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Drug Interactions between etrasimod and lomefloxacin

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

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Interactions between your drugs

Major

lomefloxacin etrasimod

Applies to: lomefloxacin and etrasimod

MONITOR CLOSELY: Due to the risk of bradycardia and atrioventricular (AV) block, the risk of QT prolongation and torsade de pointes arrhythmia may be increased during initiation of etrasimod treatment in patients receiving drugs that prolong the QT interval. Etrasimod may cause a transient decrease in heart rate during initiation of therapy. In the randomized placebo-controlled studies in patients with ulcerative colitis UC-1 and UC-2, following an initial dose of 2 mg on day 1, the greatest mean decrease from baseline in heart rate of 7.2 bpm occurred at hour 2 (UC-2) and hour 3 (UC-1). In studies UC-2 and UC-3, bradycardia was reported on day 1 in 2.9% of patients on etrasimod compared to none in the placebo group. On Day 2, bradycardia was reported in 1 patient (0.3%) treated with etrasimod compared to none in the placebo group. Overall, subjects who experienced bradycardia were generally asymptomatic. Few subjects experienced symptoms such as dizziness, and these symptoms resolved without intervention. Initiation of etrasimod treatment has also resulted in transient AV conduction delays. In the UC-1 study, after 2 mg of etrasimod on day 1 of treatment, first- or second-degree Mobitz type I AV blocks were observed in 0.7% of etrasimod- treated subjects compared to none in the placebo group. In studies UC-2 and UC-3, Mobitz type I AV blocks were observed in 0.8% of etrasimod-treated subjects compared to none in the placebo group. 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: Because bradycardia and AV block are recognized risk factors for QT prolongation and torsade de pointes arrhythmia, advice from a cardiologist should be sought if treatment with etrasimod is considered in patients with significant QT prolongation (QTcF greater than 450 msec in males or 470 msec in females), patients with arrhythmias requiring treatment with Class 1a or Class III antiarrhythmic agents, or in patients on concurrent therapy with QT prolonging drugs with a known risk of torsades de pointes or drugs that slow heart rate or AV conduction. Temporary interruption of anti-arrhythmic therapy may be required prior to initiation of etrasimod, depending on the patient's resting heart rate. Some authorities state that treatment with an anti-arrhythmic agent may be initiated in patients who have been stabilized on etrasimod therapy for at least 7 consecutive days. The manufacturer's product labeling or local treatment protocols should also be consulted for additional guidance.

References (5)
  1. (2023) "Product Information. Velsipity (etrasimod)." Pfizer U.S. Pharmaceuticals Group
  2. (2024) "Product Information. Velsipity (etrasimod)." Pfizer Australia Pty Ltd, pfpvelst11024
  3. (2024) "Product Information. Velsipity (etrasimod)." Pfizer Ltd
  4. (2024) "Product Information. Velsipity (etrasimod)." Pfizer U.S. Pharmaceuticals Group
  5. (2024) "Product Information. Velsipity (etrasimod)." Pfizer Canada ULC

Drug and food interactions

Moderate

etrasimod food

Applies to: etrasimod

GENERALLY AVOID: Coadministration with moderate inhibitors of CYP450 3A4 such as grapefruit juice in patients who known or suspected to be poor CYP450 2C9 metabolizers may increase the exposure of etrasimod. Etrasimod is primarily metabolized by the isoenzymes CYP450 3A4, 2C8, and 2C9. Pharmacokinetic studies have reported that no single enzyme system appears to dominate the elimination pathway of etrasimod. Therefore, the involvement of multiple CYP450 isoforms reduces the likelihood of drug-drug interactions when only a single CYP450 isoform is strongly or moderately inhibited by a coadministered drug. In clinical drug interaction studies, when etrasimod was administered with the dual moderate CYP450 2C9 and 3A4 inhibitor fluconazole at steady-state levels, etrasimod systemic exposure (AUC) increased by 84%. However, concomitant use with the potent CYP450 3A4 inhibitor itraconazole increased the AUC of etrasimod by 32%, which was not considered by the manufacturer to be clinically significant. The effect on etrasimod systemic exposure in CYP450 2C9 intermediate metabolizers treated with less potent CYP450 3A4 inhibitors is not known. Increased plasma concentrations of etrasimod may increase the risk of infection, bradyarrhythmia, AV conduction delays, elevated transaminase levels, and macular edema.

MANAGEMENT: Until further information is available, the consumption of grapefruit and grapefruit juice in combination with moderate to potent CYP450 2C8 inhibitors such as gemfibrozil should be avoided or limited during treatment with etrasimod in patients who are poor CYP450 2C9 metabolizers. Caution is recommended with grapefruit products consumption in patients who are intermediate CYP450 2C9 metabolizers. Patients should be advised to notify their physician if they experience potential adverse effects of etrasimod.

References (6)
  1. (2023) "Product Information. Velsipity (etrasimod)." Pfizer U.S. Pharmaceuticals Group
  2. Lee C, Taylor C, Tang Y, Caballero LV, shan k, Randle A, Grundy JS (2022) Effects of fluconazole, gemfibrozil, and rifampin on the pharmacokinetics, safety, and tolerability of etrasimod https://gut.bmj.com/content/71/Suppl_1/A142.1
  3. (2024) "Product Information. Velsipity (etrasimod)." Pfizer Australia Pty Ltd, pfpvelst11024
  4. (2024) "Product Information. Velsipity (etrasimod)." Pfizer U.S. Pharmaceuticals Group
  5. (2024) "Product Information. Velsipity (etrasimod)." Pfizer Canada ULC
  6. Harnik S, Ungar B, Loebstein R, Ben-Horin S (2024) "A Gastroenterologist's guide to drug interactions of small molecules for inflammatory bowel disease" United European Gastroenterol J, 12, p. 627-637
Moderate

lomefloxacin food

Applies to: lomefloxacin

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 (32)
  1. 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
  2. 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
  3. 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
  4. 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
  5. Yuk JH (1989) "Ciprofloxacin levels when receiving sucralfate." J Am Geriatr Soc, 262, p. 901
  6. 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
  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
  8. 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
  9. 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
  10. Akerele JO, Okhamafe AO (1991) "Influence of oral co-administered metallic drugs on ofloxacin pharmacokinetics." J Antimicrob Chemother, 28, p. 87-94
  11. Wadworth AN, Goa KL (1991) "Lomefloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use." Drugs, 42, p. 1018-60
  12. 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
  13. 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
  14. Lehto P, Kivisto KT (1994) "Effect of sucralfate on absorption of norfloxacin and ofloxacin." Antimicrob Agents Chemother, 38, p. 248-51
  15. Noyes M, Polk RE (1988) "Norfloxacin and absorption of magnesium-aluminum." Ann Intern Med, 109, p. 168-9
  16. 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
  17. Lehto P, Kivisto KT (1994) "Different effects of products containing metal ions on the absorption of lomefloxacin." Clin Pharmacol Ther, 56, p. 477-82
  18. Spivey JM, Cummings DM, Pierson NR (1996) "Failure of prostatitis treatment secondary to probable ciprofloxacin-sucralfate drug interaction." Pharmacotherapy, 16, p. 314-6
  19. (2001) "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical
  20. (2001) "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome
  21. (2001) "Product Information. Zagam (sparfloxacin)." Rhone Poulenc Rorer
  22. (2001) "Product Information. Trovan (trovafloxacin)." Pfizer U.S. Pharmaceuticals
  23. 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
  24. 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
  25. Honig PK, Gillespie BK (1998) "Clinical significance of pharmacokinetic drug interactions with over-the-counter (OTC) drugs." Clin Pharmacokinet, 35, p. 167-71
  26. Johnson RD, Dorr MB, Talbot GH, Caille G (1998) "Effect of Maalox on the oral absorption of sparfloxacin." Clin Ther, 20, p. 1149-58
  27. 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
  28. 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
  29. 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
  30. (2003) "Product Information. Factive (gemifloxacin)." *GeneSoft Inc
  31. (2010) "Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates)." Braintree Laboratories
  32. (2017) "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc.

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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