Skip to main content

Drug Interactions between Cinobac and colchicine / probenecid

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

Edit list (add/remove drugs)

Interactions between your drugs

Minor

probenecid cinoxacin

Applies to: colchicine / probenecid and Cinobac (cinoxacin)

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

Switch to consumer interaction data

Drug and food interactions

Major

colchicine food

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

Switch to consumer interaction data

Moderate

cinoxacin food

Applies to: Cinobac (cinoxacin)

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 (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.
View all 32 references

Switch to consumer interaction data

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

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer