiovascular and antidiabeticdrugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 524.

  (Review of hepatotoxicity published in 2013; diltiazem, nifedipine and verapamil have been implicated as the cause of liver injury in a small number of patients; isradipine is not specifically mentioned).
• Michel T, Hoffman BB. Calcium channel blockers. Treatment of myocardial ischemia and hypertension. In, Brunton LL, Chabner KA, Knollman KC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 766-7.

  (Textbook of pharmacology and therapeutics).
• Nelson EB, Pool JL, Taylor AA. Antihypertensive activity of isradipine in humans: a new dihydropyridine calcium channel antagonist. Clin Pharmacol Ther 1986; 40: 694-7. [PubMed: 2946507]

  (Controlled trial of isradipine in 24 patients with hypertension for 3 weeks; there were no significant changes in ALT or AST values during treatment).
• Shepherd AM, Carr AA, Davidov M, Hamilton J, Schnaper H, Velasquez M, Brockway B, Prisant LM, et al. Efficacy and safety of isradipine in hypertension. J Cardiovasc Pharmacol 1989; 13: 580-5. (Among 203 patients with hypertension given placebo or one of 5 doses of isradipine for 5 weeks, [PubMed: 2470995]

  adverse effects were mild; 19 on isradipine [11%] and 4 on placebo [10%] had an elevation of at least one liver test, but most were transient and asymptomatic).
• British Isradipine Hypertension Group. Evaluation of the safety and efficacy of isradipine in elderly patients with essential hypertension. Am J Med 1989; 86: 110-4. [PubMed: 2523644]

  (Among 118 elderly patients with hypertension treated with placebo or two doses of isradipine for up to 4 years, there were no differences in biochemical abnormalities between the placebo- and isradipine-treated groups).
• Dahlöf B. Hemodynamic response, safety, and efficacy of isradipine in the treatment of essential hypertension. Am J Med 1989; 86 (4A): 19-26. [PubMed: 2523651]

  (Among 1028 patients with hypertension treated with one of 6 different doses of isradipine in 15 different studies, side effects were more frequent at higher doses and included low rates of headache, flushing, dizziness, palpitations and peripheral edema; in one studfy of 288 patients, liver test abnormalities occurred in 6.3%).
• Sundstedt CD, Rüegg PC, Keller A, Waite R. A multicenter evaluation of the safety, tolerability, and efficacy of isradipine in the treatment of essential hypertension. Am J Med 1989; 86(4A): 98-102. [PubMed: 2523665]

  (Among 600 patients with hypertension treated with one of 3 doses of isradipine or placebo, common side effects were flushing [10.5%], headache [10.2%], and peripheral edema [4.2%]; 4 patients [0.6%] had serum aminotransferase elevations, but most were considered unrelated and all were mild, asymptomatic and did not require dose adjustment).
• 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]

  PubMed Citation (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. PubMed Citation. [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, none of which were attributed to isradipine 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 was 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 isradipine 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 isradipine).