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Drug Interactions between ofloxacin and Proben-C

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

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Interactions between your drugs

Minor

probenecid ofloxacin

Applies to: Proben-C (colchicine / probenecid) and ofloxacin

Probenecid has been shown to interfere with the urinary excretion of certain quinolone antibiotics, resulting in increased plasma quinolone concentrations in some cases. The clinical relevance of this interaction is unknown but may be greater for quinolones that undergo significant tubular secretion via the renal anion transporter system such as cinoxacin, ciprofloxacin, enoxacin, gemifloxacin, nalidixic acid, and norfloxacin. In one study, serum levels of cinoxacin reportedly doubled in the presence of probenecid, while urinary recovery in a 7-hour period was reduced by 32%. In another study (n=12), mean systemic exposure (AUC) of a 200 mg IV dose of ciprofloxacin increased by 75% and renal clearance decreased by 64% following pretreatment with multiple-dose probenecid. Likewise, probenecid has been found to reduce renal clearance of enoxacin and gemifloxacin by approximately 50%. Another study reported a threefold increase in the peak serum nalidixic acid level of two volunteers 8 hours following coadministration of a 500 mg dose of nalidixic acid and a 500 mg dose of probenecid. Also, a 1 gram dose of probenecid reduced the 12-hour urinary recovery of a single 200 mg dose of norfloxacin by about one-half in five study subjects, although serum concentrations were not significantly changed. In contrast, probenecid appears to have no clinically significant effect on the pharmacokinetics of moxifloxacin, ofloxacin, or sparfloxacin. In general, no precautions appear to be necessary during coadministration of most quinolones and probenecid. However, in the treatment of urinary tract infections, clinicians should consider the possibility of reduced antibacterial efficacy due to decreased quinolone excretion into the urine.

References

  1. Wijnands WJ, Vree TB, Baars AM, van Herwaarden CL "Pharmacokinetics of enoxacin and its penetration into bronchial secretions and lung tissue." J Antimicrob Chemother 21 (1988): 67-77
  2. Shimada J, Yamaji T, Ueda Y, Uchida H, Kusajma H, Irikura T "Mechanism of renal excretion of AM-715, a new quinolonecarboxylic acid derivative, in rabbits, dogs, and humans." Antimicrob Agents Chemother 23 (1983): 1-7
  3. Weidekamm E, Portmann R, Suter K, et al. "Single- and multiple-dose pharmacokinetics of fleroxacin, a trifluorinated quinolone, in humans." Antimicrob Agents Chemother 31 (1987): 1909-14
  4. Rodriguez N, Madsen PO, Welling PG "Influence of probenecid on serum levels and urinary excretion of cinoxacin." Antimicrob Agents Chemother 15 (1979): 465-9
  5. "Product Information. Noroxin (norfloxacin)." Merck & Co., Inc PROD (2001):
  6. Dash H, Mills J "Letter: Severe metabolic acidosis associated with nalidixic acid overdose." Ann Intern Med 84 (1976): 570-1
  7. Jaehde U, Sorgel F, Reiter A, Sigl G, Naber KG, Schunack W "Effect of probenecid on the distribution and elimination of ciprofloxacin in humans." Clin Pharmacol Ther 58 (1995): 532-41
  8. Shimada J, Nogita T, Ishibashi Y "Clinical pharmacokinetics of sparfloxacin." Clin Pharmacokinet 25 (1993): 358-69
  9. Nataraj B, Mamidi NVSR, Krishna DR "Probenecid affects the pharmacokinetics of ofloxacin in healthy volunteers." Clin Drug Invest 16 (1998): 259-62
  10. Stass H, Sachse R "Effect of probenecid on the kinetics of a single oral 400mg dose of moxifloxacin in healthy male volunteers." Clin Pharmacokinet 40 Suppl 1 (2001): 71-6
  11. "Product Information. Factive (gemifloxacin)." *GeneSoft Inc (2003):
View all 11 references

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Drug and food interactions

Major

colchicine food

Applies to: Proben-C (colchicine / probenecid)

GENERALLY AVOID: Coadministration with grapefruit juice may increase the serum concentrations of colchicine. Clinical toxicity including myopathy, neuropathy, multiorgan failure, and pancytopenia may occur. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism and P-glycoprotein efflux in the gut wall by certain compounds present in grapefruits. A published case report describes an eight-year-old patient with familial Mediterranean fever who developed acute clinical colchicine intoxication after ingesting approximately one liter of grapefruit juice per day for two months prior to hospital admission while being treated with colchicine 2 mg/day. Her condition progressed to circulatory shock and multiorgan failure, but she recovered with supportive therapy after 24 days in the hospital. In a study of 21 healthy volunteers, administration of 240 mL grapefruit juice twice a day for 4 days was found to have no significant effect on the pharmacokinetics of a single 0.6 mg dose of colchicine. However, significant interactions have been reported with other CYP450 3A4 inhibitors such as clarithromycin, diltiazem, erythromycin, ketoconazole, ritonavir, and verapamil.

MANAGEMENT: Patients treated with colchicine should be advised to avoid the consumption of grapefruit and grapefruit juice, and to contact their physician if they experience symptoms of colchicine toxicity such as abdominal pain, nausea, vomiting, diarrhea, fatigue, myalgia, asthenia, hyporeflexia, paresthesia, and numbness.

References

  1. Pettinger WA "Clonidine, a new antihypertensive drug." N Engl J Med 293 (1975): 1179-80
  2. Caraco Y, Putterman C, Rahamimov R, Ben-Chetrit E "Acute colchicine intoxication: possible role of erythromycin administration." J Rheumatol 19 (1992): 494-6
  3. Schiff D, Drislane FW "Rapid-onset colchicine myoneuropathy." Arthritis Rheum 35 (1992): 1535-6
  4. Putterman C, Ben-Chetrit E, Caraco Y, Levy M "Colchicine intoxication: clinical pharmacology, risk factors, features, and management." Semin Arthritis Rheum 21 (1991): 143-55
  5. Boomershine KH "Colchicine-induced rhabdomyolysis." Ann Pharmacother 36 (2002): 824-6
  6. "Severe colchicine-macrolide interactions." Prescrire Int 12 (2003): 18-9
  7. Tateishi T, Soucek P, Caraco Y, Guengerich FP, Wood AJ "Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation." Biochem Pharmacol 53 (1996): 111-6
  8. Dogukan A, Oymak FS, Taskapan H, Guven M, Tokgoz B, Utas C "Acute fatal colchicine intoxication in a patient on continuous ambulatory peritoneal dialysis (CAPD). Possible role of clarithromycin administration." Clin Nephrol 55 (2001): 181-2
  9. Rollot F, Pajot O, Chauvelot-Moachon L, Nazal EM, Kelaidi C, Blanche P "Acute colchicine intoxication during clarithromycin administration." Ann Pharmacother 38 (2004): 2074-7
  10. Wilbur K, Makowsky M "Colchicine myotoxicity: case reports and literature review." Pharmacotherapy 24 (2004): 1784-92
  11. Hung IF, Wu AK, Cheng VC, et al. "Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study." Clin Infect Dis 41 (2005): 291-300
  12. Cheng VC, Ho PL, Yuen KY "Two probable cases of serious drug interaction between clarithromycin and colchicine." South Med J 98 (2005): 811-3
  13. Akdag I, Ersoy A, Kahvecioglu S, Gullulu M, Dilek K "Acute colchicine intoxication during clarithromycin administration in patients with chronic renal failure." J Nephrol 19 (2006): 515-7
  14. van der Velden W, Huussen J, Ter Laak H, de Sevaux R "Colchicine-induced neuromyopathy in a patient with chronic renal failure: the role of clarithromycin." Neth J Med 66 (2008): 204-6
  15. Goldbart A, Press J, Sofer S, Kapelushnik J "Near fatal acute colchicine intoxication in a child. A case report." Eur J Pediatr 159 (2000): 895-7
  16. "Colchicine: serious interactions." Prescrire Int 17 (2008): 151-3
  17. "Product Information. Colcrys (colchicine)." AR Scientific Inc (2009):
  18. Dahan A, Amidon GL "Grapefruit juice and its constitueants augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoprotein." Pharm Res 26 (2009): 883-92
  19. McKinnell J, Tayek JA "Short term treatment with clarithromycin resulting in colchicine-induced rhabdomyolysis." J Clin Rheumatol 15 (2009): 303-5
View all 19 references

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

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