Probenecid: Drug information

For additional information see "Probenecid: Patient drug information" and "Probenecid: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table

Pharmacologic Category

Uricosuric Agent

Dosing: Adult

Cidofovir nephrotoxicity, prevention

Cidofovir nephrotoxicity, prevention (off-label use): Oral: 2 g as a single dose administered 3 hours before cidofovir infusion, followed by 1 g at 2 hours and 8 hours after cidofovir infusion (Ref).

Hyperuricemia, gout prevention

Hyperuricemia, gout prevention (alternative agent): Oral: 250 mg twice daily for 1 week, followed by 500 mg twice daily; may increase dose by 500 mg every 4 weeks as tolerated if symptoms are not controlled; usual maintenance dose: ≤2 g/day in divided doses.

Sexually transmitted infections, as a pharmacokinetic enhancer to prolong beta-lactam serum levels

Sexually transmitted infections, as a pharmacokinetic enhancer to prolong beta-lactam serum levels (adjunctive agent):

Gonococcal infection, uncomplicated: Oral: 1 g as a single dose in combination with single-dose IM cefoxitin (Ref).

Neurosyphilis, including ocular and otosyphilis:

Note: Reserve for patients unable to receive IV therapy (Ref).

Oral: 500 mg 4 times daily in combination with IM procaine penicillin for 10 to 14 days (Ref).

Pelvic inflammatory disease, mild to moderate: Oral: 1 g as a single dose in combination with IM cefoxitin as a single dose plus doxycycline and metronidazole (Ref).

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function

eGFR ≥60 mL/minute/1.73 m²: No dosage adjustment necessary (Ref).

eGFR <60 mL/minute/1.73 m²:

Cidofovir nephrotoxicity, prevention (off-label use):

Oral: No dosage adjustment of probenecid likely necessary (Ref). Note: The use and dose of cidofovir in patients with kidney dysfunction should be evaluated separately.

Hyperuricemia, gout prevention: Oral:

eGFR ≥30 to <60 mL/minute/1.73 m²: The use of alternative agents is recommended due to reduced efficacy of probenecid in patients with eGFR <60 mL/minute/1.73 m² (Ref). If use of probenecid is deemed appropriate, no dosage adjustment likely necessary; however, use with caution and frequent monitoring for safety and efficacy. Limited data demonstrate urate-lowering capability of probenecid in patients with eGFR 30 to 60 mL/minute/1.73 m² without increased risk of toxicity; however, robust evidence is lacking, and better alternatives are often available (Ref).

eGFR <30 mL/minute/1.73 m²: Use not recommended (Ref).

Sexually transmitted infections, as a pharmacokinetic enhancer to prolong beta-lactam serum levels: Oral:

Note: No dosage adjustment is necessary for single dose probenecid regimens (ie, used in combination with cefoxitin for gonococcal infection or pelvic inflammatory disease) (Ref).

eGFR <60 mL/minute/1.73 m²: Since probenecid may have limited efficacy in reducing the renal clearance of beta-lactam concentrations (ie, procaine penicillin) in patients with kidney impairment, the use of probenecid in combination with procaine penicillin for the treatment of neurosyphilis should be avoided (Ref).

Hemodialysis, intermittent (thrice weekly): Oral: Avoid use (Ref).

Peritoneal dialysis: Oral: Avoid use (Ref).

CRRT: Oral: Avoid use (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Oral: Avoid use (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Probenecid: Pediatric drug information")

Prolongation of penicillin serum levels

Prolongation of penicillin serum levels: Children ≥2 years and Adolescents: Note: Dosing for some indication-specific dosing may vary.

Patient weight ≤50 kg: Oral: Initial: 25 mg/kg/dose or 700 mg/m²/dose as a single dose; maintenance: 40 mg/kg/day or 1,200 mg /m²/day in 4 divided doses; maximum dose: 500 mg.

Patient weight >50 kg: Oral: 500 mg 4 times daily.

Gonorrhea, uncomplicated infections of cervix, urethra, and rectum

Gonorrhea, uncomplicated infections of cervix, urethra, and rectum: Adolescents >45 kg: Oral: 1,000 mg as a single dose with cefoxitin; Note: Combination of ceftriaxone and azithromycin is preferred (Ref).

Pelvic inflammatory disease

Pelvic inflammatory disease: Adolescents: Oral: 1,000 mg as a single dose with cefoxitin in combination with doxycycline with/without metronidazole (Ref).

Neurosyphilis

Neurosyphilis: Adolescents: Oral: 500 mg 4 times daily with procaine penicillin for 10 to 14 days; alternative therapy to aqueous penicillin G therapy (Ref).

Cidofovir nephrotoxicity, prevention

Cidofovir nephrotoxicity, prevention: Limited data available; various regimens have been reported (Ref):

Infants, Children, and Adolescents: Note: The manufacturer's labeling considers use in patients <2 years of age to be contraindicated; however, clinical studies have included younger ages (including infants) for this indication.

Weight-based dosing: Oral: 25 to 40 mg/kg/dose (maximum dose: 2,000 mg) administered 3 hours before cidofovir infusion and 10 to 20 mg/kg/dose (maximum dose: 1,000 mg) at 2 to 3 hours and 8 to 9 hours after cidofovir infusion.

BSA-based dosing: Oral: 1,000 or 1,250 mg/m²/dose administered 3 hours prior to cidofovir, followed by 500 to 1,250 mg/m²/dose 1 to 2 hours and 8 hours after completion.

Dosing: Kidney Impairment: Pediatric

Children ≥2 years and Adolescents: CrCl <30 mL/minute: Avoid use (reduced efficacy with renal impairment).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Flushing

Dermatologic: Alopecia, dermatitis, pruritus, urticaria

Gastrointestinal: Anorexia, gingival pain, nausea, vomiting

Genitourinary: Urinary frequency

Hematologic & oncologic: Anemia, aplastic anemia, hemolytic anemia, leukopenia

Hepatic: Hepatic necrosis

Nervous system: Dizziness, headache, pain (costovertebral)

Renal: Nephrolithiasis, nephrotic syndrome, renal colic

Miscellaneous: Fever

Postmarketing: Hypersensitivity: Anaphylaxis, severe hypersensitivity reaction

Contraindications

Hypersensitivity to probenecid or any component of the formulation; blood dyscrasias; uric acid kidney stones; children <2 years of age; initiation during an acute gout attack.

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reaction: Has been associated with rare, severe hypersensitivity reactions, including anaphylaxis. Discontinue therapy if reaction occurs.

• Gout: May cause exacerbation of acute gouty attack.

Disease-related concerns:

• G6PD deficiency: Use caution in patients with G6PD deficiency; may increase risk for hemolytic anemia.

• Peptic ulcer disease: Use with caution in patients with peptic ulcer disease.

• Kidney impairment: May not be effective in patients with kidney impairment; use with caution (ACR [FitzGerald 2020]; manufacturer’s labeling).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 500 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Probenecid Oral)

500 mg (per each): $0.98 - $3.73

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

Oral: Administer with food to minimize GI effects. Maintain adequate fluid intake.

Administration: Pediatric

Oral: Administer with food or antacids to minimize GI effects

Use: Labeled Indications

Hyperuricemia, gout prevention: Treatment of hyperuricemia associated with gout or gouty arthritis.

Sexually transmitted infections, as a pharmacokinetic enhancer to prolong beta-lactam serum levels: Adjunctive agent to beta-lactams for the elevation and prolongation of plasma levels.

Use: Off-Label: Adult

Cidofovir nephrotoxicity, prevention

Medication Safety Issues

Sound-alike/look-alike issues:

Probenecid may be confused with Procanbid

Metabolism/Transport Effects

Inhibits MRP2, OAT1/3, UGT1A4, UGT1A6

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetaminophen: Probenecid may increase the serum concentration of Acetaminophen. Probenecid may also limit the formation of at least one major non-toxic metabolite, possibly increasing the potential for formation of the toxic NAPQI metabolite. Management: Consider limiting acetaminophen use in combination with probenecid. Probenecid may reduce clearance of acetaminophen to one of its non-toxic metabolities, increasing the risk for acetaminophen toxicity, even a lower doses. Risk D: Consider therapy modification

Anagliptin: Probenecid may increase the serum concentration of Anagliptin. Risk C: Monitor therapy

Avibactam: Probenecid may increase the serum concentration of Avibactam. Risk X: Avoid combination

Baricitinib: Probenecid may increase the serum concentration of Baricitinib. Management: When baricitinib is combined with probenecid, reduce baricitinib 4 mg daily to 2 mg daily or reduce baricitinib 2 mg daily to 1 mg daily. Don't use probenecid if recommended baricitinib dose is only 1 mg daily. Risk D: Consider therapy modification

Betalactamase Inhibitors: Probenecid may increase the serum concentration of Betalactamase Inhibitors. Management: Coadministration of probenecid with amoxicillin/clavulanate is not recommended per official package labeling. Risk D: Consider therapy modification

Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy

Cefotaxime: Probenecid may increase the serum concentration of Cefotaxime. Management: Avoid cefotaxime doses greater than 6 grams per day with concurrent probenecid. Any patients receiving this combination should be monitored for evidence of cefotaxime toxicity. Risk D: Consider therapy modification

Cephalosporins: Probenecid may increase the serum concentration of Cephalosporins. Risk C: Monitor therapy

Clofarabine: OAT1/3 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy

Deferiprone: UGT1A6 Inhibitors may increase the serum concentration of Deferiprone. Risk X: Avoid combination

Dexketoprofen: Probenecid may increase the serum concentration of Dexketoprofen. Risk C: Monitor therapy

Dichlorphenamide: OAT1/3 Inhibitors may increase the serum concentration of Dichlorphenamide. Risk C: Monitor therapy

Doripenem: Probenecid may increase the serum concentration of Doripenem. Risk X: Avoid combination

Dyphylline: Probenecid may increase the serum concentration of Dyphylline. Risk C: Monitor therapy

Ertapenem: Probenecid may increase the serum concentration of Ertapenem. Risk X: Avoid combination

Ganciclovir-Valganciclovir: Probenecid may increase the serum concentration of Ganciclovir-Valganciclovir. Risk C: Monitor therapy

Gemifloxacin: Probenecid may increase the serum concentration of Gemifloxacin. Risk C: Monitor therapy

Imipenem: Probenecid may increase the serum concentration of Imipenem. Risk C: Monitor therapy

Ketoprofen: Probenecid may increase the serum concentration of Ketoprofen. Risk C: Monitor therapy

Ketorolac (Nasal): Probenecid may increase the serum concentration of Ketorolac (Nasal). Risk X: Avoid combination

Ketorolac (Systemic): Probenecid may increase the serum concentration of Ketorolac (Systemic). Risk X: Avoid combination

Loop Diuretics: Probenecid may diminish the diuretic effect of Loop Diuretics. Probenecid may increase the serum concentration of Loop Diuretics. Risk C: Monitor therapy

LORazepam: Probenecid may increase the serum concentration of LORazepam. Management: Reduce lorazepam dose 50% during coadministration with probenecid. Monitor for increased and prolonged lorazepam effects, particularly CNS depressant effects. Patients using lorazepam ER capsules should be switched to lorazepam tablets. Risk D: Consider therapy modification

Meropenem: Probenecid may increase the serum concentration of Meropenem. Risk X: Avoid combination

Methotrexate: Probenecid may increase the serum concentration of Methotrexate. Management: If possible, the concomitant use of methotrexate and probenecid should be avoided. If used concomitantly, monitor closely for increased methotrexate serum concentrations and toxicities. Methotrexate dose reductions may be needed. Risk D: Consider therapy modification

Minoxidil (Systemic): Probenecid may increase the serum concentration of Minoxidil (Systemic). Risk C: Monitor therapy

Mycophenolate: Probenecid may increase the serum concentration of Mycophenolate. Risk C: Monitor therapy

Nitrofurantoin: Probenecid may diminish the therapeutic effect of Nitrofurantoin. Probenecid may increase the serum concentration of Nitrofurantoin. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Probenecid may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Oseltamivir: Probenecid may increase serum concentrations of the active metabolite(s) of Oseltamivir. Risk C: Monitor therapy

Pegloticase: Probenecid may enhance the adverse/toxic effect of Pegloticase. Specifically, Probenecid may blunt increases in serum urate that would signal an elevated risk of anaphylaxis and infusion reactions. Risk X: Avoid combination

Penicillins: Probenecid may increase the serum concentration of Penicillins. Risk C: Monitor therapy

Pexidartinib: UGT1A4 Inhibitors may increase the serum concentration of Pexidartinib. Management: If combined use cannot be avoided, pexidartinib dose should be reduced as follows: reduce pexidartinib doses of 500 mg or 375 mg daily to 125 mg twice daily; reduce pexidartinib 250 mg daily to 125 mg once daily. Risk D: Consider therapy modification

Phenprocoumon [INT]: Probenecid may decrease the serum concentration of Phenprocoumon [INT]. Risk C: Monitor therapy

PRALAtrexate: Probenecid may increase the serum concentration of PRALAtrexate. Management: Avoid coadministration of pralatrexate with probenecid. If coadministration cannot be avoided, closely monitor for increased pralatrexate serum concentrations or possible toxicity with concomitant use of probenecid. Risk D: Consider therapy modification

Propacetamol: Probenecid may increase serum concentrations of the active metabolite(s) of Propacetamol. Specifically, accetaminophen exposure may be increased. Probenecid may also limit the formation of at least one major non-toxic acetaminophen metabolite, possibly increasing the formation of the toxic NAPQI metabolite. Management: Consider limiting the use of propacetamide in patients who are also taking probenecid. Patients may be at an increased risk for toxicity, even if reduced propacetamide doses are used. Risk D: Consider therapy modification

Quinolones: Probenecid may decrease the excretion of Quinolones. Specifically, probenecid may decreased the renal excretion of quinolone antibiotics. Probenecid may increase the serum concentration of Quinolones. Risk C: Monitor therapy

RifAMPin: Probenecid may increase the serum concentration of RifAMPin. Risk C: Monitor therapy

Roxadustat: Probenecid may increase the serum concentration of Roxadustat. Risk C: Monitor therapy

Salicylates: May diminish the therapeutic effect of Probenecid. Risk X: Avoid combination

Sodium Benzoate: Probenecid may diminish the therapeutic effect of Sodium Benzoate. Risk C: Monitor therapy

Sulbactam: Probenecid may increase the serum concentration of Sulbactam. Management: Recommendations for management of this interaction vary by specific sulbactam-containing product. Coadministration of probenecid with sulbactam/durlobactam is not recommended, but no specific actions are recommended for ampicillin/sulbactam. Risk D: Consider therapy modification

Sulfonylureas: Probenecid may increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Thiopental: Probenecid may enhance the adverse/toxic effect of Thiopental. Specifically, anesthetic potency and duration may be enhanced. Risk C: Monitor therapy

Urea Cycle Disorder Agents: Probenecid may increase serum concentrations of the active metabolite(s) of Urea Cycle Disorder Agents. Specifically, concentrations of phenylacetate and phenylacetylglutamine may be increased. Risk C: Monitor therapy

Vadadustat: OAT1/3 Inhibitors may increase the serum concentration of Vadadustat. Risk C: Monitor therapy

Zidovudine: Probenecid may increase the serum concentration of Zidovudine. Risk C: Monitor therapy

Pregnancy Considerations

Probenecid crosses the placenta. Based on available data, an increased risk of adverse fetal events have not been reported (Gutman, 2012).

Dietary Considerations

Drug may cause GI upset; take with food if GI upset. Drink plenty of fluids.

Monitoring Parameters

Serum uric acid, kidney function, CBC.

Reference Range

Uric acid, serum:

Adults:

Normal values: 3 to 7 mg/dL (SI: 178.5 to 416.5 micromole/L). Note: Reference ranges may vary depending on the laboratory.

Goal during therapy: <6 mg/dL (SI: <357 micromole/L); <5 mg/dL (SI: <297.5 micromole/L) in patients with severe gout (eg, tophi, frequent attacks, chronic arthropathy) (EULAR [Richette 2017]). Levels <3 mg/dL (SI: <178.5 micromole/L) are not recommended long-term (EULAR [Richette 2017]).

Note: Serum uric acid values >7 mg/dL (SI: >416.5 micromole/L) do not necessarily represent clinical gout; the American College of Rheumatology clinical practice guidelines recommend against initiating pharmacologic management of asymptomatic hyperuricemia (ACR [FitzGerald 2020]).

Mechanism of Action

Competitively inhibits the reabsorption of uric acid at the proximal convoluted tubule, thereby promoting its excretion and reducing serum uric acid levels; increases plasma levels of weak organic acids (penicillins, cephalosporins, or other beta-lactam antibiotics) by competitively inhibiting their renal tubular secretion

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Effect on penicillin levels: 2 hours; Uric acid renal clearance: 30 minutes

Absorption: Rapid and complete

Protein binding: 85% to 95%

Metabolism: Hepatic

Half-life elimination (dose dependent): Normal renal function: 6 to 12 hours

Time to peak, serum: 2 to 4 hours

Excretion: Urine

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Benemid;
(AU) Australia: Benemid | Pro cid;
(CH) Switzerland: Santuril;
(CZ) Czech Republic: Benemid;
(EE) Estonia: Benemid | Probenecid biokanol;
(FI) Finland: Probecid;
(FR) France: Benemide | Probenecid biokanol | Santuril;
(GB) United Kingdom: Benemid;
(GR) Greece: Benemid;
(HU) Hungary: Benemid;
(ID) Indonesia: Probenid;
(IE) Ireland: Benemid;
(IN) India: Bencid;
(IT) Italy: Probenec;
(JP) Japan: Benecid | Probenemid;
(LT) Lithuania: Benemid;
(LV) Latvia: Benemid | Probenecid Weimer;
(MX) Mexico: Benecid;
(NL) Netherlands: Benemid;
(NO) Norway: Probecid;
(PH) Philippines: Benemid;
(PL) Poland: Benemid | Benemide | Probenecid Weimer;
(PR) Puerto Rico: Benemid;
(PT) Portugal: Benemid;
(RU) Russian Federation: Probenecid biokanol;
(SE) Sweden: Probecid;
(TH) Thailand: Bencid | Benecid | Benemid | Proben;
(TN) Tunisia: Benemide;
(TW) Taiwan: Benemid | Brucid | Procid | Pronid;
(UA) Ukraine: Santuril;
(ZA) South Africa: Proben

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Probenecid: Drug information