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Drug Interactions between gatifloxacin and gepirone

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

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Major

gatifloxacin gepirone

Applies to: gatifloxacin and gepirone

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Certain quinolones, including gatifloxacin and moxifloxacin, 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 have been reported in patients taking gatifloxacin. These cases primarily involved patients with underlying medical conditions for which they were receiving concomitant medications known to prolong the QTc interval. Rare cases of tachycardia have been reported with moxifloxacin. 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: Coadministration of gatifloxacin or moxifloxacin with other drugs that can prolong the QT interval should generally be avoided. Caution and clinical monitoring are recommended if concomitant use is required. 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

  1. "Product Information. Avelox (moxifloxacin)." Bayer PROD (2001):
  2. "Product Information. Tequin (gatifloxacin)." Bristol-Myers Squibb PROD (2001):
  3. Siepmann M, Kirch W "Drug points - Tachycardia associated with moxifloxacin." Br Med J 322 (2001): 23
  4. Owens RC "Risk assessment for antimicrobial agent-induced QTc interval prolongation and torsades de pointes." Pharmacotherapy 21 (2001): 301-19
  5. Iannini PB, Circiumaru I "Gatifloxacin-induced QTc prolongation and ventricular tachycardia." Pharmacotherapy 21 (2001): 361-2
  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
  7. Iannini PB, Doddamani S, Byazrova E, Curciumaru I, Kramer H "Risk of torsades de pointes with non-cardiac drugs." BMJ 322 (2001): 46-7
  8. Ball P "Quinolone-induced QT interval prolongation: a not-so-unexpected class effect." J Antimicrob Chemother 45 (2000): 557-9
  9. 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
  10. White CM, Grant EM, Quintiliani R "Moxifloxacin does increase the corrected QT interval." Clin Infect Dis 33 (2001): 1441-2
  11. Frothingham R "Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin." Pharmacotherapy 21 (2001): 1468-72
  12. 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
  13. Oliphant CM, Green GM "Quinolones: a comprehensive review." Am Fam Physician 65 (2002): 455-64
  14. Owens RC Jr, Ambrose PG "Torsades de pointes associated with fluoroquinolones." Pharmacotherapy 22 (2002): 663-8; discussion 668-72
  15. 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
  16. Ansari SR, Chopra N "Gatifloxacin and Prolonged QT Interval." Am J Med Sci 327 (2004): 55-6
  17. Iannini PB "Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval." Expert Opin Drug Saf 1 (2002): 121-8
  18. Owens RC "QT Prolongation with Antimicrobial Agents : Understanding the Significance." Drugs 64 (2004): 1091-124
  19. Katritsis D, Camm AJ "Quinolones: cardioprotective or cardiotoxic." Pacing Clin Electrophysiol 26 (2003): 2317-20
  20. Stahlmann R "Clinical toxicological aspects of fluoroquinolones." Toxicol Lett 127 (2002): 269-77
  21. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  22. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  23. Dale KM, Lertsburapa K, Kluger J, White CM "Moxifloxacin and torsade de pointes." Ann Pharmacother 41 (2007): 336-40
  24. Falagas ME, Rafailidis PI, Rosmarakis ES "Arrhythmias associated with fluoroquinolone therapy." Int J Antimicrob Agents 29 (2007): 374-9
  25. 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
  26. Cerner Multum, Inc. "Australian Product Information." O 0
View all 26 references

Drug and food interactions

Moderate

gepirone food

Applies to: gepirone

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the plasma concentrations and effects of gepirone. The proposed mechanism is inhibition of CYP450 3A4 mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. For example, when subjects who were at steady state on the strong CYP450 3A4 inhibitor ketoconazole (200 mg twice daily) received a single dose of gepirone (36.3 mg), the maximum plasma concentration (Cmax) and systemic exposure (AUC) of gepirone increased by approximately 5-fold. Similarly, when subjects who were at steady state on the moderate CYP450 3A4 inhibitor verapamil (80 mg three times daily) received a single dose of gepirone (18.2 mg), the maximum plasma concentration (Cmax) and systemic exposure (AUC) of gepirone increased by approximately 2.6-fold. In general, the effects of grapefruit products are concentration-, dose-, and preparation-dependent and can vary widely among both brands and individual patients. Some preparations have demonstrated strong CYP450 3A4 inhibition, while others have demonstrated moderate inhibition.

ADJUST DOSING INTERVAL: Food enhances the bioavailability of gepirone and its major active metabolites (3'-OH-gepirone and 1-PP). The magnitude of the effect is dependent on the fat content of the meal, but the systemic exposure of gepirone and its major metabolites was consistently higher under fed conditions as compared to the fasted state. The peak plasma concentration (Cmax) of gepirone after intake of a low-fat (about 200 calorie) breakfast was 27% higher, after a medium-fat (about 500 calorie) breakfast was 55% higher, and after a high-fat (about 850 calorie) breakfast was 62% higher than the Cmax achieved in the fasted state. Likewise, the systemic exposure (AUC) of gepirone was about 14% higher after a low-fat breakfast, 22% higher after a medium-fat breakfast, and 32% to 37% higher after a high-fat breakfast when compared to the AUC achieved in the fasted state. The effect of varying amounts of fat on the AUC and Cmax of 3'-OH-gepirone and 1-PP were similar to that of gepirone.

MANAGEMENT: Coadministration of gepirone with grapefruit products should be avoided. If grapefruit juice is consumed, monitoring for adverse effects (e.g., QT prolongation, serotonin syndrome, dizziness, nausea, insomnia, abdominal pain, and/or dyspepsia) should be considered. Gepirone should be taken orally with food at the approximately the same time each day. Tablets should be swallowed whole.

References

  1. "Product Information. Exxua (gepirone)." Mission Pharmacal Company 1 (2023):
  2. FDA. U.S. Food and Drug Administration "Grapefruit juice and some drugs don't mix. https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix" (2024):
  3. Chen M, Zhou S, Fabriaga E, Zhang P, Zhou Q "Food-drug interactions precipitated by fruit juices other than grapefruit juice: an update review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326888/" (2024):
  4. Kiani J, Imam SZ "Medicinal importance of grapefruit juice and its interaction with various drugs. https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-6-33" (2024):
View all 4 references
Minor

gatifloxacin food

Applies to: gatifloxacin

Information for this minor interaction is available on the professional version.

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

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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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