Probenecid
Probenecid is a generic medication for the drug :
Probenecid medication comes in several different strengths; click on the strength you need to view prices from pharmacies competing to earn your business.
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Probenecid 500 mg
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Probenecid/Colchicine 500mg/0.5mg
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Drug Interactions
Probenecid
Drug-Drug Interactions
| Interacting Drug | Effect | Clinical Comment |
|---|---|---|
| Acetaminophen | Decreased clearance of acetaminophen. | Clinical significance not known. Avoid use of high doses of acetaminophen during treatment with probenecid. |
| Acyclovir | Increased serum levels of acyclovir probably due to decreased renal excretion. Valacyclovir is a prodrug of acyclovir. | Not of clinical significance because of the wide therapeutic index of acyclovir. |
| Allopurinol | Probenecid increases renal excretion of oxypurinol, the active metabolite of allopurinol. Allopurinol decreases metabolism of probenecid. | Not clinically significant. Has not been reported to increase precipitation of uric acid. |
| Aminosalicylates | Serum levels of aminosalicylic acid are increased two- to four-fold by probenecid. | Avoid use of probenecid if possible. If the combination is used, consider adjusting the dose of the aminosalicylate and monitor the patient for signs of toxicity. |
| Benzodiazepines (i.e., lorazepam, midazolam) | Probenecid decreases clearance and prolongs the elimination half-life of lorazepam. The onset of midazolam-induced “sleep” is faster in the presence of probenecid. | Consider reducing the dose of the benzodiazepine. Warn patients about, and/or monitor for the signs of benzodiazepine excess including rapid onset, pronounced sedation. Patients receiving probenecid may require lower doses of midazolam to induce anesthesia. |
| Captopril | Probenecid decreases renal clearance of captopril. | Unknown if interaction occurs with other angiotensin converting enzyme inhibitors. Monitor patients for signs of increased hypotensive effects. |
| Cephalosporin antibiotics | Probenecid increases the serum levels of many cephalosporin antibiotics by inhibiting urinary excretion. | Generally not of clinical significance. The interaction between probenecid and cefazolin, and probenecid and cefoxitin are exploited in order to reduce the frequency of administration of cefazolin (see CPhA monographs, Cefazolin and Cefoxitin). |
| Chlorpropamide | Probenecid increases the elimination half-life of chlorpropamide. | Monitor blood sugar levels in patients receiving probenecid and chlorpropamide and adjust the dose of chlorpropamide if necessary. |
| Dapsone | Probenecid reduces urinary excretion of dapsone and its metabolites resulting in a marked increase in the serum levels of dapsone. | Clinical significance unknown. Monitor patients for signs and symptoms of hematologic toxicity associated with dapsone. |
| Famotidine | Serum levels of famotidine are increased when administered with probenecid. | Unlikely to be of clinical significance |
| Fexofenadine | Probenecid significantly decreases renal clearance of fexofenadine. | Clinical significance unknown |
| Furosemide | Probenecid decreases renal clearance of furosemide but does not impair the diuretic effects of the drug. | Clinical significance unknown |
| Ganciclovir | Increased serum levels of ganciclovir probably due to decreased renal excretion. | Clinical significance uncertain. Monitor patients for adverse events of ganciclovir. |
| Heparin | Limited evidence suggests that probenecid may potentiate the anticoagulant effects of heparin. | Monitor aPTT and adjust the dose of heparin accordingly. Monitor patients for bleeding. |
| Morphine | Probenecid significantly decreased clearance of morphine-6-glucuronide, a pharmacologically active metabolite of morphine. | Patients receiving probenecid may require lower or less frequent doses of morphine. Monitor patients receiving the combination closely. |
| Mycophenolate mofetil | Probenecid inhibits renal tubular secretion of mycophenolic acid, a pharmacologically active metabolite of mycophenolate mofetil thereby increasing its plasma concentrations. | Monitor mycophenolate levels and monitor for signs and symptoms of mycophenolate toxicity, e.g., gastrointestinal intolerance, hematologic abnormalities such as neutropenia. Adjust the dose of mycophenolate, if necessary. |
| NSAIDs | Probenecid inhibits conjugation of ketoprofen and diflunisal and excretion of naproxen. The serum half life is prolonged and serum levels of ketorolac and tenoxicam increase when co-administered with probenecid. | Avoid concurrent use of ketorolac and probenecid. The clinical significance of other interactions is not established. |
| Nucleoside reverse transcriptase inhibitors (zalcitabine, zidovudine) | Retards elimination of zalcitabine and zidovudine. Probenecid is assumed to retard renal excretion of zalcitabine and to inhibit glucuronidation of zidovudine. | The combination of zalcitabine and probenecid is reported to be well tolerated. The incidence of zidovudine-related adverse events (rash, malaise, fever and myalgia) increases when the drug is co-administered with probenecid. Avoid use of probenecid in patients receiving zidovudine. If concurrent use cannot be avoided, monitor patients for adverse events of zidovudine. |
| Olanzapine | Probenecid significantly increases Cmax and AUC0-24h, without affecting clearance of olanzapine, presumably because of inhibition of UDP glucuronosyltransferase and a resulting decrease in the rate of glucuronidation. | Monitor patients for signs of olanzapine excess. |
| Oseltamivir | Probenecid completely blocks renal excretion of oseltamivir. Systemic exposure to oseltamivir increases by 2.5-fold. | Clinical significance unknown |
| Penicillins (e.g., amoxicillin, ampicillin, piperacillin, ticarcillin) | Probenecid inhibits renal tubular excretion of penicillins. | This interaction has been exploited to increase serum levels of penicillins. |
| Pramipexole | Probenecid reduces clearance of pramipexole by approximately one-third. | Clinical significance uncertain. Monitor patients receiving the combination for adverse events of pramipexole. |
| Pyrazinamide | Pyrazinamide inhibits renal excretion of uric acid. Pyrazinamide also reduces metabolism of probenecid and probenecid retards elimination of pyrazinamide. The net effect of these changes is a reduced uricosuric effect of probenecid. | Consider alternative antitubercular agents in patients with gout. If probenecid is used to treat pyrazinamide-induced hyperuricemia, higher dosages of probenecid may be required. |
| Quinolone antibacterial agents (ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin) | Probenecid reduces renal clearance of ciprofloxacin, levofloxacin, norfloxacin and ofloxacin, but not moxifloxacin. | Unlikely to be clinically significant |
| Salicylates including acetylsalicylic acid (ASA) | The uricosuric effects of salicylates, (with the exception of low dose ASA ≤325 mg/day) including high dose ASA, antagonize those of probenecid. | Avoid concurrent use of salicylates including high dose ASA in patients receiving probenecid (use an alternative if possible). Concurrent use of ASA 325 mg/day or less is compatible with probenecid. |
| Sulfinpyrazone | Probenecid inhibits renal tubular excretion of sulfinpyrazone with no changes in the uricosuric effect compared with administering either drug alone. | Clinical significance is unknown. Concomitant use for the treatment of gout is not recommended. |
| Thiopental | Probenecid prolongs the duration of thiopental-induced anesthesia, possibly because of competitive binding to albumin. | Reduced dosages of anesthetic may be required in patients receiving probenecid. |
| Valacyclovir | See Acyclovir. | See Acyclovir. |
OverviewProbenecid inhibits excretion of weak organic acids in the proximal and distal convoluted tubules, altering the pharmacokinetics of many drugs. It also inhibits glucuronidation of some drugs. Probenecid inhibits renal tubular excretion of many β-lactam antibacterial agents (e.g., cephalosporins and penicillins), an interaction that has been exploited clinically to maintain serum levels of the antibacterial agent, thereby reducing the frequency of administration. Probenecid does not alter serum levels of ceftriaxone or ceftazidime. Probenecid does not alter the pharmacokinetics of digoxin or theophylline. Dosage and AdministrationRecommended Dose and Dosage Adjustment
Adult Patients with Renal ImpairmentAvoid use of probenecid in patients with creatinine clearance <50 mL/min. As a uricosuric agent, the drug is ineffective in these individuals. Probenecid
AdministrationGastrointestinal adverse events may be minimized by taking probenecid with food or antacids. Maintain fluid intake to ensure urinary output of 2 to 3 L/day. Alkalinization of the urine, for example with sodium bicarbonate, during the first few days of therapy is desirable as it may prevent stone formation. Adverse ReactionsHepatic/Biliary/Pancreatichepatic necrosis. Genitourinaryformation of uric acid stones. Gastrointestinalanorexia, nausea, vomiting. Hematologicanemia, aplastic anemia, hemolytic anemia, leukopenia. Musculoskeletalacute gouty arthritis. Immuneanaphylaxis, hypersensitivity reactions. Neurologicheadache, dizziness. Adverse Drug Reactions OverviewThe most common adverse reactions associated with probenecid include headache, anorexia, nausea and vomiting. Initiating treatment with low doses and increasing the dose as tolerance develops is recommended. Dermatologicrash, dermatitis, pruritus, alopecia. Cardiovascularhypotension, flushing. Ear/Nose/Throatsore gums. Indications and Clinical UseProbenecid is indicated for:
Other Clinical Uses: Probenecid has a long history of use in combination with β-lactam antibacterial agents for the treatment of particular infectious diseases. Probenecid has no intrinsic clinically antibacterial properties; however, the drug retards renal excretion of many β-lactam antibacterial agents. When administered together the serum concentrations of the antibacterial agent are sustained and allow for decreased clearance. Currently, the combinations of probenecid plus β-lactam antibacterials are used as an inexpensive antibacterial regimen for outpatient treatment of certain infections:
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