Probenecid
BENEMID
Pronunciation: proe-BEN-e-sid
“Proboscis nekkid”
OAT inhibitor
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.
Probenecid prescription history
Animated chart of estimated U.S. prescriptions per year, Gout meds (1918–2026). Probenecid enters in 1951 (estimated).
FDA-approved for
- gout (~1951)
Principal riskStones without hydration; it raises methotrexate toxicity
Sulfonamide
Sulfonamide-derived drug — label silent
An N,N-dipropyl sulfonamide with no N4 aromatic amine and no N1 heterocycle; the label carries no sulfonamide warning. Not named by Khan; the evidence for the non-antimicrobials as a group says cross-reactivity is unlikely.
Open the sulfonamide hypersensitivity presentation → · sources [n] are on its References slide.
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.
FDA label
Read the full label on DailyMed ↗
NO BOXED WARNINGS
| 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
Available strengths
- tab 500 mg
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
Cost
| Strength | #/mo | generic $/mo | CostPlus | |
|---|---|---|---|---|
| 500 mg | tab | 60 BID | $38.17 | offered |
Generic entry1982
Open Probenecid in the interactive console ↗
Memory aids: interaction avatars
Open Probenecid in the interactive console ↗
Self-check
- Probenecid: Below what eGFR is it described as ineffective?
30. - Probenecid: Which antimetabolite's toxicity increases?
Methotrexate.