Probenecid
BENEMID
What it isUricosuric blocking renal urate reabsorption; gout, and used deliberately to raise penicillin levels.
Why this oneIt lowers urate in underexcretors, and its blockade of tubular secretion is exploited to prolong beta-lactam exposure.
What limits itIneffective below eGFR 30, and it precipitates stones without hydration and alkalinization. It raises methotrexate toxicity.
FDA-approved for
- gout (~1951)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Hyperuricemia of gout and gouty arthritis | Adult | 250 mg BID x1 week | 500 mg BID | Usually <=2000 mg/day (increase 500 mg q4wk as needed) |
| Adjuvant to penicillin/beta-lactam therapy (raises antibiotic levels) | Adult | 500 mg QID (2 g/day) | 2 g/day divided | 2 g/day; reduce in elderly with renal impairment |
| Adjuvant to penicillin therapy | Children 2-14 yr (<=50 kg) | 25 mg/kg initial | 40 mg/kg/day divided QID | >50 kg: use adult dose |
| Uncomplicated gonorrhea (with penicillin/ampicillin/amoxicillin regimen) | Adult | 1 g PO once | Single dose | 1 g x1 |
Titration Gout: increase by 500 mg/day every 4 weeks if arthritis symptoms uncontrolled or 24-h urate excretion <=700 mg (usually not above 2 g/day)
Renal May be ineffective when GFR <=30 mL/min; dosage requirements may be increased in renal impairment; not recommended with penicillins in known renal impairment
Hepatic Undefined
Half-tablet (250 mg) dosing uses the scored 500 mg tablet
Instructions
- Do not start until an acute gouty attack has subsided; if an attack is precipitated during therapy, continue probenecid and treat the attack (e.g., colchicine)
- Maintain liberal fluid intake and alkalinize urine (sodium bicarbonate 3-7.5 g/day or potassium citrate 7.5 g/day) until serum urate normalizes
- Gastric intolerance may indicate overdosage — reduce dose
- After >=6 months attack-free with normal urate, may decrease by 500 mg every 6 months
Contraindications
- Children under 2 years of age
- Known blood dyscrasias
- Uric acid kidney stones
- Initiation during an acute gouty attack
- Concomitant salicylates (any dose — antagonize uricosuric action; use acetaminophen instead)
Cautions
- Exacerbation of gout on initiation — treat with colchicine or other appropriate therapy
- Severe allergic reactions and anaphylaxis (rare; typically within hours of re-administration) — stop drug
- Hematuria, renal colic, and uric acid stone formation — prevent with alkalinization and liberal fluids
- Increases plasma methotrexate concentrations/toxicity — reduce methotrexate dose and monitor levels
- Use caution with history of peptic ulcer
- May cause false-positive urine reducing-substance (glucose) tests
Adverse reactions
- Headache, dizziness
- Precipitation of acute gouty arthritis
- Nausea, vomiting, anorexia, sore gums; hepatic necrosis (rare)
- Nephrotic syndrome, uric acid stones with/without hematuria, renal colic, urinary frequency
- Anaphylaxis, fever, urticaria, pruritus
- Aplastic anemia, leukopenia, hemolytic anemia (may be G6PD-related), anemia
- Dermatitis, alopecia, flushing
Pregnancy Crosses the placenta and appears in cord blood; weigh anticipated benefit against possible hazards.
Lactation Undefined
NO BOXED WARNINGS
Principal riskStones without hydration; it raises methotrexate toxicity
Cost, est. cash$10–$300/month
Generic entry1982
Classes and tags
Clinical profile
Legacy pregnancy categoryC
Defining liabilityGenerally tolerated at therapeutic doses; clinically important risks are agent-specific and increase with interactions or organ impairment.
Mechanism of action: Probenecid ballicule
Open Probenecid in the interactive console ↗
Memory aids: mascots and interaction avatars
OAT inhibitor
