PROBENECID

PROBENECID
(proe-ben'e-sid)
Benemid, Benuryl , Probalan, SK-Probenecid
Classifications: antigout agent; sulfonamide; uricosuric agent;
Therapeutic:antigout
; uricosuric agent
Pregnancy Category: B

Availability

0.5 g tablet

Action

Sulfonamide-derivative renal tubular blocking agent. In sufficiently high doses, competitively inhibits renal tubular reabsorption of uric acid, thereby promoting its excretion and reducing serum urate levels.

Therapeutic Effect

Prevents formation of new tophaceous deposits and causes gradual shrinking of old tophi by preventing uric acid build-up in the serum and tissues. As an additive to penicillin, it increases the serum concentration of the antibiotic, and also prolongs the serum concentration of the penicillins.

Uses

Hyperuricemia in chronic gouty arthritis and tophaceous gout.

Unlabeled Uses

Adjuvant to therapy with penicillin G and penicillin analogs to elevate and prolong plasma concentrations of these antibiotics; to promote uric acid excretion in hyperuricemia secondary to administration of thiazides and related diuretics, furosemide, ethacrynic acid, pyrazinamide.

Contraindications

Blood dyscrasias; uric acid kidney stones; during or within 2–3 wk of acute gouty attack; overexcretion of uric acid (>1000 mg/d); patients with creatinine clearance <50 mg/min; use with penicillin in presence of known renal impairment; use for hyperuricemia secondary to cancer chemotherapy. Safe use in children <2 y is not established.

Cautious Use

History of peptic ulcer; pregnancy (category B), lactation.

Route & Dosage

Gout
Adult: PO 250 mg b.i.d. for 1 wk, then 500 mg b.i.d. (max: 3 g/d)

Adjunct for Penicillin or Cephalosporin Therapy
Adult: PO 500 mg q.i.d. or 1 g with single dose therapy (e.g., gonorrhea)
Child (2–14 y or <50 kg): PO 25–40 mg/kg/d in 4 divided doses

Administration

Oral
  • Therapy is usually not initiated during an acute gouty attack. Consult physician.
  • Minimize GI adverse effects by giving after meals, with food, milk, or antacid (prescribed). If symptoms persist, dosage reduction may be required.
  • Give with a full glass of water if not contraindicated.
  • Be aware that physician may prescribe concurrent prophylactic doses of colchicine for first 3–6 mo of therapy because frequency of acute gouty attacks may increase during first 6–12 mo of therapy.

Adverse Effects (≥1%)

Body as a Whole: Flushing, dizziness, fever, anaphylaxis. CNS: Headache. GI: Nausea, vomiting, anorexia, sore gums, hepatic necrosis (rare). Urogenital: Urinary frequency. Hematologic: Anemia, hemolytic anemia (possibly related to G6PD deficiency), aplastic anemia (rare). Musculoskeletal: Exacerbations of gout, uric acid kidney stones. Skin: Dermatitis, pruritus. Respiratory: Respiratory depression.

Diagnostic Test Interference

False-positive urine glucose tests are possible with Benedict's solution or Clinitest [glucose oxidase methods not affected (e.g., Clinistix, TesTape)].

Interactions

Drug: salicylates may decrease uricosuric activity; may decrease methotrexate elimination, causing increased toxicity; decreases nitrofurantoin efficacy and increases its toxicity. Decreases clearance of penicillins, cephalosporins, and NSAIDs.

Pharmacokinetics

Absorption: Readily from GI tract. Onset: 30 min. Peak: 2–4 h. Duration: 8 h. Distribution: Crosses placenta. Metabolism: In liver. Elimination: In urine. Half-Life: 4–17 h.

Nursing Implications

Assessment & Drug Effects

  • Decrease daily dosage with caution by 0.5 g q6mo to lowest effective dosage that maintains stable serum urate levels when gouty attacks have been absent for 6 mo or more and serum urate levels are controlled.
  • Lab tests: Periodic serum urate levels, Hct and Hgb, and urinalysis. Determine acid–base balance periodically when urinary alkalinizers are used. Some physicians prescribe acetazolamide at bedtime to keep urine alkaline and dilute throughout night.
  • Patients taking sulfonylureas may require dosage adjustment. Probenecid enhances hypoglycemic actions of these drugs (see DIAGNOSTIC TEST INTERFERENCES).
  • Expect urate tophaceous deposits to decrease in size. Classic locations are in cartilage of ear pinna and big toe, but they can occur in bursae, tendons, skin, kidneys, and other tissues.

Patient & Family Education

  • Drink fluid liberally (approximately 3000 mL/d) to maintain daily urinary output of at least 2000 mL or more. This is important because increased uric acid excretion promoted by drug predisposes to renal calculi.
  • Physician may advise restriction of high-purine foods during early therapy until uric acid level stabilizes. Foods high in purine include organ meats (sweetbreads, liver, kidney), meat extracts, meat soups, gravy, anchovies, and sardines. Moderate amounts are present in other meats, fish, seafood, asparagus, spinach, peas, dried legumes, wild game.
  • Avoid alcohol because it may increase serum urate levels.
  • Do not stop taking drug without consulting physician. Irregular dosage schedule may sharply elevate serum urate level and precipitate acute gout.
  • Be aware that lifelong therapy is usually required in patients with symptomatic hyperuricemia. Keep scheduled appointments with physician and for kidney function and hematology lab work.
  • Report symptoms of hypersensitivity to physician. Discontinuation of drug is indicated.
  • Do not take aspirin or other OTC medications without consulting physician. If a mild analgesic is required, acetaminophen is usually allowed.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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