Uricosuric / antibiotic adjuvant (tubular secretion blocker)
Probenecid is a uricosuric drug used in gout to lower blood uric acid levels by increasing its elimination in the urine. It is also used as an adjuvant to certain antibiotics (penicillins and others), as it delays their elimination and prolongs blood levels, increasing antibiotic efficacy.
Also known as: Probenecida, Benemid
Cephalexin + probenecid: probenecid inhibits cephalexin tubular secretion — combination not recommended.
The FDA cephalexin label explicitly documents: "Probenecid - The renal excretion of cephalexin is inhibited by probenecid. Co-administration of probenecid with cephalexin is not recommended" (section 7.2). Probenecid blocks the renal tubular secretion of beta-lactams, raising and prolonging serum cephalexin concentrations — historically used to prolong penicillin levels, but increasing the risk of dose-dependent adverse effects (neurotoxicity, diarrhoea, skin reactions). In the elderly and renally impaired, the risk of neurotoxicity (confusion, myoclonus) is higher. The practical guidance is to avoid the combination; if probenecid is essential (e.g., as a uricosuric in a patient with infection), consider reducing the cephalexin dose or extending the interval and monitor for signs of toxicity.
Cephalexin + probenecid: probenecid inhibits cephalexin tubular secretion — combination not recommended.
The FDA cephalexin label documents: "Probenecid - The renal excretion of cephalexin is inhibited by probenecid. Co-administration of probenecid with cephalexin is not recommended" (7.2). Probenecid blocks the renal tubular secretion of beta-lactams, raising and prolonging serum cephalexin concentrations (risk of dose-dependent toxicity/adverse effects).
Monitor for signs of toxicity (neurotoxicity, diarrhoea, skin reactions) if the combination is used.
Neurotoxicity (confusion, myoclonus) or increased adverse effects with the combination.
Avoid the combination; if probenecid is essential, consider reducing the cephalexin dose or extending the interval.
DailyMed/FDA (NIH/NLM) — approved Cephalexin label (PREFERRED PHARMACEUTICALS), section 7.2: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=553485f8-890d-4929-a6bb-905221cf411d ; approved Probenecid label (MARLEX): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d552de5-2d18-4464-bcaf-0311fa3f080d
Cefazolin + probenecid: probenecid decreases cefazolin tubular secretion — combination not recommended.
The FDA cefazolin label documents: "Probenecid may decrease renal tubular secretion of cephalosporins when used concurrently, resulting in increased and more prolonged cephalosporin blood levels. Co-administration of probenecid with Cefazolin is not recommended" (section 7). The mechanism is identical to other cephalosporins — probenecid blockade of renal tubular secretion, raising serum cefazolin concentrations. The combination has no therapeutic benefit in current practice (unlike the historical use as a penicillin adjuvant) and increases the risk of dose-dependent adverse effects. The practical guidance is to avoid the combination; if unavoidable, consider reducing the cefazolin dose and monitor for signs of toxicity, especially in the renally impaired.
Cefazolin + probenecid: probenecid decreases cefazolin tubular secretion — combination not recommended.
The FDA cefazolin label documents: "Probenecid may decrease renal tubular secretion of cephalosporins when used concurrently, resulting in increased and more prolonged cephalosporin blood levels. Co-administration of probenecid with Cefazolin is not recommended" (7). The mechanism is identical to other cephalosporins — blockade of renal tubular secretion.
Monitor for signs of toxicity if the combination is used.
Increased adverse effects or neurotoxicity with the combination.
Avoid the combination; if probenecid is essential, consider reducing the cefazolin dose.
DailyMed/FDA (NIH/NLM) — approved Cefazolin label (MEDICAL PURCHASING SOLUTIONS), section 7: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=79787707-c84f-f229-e053-2a91aa0a1f16 ; approved Probenecid label (MARLEX): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d552de5-2d18-4464-bcaf-0311fa3f080d
Cefotaxime + probenecid: probenecid inhibits cephalosporin tubular secretion — raises serum concentrations.
The Prontuário Terapêutico documents in the cephalosporin introduction (1.1.2): "Probenecid competitively inhibits the tubular secretion of most cephalosporins, causing a significant increase in their serum concentrations". Cefotaxime is excreted by renal tubular secretion, so probenecid raises and prolongs its plasma concentrations. Although the combination was historically used to prolong antibiotic levels, it is not recommended in current practice — the increased exposure may potentiate dose-dependent adverse effects, including neurotoxicity in the elderly and renally impaired. The practical guidance is to avoid the combination; if probenecid is essential, consider reducing the cefotaxime dose and monitor for signs of toxicity.
Cefotaxime + probenecid: probenecid inhibits cephalosporin tubular secretion — raises serum concentrations.
The Prontuário Terapêutico documents in the cephalosporin introduction (1.1.2): "Probenecid competitively inhibits the tubular secretion of most cephalosporins, causing a significant increase in their serum concentrations". Cefotaxime is excreted by tubular secretion — probenecid raises and prolongs its concentrations.
Monitor for signs of toxicity if the combination is used.
Increased adverse effects or neurotoxicity with the combination.
Avoid the combination; if probenecid is essential, consider reducing the cefotaxime dose.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Cephalosporins, 1.1.2 ; approved Probenecid label (MARLEX): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d552de5-2d18-4464-bcaf-0311fa3f080d
Cefuroxime + probenecid: probenecid increases systemic exposure to cefuroxime — combination not recommended.
The FDA cefuroxime label documents: "Co-administration with probenecid increases systemic exposure to cefuroxime axetil tablets and is therefore not recommended" (section 7.3). Probenecid blocks the renal tubular secretion of cefuroxime, raising its serum concentrations and prolonging exposure. Although the combination was historically explored to prolong antibiotic levels, it is not recommended in current practice — the increased exposure may potentiate dose-dependent adverse effects (neurotoxicity, diarrhoea, skin reactions). The practical guidance is to avoid the combination; if probenecid is essential (e.g., uricosuric in a gout patient with infection), consider reducing the cefuroxime dose and monitor for signs of toxicity.
Cefuroxime + probenecid: probenecid increases systemic exposure to cefuroxime — combination not recommended.
The FDA cefuroxime label documents: "Co-administration with probenecid increases systemic exposure to cefuroxime axetil tablets and is therefore not recommended" (7.3). Probenecid blocks cefuroxime tubular secretion, raising its serum concentrations.
Monitor for signs of toxicity if the combination is used.
Increased adverse effects or neurotoxicity with the combination.
Avoid the combination; if probenecid is essential, consider reducing the cefuroxime dose.
DailyMed/FDA (NIH/NLM) — approved Cefuroxime axetil label (WOCKHARDT), section 7.3: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=708b7a4d-ba1f-47b5-be4d-a01c2a7017ff ; approved Probenecid label (MARLEX): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d552de5-2d18-4464-bcaf-0311fa3f080d
Pyrazinamide + probenecid: pyrazinamide antagonises the uricosuric effect of probenecid.
The Prontuário Terapêutico documents in the pyrazinamide monograph (1.1.12): "Pyrazinamide antagonises the effects of probenecid and sulfinpyrazone". Pyrazinamide reduces renal uric acid excretion (a well-known, dose-dependent hyperuricaemic effect), counteracting the uricosuric effect of probenecid — which depends on increased tubular urate excretion. The clinical consequence is loss of efficacy of uricosuric treatment in gout patients undergoing antituberculosis therapy. The practical guidance is to monitor serum uric acid and gout signs (acute joint pain) in patients treated with probenecid during pyrazinamide, and consider adjusting the uricosuric or an alternative during the tuberculosis regimen.
Pyrazinamide + probenecid: pyrazinamide antagonises the uricosuric effect of probenecid.
The Prontuário Terapêutico documents in the pyrazinamide monograph (1.1.12): "Pyrazinamide antagonises the effects of probenecid and sulfinpyrazone". Pyrazinamide reduces renal uric acid excretion (hyperuricaemia), counteracting the uricosuric effect of probenecid.
Watch for gout signs (acute joint pain) in gout patients treated with probenecid.
Gout flare or symptomatic hyperuricaemia with the combination.
Monitor uric acid in patients on uricosuric treatment during pyrazinamide therapy; consider adjustment.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Pyrazinamide, 1.1.12 ; approved Probenecid label (MARLEX): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d552de5-2d18-4464-bcaf-0311fa3f080d
Phenoxymethylpenicillin + probenecid: probenecid inhibits penicillin tubular secretion — raises serum concentrations.
The Prontuário Terapêutico documents in the phenoxymethylpenicillin monograph (1.1.1.1): "Probenecid competitively inhibits the tubular secretion of penicillins, causing a significant increase in their serum concentrations". Historically, probenecid was used as an adjuvant to prolong serum penicillin levels (including in syphilis and gonorrhoea treatment), but this practice is now reserved for specific indications and should not be done routinely. The raised concentrations may potentiate dose-dependent adverse effects of penicillins (neurotoxicity at high doses, more intense allergic reactions). The practical guidance is to avoid the combination routinely; if probenecid is used as an adjuvant for a specific indication, monitor for signs of toxicity and adjust the penicillin dose.
Phenoxymethylpenicillin + probenecid: probenecid inhibits penicillin tubular secretion — raises serum concentrations.
The Prontuário Terapêutico documents in the phenoxymethylpenicillin monograph (1.1.1.1): "Probenecid competitively inhibits the tubular secretion of penicillins, causing a significant increase in their serum concentrations". Historically probenecid was used as an adjuvant to prolong penicillin levels — today the combination is not routinely recommended.
Monitor for signs of toxicity if the combination is used.
Increased adverse effects with the combination.
Avoid routine combination; if probenecid is used as an adjuvant (e.g., specific indications), monitor for toxicity.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Phenoxymethylpenicillin, 1.1.1.1 ; approved Probenecid label (MARLEX): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d552de5-2d18-4464-bcaf-0311fa3f080d
No documented food or drink interactions.
FDA label (PRECAUTIONS): probenecid may not be effective in chronic renal insufficiency, particularly when GFR is ≤ 30 mL/min; because of its mechanism of action, it is not recommended in conjunction with a penicillin in the presence of known renal impairment. Uricosuric efficacy depends on renal tubular function.
Consider a therapeutic alternative in renal impairment (GFR ≤ 30 mL/min); assess the need for the combination with penicillins in the renal patient.
DailyMed/FDA (NIH/NLM) — approved Probenecid label, PRECAUTIONS section: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d552de5-2d18-4464-bcaf-0311fa3f080d
FDA label (CONTRAINDICATIONS): probenecid is not recommended in persons with known uric acid kidney stones. Uricosuria increases urinary uric acid excretion, which may precipitate crystallisation and stone formation in acidic urine.
Contraindicated in uric acid renal lithiasis; if used, alkalinise the urine and maintain liberal fluid intake.
DailyMed/FDA (NIH/NLM) — approved Probenecid label, CONTRAINDICATIONS section: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d552de5-2d18-4464-bcaf-0311fa3f080d
FDA label (PRECAUTIONS): "Use with caution in patients with a history of peptic ulcer." The mechanism is not fully clarified, but the caution is recorded in the label.
Use with caution in patients with a history of peptic ulcer; monitor gastrointestinal symptoms.
DailyMed/FDA (NIH/NLM) — approved Probenecid label, PRECAUTIONS section: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d552de5-2d18-4464-bcaf-0311fa3f080d
FDA label (Use in Pregnancy): "Probenecid crosses the placenta barrier and appears in cord blood. The use of any drug in women of childbearing potential requires that the anticipated benefit be weighed against the possible hazards." No adequate and well-controlled studies in pregnant women.
Crosses the placenta and appears in cord blood; use only if the anticipated benefit justifies the risk.
No label data on excretion in breast milk; the safety profile in breastfed infants is not established.
Weigh benefit/risk in women of childbearing potential (label does not require specific contraception).
DailyMed/FDA (NIH/NLM) — approved Probenecid label, WARNINGS section (Use in Pregnancy): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d552de5-2d18-4464-bcaf-0311fa3f080d
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Uricosuric: reduces tubular reabsorption of urate, increasing urinary uric acid excretion and lowering serum levels; effective uricosuria reduces the miscible urate pool and promotes resorption of urate deposits. Antibiotic adjuvant: inhibits tubular secretion of penicillins, raising plasma levels 2- to 4-fold (FDA label CLINICAL PHARMACOLOGY).
Renal tubular transport blocker: competitively inhibits tubular reabsorption of urate and tubular secretion of several compounds (penicillins, PAH, PAS, indomethacin, sulfonamides, sulfonylureas, among others), increasing their excretion or plasma levels.
The label does not quantify oral absorption; the drug is well absorbed orally (oral tablet use, 500 mg). Uricosuric efficacy requires preserved renal function.
The label does not detail metabolism; the drug and metabolites (including the acyl glucuronide) are eliminated renally, with tubular reabsorption — excretion is dependent on renal function (ineffective with GFR ≤ 30 mL/min).
The label does not document probenecid half-life; it records that probenecid increases the mean plasma elimination half-life of several drugs (indomethacin, acetaminophen, naproxen, ketoprofen, lorazepam, rifampin) by inhibiting renal transport.
