Drug Interactions between chlorpromazine and norfloxacin
This report displays the potential drug interactions for the following 2 drugs:
- chlorpromazine
- norfloxacin
Interactions between your drugs
chlorproMAZINE norfloxacin
Applies to: chlorpromazine and norfloxacin
MONITOR: Certain quinolones, including levofloxacin, norfloxacin, and ofloxacin, may cause dose-related prolongation of the QT interval in some patients. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. During postmarketing surveillance, rare cases of torsade de pointes and ventricular tachycardia have been reported in patients taking levofloxacin, norfloxacin, and ofloxacin. The levofloxacin cases primarily involved patients with underlying medical conditions or taking concomitant medications that may have been contributory. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).
MANAGEMENT: Although the risk of a serious interaction is probably low, caution is recommended if levofloxacin, norfloxacin, or ofloxacin is used in combination with other drugs that can prolong the QT interval. Since the magnitude of QTc prolongation increases with increasing plasma concentrations of the quinolone, recommended dosages and intravenous infusion rates should not be exceeded. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.
References
- (2001) "Product Information. Floxin (ofloxacin)." Ortho McNeil Pharmaceutical
- Thomas M, Maconochie JG, Fletcher E (1996) "The dilemma of the prolonged QT interval in early drug studies." Br J Clin Pharmacol, 41, p. 77-81
- (2001) "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical
- Samaha FF (1999) "QTC interval prolongation and polymorphic ventricular tachycardia in association with levofloxacin." Am J Med, 107, p. 528-9
- Iannini PB, Doddamani S, Byazrova E, Curciumaru I, Kramer H (2001) "Risk of torsades de pointes with non-cardiac drugs. Prolongation of QT interval is probably a class effect of fluoroquinolones." Br Med J, 322, p. 46-7
- Owens RC (2001) "Risk assessment for antimicrobial agent-induced QTc interval prolongation and torsades de pointes." Pharmacotherapy, 21, p. 301-19
- Ball P (2000) "Quinolone-induced QT interval prolongation: a not-so-unexpected class effect." J Antimicrob Chemother, 45, p. 557-9
- Kang J, Wang L, Chen XL, Triggle DJ, Rampe D (2001) "Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG." Mol Pharmacol, 59, p. 122-6
- Kahn JB (2001) "Latest industry information on the safety profile of levofloxacin in the US." Chemotherapy, 47 Suppl 3, p. 32-7
- Frothingham R (2001) "Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin." Pharmacotherapy, 21, p. 1468-72
- Oliphant CM, Green GM (2002) "Quinolones: a comprehensive review." Am Fam Physician, 65, p. 455-64
- Owens RC Jr, Ambrose PG (2002) "Torsades de pointes associated with fluoroquinolones." Pharmacotherapy, 22, 663-8; discussion 668-72
- Noel GJ, Natarajan J, Chien S, Hunt TL, Goodman DB, Abels R (2003) "Effects of three fluoroquinolones on QT interval in healthy adults after single doses." Clin Pharmacol Ther, 73, p. 292-303
- Iannini PB (2002) "Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval." Expert Opin Drug Saf, 1, p. 121-8
- Owens RC (2004) "QT Prolongation with Antimicrobial Agents : Understanding the Significance." Drugs, 64, p. 1091-124
- Nykamp DL, Blackmon CL, Schmidt PE, Roberson AG (2005) "QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine." Ann Pharmacother, 39, p. 543-6
- Katritsis D, Camm AJ (2003) "Quinolones: cardioprotective or cardiotoxic." Pacing Clin Electrophysiol, 26, p. 2317-20
- Stahlmann R (2002) "Clinical toxicological aspects of fluoroquinolones." Toxicol Lett, 127, p. 269-77
- Makaryus AN, Byrns K, Makaryus MN, Natarajan U, Singer C, Goldner B (2006) "Effect of ciprofloxacin and levofloxacin on the QT interval: is this a significant "clinical" event?" South Med J, 99, p. 52-6
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Falagas ME, Rafailidis PI, Rosmarakis ES (2007) "Arrhythmias associated with fluoroquinolone therapy." Int J Antimicrob Agents, 29, p. 374-9
- Cerner Multum, Inc. "Australian Product Information."
Drug and food interactions
norfloxacin food
Applies to: norfloxacin
ADJUST DOSING INTERVAL: Concurrent ingestion of meals, dairy products (milk, yogurt) or calcium-fortified foods (i.e., cereal, orange juice) may decrease the absorption of oral norfloxacin. The mechanism is chelation of calcium and the quinolone, resulting in decreased bioavailability. In the case of orange juice, inhibition of intestinal transport mechanisms (P-glycoprotein or organic anion-transporting polypeptides) by flavones may also be involved.
MANAGEMENT: Oral norfloxacin should be taken at least one hour before or two hours after a meal, milk, or other dairy products or calcium-fortified foods.
References
- (2002) "Product Information. Cipro (ciprofloxacin)." Bayer
- Yuk JH, Nightingale CH, Sweeney KR, Quintiliani R, Lettieri JT, Forst RW (1989) "Relative bioavailability in healthy volunteers of ciprofloxacin administered through a nasogastric tube with and without enteral feeding." Antimicrob Agents Chemother, 33, p. 1118-20
- Yuk JH, Nightingale CH, Quintiliani R (1990) "Absorption of ciprofloxacin administered through a nasogastric or a nasoduodenal tube in volunteers and patients receiving enteral nutrition." Diagn Microbiol Infect Dis, 13, p. 99-102
- Noer BL, Angaran DW (1990) "The effect of enteral feedings on ciprofloxacin pharmacokinetics." Pharmacotherapy, 10, p. 254
- Neuhofel AL, Wilton JH, Victory JM, Hejmanowsk LG, Amsden GW (2002) "Lack of bioequivalence of ciprofloxacin when administered with calcium-fortified orange juice: a new twist on an old interaction." J Clin Pharmacol, 42, p. 461-6
- Wallace AW, Victory JM, Amsden GW (2003) "Lack of bioequivalence of gatifloxacin when coadministered with calcium-fortified orange juice in healthy volunteers." J Clin Pharmacol, 43, p. 92-6
- Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67
chlorproMAZINE food
Applies to: chlorpromazine
GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.
MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.
References
- Lutz EG (1976) "Neuroleptic-induced akathisia and dystonia triggered by alcohol." JAMA, 236, p. 2422-3
- Freed E (1981) "Alcohol-triggered-neuroleptic-induced tremor, rigidity and dystonia." Med J Aust, 2, p. 44-5
norfloxacin food
Applies to: norfloxacin
ADJUST DOSING INTERVAL: Oral preparations that contain magnesium, aluminum, or calcium may significantly decrease the gastrointestinal absorption of quinolone antibiotics. Absorption may also be reduced by sucralfate, which contains aluminum, as well as other polyvalent cations such as iron and zinc. The mechanism is chelation of quinolones by polyvalent cations, forming a complex that is poorly absorbed from the gastrointestinal tract. The bioavailability of ciprofloxacin has been reported to decrease by as much as 90% when administered with antacids containing aluminum or magnesium hydroxide.
MANAGEMENT: When coadministration cannot be avoided, quinolone antibiotics should be dosed either 2 to 4 hours before or 4 to 6 hours after polyvalent cation-containing products to minimize the potential for interaction. When coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering fluoroquinolone antibiotics at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium. Please consult individual product labeling for specific recommendations.
References
- Polk RE, Helay DP, Sahai J, Drwal L, Racht E (1989) "Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers." Antimicrob Agents Chemother, 33, p. 1841-4
- Nix DE, Watson WA, Lener ME, et al. (1989) "Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin." Clin Pharmacol Ther, 46, p. 700-5
- Garrelts JC, Godley PJ, Peterie JD, Gerlach EH, Yakshe CC (1990) "Sucralfate significantly reduces ciprofloxacin concentrations in serum." Antimicrob Agents Chemother, 34, p. 931-3
- Frost RW, Lasseter KC, Noe AJ, Shamblen EC, Lettieri JT (1992) "Effects of aluminum hydroxide and calcium carbonate antacids on the bioavailability of ciprofloxacin." Antimicrob Agents Chemother, 36, p. 830-2
- Yuk JH (1989) "Ciprofloxacin levels when receiving sucralfate." J Am Geriatr Soc, 262, p. 901
- Deppermann KM, Lode H, Hoffken G, Tschink G, Kalz C, Koeppe P (1989) "Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid." Antimicrob Agents Chemother, 33, p. 1901-7
- Campbell NR, Kara M, Hasinoff BB, Haddara WM, McKay DW (1992) "Norfloxacin interaction with antacids and minerals." Br J Clin Pharmacol, 33, p. 115-6
- Parpia SH, Nix DE, Hejmanowski LG, Goldstein HR, Wilton JH, Schentag JJ (1989) "Sucralfate reduces the gastrointestinal absorption of norfloxacin." Antimicrob Agents Chemother, 33, p. 99-102
- Nix DE, Wilton JH, Ronald B, Distlerath L, Williams VC, Norman A (1990) "Inhibition of norfloxacin absorption by antacids." Antimicrob Agents Chemother, 34, p. 432-5
- Akerele JO, Okhamafe AO (1991) "Influence of oral co-administered metallic drugs on ofloxacin pharmacokinetics." J Antimicrob Chemother, 28, p. 87-94
- Wadworth AN, Goa KL (1991) "Lomefloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use." Drugs, 42, p. 1018-60
- Shimada J, Shiba K, Oguma T, et al. (1992) "Effect of antacid on absorption of the quinolone lomefloxacin." Antimicrob Agents Chemother, 36, p. 1219-24
- Sahai J, Healy DP, Stotka J, Polk RE (1993) "The influence of chronic administration of calcium carbonate on the bioavailability of oral ciprofloxacin." Br J Clin Pharmacol, 35, p. 302-4
- Lehto P, Kivisto KT (1994) "Effect of sucralfate on absorption of norfloxacin and ofloxacin." Antimicrob Agents Chemother, 38, p. 248-51
- Noyes M, Polk RE (1988) "Norfloxacin and absorption of magnesium-aluminum." Ann Intern Med, 109, p. 168-9
- Grasela TH Jr, Schentag JJ, Sedman AJ, et al. (1989) "Inhibition of enoxacin absorption by antacids or ranitidine." Antimicrob Agents Chemother, 33, p. 615-7
- Lehto P, Kivisto KT (1994) "Different effects of products containing metal ions on the absorption of lomefloxacin." Clin Pharmacol Ther, 56, p. 477-82
- Spivey JM, Cummings DM, Pierson NR (1996) "Failure of prostatitis treatment secondary to probable ciprofloxacin-sucralfate drug interaction." Pharmacotherapy, 16, p. 314-6
- (2001) "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical
- (2001) "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome
- (2001) "Product Information. Zagam (sparfloxacin)." Rhone Poulenc Rorer
- (2001) "Product Information. Trovan (trovafloxacin)." Pfizer U.S. Pharmaceuticals
- Teng R, Dogolo LC, Willavize SA, Friedman HL, Vincent J (1997) "Effect of Maalox and omeprazole on the bioavailability of trovafloxacin." J Antimicrob Chemother, 39 Suppl B, p. 93-7
- Zix JA, Geerdes-Fenge HF, Rau M, Vockler J, Borner K, Koeppe P, Lode H (1997) "Pharmacokinetics of sparfloxacin and interaction with cisapride and sucralfate." Antimicrob Agents Chemother, 41, p. 1668-72
- Honig PK, Gillespie BK (1998) "Clinical significance of pharmacokinetic drug interactions with over-the-counter (OTC) drugs." Clin Pharmacokinet, 35, p. 167-71
- Johnson RD, Dorr MB, Talbot GH, Caille G (1998) "Effect of Maalox on the oral absorption of sparfloxacin." Clin Ther, 20, p. 1149-58
- Lober S, Ziege S, Rau M, Schreiber G, Mignot A, Koeppe P, Lode H (1999) "Pharmacokinetics of gatifloxacin and interaction with an antacid containing aluminum and magnesium." Antimicrob Agents Chemother, 43, p. 1067-71
- Allen A, Vousden M, Porter A, Lewis A (1999) "Effect of Maalox((R)) on the bioavailability of oral gemifloxacin in healthy volunteers." Chemotherapy, 45, p. 504-11
- Kamberi M, Nakashima H, Ogawa K, Oda N, Nakano S (2000) "The effect of staggered dosing of sucralfate on oral bioavailability of sparfloxacin." Br J Clin Pharmacol, 49, p. 98-103
- (2003) "Product Information. Factive (gemifloxacin)." *GeneSoft Inc
- (2010) "Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates)." Braintree Laboratories
- (2017) "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc.
norfloxacin food
Applies to: norfloxacin
MONITOR: Coadministration with certain quinolones may increase the plasma concentrations and pharmacologic effects of caffeine due to inhibition of the CYP450 1A2 metabolism of caffeine. Quinolones that may inhibit CYP450 1A2 include ciprofloxacin, enoxacin, grepafloxacin, nalidixic acid, norfloxacin, pipemidic acid, and pefloxacin (not all commercially available). In healthy volunteers, enoxacin (100 to 400 mg twice daily) increased systemic exposure (AUC) of caffeine by 2- to 5-fold and reduced its clearance by approximately 80%. Pipemidic acid (400 to 800 mg twice daily) increased AUC of caffeine by 2- to 3-fold and reduced its clearance by approximately 60%. Ciprofloxacin (250 to 750 mg twice daily) increased AUC and elimination half-life of caffeine by 50% to over 100%, and reduced its clearance by 30% to 50%. Norfloxacin 400 mg twice daily increased caffeine AUC by 16%, while 800 mg twice daily increased caffeine AUC by 52% and reduced its clearance by 35%. Pefloxacin (400 mg twice daily) has been shown to reduce caffeine clearance by 47%.
MANAGEMENT: Patients using caffeine-containing products should be advised that increased adverse effects such as headache, tremor, restlessness, nervousness, insomnia, tachycardia, and blood pressure increases may occur during coadministration with quinolones that inhibit CYP450 1A2. Caffeine intake should be limited when taking high dosages of these quinolones. If an interaction is suspected, other quinolones such as gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, and ofloxacin may be considered, since they are generally believed to have little or no effect on CYP450 1A2 or have been shown not to interact with caffeine.
References
- Polk RE (1989) "Drug-drug interactions with ciprofloxacin and other fluoroquinolones." Am J Med, 87, s76-81
- Healy DP, Polk RE, Kanawati L, Rock DT, Mooney ML (1989) "Interaction between oral ciprofloxacin and caffeine in normal volunteers." Antimicrob Agents Chemother, 33, p. 474-8
- Harder S, Fuhr U, Staib AH, Wolf T (1989) "Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations." Am J Med, 87, p. 89-91
- Carbo ML, Segura J, De la Torre R, et al. (1989) "Effect of quinolones on caffeine disposition." Clin Pharmacol Ther, 45, p. 234-40
- (1993) "Product Information. Penetrax (enoxacin)." Rhone-Poulenc Rorer, Collegeville, PA.
- Mahr G, Sorgel F, Granneman GR, et al. (1992) "Effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine." Clin Pharmacokinet, 22, p. 90-7
- (2002) "Product Information. Cipro (ciprofloxacin)." Bayer
- (2001) "Product Information. Noroxin (norfloxacin)." Merck & Co., Inc
- Staib AH, Stille W, Dietlein G, et al. (1987) "Interaction between quinolones and caffeine." Drugs, 34 Suppl 1, p. 170-4
- Stille W, Harder S, Micke S, et al. (1987) "Decrease of caffeine elimination in man during co-administration of 4-quinolones." J Antimicrob Chemother, 20, p. 729-34
- Harder S, Staib AH, Beer C, Papenburg A, Stille W, Shah PM (1988) "4-Quinolones inhibit biotransformation of caffeine." Eur J Clin Pharmacol, 35, p. 651-6
- Nicolau DP, Nightingale CH, Tessier PR, et al. (1995) "The effect of fleroxacin and ciprofloxacin on the pharmacokinetics of multiple dose caffeine." Drugs, 49 Suppl 2, p. 357-9
- (2001) "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome
- Carrillo JA, Benitez J (2000) "Clinically significant pharmacokinetic interactions between dietary caffeine and medications." Clin Pharmacokinet, 39, p. 127-53
- Fuhr U, Wolff T, Harder S, Schymanski P, Staib AH (1990) "Quinolone inhibition of cytochrome P-450 dependent caffeine metabolism in human liver microsomes." Drug Metab Dispos, 18, p. 1005-10
- Kinzig-Schippers M, Fuhr U, Zaigler M, et al. (1999) "Interaction of pefloxacin and enoxacin with the human cytochrome P450 enzyme CYP1A2." Clin Pharmacol Ther, 65, p. 262-74
- Healy DP, Schoenle JR, Stotka J, Polk RE (1991) "Lack of interaction between lomefloxacin and caffeine in normal volunteers." Antimicrob Agents Chemother, 35, p. 660-4
Therapeutic duplication warnings
No warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
Further information
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