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Drug Interactions between chloroquine and ofloxacin

This report displays the potential drug interactions for the following 2 drugs:

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Major

chloroquine ofloxacin

Applies to: chloroquine and ofloxacin

GENERALLY AVOID: Chloroquine and hydroxychloroquine can cause dose-related prolongation of the QT interval. 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. 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 advanced age, 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). Currently available data seem to suggest a significantly higher risk of QTc prolongation (>= 60 msec increase from baseline or absolute QTc >=500 msec ) in COVID-19 patients treated with hydroxychloroquine or chloroquine, with or without azithromycin, than has been previously reported in other settings. Because COVID-19 may disproportionately affect the elderly and individuals with preexisting heart disease, and cardiac complications such as myocarditis and cardiomyopathy as well as organ failure may occur in patients with severe COVID-19, it appears likely that hospitalized patients with COVID-19 may represent a particularly susceptible and high-risk population, and other, less critically ill patients may not have the same arrhythmic risk.

MANAGEMENT: Coadministration of chloroquine or hydroxychloroquine with other drugs that can prolong the QT interval should generally be avoided, particularly in patients with baseline QT prolongation (e.g., QTc >=500 msec) or congenital long QT syndrome. Close monitoring of QTc interval, electrolyte levels, and renal and hepatic function is recommended if concomitant use is required and benefits are anticipated to outweigh the risks. Electrolyte abnormalities should be corrected prior to initiating treatment with chloroquine or hydroxychloroquine. 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. Because chloroquine and hydroxychloroquine are eliminated slowly from the body, the potential for drug interactions should be observed for a prolonged period following their discontinuation.

References

  1. "Product Information. Plaquenil (hydroxychloroquine)." Apothecon Inc (2022):
  2. "Product Information. Chloroquine Phosphate (chloroquine)." West Ward Pharmaceutical Corporation (2005):
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. "Product Information. Hydroxychloroquine Sulfate (hydroxychloroquine)." Prasco Laboratories (2017):
  5. US Food and Drug Administration "Hydroxychloroquine or Chloroquine for COVID-19: Drug Safety Communication - FDA Cautions Against Use Outside of the Hospital Setting or a Clinical Trial Due to Risk of Heart Rhythm Problems. https://www.fda.gov/safety/medical-product-safety-information/h" (2020):
  6. US Food and Drug Administration "FACT SHEET FOR HEALTH CARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF HYDROXYCHLOROQUINE SULFATE SUPPLIED FROM THE STRATEGIC NATIONAL STOCKPILE FOR TREATMENT OF COVID-19 IN CERTAIN HOSPITALIZED PATIENTS. https://www.fda.gov/media/136537/download" (2020):
  7. US Food and Drug Administration "FACT SHEET FOR HEALTH CARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF CHLOROQUINE PHOSPHATE SUPPLIED FROM THE STRATEGIC NATIONAL STOCKPILE FOR TREATMENT OF COVID-19 IN CERTAIN HOSPITALIZED PATIENTS. https://www.fda.gov/media/136535/download" (2020):
  8. National Institutes of Health (NIH) "Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. https://covid19treatmentguidelines.nih.gov/" (2020):
  9. Mercuro NJ, Yen CF, Shim DJ, et al. "Risk of QT interval prolongation associated with the use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19)" JAMA Cardiol May 1:e201834 (2020): epub ahead of print
  10. Bonow RO, Hernandez AF, Turakhia M "Hydroxychloroquine, coronavirus disease 2019, and QT prolongation." JAMA Cardiol May 1 (2020): epub ahead of print
  11. Bessiere F, Roccia H, Deliniere A, et al. "Assessment of QT intervals in a case series of patients with coronavirus disease 2019 (COVID-19) infection treated with hydroxychloroquine alone or in combination with azithromycin in an intensive care unit." JAMA Cardiol May 1 (2020): epub ahead of print
  12. Saleh M, Gabriels J, ChangD, et al. "The effect of chloroquine, hydroxychloroquine and azithromycin on the corrected QT interval in patients with SARS-CoV-2 infection." Circ Arrhythm Electrophysiol Apr 29 (2020): epub ahead of print
  13. Javelot H, El-Hage W, Meyer G, Becker G, Michel B, Hingray C "COVID-19 and (hydroxy)chloroquine-azithromycin combination: should we take the risk for our patients?" Br J Clin Pharmacol Apr 29 (2020): epub ahead of print
  14. Sacher F, Fauchier L, Boveda S, et al. "Use of drugs with potential cardiac effect in the setting of SARS-CoV-2 infection." Arch Cardiovasc Dis Apr 24 (2020): epub ahead of print
  15. Smit C, Peeters MYM, van den Anker JN, Knibbe CAJ "Chloroquine for SARS-CoV-2: Implications of its unique pharmacokinetic and safety properties." Clin Pharmacokinet Ar 18 (2020): epub ahead of print
  16. Roden DM, Harrington RA, Poppas A, Russo AM "Considerations for drug interactions on QTc in exploratory COVID-19 (Coroanvirus disease 2019) treatment." Heart Rhythm Apr 14 (2020): epub ahead of print
  17. Sapp JL, Alqarawi W, MacIntyre CJ, et al. "Guidance on minimizing risk of drug-induced ventricular arrhythmia during treatment of COVID-19: A statement from the Canadian Heart Rhythm Society." Can J Cardiol Apr 8 (2020): epub ahead of print
  18. Kapoor A, Pandurangi U, Arora V, et al. "Cardiovascular risks of hydroxychloroquine in treatment and prophylaxis of COVID-19 patients: A scientific statement from the Indian Heart Rhythm Society." Indian Pacing Electorphysiol J Apr 8 (2020): epub ahead of print
  19. Giudicessi JR, Noseworthy PA, Friedman PA, Ackerman MJ "Urgent guidance for navigating and circumventing the QTc-prolonging and torsadogenic potential of possible pharmacotherapies for coronavirus disease 19 (COVID-19)" Mayo Clin Proc Apr 7 (2020): epub ahead of print
  20. Borba MGS, Val FFA, Sampaio VS, et al. "Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 1 (SARS-CoV-2) infection: A randomized clinical trial." JAMA Netw Open Apr 1 (2020): epub ahead of print
  21. mitra RL, Greenstein SA, Epstein lm "An algorithm for managing QT prolongation in coronavirus disease 2019 (COVID-19) patients treated with either chloroquine or hydroxychloroquine in conjunction with azithromycin; Possible benefits of intravenous lidocaine." HeartRythm Case Rep Apr 1 (2020): epub ahead of print
View all 21 references

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Drug and food interactions

Moderate

chloroquine food

Applies to: chloroquine

GENERALLY AVOID: Theoretically, grapefruit and grapefruit juice may increase the plasma concentrations of hydroxychloroquine or chloroquine and the risk of toxicities such as QT interval prolongation and ventricular arrhythmias. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Following coadministration with cimetidine, a weak to moderate CYP450 3A4 inhibitor, a 2-fold increase in chloroquine exposure occurred. Since chloroquine and hydroxychloroquine have similar structures and metabolic elimination pathways, a similar interaction may be observed with hydroxychloroquine. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract during hydroxychloroquine or chloroquine therapy.

References

  1. Cerner Multum, Inc. "Australian Product Information." O 0

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Moderate

ofloxacin food

Applies to: ofloxacin

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

  1. Polk RE, Helay DP, Sahai J, Drwal L, Racht E "Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers." Antimicrob Agents Chemother 33 (1989): 1841-4
  2. Nix DE, Watson WA, Lener ME, et al. "Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin." Clin Pharmacol Ther 46 (1989): 700-5
  3. Garrelts JC, Godley PJ, Peterie JD, Gerlach EH, Yakshe CC "Sucralfate significantly reduces ciprofloxacin concentrations in serum." Antimicrob Agents Chemother 34 (1990): 931-3
  4. Frost RW, Lasseter KC, Noe AJ, Shamblen EC, Lettieri JT "Effects of aluminum hydroxide and calcium carbonate antacids on the bioavailability of ciprofloxacin." Antimicrob Agents Chemother 36 (1992): 830-2
  5. Yuk JH "Ciprofloxacin levels when receiving sucralfate." J Am Geriatr Soc 262 (1989): 901
  6. Deppermann KM, Lode H, Hoffken G, Tschink G, Kalz C, Koeppe P "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 (1989): 1901-7
  7. Campbell NR, Kara M, Hasinoff BB, Haddara WM, McKay DW "Norfloxacin interaction with antacids and minerals." Br J Clin Pharmacol 33 (1992): 115-6
  8. Parpia SH, Nix DE, Hejmanowski LG, Goldstein HR, Wilton JH, Schentag JJ "Sucralfate reduces the gastrointestinal absorption of norfloxacin." Antimicrob Agents Chemother 33 (1989): 99-102
  9. Nix DE, Wilton JH, Ronald B, Distlerath L, Williams VC, Norman A "Inhibition of norfloxacin absorption by antacids." Antimicrob Agents Chemother 34 (1990): 432-5
  10. Akerele JO, Okhamafe AO "Influence of oral co-administered metallic drugs on ofloxacin pharmacokinetics." J Antimicrob Chemother 28 (1991): 87-94
  11. Wadworth AN, Goa KL "Lomefloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use." Drugs 42 (1991): 1018-60
  12. Shimada J, Shiba K, Oguma T, et al. "Effect of antacid on absorption of the quinolone lomefloxacin." Antimicrob Agents Chemother 36 (1992): 1219-24
  13. Sahai J, Healy DP, Stotka J, Polk RE "The influence of chronic administration of calcium carbonate on the bioavailability of oral ciprofloxacin." Br J Clin Pharmacol 35 (1993): 302-4
  14. Lehto P, Kivisto KT "Effect of sucralfate on absorption of norfloxacin and ofloxacin." Antimicrob Agents Chemother 38 (1994): 248-51
  15. Noyes M, Polk RE "Norfloxacin and absorption of magnesium-aluminum." Ann Intern Med 109 (1988): 168-9
  16. Grasela TH Jr, Schentag JJ, Sedman AJ, et al. "Inhibition of enoxacin absorption by antacids or ranitidine." Antimicrob Agents Chemother 33 (1989): 615-7
  17. Lehto P, Kivisto KT "Different effects of products containing metal ions on the absorption of lomefloxacin." Clin Pharmacol Ther 56 (1994): 477-82
  18. Spivey JM, Cummings DM, Pierson NR "Failure of prostatitis treatment secondary to probable ciprofloxacin-sucralfate drug interaction." Pharmacotherapy 16 (1996): 314-6
  19. "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical PROD (2001):
  20. "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome PROD (2001):
  21. "Product Information. Zagam (sparfloxacin)." Rhone Poulenc Rorer PROD (2001):
  22. "Product Information. Trovan (trovafloxacin)." Pfizer U.S. Pharmaceuticals PROD (2001):
  23. Teng R, Dogolo LC, Willavize SA, Friedman HL, Vincent J "Effect of Maalox and omeprazole on the bioavailability of trovafloxacin." J Antimicrob Chemother 39 Suppl B (1997): 93-7
  24. Zix JA, Geerdes-Fenge 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
  25. Honig PK, Gillespie BK "Clinical significance of pharmacokinetic drug interactions with over-the-counter (OTC) drugs." Clin Pharmacokinet 35 (1998): 167-71
  26. Johnson RD, Dorr MB, Talbot GH, Caille G "Effect of Maalox on the oral absorption of sparfloxacin." Clin Ther 20 (1998): 1149-58
  27. Lober S, Ziege S, Rau M, Schreiber G, Mignot A, Koeppe P, Lode H "Pharmacokinetics of gatifloxacin and interaction with an antacid containing aluminum and magnesium." Antimicrob Agents Chemother 43 (1999): 1067-71
  28. Allen A, Vousden M, Porter A, Lewis A "Effect of Maalox((R)) on the bioavailability of oral gemifloxacin in healthy volunteers." Chemotherapy 45 (1999): 504-11
  29. Kamberi M, Nakashima H, Ogawa K, Oda N, Nakano S "The effect of staggered dosing of sucralfate on oral bioavailability of sparfloxacin." Br J Clin Pharmacol 49 (2000): 98-103
  30. "Product Information. Factive (gemifloxacin)." *GeneSoft Inc (2003):
  31. "Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates)." Braintree Laboratories (2010):
  32. "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc. (2017):
View all 32 references

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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.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

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