Drug General Information (ID: DDIB7531C9)
Drug Name			Ciprofloxacin		Drug Info		Bepridil		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Quinolones/Antibiotics				Antiarrhythmic Agents
Structure

Mechanism of Ciprofloxacin-Bepridil Interaction (Severity Level: Major)
Increased risk of prolong QT interval Click to Show/Hide Mechanism Graph
Drug Name		Ciprofloxacin				Bepridil
Mechanism		Prolong QT interval				Prolong QT interval
Key Mechanism Factor 1
		Factor Name		QT interval
		Factor Description		Long QT syndrome is a heart signaling disorder that can cause a fast, chaotic heartbeat (arrhythmia). Many people may not exhibit symptoms, and usually the condition is detected during routine medical tests. In others, the most common symptoms include: sudden fainting, palpitations, dizziness, seizures, sudden death.
Mechanism Description		Increased risk of prolong QT interval by the combination of Ciprofloxacin and Bepridil

Recommended Action
Management		Product labeling for certain quinolones recommends avoiding concomitant therapy with class IA (e.g., disopyramide, quinidine, procainamide) and class III (e.g., amiodarone, dofetilide, ibutilide, sotalol) antiarrhythmic agents, as well as bepridil.

References
1	Ansari SR, Chopra N "Gatifloxacin and Prolonged QT Interval." Am J Med Sci 327 (2004): 55-6. [PMID: 14722399]
2	Ball P "Quinolone-induced QT interval prolongation: a not-so-unexpected class effect." J Antimicrob Chemother 45 (2000): 557-9. [PMID: 10797074]
3	Bertino JS Jr, Owens RC Jr, Carnes TD, Iannini PB "Gatifloxacin-associated corrected QT interval prolongation, torsades de pointes, and ventricular fibrillation in patients with known risk factors." Clin Infect Dis 34 (2002): 861-3. [PMID: 11830802]
4	Dale KM, Lertsburapa K, Kluger J, White CM "Moxifloxacin and torsade de pointes." Ann Pharmacother 41 (2007): 336-40. [PMID: 17284508]
5	Demolis JL, Charransol A, Funck-Brentano C, Jaillon P "Effects of a single oral dose of sparfloxacin on ventricular repolarization in healthy volunteers." Br J Clin Pharmacol 41 (1996): 499-503. [PMID: 8799513]
6	Demolis JL, Kubitza D, Tenneze L, Funck-Bretano C "Effect of a single oral dose of moxifloxacin (400 mg and 800 mg) on ventricular repolarization in healthy subjects." Clin Pharmacol Ther 68 (2000): 658-66. [PMID: 11180026]
7	Dupont H, Timsit JF, Souweine B, Gachot B, Wolff M, Regnier B "Torsades de pointe probably related to sparfloxacin." Eur J Clin Microbiol Infect Dis 15 (1996): 350-1. [PMID: 8781892]
8	Falagas ME, Rafailidis PI, Rosmarakis ES "Arrhythmias associated with fluoroquinolone therapy." Int J Antimicrob Agents 29 (2007): 374-9. [PMID: 17241772]
9	Frothingham R "Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin." Pharmacotherapy 21 (2001): 1468-72. [PMID: 11765299]
10	Iannini PB "Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval." Expert Opin Drug Saf 1 (2002): 121-8. [PMID: 12904146]
11	Iannini PB, Circiumaru I "Gatifloxacin-induced QTc prolongation and ventricular tachycardia." Pharmacotherapy 21 (2001): 361-2. [PMID: 11253862]
12	Iannini PB, Doddamani S, Byazrova E, Curciumaru I, Kramer H "Risk of torsades de pointes with non-cardiac drugs." BMJ 322 (2001): 46-7. [PMID: 11141163]
13	Jaillon P, Morganroth J, Brumpt I, Talbot G "Overview of electrocardiographic and cardiovascular safety data for sparfloxacin. Sparfloxacin Safety Group." J Antimicrob Chemother 37(suppl a) (1996): 161-7. [PMID: 8737135]
14	Kang J, Wang L, Chen XL, Triggle DJ, Rampe D "Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG." Mol Pharmacol 59 (2001): 122-6. [PMID: 11125032]
15	Katritsis D, Camm AJ "Quinolones: cardioprotective or cardiotoxic." Pacing Clin Electrophysiol 26 (2003): 2317-20. [PMID: 14675020]
16	Lipsky BA, Dorr MB, Magner DJ, Talbot GH "Safety profile of sparfloxacin, a new fluoroquinolone antibiotic." Clin Ther 21 (1999): 148-59. [PMID: 10090432]
17	Makaryus AN, Byrns K, Makaryus MN, Natarajan U, Singer C, Goldner B "Effect of ciprofloxacin and levofloxacin on the QT interval: is this a significant "clinical" event?" South Med J 99 (2006): 52-6. [PMID: 16466123]
18	Noel GJ, Natarajan J, Chien S, Hunt TL, Goodman DB, Abels R "Effects of three fluoroquinolones on QT interval in healthy adults after single doses." Clin Pharmacol Ther 73 (2003): 292-303. [PMID: 12709719]
19	Oliphant CM, Green GM "Quinolones: a comprehensive review." Am Fam Physician 65 (2002): 455-64. [PMID: 11858629]
20	Owens RC "QT Prolongation with Antimicrobial Agents : Understanding the Significance." Drugs 64 (2004): 1091-124. [PMID: 15139788]
21	Owens RC "Risk assessment for antimicrobial agent-induced QTc interval prolongation and torsades de pointes." Pharmacotherapy 21 (2001): 301-19. [PMID: 11253855]
22	Owens RC Jr, Ambrose PG "Torsades de pointes associated with fluoroquinolones." Pharmacotherapy 22 (2002): 663-8 discussion 668-72. [PMID: 12013370]
23	Product Information. Avelox (moxifloxacin) Bayer, West Haven, CT.
24	Product Information. Factive (gemifloxacin). GeneSoft Inc, San Francisco, CA.
25	Product Information. Floxin (ofloxacin). Ortho Pharmaceutical Corporation, Raritan, NJ.
26	Product Information. Levaquin (levofloxacin). Ortho Pharmaceutical Corporation, Raritan, NJ.
27	Product Information. Maxaquin (lomefloxacin). Searle, Skokie, IL.
28	Product Information. Noroxin (norfloxacin). Merck & Co, Inc, West Point, PA.
29	Product Information. Tequin (gatifloxacin) Bristol-Myers Squibb, Princeton, NJ.
30	Product Information. Zagam (sparfloxacin). Rhone-Poulenc Rorer, Collegeville, PA.
31	Samaha FF "QTC interval prolongation and polymorphic ventricular tachycardia in association with levofloxacin." Am J Med 107 (1999): 528-9. [PMID: 10569314]
32	Siepmann M, Kirch W "Drug points - Tachycardia associated with moxifloxacin." Br Med J 322 (2001): 23. [PMID: 11141146]
33	Stahlmann R "Clinical toxicological aspects of fluoroquinolones." Toxicol Lett 127 (2002): 269-77. [PMID: 12052667]
34	Thomas M, Maconochie JG, Fletcher E "The dilemma of the prolonged QT interval in early drug studies." Br J Clin Pharmacol 41 (1996): 77-81. [PMID: 8838432]
35	Tsikouris JP, Peeters MJ, Cox CD, Meyerrose GE, Seifert CF "Effects of three fluoroquinolones on QT analysis after standard treatment courses." Ann Noninvasive Electrocardiol 11 (2006): 52-6. [PMID: 16472283]
36	White CM, Grant EM, Quintiliani R "Moxifloxacin does increase the corrected QT interval." Clin Infect Dis 33 (2001): 1441-2. [PMID: 11565091]
37	Zix JA, GeerdesFenge HF, Rau M, Vockler J, Borner K, Koeppe P, Lode H "Pharmacokinetics of sparfloxacin and interaction with cisapride and sucralfate." Antimicrob Agents Chemother 41 (1997): 1668-72. [PMID: 9257738]