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Drug Interactions between Proben-C and Zosyn

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

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Interactions between your drugs

Moderate

probenecid tazobactam

Applies to: Proben-C (colchicine / probenecid) and Zosyn (piperacillin / tazobactam)

MONITOR: Coadministration with probenecid may increase and prolong the serum concentrations of tazobactam. The mechanism is competitive inhibition by probenecid of the renal tubular secretion of tazobactam via OAT1 and OAT3. A one gram oral dose of probenecid reduced the clearance of tazobactam (administered by injection in combination with piperacillin) by approximately 20% to 25% and prolonged its half-life by 71%. The peak plasma concentration was not affected.

MANAGEMENT: Although the clinical relevance of this interaction has not been established, caution may be advisable when probenecid must be used with tazobactam-containing preparations. The product labeling for piperacillin-tazobactam recommends avoiding concomitant use with probenecid unless the benefit outweighs the risk.

References

  1. "Product Information. Zosyn (piperacillin-tazobactam)." Lederle Laboratories PROD (2001):
  2. "Product Information. Zerbaxa (ceftolozane-tazobactam)." Cubist Pharmaceuticals Inc (2015):

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Minor

probenecid piperacillin

Applies to: Proben-C (colchicine / probenecid) and Zosyn (piperacillin / tazobactam)

Probenecid may increase the plasma concentrations and half-lives of penicillins. The mechanism is competitive inhibition by probenecid of the renal tubular secretion of penicillins. While this interaction is often exploited to enhance the antibacterial effect of penicillins, toxicity may occur and should be considered if high penicillin dosages are administered intravenously.

References

  1. Sommers DK, Schoeman HS "Drug interactions with urate excretion in man?" Eur J Clin Pharmacol 32 (1987): 499-502
  2. Waller ES, Sharanevych MA, Yakatan GJ "The effect of probenecid on nafcillin disposition." J Clin Pharmacol 22 (1982): 482-9
  3. Shanson DC, McNabb R, Hajipieris P "The effect of probenecid on serum amoxycillin concentrations up to 18 hours after a single 3g oral dose of amoxycillin: possible implications for preventing endocarditis." J Antimicrob Chemother 13 (1984): 629-32
  4. Sutherland R, Croydon EA, Rolinson GN "Amoxycillin: a new semi-synthetic penicillin." Br Med J 3 (1972): 13-6
  5. Allen MB, Fitzpatrick RW, Barratt A, Cole RB "The use of probenecid to increase the serum amoxycillin levels in patients with bronchiectasis." Respir Med 84 (1990): 143-6
  6. Gibaldi M, Schwartz MA "Apparent effect of probenecid on the distribution of penicillins in man." Clin Pharmacol Ther 9 (1968): 345-9
View all 6 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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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.

Further information

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