Drug Interactions between loracarbef and Proben-C
This report displays the potential drug interactions for the following 2 drugs:
- loracarbef
- Proben-C (colchicine/probenecid)
Interactions between your drugs
probenecid loracarbef
Applies to: Proben-C (colchicine / probenecid) and loracarbef
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
- Pitkin D, Dubb J, Actor P, et al. (1981) "Kinetics and renal handling of cefonicid." Clin Pharmacol Ther, 30, p. 587-93
- Luthy R, Blaser J, Bonetti A, Simmen H, Wise R, Siegenthaler W (1981) "Comparative multiple-dose pharmacokinetics of cefotaxime, moxalactam, and ceftazidime." Antimicrob Agents Chemother, 20, p. 567-75
- Kercsmar CM, Stern RC, Reed MD, et al. (1983) "Ceftazidime in cystic fibrosis: pharmacokinetics and therapeutic response." J Antimicrob Chemother, 12, p. 289-95
- Vlasses PH, Holbrook AM, Schrogie JJ, Rogers JD, Ferguson RK, Abrams WB (1980) "Effect of orally administered probenecid on the pharmacokinetics of cefoxitin." Antimicrob Agents Chemother, 17, p. 847-55
- Reeves DS, Bullock DW, Bywater MJ, Holt HA, White LO, Thornhill DP (1981) "The effect of probenecid on the pharmacokinetics and distribution of cefoxitin in healthy volunteers." Br J Clin Pharmacol, 11, p. 353-9
- LeBel M, Paone RP, Lewis GP (1983) "Effect of probenecid on the pharmacokinetics of ceftizoxime." J Antimicrob Chemother, 12, p. 147-55
- Stoeckel K, Trueb V, Dubach UC, McNamara PJ (1988) "Effect of probenecid on the elimination and protein binding of ceftriaxone." Eur J Clin Pharmacol, 34, p. 151-6
- Ko H, Cathcart KS, Griffith DL, Peters GR, Adams WJ (1989) "Pharmacokinetics of intravenously administered cefmetazole and cefoxitin and effects of probenecid on cefmetazole elimination." Antimicrob Agents Chemother, 33, p. 356-61
- Santoro J, Agarwal BN, Martinelli R, et al. (1978) "Pharmacology of cefaclor in normal volunteers and patients with renal failure." Antimicrob Agents Chemother, 13, p. 951-4
- Welling PG, Dean S, Selen A, et al. (1979) "Probenecid: an unexplained effect on cephalosporin pharmacology." Br J Clin Pharmacol, 8, p. 491-5
- Marino EL, Dominguez-Gil A (1981) "The pharmacokinetics of cefadroxil associated with probenecid." Int J Clin Pharmacol Ther Toxicol, 19, p. 506-8
- Mischler TW, Sugerman AA, Willard DA, et al. (1974) "Influence of probenecid and food on the bioavailability of cephradine in normal male subjects." J Clin Pharmacol, 14, p. 604-11
- Shukla UA, Pittman KA, Barbhaiya RH (1992) "Pharmacokinetic interactions of cefprozil with food, propantheline, metoclopramide, and probenecid in healthy volunteers." J Clin Pharmacol, 32, p. 725-31
- Ings RM, Reeves DS, White LO, et al. (1985) "The human pharmacokinetics of cefotaxime and its metabolites and the role of renal tubular secretion on their elimination." J Pharmacokinet Biopharm, 13, p. 121-42
- Griffith RS, Black HR, Brier GL, Wolny JD (1977) "Effect of probenecid on the blood levels and urinary excretion of cefamandole." Antimicrob Agents Chemother, 11, p. 809-12
- Meister F, et al. (1986) "Reduction of ceftizoxime dosing interval by coadministration of probenecid." Clin Pharmacol Ther, 39, p. 210
- "Product Information. Vantin (cefpodoxime)." Pharmacia and Upjohn
- Ko H, Cathcart KS, Peters GR, Griffith DL, Adams WJ (1988) "Comparative single dose pharmacokinetics of cefmetazole and cefoxitin and the effects of probenecid on cefmetazole disposition in humans." Pharm Res, 5, s152
- (2002) "Product Information. Fortaz (ceftazidime)." Glaxo Wellcome
- (2002) "Product Information. Tazicef (ceftazidime)." SmithKline Beecham
- (2002) "Product Information. Rocephin (ceftriaxone)." Roche Laboratories
- (2002) "Product Information. Ceftin (cefuroxime)." Glaxo Wellcome
- Brown GR (1993) "Cephalosporin-probenecid drug interactions." Clin Pharmacokinet, 24, p. 289-300
- Brown G, Zemcov SJ, Clarke AM (1993) "Effect of probenecid on cefazolin serum concentrations." J Antimicrob Chemother, 31, p. 1009-11
- Nooyen SM, Overbeek BP, Delariviere AB, Storm AJ, Langemeyer JJ (1994) "Prospective randomised comparison of single-dose versus multiple-dose cefuroxime for prophylaxis in coronary artery bypass grafting." Eur J Clin Microbiol Infect Dis, 13, p. 1033-7
- (2001) "Product Information. Omnicef (cefdinir)." Parke-Davis
- Garton AM, Rennie RP, Gilpin J, Marrelli M, Shafran SD (1997) "Comparison of dose doubling with probenecid for sustaining serum cefuroxime levels." J Antimicrob Chemother, 40, p. 903-6
- Spina SP, Dillon EC (2003) "Effect of chronic probenecid therapy on cefazolin serum concentrations." Ann Pharmacother, 37, p. 621-4
Drug and food interactions
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
- Pettinger WA (1975) "Clonidine, a new antihypertensive drug." N Engl J Med, 293, p. 1179-80
- Caraco Y, Putterman C, Rahamimov R, Ben-Chetrit E (1992) "Acute colchicine intoxication: possible role of erythromycin administration." J Rheumatol, 19, p. 494-6
- Schiff D, Drislane FW (1992) "Rapid-onset colchicine myoneuropathy." Arthritis Rheum, 35, p. 1535-6
- 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
- Boomershine KH (2002) "Colchicine-induced rhabdomyolysis." Ann Pharmacother, 36, p. 824-6
- (2003) "Severe colchicine-macrolide interactions." Prescrire Int, 12, p. 18-9
- 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
- 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
- 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
- Wilbur K, Makowsky M (2004) "Colchicine myotoxicity: case reports and literature review." Pharmacotherapy, 24, p. 1784-92
- 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
- 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
- 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
- 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
- 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
- (2008) "Colchicine: serious interactions." Prescrire Int, 17, p. 151-3
- (2009) "Product Information. Colcrys (colchicine)." AR Scientific Inc
- 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
- McKinnell J, Tayek JA (2009) "Short term treatment with clarithromycin resulting in colchicine-induced rhabdomyolysis." J Clin Rheumatol, 15, p. 303-5
loracarbef food
Applies to: loracarbef
ADJUST DOSING INTERVAL: Loracarbef may exhibit reduced gastrointestinal absorption in the presence of food. When loracarbef capsules were administered with food, the peak plasma concentrations were 50% to 60% of concentrations after administration in a fasting state and were reached 30 to 60 minutes later. Area under the concentration-time curve (AUC) was not affected. The therapeutic effect of the antimicrobial may be reduced.
MANAGEMENT: Loracarbef should be administered at least one hour before or two hours after eating.
References
- (2002) "Product Information. Lorabid (loracarbef)." Lilly, Eli and Company
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
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
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