probenecid

Anti-Gout Agents

Administer probenecid with food or antacids to minimize gastrointestinal adverse effects.
A liberal fluid intake is recommended during therapy to help avoid urate crystallization/stones in the urine.
In patients with gout, alkalization of the urine is typically used concurrently until the serum urate level returns to normal limits and tophaceous deposits disappear. Thereafter, alkalization of the urine and the usual dietary restriction of purine-producing foods may be somewhat relaxed.

hepatic necrosis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
nephrotic syndrome / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known

hematuria / Delayed / Incidence not known
gout / Delayed / Incidence not known
nephrolithiasis / Delayed / Incidence not known
costovertebral pain / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known

nausea / Early / Incidence not known
vomiting / Early / Incidence not known
anorexia / Delayed / Incidence not known
fever / Early / Incidence not known
pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
flushing / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
polyuria / Early / Incidence not known
headache / Early / Incidence not known
dizziness / Early / Incidence not known

Rx

Oral uricosuric agent
Used to treat hyperuricemia associated with chronic gout; not effective for acute gout attacks
Occasionally used with colchicine or selected antibiotics to delay the renal clearance of these drugs and prolong effect

250 mg PO twice daily for 1 week, then 500 mg PO twice daily.

500 mg PO 4 times per day. The phenolsulfonphthalein (PSP) excretion test may be used to determine the effectiveness of probenecid in retarding penicillin excretion and maintaining therapeutic levels. The renal clearance of PSP is reduced to about one-fifth the normal rate when the dosage of probenecid is adequate.

500 mg PO 4 times per day. The phenolsulfonphthalein (PSP) excretion test may be used to determine the effectiveness of probenecid in retarding penicillin excretion and maintaining therapeutic levels. The renal clearance of PSP is reduced to about one-fifth the normal rate when the dosage of probenecid is adequate.

25 mg/kg/dose PO initially, followed by maintenance dose of 40 mg/kg/day (Max: 2,000 mg/day) PO in 4 divided doses. The phenolsulfonphthalein (PSP) excretion test may be used to determine the effectiveness of probenecid in retarding penicillin excretion and maintaining therapeutic levels. The renal clearance of PSP is reduced to about one-fifth the normal rate when the dosage of probenecid is adequate.

1 gram PO as a single dose to be given concurrently with IM cefoxitin.

1 gram PO as a single dose to be given concurrently with IM cefoxitin.

500 mg PO 4 times per day for 10 to 14 days in combination with procaine penicillin G.

500 mg PO 4 times per day for 10 to 14 days in combination with procaine penicillin G.

2 g PO given 3 hours prior to each cidofovir infusion, followed by 1 g PO at 2 and 8 hours following the completion of the cidofovir infusion.

25 to 40 mg/kg/dose (Max: 2 g/dose) PO given 3 hours prior to each cidofovir infusion, followed by 10 to 20 mg/kg/dose (Max: 1 g/dose) PO at 2 and 8 hours following the completion of the cidofovir infusion.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

CrCl more than 50 mL/minute: Use with caution in patients with gout with renal impairment; adjust dosage to needed therapeutic response. Probenecid has been used in patients with some renal impairment, as some degree of renal impairment may be present in patients with gout. Use a reduced initial dosage in patients with renal impairment and titrate to response. A total daily dosage of 1,000 mg/day may be adequate. However, if necessary, the daily dosage may be increased by 500 mg increments every 4 weeks within tolerance (and usually not above 2,000 mg/day) if symptoms of gouty arthritis are not controlled or the 24 hour uric acid excretion is not above 700 mg. Because of its mechanism of action, probenecid is not recommended in conjunction with a penicillin medication in the presence of known renal impairment.
CrCl 50 mL/minute or less: Avoid use of drug. Probenecid may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is 30 mL/minute or less.

Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Major) Concomitant use of probenecid with zidovudine, ZDV may produce substantially higher serum concentrations of zidovudine.
Acetaminophen; Aspirin, ASA; Caffeine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Acetaminophen; Aspirin: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Acetaminophen; Aspirin; Diphenhydramine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Acetaminophen; Ibuprofen: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Acyclovir: (Moderate) Probenecid decreases the renal tubular secretion of acyclovir and can increase serum and CSF concentrations of acyclovir, increasing the potential for toxicity. This interaction would appear to be more significant for parenteral acyclovir.
Allopurinol: (Minor) Uricosuric agents are likely to increase the excretion of the active metabolite of allopurinol, oxypurinol. Although uricosuric agents increase the renal excretion of oxypurinol, the antihyperuricemic effects of allopurinol may be additive when administered with either probenecid or sulfinpyrazone.
Aminosalicylate sodium, Aminosalicylic acid: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Amlodipine; Celecoxib: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Amoxicillin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Amoxicillin; Clavulanic Acid: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Ampicillin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Ampicillin; Sulbactam: (Moderate) Monitor for an increase in sulbactam-related adverse effects if concomitant use with probenecid is necessary. Concomitant use may increase sulbactam exposure. Sulbactam is an OAT1 substrate and probenecid is an OAT1 inhibitor. (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Aspirin, ASA: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Butalbital; Caffeine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Caffeine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Caffeine; Orphenadrine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Carisoprodol: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Carisoprodol; Codeine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Dipyridamole: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Omeprazole: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Oxycodone: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Baricitinib: (Major) Reduce the recommended baricitinib dose by half in patients receiving concomitant therapy with probenecid. If the recommended dose is 4 mg daily, reduce to 2 mg daily. If the recommended dose is 2 mg daily, reduce to 1 mg daily. If the recommended dose is 1 mg daily, consider discontinuing probenecid. Coadministration of baricitinib and probenecid results in increased baricitinib exposure. In a drug interaction study, administration of probenecid increased baricitinib exposure by 2-fold. Baricitinib is an OAT3 substrate and probenecid is a strong OAT3 inhibitor.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Bismuth Subsalicylate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Bromocriptine: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., probenecid), which may alter their effectiveness and risk for side effects.
Bumetanide: (Moderate) Probenecid can interfere with the natriuresis and plasma renin activity increases caused by diuretics such as bumetanide. Bumetanide can in turn increase the levels of serum uric acid, antagonizing the effects of probenecid.
Bupivacaine; Meloxicam: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Butalbital; Aspirin; Caffeine; Codeine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Cabozantinib: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with probenecid is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and probenecid is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Caffeine; Sodium Benzoate: (Moderate) Renal excretion of phenylacetylglutamine and hippuric acid may be affected by probenecid through competitive inhibition. These competitive reactions could be significant, as the overall usefulness of sodium benzoate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. Use with caution.
Captopril: (Moderate) Probenecid decreases the renal tubular secretion of captopril, resulting in higher captopril serum concentrations. If probenecid is given to a patient stabilized on captopril, hypotension may occur. This interaction would appear to be of lesser significance if captopril is added after probenecid therapy is in place.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Probenecid decreases the renal tubular secretion of captopril, resulting in higher captopril serum concentrations. If probenecid is given to a patient stabilized on captopril, hypotension may occur. This interaction would appear to be of lesser significance if captopril is added after probenecid therapy is in place.
Carbacephems: (Minor) Renal tubular secretion of loracarbef is inhibited by probenecid, resulting in higher, approximately 80% increase in AUC, serum levels of loracarbef. The interaction also increases the normal half-life of loracarbef from 1 to 1.5 hours.
Carbidopa; Levodopa; Entacapone: (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation or intestinal beta-glucuronidation such as probenecid. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
Cefaclor: (Minor) Probenecid competitively inhibits renal tubular secretion of cefaclor, thereby causing higher serum concentrations and prolonged elimination of cefaclor.
Cefotaxime: (Minor) Probenecid competitively inhibits renal tubular secretion of cefotaxime, thereby causing higher, prolonged serum levels of the drug.
Cefpodoxime: (Minor) Renal excretion of cefpodoxime is inhibited by probenecid.
Cefprozil: (Minor) Probenecid competitively inhibits renal tubular secretion of cefprozil, causing higher, prolonged serum levels of the drug. In the oral treatment of pediatric osteomyelitis, probenecid is intentionally administered with cefprozil to achieve higher serum concentrations.
Ceftazidime; Avibactam: (Major) Avoid concurrent administration of ceftazidime; avibactam with probenicid. Use of these medications together may decrease the renal clearance of avibactam; thereby resulting in prolonged drug exposures. Avibactam is a substrate of the renal organic anion transporters (OAT)1 and OAT3; probenecid is a potent inhibitor of these transporters. An in vitro study found probencid blocked 56% to 70% of avibactam uptake by these transporters.
Ceftolozane; Tazobactam: (Minor) Probenecid may prolong serum concentrations of tazobactam when coadministered with ceftolozane; tazobactam. Probenecid has been shown to prolong the half-life of tazobactam by 71% when coadministered. The clinical significance of this interaction has not been established.
Celecoxib: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Celecoxib; Tramadol: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Cephalexin: (Minor) Probenecid competitively inhibits renal tubular secretion of cephalexin, causing higher, prolonged serum levels of the drug.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Choline Salicylate; Magnesium Salicylate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Cidofovir: (Minor) Probenecid impairs the tubular secretion of cidofovir. While cidofovir serum concentrations are higher as a result of the effects of probenecid, probenecid is recommended for use in combination with cidofovir to offset cidofovir-induced nephrotoxicity.
Ciprofloxacin: (Minor) Probenecid decreases renal secretion of ciprofloxacin by 50%, resulting in elevated ciprofloxacin serum concentrations and prolonging its half-life.
Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and probenecid, an inhibitor of OAT1 and OAT3, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g., hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OAT3 inhibitors.
Dapsone: (Minor) Current evidence suggests that probenecid can inhibit the renal excretion of dapsone, resulting in elevated plasma concentrations. Dapsone toxicity as a result of this interaction has not been studied, so patients receiving these agents concurrently should be monitored for hemolytic anemia, methemoglobinemia, and/or peripheral neuropathy with muscle weakness. This interaction may, however, be beneficial in treating organisms that are resistant to dapsone.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Deferiprone: (Major) Avoid the concomitant use of deferiprone and probenecid. Deferiprone is a UDP glucuronosyltransferase (UGT) 1A6 substrate, and probenecid inhibits this enzyme. The in vitro glucuronidation of deferiprone is reduced by 78% in the presence of phenylbutazone, another UGT1A6 inhibitor. Similar results may be seen when deferiprone and probenecid are administered concomitantly.
Diazoxide: (Moderate) Diazoxide can cause hyperuricemia. Dosages of concomitantly administered antigout medications, including probenecid, may require adjustment.
Dichlorphenamide: (Moderate) Monitor for increased toxicity of dichlorphenamide, including hypokalemia and hyperchloremic metabolic acidosis, if probenecid and dichlorphenamide are coadministered. Dichlorphenamide is a substrate for OAT1 and OAT3. Probenecid may increase exposure to dichlorphenamide through OAT1 and OAT3 inhibition. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Diclofenac; Misoprostol: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Dicloxacillin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Diflunisal: (Major) Probenecid can affect the pharmacokinetics of diflunisal. In healthy males, probenecid inhibits both renal and biliary excretion of and slightly decreases the protein binding of diflunisal. It has been proposed that the decreased clearance of diflunisal may result in an increased concentration of the glucuronide metabolites. Diflunisal does have uricosuric effects; however, it is not known whether diflunisal affects the activity of probenicid. Reduction of the diflunisal dose may be necessary when it is used together with probenecid.
Diphenhydramine; Ibuprofen: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Diphenhydramine; Naproxen: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Doripenem: (Moderate) Probenecid inhibits the renal excretion of doripenem by competing with doripenem for active tubular secretion. The elimination half-life of doripenem is increased by 53% and the extent of systemic exposure (AUC) to doripenem is increased by 75%. Concurrent administration of doripenem with probenecid is not recommended.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Eluxadoline: (Minor) Systemic exposure (AUC) and maximum plasma concentration of eluxadoline are increased by 35% and 31%, respectively, when administered concurrently with probenecid. According to the manufacturer, the increase in exposure is not expected to be clinically meaningful; no dosage adjustments are required during coadministration with probenecid.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Entacapone: (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation or intestinal beta-glucuronidation such as probenecid. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
Ertapenem: (Minor) Probenecid inhibits the renal excretion of ertapenem by competing with them for active tubular secretion. In some instances, this effect is used therapeutically to increase availability of the antimicrobial agent. However, the elimination half-life of ertapenem is increased only from 4 to 4.8 hours. Concurrent administration of ertapenem with probenecid is not recommended.
Ethacrynic Acid: (Moderate) Probenecid has uricosuric actions. Ethacrynic acid can also cause hyperuricemia. Although this effect represents a pharmacodynamic interaction, dosage adjustments of probenecid may be necessary if ethacrynic acid is administered to patients being treated with probenecid.
Ethambutol: (Moderate) Probenecid has uricosuric actions. Ethambutol can also cause hyperuricemia. Although this effect represents a pharmacodynamic interaction, dosage adjustments of probenecid may be necessary if ethambutol is administered to patients being treated with probenecid.
Etodolac: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Famciclovir: (Moderate) Probenecid undergoes both renal tubular secretion and renal tubular reabsorption. Concomitant administration of probenecid with famciclovir may impair clearance of the active metabolite, penciclovir. Probenecid should be avoided during therapy with famciclovir.
Fenoprofen: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Flurbiprofen: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Furosemide: (Moderate) Probenecid can interfere with the natriuresis and plasma renin activity increases caused by diuretics such as furosemide. Furosemide can in turn increase the levels of serum uric acid, antagonizing the effects of probenecid.
Ganciclovir: (Moderate) Ganciclovir should be used with probenecid with caution. Probenecid can inhibit renal tubular secretion of ganciclovir, possibly potentiating ganciclovir toxicity. Patients should be monitored for increased ganciclovir toxicity when taking probenecid with ganciclovir.
Gemifloxacin: (Minor) Probenecid, 4.5 g total dose, reduced the mean renal clearance of a single 320-mg dose of gemifloxacin by approximately 50%, increased the AUC by 45%, increased the Cmax by 8%, and prolonged the mean half by 1.6 hours.
Glycerol Phenylbutyrate: (Moderate) Probenecid may inhibit renal excretion of glycerol phenylbutyrate metabolites, including phenylacetate (PAA) and phenylacetylglutamine (PAGN). PAA has been associated with neurotoxicity. If probenecid must be used in combination with glycerol phenylbutyrate, monitor the patient closely for signs and symptoms of neurotoxicity. In addition, because probenecid alters PAGN excretion, use caution when interpreting urinary PAGN concentrations for the purpose of dosage adjustments.
Hydrocodone; Ibuprofen: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Hydroxyurea: (Major) Hydroxyurea may raise the serum uric acid concentration, so dosage adjustment of uricosuric medications such as probenecid may be necessary.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Ibuprofen: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Ibuprofen; Famotidine: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Ibuprofen; Oxycodone: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Ibuprofen; Pseudoephedrine: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Imipenem; Cilastatin: (Major) Concomitant use of imipenem and probenecid is not recommended. Probenecid competitively inhibits renal tubular secretion and causes increased serum concentrations of imipenem and prolonged half-life.
Imipenem; Cilastatin; Relebactam: (Major) Concomitant use of imipenem and probenecid is not recommended. Probenecid competitively inhibits renal tubular secretion and causes increased serum concentrations of imipenem and prolonged half-life.
Indomethacin: (Major) Probenecid reduces the clearance of indomethacin, and a lower dosage of indomethacin may be required to produce a therapeutic effect.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Concomitant use of rifampin and probenecid may result in increased serum concentrations of rifampin. Monitor for increased rifampin toxicity during coadministration. (Minor) Because pyrazinamide can increase serum uric acid levels and precipitate gouty attacks, the dosages of antigout agents, including probenecid, may need to be adjusted.
Isoniazid, INH; Rifampin: (Moderate) Concomitant use of rifampin and probenecid may result in increased serum concentrations of rifampin. Monitor for increased rifampin toxicity during coadministration.
Ketoprofen: (Major) Concomitant administration of ketoprofen with probenecid can increase plasma concentrations of ketoprofen. Simultaneous use of these agents is not recommended.
Ketorolac: (Contraindicated) Simultaneous use of ketorolac and probenecid is contraindicated. Concomitant administration of ketorolac with probenecid can result in substantially increased plasma concentrations of ketorolac through decreased clearance. The elimination half-life of ketorolac is approximately doubled.
Lamivudine, 3TC; Zidovudine, ZDV: (Major) Concomitant use of probenecid with zidovudine, ZDV may produce substantially higher serum concentrations of zidovudine.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Lesinurad; Allopurinol: (Minor) Uricosuric agents are likely to increase the excretion of the active metabolite of allopurinol, oxypurinol. Although uricosuric agents increase the renal excretion of oxypurinol, the antihyperuricemic effects of allopurinol may be additive when administered with either probenecid or sulfinpyrazone.
Levetiracetam: (Minor) The renal clearance of the major metabolite of levetiracetam, UCB L057, is decreased by 60 percent in the presence of probenecid. This is probably related to competitive inhibition of tubular secretion of UCB L057. The clinical significance of this is unknown.
Lorazepam: (Moderate) Monitor for an increase in lorazepam-related adverse reactions and consider reducing the dose of lorazepam if concomitant use of lorazepam and probenecid is necessary. Avoid lorazepam extended-release capsules and utilize lorazepam immediate-release dosage forms that can be easily titrated. Coadministration of lorazepam with probenecid may cause a more rapid onset or prolonged effect of lorazepam due to increased half-life and decreased total clearance. Lorazepam is an UGT substrate and probenecid is an UGT inhibitor.
Lumateperone: (Major) Avoid coadministration of lumateperone and probenecid as concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a UGT substrate; probenecid is a UGT inhibitor.
Mafenide: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Magnesium Salicylate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and probenecid as increased maraviroc concentrations may occur. Maraviroc is a substrate of multidrug resistance-associated protein (MRP2); probenecid is an inhibitor of MRP2. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
Mecamylamine: (Moderate) Probenecid has uricosuric actions. Mecamylamine can also cause hyperuricemia. Although this effect represents a pharmacodynamic interaction, dosage adjustments of probenecid may be necessary if mecamylamine is administered to patients being treated with probenecid.
Meclofenamate Sodium: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Mefenamic Acid: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Meloxicam: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Meropenem: (Moderate) Concurrent administration of meropenem with probenecid is not recommended as probenecid inhibits the renal excretion of meropenem by competing for active tubular secretion. After administration of probenecid with meropenem, the mean systemic exposure of meropenem increased by 56% and the half-life increased by 38%. Meropenem is a substrate of OAT1 and OAT3 transporters in the proximal tubule of the kidney, and probenecid is an inhibitor of these drug transporters.
Meropenem; Vaborbactam: (Moderate) Concurrent administration of meropenem with probenecid is not recommended as probenecid inhibits the renal excretion of meropenem by competing for active tubular secretion. After administration of probenecid with meropenem, the mean systemic exposure of meropenem increased by 56% and the half-life increased by 38%. Meropenem is a substrate of OAT1 and OAT3 transporters in the proximal tubule of the kidney, and probenecid is an inhibitor of these drug transporters.
Methenamine; Sodium Salicylate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Methotrexate: (Contraindicated) Probenecid inhibits renal elimination of methotrexate, which can cause increased plasma levels and toxicity of methotrexate. In addition, methotrexate can increase uric acid production. Probenecid has also been associated with decreased clearance of methotrexate from the CSF. Concomitant use of methotrexate and probenecid is not recommended because of the increased risk of uric acid neuropathy. If coadministration is necessary, patients receiving this combination should be closely monitored.
Mycophenolate: (Minor) Probenecid is a known inhibitor of renal tubular secretion, and the inactive metabolite, MPAG undergoes tubular secretion. Increased MPAG concentrations can cause increased mycophenolic acid systemic exposure and thus, adverse effects. Patients receiving both drugs should be monitored carefully.
Nabumetone: (Major) The effects of probenecid on the elimination of nabumetone has not been studied, but probenecid decreases the elimination of other NSAIDs such as naproxen, potentially increasing the effectiveness and/or toxicity. Caution should be exercised when administering probenecid with nabumetone; nabumetone and naproxen are chemically similar, and probenecid has been shown to affect the pharmacokinetics of naproxen.
Nafcillin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Naproxen: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance.
Naproxen; Esomeprazole: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance.
Naproxen; Pseudoephedrine: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance.
Nitrofurantoin: (Moderate) High doses of probenecid can inhibit the renal tubular secretion of nitrofurantoin, leading to a decrease in renal clearance. Nitrofurantoin serum concentrations can increase, elevating the risk of toxicity. Lower doses of nitrofurantoin should be used when probenecid is used.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Oseltamivir: (Minor) Coadministration of oseltamivir and probenecid results in a two-fold increase in exposure to oseltamivir carboxylate due to a decrease in active anionic tubular secretion in the kidney. However, due to the safety margin of oseltamivir carboxylate, no dosage adjustments are required when oseltamivir is given concomitantly with probenecid.
Oxacillin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Oxaprozin: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents. Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Pegloticase: (Major) Oral urate-lowering medications, including allopurinol, febuxostat, probenecid, and sulfinpyrazone may potentially blunt the rise of serum uric acid levels in patients taking pegloticase. Since patients who have lost therapeutic response to pegloticase are at higher risk of developing anaphylaxis and infusion reactions, oral urate-lowering therapy should be discontinued prior to pegloticase initiation and withheld during the course of treatment.
Penicillin G Benzathine: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Penicillin G Benzathine; Penicillin G Procaine: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Penicillin G Procaine: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Penicillin G: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Penicillin V: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Penicillins: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and probenecid due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If probenecid is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of probenecid. Pexidartinib is a UGT substrate; probenecid is a UGT inhibitor. Coadministration of probenecid increased pexidartinib exposure by 60%.
Phentermine; Topiramate: (Minor) Probenecid may increase the renal clearance of topiramate resulting in lower topiramate concentrations. Although not evaluated in humans, animal studies using probenecid along with topiramate showed a significant increase in renal clearance of topiramate. This suggests that topiramate may undergo renal tubular reabsorption. Probenecid may block renal tubular reabsorption of topiramate, thus increasing the renal clearance of the drug.
Piperacillin; Tazobactam: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed. (Minor) Probenecid may prolong serum concentrations of tazobactam when coadministered with ceftolozane; tazobactam. Probenecid has been shown to prolong the half-life of tazobactam by 71% when coadministered. The clinical significance of this interaction has not been established.
Piroxicam: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Pralatrexate: (Major) Coadministration of increasing doses of probenecid, a uricosuric drug, and pralatrexate resulted in a delayed clearance of pralatrexate and a commensurate increase in systemic exposure of pralatrexate.
Pyrazinamide, PZA: (Minor) Because pyrazinamide can increase serum uric acid levels and precipitate gouty attacks, the dosages of antigout agents, including probenecid, may need to be adjusted.
Rifampin: (Moderate) Concomitant use of rifampin and probenecid may result in increased serum concentrations of rifampin. Monitor for increased rifampin toxicity during coadministration.
Salicylates: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Salsalate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Silodosin: (Major) KMD-3213G, the primary metabolite of silodosin, is formed from direct conjugation of silodosin by UDP-glucuronosyltransferase 2B7 (UBT2B7). In theory, coadministration of silodosin with UBT2B7 inhibitors such as probenecid may increase silodosin plasma concentrations.
Sodium Benzoate; Sodium Phenylacetate: (Moderate) Renal excretion of phenylacetylglutamine and hippuric acid may be affected by probenecid through competitive inhibition. These competitive reactions could be significant, as the overall usefulness of sodium benzoate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. Use with caution.
Sodium Phenylbutyrate: (Major) Avoid coadministration of probenecid and sodium phenylbutyrate. Coadministration may increase the risk for potential for neurotoxicity. Probenecid may inhibit renal excretion of the metabolites of sodium phenylbutyrate, including phenylacetate and phenylacetylglutamine.
Sodium Phenylbutyrate; Taurursodiol: (Major) Avoid coadministration of probenecid and sodium phenylbutyrate. Coadministration may increase the risk for potential for neurotoxicity. Probenecid may inhibit renal excretion of the metabolites of sodium phenylbutyrate, including phenylacetate and phenylacetylglutamine.
Stavudine, d4T: (Minor) Stavudine undergoes active tubular secretion, and renal elimination may be affected by probenecid, a drug known to interfere with tubular secretion. Resultant increases in serum levels can lead to toxicity.
Sulbactam; Durlobactam: (Moderate) Monitor for an increase in sulbactam-related adverse effects if concomitant use with probenecid is necessary. Concomitant use may increase sulbactam exposure. Sulbactam is an OAT1 substrate and probenecid is an OAT1 inhibitor.
Sulfadiazine: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Sulfasalazine: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Sulfonamides: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Sulfonylureas: (Moderate) Probenecid is highly protein bound, and the hypoglycemic effect of sulfonylureas made be potentiated if these drugs are coadministered.
Sulindac: (Major) Increases in the plasma concentration of sulindac and the inactive sulfone metabolite have been observed following concomitant administration with probenecid; however, the plasma concentration of the active sulfide metabolite was only slightly affected. The mechanism of this interaction may be through the inhibition of renal clearance. Concurrent use of probenecid and sulindac also modestly reduced the uricosuric action of probenecid. Monitor patients for signs and symptoms of sulindac toxicity if probenecid and sulindac are used concurrently.
Sumatriptan; Naproxen: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Thiazide diuretics: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Tolmetin: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Topiramate: (Minor) Probenecid may increase the renal clearance of topiramate resulting in lower topiramate concentrations. Although not evaluated in humans, animal studies using probenecid along with topiramate showed a significant increase in renal clearance of topiramate. This suggests that topiramate may undergo renal tubular reabsorption. Probenecid may block renal tubular reabsorption of topiramate, thus increasing the renal clearance of the drug.
Triamterene: (Moderate) Probenecid has uricosuric actions. Triamterene can also cause hyperuricemia. Although this effect represents a pharmacodynamic interaction, dosage adjustments of probenecid may be necessary if triamterene is administered to patients being treated with probenecid.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Probenecid has uricosuric actions. Triamterene can also cause hyperuricemia. Although this effect represents a pharmacodynamic interaction, dosage adjustments of probenecid may be necessary if triamterene is administered to patients being treated with probenecid.
Valacyclovir: (Moderate) Probenecid can reduce the renal tubular secretion of valacyclovir when these agents are coadministered, causing an increase in the serum concentration and elimination half-life of valacyclovir.
Valganciclovir: (Moderate) Probenecid may inhibit renal tubular secretion of valganciclovir, possibly potentiating valganciclovir toxicity. Patients should be monitored for increased valganciclovir toxicity when taking probenecid.
Vonoprazan; Amoxicillin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Vonoprazan; Amoxicillin; Clarithromycin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Zidovudine, ZDV: (Major) Concomitant use of probenecid with zidovudine, ZDV may produce substantially higher serum concentrations of zidovudine.

Probenecid Oral Tab: 500mg

2 grams/day PO.

2 grams/day PO.

more than 50 kg: 2 grams/day PO.
50 kg or less: 40 mg/kg/day (1.2 grams/m2/day) PO (not to exceed 2 grams/day PO).

2 to 12 years and more than 50 kg: 2 grams/day PO.
2 to 12 years and 50 kg or less: 40 mg/kg/day (1.2 grams/m2/day) PO (not to exceed 2 grams/day PO).
Less than 2 years: Use is contraindicated.

Use is contraindicated.

Use is contraindicated.

Probenecid is a uricosuric and renal tubular blocking agent. It inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits. Probenecid also competitively inhibits the active reabsorption of uric acid at the proximal convoluted tubule, facilitating urinary excretion of uric acid and decreasing plasma urate concentrations. The drug does not affect the glomerular filtration rate or reabsorption of glucose, arginine, urea, sodium, potassium, and chloride. The tubular reabsorption of phosphorus is inhibited in hypoparathyroid but not in euparathyroid individuals.
 
At the level of the proximal and distal tubules, probenecid inhibits the secretion of weak acids, thereby increasing plasma concentrations. Some of the medications affected by this action of probenecid include most cephalosporins and penicillins, and other beta-lactam-related antibiotics such as aztreonam and imipenem; indomethacin; and methotrexate. In some cases, probenecid administration can more than double the serum concentrations of the affected drug. Elimination half-life is prolonged correspondingly.

Probenecid is administered orally. The drug distributes throughout the body tissues and is 75% to 95% plasma protein-bound, predominantly to albumin. Probenecid undergoes hepatic metabolism resulting in active metabolites. Both parent drug and active metabolites are eliminated renally, mainly by tubular secretion. Small amounts of unchanged probenecid are filtered at the glomeruli. The parent drug is nearly completely reclaimed via tubular reabsorption; minor amounts of metabolites undergo tubular reabsorption. The plasma half-life of probenecid is dose-dependent. Half-life ranges from 3 to 8 hours for a 500 mg dose and 6 to 12 hours for larger doses. Both unchanged drug and its metabolites are excreted in the urine; the unchanged drug is reabsorbed.[42116]
 
Affected cytochrome P450 isoenzymes and drug transporters: OAT1 and OAT3
Probenecid inhibits the drug transporters OAT1 and OAT3.[56579] Probenecid inhibits the tubular secretion of penicillin and usually increases penicillin plasma levels by any route the antibiotic is given. A 2-fold to 4-fold elevation has been demonstrated for various penicillins. Probenecid also has been reported to inhibit the renal transport of many other compounds including, but not limited to, indomethacin, methotrexate, sulfonamides, and sulfonylureas. Probenecid does not influence plasma concentrations of salicylates, nor the excretion of streptomycin, chloramphenicol, chlortetracycline, oxytetracycline, or neomycin.[42116]

Probenecid is completely absorbed following an oral dose.

Use of probenecid during pregnancy is recommended only if the potential benefits to the mother outweigh the potential risks to the fetus. Probenecid crosses the placental barrier and appears in cord blood. There are no adequate and well controlled studies in pregnant women. Case reports of use for the treatment of hyperuricemia associated with gout or as single-doses with ampicillin for the treatment of urinary tract infection during pregnancy have not noted adverse fetal effects.

The label for probenecid does not note any particular cautions for the use of probenecid during lactation. Data are limited regarding use of probenecid during breast-feeding; however, one case report has documented probenecid excretion into human milk. In this report, a 30-year-old lactating mother was administered probenecid (500 mg PO four times daily) in combination with cephalexin for a breast infection. After 16 days of treatment, 12 milk samples were collected. The average probenecid milk concentration was 964 mcg/L, corresponding to a relative infant dose 0.7% of the maternal weight-adjusted dose. Symptoms of severe diarrhea, discomfort, and crying were observed in the infant, and these were determined by the authors to be possibly related to probenecid, but more probably associated with cephalexin.[32196]