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Drug Interactions between Proben-C and Vantin

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

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Interactions between your drugs

Moderate

probenecid cefpodoxime

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

MONITOR: Coadministration with probenecid may increase and prolong the serum concentrations of some cephalosporins. The proposed mechanism is competitive inhibition of renal tubular secretion by probenecid, although data suggest other mechanisms may also be involved. The magnitude of interaction appears to be dependent on the dose and timing of administration of probenecid, with greater pharmacokinetic changes reported when larger doses of probenecid are used and when probenecid is administered with or immediately before cephalosporin administration. Increases of 30% to more than 100% in systemic exposure and half-life, and decreases of approximately 30% to 60% in clearance, have been reported for various cephalosporins studied.

MANAGEMENT: Although probenecid has been used therapeutically to enhance serum levels of various beta-lactam antibiotics, the potential for increased adverse effects should be considered when probenecid is added to existing cephalosporin therapy, particularly when the latter is given at high dosages or to patients who are elderly or have renal dysfunction. Adjustment of the cephalosporin dosage may be required in accordance with the individual product labeling. For example, cefotaxime dosage should generally not exceed 6 grams/day when administered with probenecid. Probenecid reportedly does not affect the elimination of ceftazidime or ceftriaxone.

References

  1. Pitkin D, Dubb J, Actor P, et al. "Kinetics and renal handling of cefonicid." Clin Pharmacol Ther 30 (1981): 587-93
  2. Luthy R, Blaser J, Bonetti A, Simmen H, Wise R, Siegenthaler W "Comparative multiple-dose pharmacokinetics of cefotaxime, moxalactam, and ceftazidime." Antimicrob Agents Chemother 20 (1981): 567-75
  3. Kercsmar CM, Stern RC, Reed MD, et al. "Ceftazidime in cystic fibrosis: pharmacokinetics and therapeutic response." J Antimicrob Chemother 12 (1983): 289-95
  4. Vlasses PH, Holbrook AM, Schrogie JJ, Rogers JD, Ferguson RK, Abrams WB "Effect of orally administered probenecid on the pharmacokinetics of cefoxitin." Antimicrob Agents Chemother 17 (1980): 847-55
  5. Reeves DS, Bullock DW, Bywater MJ, Holt HA, White LO, Thornhill DP "The effect of probenecid on the pharmacokinetics and distribution of cefoxitin in healthy volunteers." Br J Clin Pharmacol 11 (1981): 353-9
  6. LeBel M, Paone RP, Lewis GP "Effect of probenecid on the pharmacokinetics of ceftizoxime." J Antimicrob Chemother 12 (1983): 147-55
  7. Stoeckel K, Trueb V, Dubach UC, McNamara PJ "Effect of probenecid on the elimination and protein binding of ceftriaxone." Eur J Clin Pharmacol 34 (1988): 151-6
  8. Ko H, Cathcart KS, Griffith DL, Peters GR, Adams WJ "Pharmacokinetics of intravenously administered cefmetazole and cefoxitin and effects of probenecid on cefmetazole elimination." Antimicrob Agents Chemother 33 (1989): 356-61
  9. Santoro J, Agarwal BN, Martinelli R, et al. "Pharmacology of cefaclor in normal volunteers and patients with renal failure." Antimicrob Agents Chemother 13 (1978): 951-4
  10. Welling PG, Dean S, Selen A, et al. "Probenecid: an unexplained effect on cephalosporin pharmacology." Br J Clin Pharmacol 8 (1979): 491-5
  11. Marino EL, Dominguez-Gil A "The pharmacokinetics of cefadroxil associated with probenecid." Int J Clin Pharmacol Ther Toxicol 19 (1981): 506-8
  12. Mischler TW, Sugerman AA, Willard DA, et al. "Influence of probenecid and food on the bioavailability of cephradine in normal male subjects." J Clin Pharmacol 14 (1974): 604-11
  13. Shukla UA, Pittman KA, Barbhaiya RH "Pharmacokinetic interactions of cefprozil with food, propantheline, metoclopramide, and probenecid in healthy volunteers." J Clin Pharmacol 32 (1992): 725-31
  14. Ings RM, Reeves DS, White LO, et al. "The human pharmacokinetics of cefotaxime and its metabolites and the role of renal tubular secretion on their elimination." J Pharmacokinet Biopharm 13 (1985): 121-42
  15. Griffith RS, Black HR, Brier GL, Wolny JD "Effect of probenecid on the blood levels and urinary excretion of cefamandole." Antimicrob Agents Chemother 11 (1977): 809-12
  16. Meister F, et al. "Reduction of ceftizoxime dosing interval by coadministration of probenecid." Clin Pharmacol Ther 39 (1986): 210
  17. "Product Information. Vantin (cefpodoxime)." Pharmacia and Upjohn PROD
  18. Ko H, Cathcart KS, Peters GR, Griffith DL, Adams WJ "Comparative single dose pharmacokinetics of cefmetazole and cefoxitin and the effects of probenecid on cefmetazole disposition in humans." Pharm Res 5 (1988): s152
  19. "Product Information. Fortaz (ceftazidime)." Glaxo Wellcome PROD (2002):
  20. "Product Information. Tazicef (ceftazidime)." SmithKline Beecham PROD (2002):
  21. "Product Information. Rocephin (ceftriaxone)." Roche Laboratories PROD (2002):
  22. "Product Information. Ceftin (cefuroxime)." Glaxo Wellcome PROD (2002):
  23. Brown GR "Cephalosporin-probenecid drug interactions." Clin Pharmacokinet 24 (1993): 289-300
  24. Brown G, Zemcov SJ, Clarke AM "Effect of probenecid on cefazolin serum concentrations." J Antimicrob Chemother 31 (1993): 1009-11
  25. Nooyen SM, Overbeek BP, Delariviere AB, Storm AJ, Langemeyer JJ "Prospective randomised comparison of single-dose versus multiple-dose cefuroxime for prophylaxis in coronary artery bypass grafting." Eur J Clin Microbiol Infect Dis 13 (1994): 1033-7
  26. "Product Information. Omnicef (cefdinir)." Parke-Davis PROD (2001):
  27. Garton AM, Rennie RP, Gilpin J, Marrelli M, Shafran SD "Comparison of dose doubling with probenecid for sustaining serum cefuroxime levels." J Antimicrob Chemother 40 (1997): 903-6
  28. Spina SP, Dillon EC "Effect of chronic probenecid therapy on cefazolin serum concentrations." Ann Pharmacother 37 (2003): 621-4
View all 28 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

cefpodoxime food

Applies to: Vantin (cefpodoxime)

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of cefpodoxime proxetil tablets. Following a 200 mg dose taken with food, the extent of absorption (mean AUC) was 21% to 33% higher and the mean peak plasma concentration (Cmax) 19% higher than under fasting conditions. Time to peak concentration (Tmax) was not significantly different between fed and fasted states. On the contrary, when a 200 mg dose of the suspension was taken with food, the mean AUC and Cmax were not significantly different than those under fasting conditions, although the rate of absorption was slower with food (48% increase in Tmax ).

MANAGEMENT: To ensure maximal oral absorption, cefpodoxime proxetil tablets should be administered with or immediately after a meal.

References

  1. Hughes GS, Heald DL, Barker KB, et al. "The effects of gastric pH and food on the pharmacokinetics of a new oral cephalosporin, cefpodoxime proxetil." Clin Pharmacol Ther 46 (1989): 674-85
  2. "Product Information. Vantin (cefpodoxime)." Pharmacia and Upjohn PROD
  3. Borin MT, Driver MR, Forbes KK "Effect of timing of food on absorption of cefpodoxime proxetil." J Clin Pharmacol 35 (1995): 505-9

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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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