(1)probenecid increases levels of glyburide by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.glycerol phenylbutyrateMonitor Closely (1)probenecid, glycerol phenylbutyrate. decreasing renal clearance. Use Caution/Monitor. Probenecid may inhibit the renal excretion glycerol phenylbutyrate metabolites PAA and PAGN; caution when adjusting doses based on these metabolite levels.hydrochlorothiazideMonitor Closely (1)hydrochlorothiazide will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.hydroxyureaMonitor Closely (1)hydroxyurea increases levels of probenecid by Other (see comment). Use Caution/Monitor. Comment: Dosage adjustment of probenecid may be needed.ibuprofenMonitor Closely (1)ibuprofen will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.ibuprofen IVMonitor Closely (1)ibuprofen IV will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.imidaprilMinor (1)probenecid increases effects of imidapril by unspecified interaction mechanism. Minor/Significance Unknown.imipenem/cilastatinSerious - Use Alternative (1)probenecid increases levels of imipenem/cilastatin by decreasing renal clearance. Avoid or Use Alternate Drug. Coadministration increases the plasma level and half-life of imipenem.imipenem/cilastatin/relebactamSerious - Use Alternative (1)probenecid increases levels of imipenem/cilastatin/relebactam by decreasing renal clearance. Avoid or Use Alternate Drug. Coadministration increases the plasma level and half-life of imipenem.indapamideMonitor Closely (1)indapamide will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.indomethacinMonitor Closely (1)indomethacin will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.ketoprofenMonitor Closely (1)ketoprofen will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.ketorolacMonitor Closely (1)ketorolac will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (1)probenecid increases levels of ketorolac by decreasing renal clearance. Contraindicated.ketorolac intranasalMonitor Closely (1)ketorolac intranasal will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (1)probenecid increases levels of ketorolac intranasal by decreasing renal clearance. Contraindicated.lisinoprilMinor (1)probenecid increases effects of lisinopril by unspecified interaction mechanism. Minor/Significance Unknown.lornoxicamMonitor Closely (1)lornoxicam will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.mavacamtenMonitor Closely (1)probenecid will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose. meclofenamateMonitor Closely (1)meclofenamate will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.mefenamic acidMonitor Closely (1)mefenamic acid will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.meloxicamMonitor Closely (1)meloxicam will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.meropenemMonitor Closely (1)probenecid increases levels of meropenem by decreasing elimination. Use Caution/Monitor.meropenem/vaborbactamSerious - Use Alternative (1)probenecid increases levels of meropenem/vaborbactam by decreasing elimination. Avoid or Use Alternate Drug. Probenecid competes withe meropenem for active tubular secretion.mesalamineMonitor Closely (2)mesalamine will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor. mesalamine decreases effects of probenecid by unknown mechanism. Use Caution/Monitor.methohexitalMinor (1)probenecid increases levels of methohexital by unknown mechanism. Minor/Significance Unknown.methotrexateMonitor Closely (1)probenecid will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Methotrexate plasma levels, therapeutic effects, and toxicity may be enhanced. Monitor methotrexate concentrations and adjust dose accordingly.Serious - Use Alternative (1)probenecid increases levels of methotrexate by acidic (anionic) drug competition for renal tubular clearance. Avoid or Use Alternate Drug. If combination must be used, decrease methotrexate dose; also, methotrexate increases uric acid production and risk for uric acid neuropathy.methyclothiazideMonitor Closely (1)methyclothiazide will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.metolazoneMonitor Closely (1)metolazone will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.moexiprilMinor (1)probenecid increases effects of moexipril by unspecified interaction mechanism. Minor/Significance Unknown.mycophenolateMonitor Closely (1)probenecid increases levels of mycophenolate by decreasing renal clearance. Use Caution/Monitor. Probenecid may interfere with renal tubular secretion of mycophenolate active metabolites.nabumetoneMonitor Closely (1)nabumetone will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.nafcillinMonitor Closely (1)probenecid will increase the level or effect of nafcillin by decreasing renal clearance. Use Caution/Monitor.Serious - Use Alternative (1)nafcillin, probenecid. Either increases levels of the other by decreasing renal clearance. Avoid or Use Alternate Drug.naproxenMonitor Closely (1)naproxen will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.oseltamivirMonitor Closely (1)probenecid increases levels of oseltamivir by Other (see comment). Use Caution/Monitor. Comment: Coadministration of probenecid results in a 2-fold increase in exposure to oseltamivir carboxylate because of a decrease in active anionic tubular secretion in the kidney. No dosage adjustments are required with probenecid coadministration.oxaprozinMonitor Closely (1)oxaprozin will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.parecoxibMonitor Closely (1)parecoxib will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.penicillin G aqueousMonitor Closely (1)probenecid increases levels of penicillin G aqueous by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.penicillin VKMinor (1)probenecid will increase the level or effect of penicillin VK by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.perindoprilMinor (1)probenecid increases effects of perindopril by unspecified interaction mechanism. Minor/Significance Unknown.piperacillinMonitor Closely (1)probenecid will increase the level or effect of piperacillin by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.piroxicamMonitor Closely (1)piroxicam will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.pivmecillinamSerious - Use Alternative (1)pivmecillinam, probenecid. Either increases levels of the other by decreasing renal clearance. Avoid or Use Alternate Drug.pralatrexateMonitor Closely (1)probenecid increases levels of pralatrexate by decreasing renal clearance. Use Caution/Monitor.primaquineMinor (1)primaquine, probenecid. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hemolysis in G6PD deficient pts.pyrazinamideMonitor Closely (1)pyrazinamide decreases effects of probenecid by unknown mechanism. Use Caution/Monitor.quinaprilMinor (1)probenecid increases effects of quinapril by unspecified interaction mechanism. Minor/Significance Unknown.ramiprilMinor (1)probenecid increases effects of ramipril by unspecified interaction mechanism. Minor/Significance Unknown.rifampinMonitor Closely (1)probenecid will increase the level or effect of rifampin by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use with probenecid increase concentration of rifampin which may increase risk of toxicity; monitor for adverse reactions during coadministrationrose hipsMonitor Closely (1)rose hips will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.salicylates (non-asa)Monitor Closely (2)salicylates (non-asa) will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor. salicylates (non-asa) decreases effects of probenecid by unknown mechanism. Use Caution/Monitor.salsalateMonitor Closely (2)salsalate will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor. salsalate decreases effects of probenecid by unknown mechanism. Use Caution/Monitor.sodium phenylacetateMonitor Closely (1)probenecid increases levels of sodium phenylacetate by decreasing renal clearance. Use Caution/Monitor.sodium phenylbutyrateMonitor Closely (1)probenecid increases levels of sodium phenylbutyrate by decreasing renal clearance. Use Caution/Monitor.sulfadiazineMinor (1)probenecid increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.sulfamethoxazoleMinor (1)probenecid increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.sulfasalazineMonitor Closely (2)sulfasalazine will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor. sulfasalazine decreases effects of probenecid by unknown mechanism. Use Caution/Monitor.sulfisoxazoleMinor (1)probenecid increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.sulindacMonitor Closely (1)sulindac will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.temocillinSerious - Use Alternative (1)temocillin, probenecid. Either increases levels of the other by decreasing renal clearance. Avoid or Use Alternate Drug.tenofovir DFMonitor Closely (1)probenecid increases levels of tenofovir DF by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .ticarcillinSerious - Use Alternative (1)ticarcillin, probenecid. Either increases levels of the other by decreasing renal clearance. Avoid or Use Alternate Drug.tolazamideMonitor Closely (1)probenecid increases levels of tolazamide by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.tolbutamideMonitor Closely (1)probenecid increases levels of tolbutamide by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.tolfenamic acidMonitor Closely (1)tolfenamic acid will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.tolmetinMonitor Closely (1)tolmetin will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.trandolaprilMinor (1)probenecid increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.valacyclovirMinor (1)probenecid increases levels of valacyclovir by decreasing renal clearance. Minor/Significance Unknown.valganciclovirMonitor Closely (1)probenecid will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.willow barkMonitor Closely (2)willow bark will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor. willow bark decreases effects of probenecid by unknown mechanism. Use Caution/Monitor.zidovudineMonitor Closely (1)probenecid increases levels of zidovudine by decreasing metabolism. Use Caution/Monitor. 1-10% Headache Nausea Vomiting Loss of appetite GI upset Rash Flushing Dizziness Fever Aplastic anemia Hemolytic anemia Leukopenia Renal calculi Nephrotic syndrome (rare) Exacerbation of gout Gouty arthritis Hepatic necrosis (rare) Contraindications <2 years Uric acid kidney stones, acute gouty arthritis Hypersensitivity Blood dyscrasias Administration during gouty attack Small or large dose aspirin therapy Cautions Use caution in patients with G6PD deficiency; may increase risk for hemolytic anemia Use caution in patients with peptic ulcer disease Salicylates may reduce the therapeutic effects of probenecid (effect may be pronounced with high chronic doses May cause exacerbation of acute gouty attack; in such cases colchicine or other appropriate therapy is advisable May increase serum concentration of methotrexate; if probenecid is given with methotrexate, reduce dosage of methotrexate and monitor serum levels Hematuria, renal colic, costovertebral pain, and formation of uric acid stones associated with use of probenecid in gouty patients may be prevented by alkalization of the urine and a liberal fluid intake; in these cases when alkali is administered, the acid-base balance of the patient should be watched Rarely, severe allergic reactions and anaphylaxis have been reported with the use of probenecid; most of these have been reported to occur within several hours after readministration following prior usage of the drug; the appearance of hypersensitivity reactions requires cessation of therapy with probenecid; discontinue drug if allergic reaction occurs Probenecid has been used in patients with some renal impairment, but dosage requirements may be increased; probenecid may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is ≤30 mL/minute because of its mechanism of action, probenecid is not recommended in conjunction with penicillin in the presence of known renal impairment Drug interaction overview In patients on probenecid the use of salicylates in either small or large doses is contraindicated because antagonizes the uricosuric action of probenecid; the biphasic action of salicylates in the renal tubules accounts for the so-called “paradoxical effect” of uricosuric agents; in patients on probenecid who require a mild analgesic agent the use of acetaminophen rather than small doses of salicylates would be preferred Concomitant administration of probenecid increases mean plasma elimination half-life of a number of drugs which can lead to increased plasma concentrations; these include agents such as indomethacin, acetaminophen, naproxen, ketoprofen, meclofenamate, lorazepam, and rifampin Although clinical significance of this observation has not been established, a lower dosage of the drug may be required to produce a therapeutic effect, and increases a dosage of the drug in question should be made cautiously and in small increments when probenecid is being coadministered Although specific instances of toxicity due to potential interaction have not been observed to date, physicians should be alert to this possibility Probenecid given concomitantly with sulindac had only a slight effect on plasma sulfide levels, while plasma levels of sulindac and sulfone were increased; sulindac was shown to produce a modest reduction in uricosuric action of probenecid, which probably is not significant under most circumstances Pregnancy Probenecid crosses 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 possible hazards Lactation Not known if distributed into breast milk, use with cautionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal