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Drug Interactions between enoxacin and TheoCap

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

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Interactions between your drugs

Major

enoxacin theophylline

Applies to: enoxacin and TheoCap (theophylline)

GENERALLY AVOID: Enoxacin has been shown to reduce theophylline clearance by up to 75%. The mechanism is inhibition of CYP450 1A2 hepatic metabolism. Theophylline serum levels increase 1.5 to 3.0 times when enoxacin is administered concurrently. Patients with chronic obstructive pulmonary disease, congestive heart failure, or cirrhosis may have slower theophylline clearance rates; therefore, they may be at greater risk of developing theophylline toxicity.

MANAGEMENT: If possible, enoxacin therapy should be avoided in patients receiving theophylline. Levofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, trovafloxacin, and lomefloxacin have been reported to cause minor or no changes in theophylline levels and may be considered as alternatives. If enoxacin is given concomitantly with theophylline, the theophylline dosage should be reduced approximately 50% or more, and theophylline serum levels should be closely monitored. Patients should be advised to report any signs of theophylline toxicity including nausea, vomiting, diarrhea, headache, restlessness, insomnia, seizures, or irregular heartbeats to their physician.

References

  1. Wijnands WJ, Vree TB "Interaction between the fluoroquinolones and the bronchodilator theophylline." J Antimicrob Chemother 22 (1988): 109-14
  2. Sano M, Kawakatsu K, Yamamoto I, et al. "Inhibitory effect of enoxacin, ofloxacin and norfloxacin on renal excretion of theophylline in humans." Eur J Clin Pharmacol 36 (1989): 323-4
  3. Wijnands WJ, Vree TB, Baars AM, van Herwaarden CL "Steady-state kinetics of the quinolone derivatives ofloxacin, enoxacin, ciprofloxacin and pefloxacin during maintneance treatment with theophylline." Drugs 34 (1987): 159-69
  4. Sorgel F, Mahr G, Granneman GR, et al. "Effects of 2 quinolone antibacterials, temafloxacin and enoxacin, on theophylline pharmacokinetics." Clin Pharmacokinet 22 (1992): 65-74
  5. Koup JR, Toothaker RD, Posvar E, et al. "Theophylline dosage adjustment during enoxacin coadministration." Antimicrob Agents Chemother 34 (1990): 803-7
  6. Rogge MC, Solomon WR, Sedman AJ, et al. "The theophylline-enoxacin interaction. II: Changes in the disposition of theophylline and its metabolites during intermittent administration of enoxacin." Clin Pharmacol Ther 46 (1989): 420-8
  7. Wijnands GJ, Vree TB, Janssen TJ, Guelen PJ "Drug-drug interactions affecting fluoroquinolones." Am J Med 87 (1989): s47-51
  8. Harris JM "Drug interaction affecting theophylline clearance." J Pediatr 116 (1990): 838-9
  9. Takagi K, Hasegawa T, Ogura Y, et al. "Comparative studies on interaction between theophylline and quinolones." J Asthma 25 (1988): 63-70
  10. Rogge MC, Solomon WR, Sedman AJ, et al. "The theophylline-enoxacin interaction. I: effect of enoxacin dose size on theophylline disposition." Clin Pharmacol Ther 44 (1988): 579-87
  11. Takagi K, Hasegawa T, Yamaki K, et al. "Interaction between theophylline and enoxacin." Int J Clin Pharmacol Ther Toxicol 26 (1988): 288-92
  12. Beckmann J, Elsaber W, Gundert-Remy U, Hertrampf R "Enoxacin: a potent inhibitor of theophylline metabolism." Eur J Clin Pharmacol 33 (1987): 227-30
  13. Wijnands WJ, Van Herwaarden CL "Enoxacin raises plasma theophylline concentrations." Lancet 2 (1984): 108-9
  14. Wijnands WJ, Vree TB, van Herwaarden CL "Enoxacin decreases the clearance of theophylline in man." Br J Clin Pharmacol 20 (1985): 583-8
  15. Sana M, Kawakatsu K, Ohkita C, et al. "Effects of enoxacin, ofloxacin and norfloxacin on theophylline disposition in humans." Eur J Clin Pharmacol 35 (1988): 161-5
  16. Sijnands WJ, Vree TB, Baars AM, Van Herwaarden CL "Steady-state kinetics of the quinolone derivatives ofloxacin, enoxacin, ciprofloxacin and pefloxacin during maintenance treatment with theopylline." Drugs 34 (1987): 159-69
  17. Upton RA "Pharmacokinetic interactions between theophylline and other medication (Part I)." Clin Pharmacokinet 20 (1991): 66-80
  18. Limbird LE eds., Gilman AG, Hardman JG "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill (1995):
View all 18 references

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Drug and food interactions

Moderate

theophylline food

Applies to: TheoCap (theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

ADJUST DOSING INTERVAL: Administration of theophylline with continuous enteral nutrition may reduce the serum levels or the rate of absorption of theophylline. The mechanism has not been reported. In one case, theophylline levels decreased by 53% in a patient receiving continuous nasogastric tube feedings and occurred with both theophylline tablet and liquid formulations, but not with intravenous aminophylline.

MANAGEMENT: When administered to patients receiving continuous enteral nutrition , some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of theophylline is given; rapid-release formulations are preferable, and theophylline levels should be monitored.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8
  3. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67

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Moderate

enoxacin food

Applies to: enoxacin

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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Moderate

enoxacin food

Applies to: enoxacin

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

  1. Polk RE "Drug-drug interactions with ciprofloxacin and other fluoroquinolones." Am J Med 87 (1989): s76-81
  2. Healy DP, Polk RE, Kanawati L, Rock DT, Mooney ML "Interaction between oral ciprofloxacin and caffeine in normal volunteers." Antimicrob Agents Chemother 33 (1989): 474-8
  3. Harder S, Fuhr U, Staib AH, Wolf T "Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations." Am J Med 87 (1989): 89-91
  4. Carbo ML, Segura J, De la Torre R, et al. "Effect of quinolones on caffeine disposition." Clin Pharmacol Ther 45 (1989): 234-40
  5. "Product Information. Penetrax (enoxacin)." Rhone-Poulenc Rorer, Collegeville, PA. (1993):
  6. Mahr G, Sorgel F, Granneman GR, et al. "Effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine." Clin Pharmacokinet 22 (1992): 90-7
  7. "Product Information. Cipro (ciprofloxacin)." Bayer PROD (2002):
  8. "Product Information. Noroxin (norfloxacin)." Merck & Co., Inc PROD (2001):
  9. Staib AH, Stille W, Dietlein G, et al. "Interaction between quinolones and caffeine." Drugs 34 Suppl 1 (1987): 170-4
  10. Stille W, Harder S, Micke S, et al. "Decrease of caffeine elimination in man during co-administration of 4-quinolones." J Antimicrob Chemother 20 (1987): 729-34
  11. Harder S, Staib AH, Beer C, Papenburg A, Stille W, Shah PM "4-Quinolones inhibit biotransformation of caffeine." Eur J Clin Pharmacol 35 (1988): 651-6
  12. Nicolau DP, Nightingale CH, Tessier PR, et al. "The effect of fleroxacin and ciprofloxacin on the pharmacokinetics of multiple dose caffeine." Drugs 49 Suppl 2 (1995): 357-9
  13. "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome PROD (2001):
  14. Carrillo JA, Benitez J "Clinically significant pharmacokinetic interactions between dietary caffeine and medications." Clin Pharmacokinet 39 (2000): 127-53
  15. Fuhr U, Wolff T, Harder S, Schymanski P, Staib AH "Quinolone inhibition of cytochrome P-450 dependent caffeine metabolism in human liver microsomes." Drug Metab Dispos 18 (1990): 1005-10
  16. Kinzig-Schippers M, Fuhr U, Zaigler M, et al. "Interaction of pefloxacin and enoxacin with the human cytochrome P450 enzyme CYP1A2." Clin Pharmacol Ther 65 (1999): 262-74
  17. Healy DP, Schoenle JR, Stotka J, Polk RE "Lack of interaction between lomefloxacin and caffeine in normal volunteers." Antimicrob Agents Chemother 35 (1991): 660-4
View all 17 references

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Moderate

theophylline food

Applies to: TheoCap (theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8

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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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