Methotrexate
Contraindicated
Database
Reduces renal secretion and increases plasma levels of methotrexate.
Avoid combination.
Source: DDInter
Drug reference
probenecid
Uricosuric
Uricosuric
CDSCO approved
EXCRETION
—
not curated
INTERACTIONS
7 major
incl. contraindicated
PREGNANCY
C
FDA category + note
Top interactionssee all 12 →
- MethotrexateContraindicatedDatabaseDDInter
- BaricitinibSevereDatabaseDDInter
- Glycerol PhenylbutyrateSevereDatabaseDDInter
- KetorolacSevereDatabaseDDInter
Mechanism
Probenecid inhibits URAT1, the urate transporter on renal tubular cells that facilitates reabsorption of urate from the urine, thereby promoting urate excretion. It also competes with penicillin at organic anion transporters OAT1 and OAT3 in tubular secretion.
Indications
hyperuricemia (gout)prolonging therapeutic effect of penicillinHyperuricemia associated with gout (but not for acute attacks)Adjuvant to prolong the dwell time of penicillin and other β-lactam antibiotics in the body
Dosing
- Adult
- For gout: starting dose is 250 mg twice daily, increasing over 1 to 2 weeks to 500 to 1000 mg twice daily. After 6 months, if serum uric acid levels are within normal limits and no gout attacks, dose may be tapered off by 500 mg every 6 months. As an adjuvant to prolong penicillin dwell time: 1–2 g/day.
Pharmacokinetics
Onset
Absorbed completely after oral administration. Peak plasma concentrations are reached in 2 to 4 h.
Half-life
Dose dependent, varies from less than 5 to more than 8 h (plasma)
Protein binding
Between 85% and 95% of the drug is bound to plasma albumin.
Metabolism
Hydroxylated to metabolites that retain carboxyl function and have uricosuric activity. A small amount of probenecid glucuronide appears in the urine.
Excretion
Probenecid blocks the active transport of organic acids (like penicillin) and uric acid in the renal tubules.
Contraindications
- Ineffective in patients with renal insufficiency
- Should be avoided in patients with creatinine clearance of less than 50 mL/min
- Should not be used in gouty patients with nephrolithiasis
- Should not be used in gouty patients with overproduction of uric acid
Side effects
Common
Mild GI irritation (in approximately 2% of patients, increased at higher doses)Hypersensitivity reactions (in 2% to 4% of patients, usually mild)
Serious
- CNS stimulation (with substantial overdosage)
- Convulsions (with substantial overdosage)
- Death from respiratory failure (with substantial overdosage)
Pregnancy & lactation
Pregnancy
C
Drug interactions
Baricitinib
Severe
Database
Decreases renal clearance and increases the AUC of baricitinib.
Not specified, but implies dose adjustment or monitoring.
Source: DDInter
Glycerol Phenylbutyrate
Severe
Database
Clinical effect not specified
Source: DDInter
Ketorolac
Severe
Database
Increased plasma concentrations of ketorolac, thereby promoting adverse effects.
Ketorolac should not be used in combination with probenecid.
Source: DDInter
Pegloticase
Severe
Database
Clinical effect not specified
Source: DDInter
Pexidartinib
Severe
Database
Clinical effect not specified
Source: DDInter
Phenylbutyric Acid
Severe
Database
Clinical effect not specified
Source: DDInter
Bendroflumethiazide
Moderate
Textbook
Attenuates the diuretic response to thiazides.
Not explicitly stated, but suggests caution or dose adjustment.
Source: G&G 14e · p567
Cephalosporins
Moderate
Textbook
Increased cephalosporin levels.
Source: KDT 7e · p215
Chlorthalidone
Moderate
Textbook
Attenuates the diuretic response to thiazides.
Not explicitly stated, but suggests caution or dose adjustment.
Source: G&G 14e · p567
Ethambutol
Moderate
Textbook
Reduced efficacy of probenecid.
Source: KDT 7e · p215
Hydrochlorothiazide
Moderate
Textbook
Attenuates the diuretic response to thiazides.
Not explicitly stated, but suggests caution or dose adjustment.
Source: G&G 14e · p567
Related guidelines
Other Unclassified drugs
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Sources: KD Tripathi 7e, Goodman & Gilman 14e·Verified: 2026-05-10 · House clinical team