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Probenecid

Pronunciation

Pronunciation

(proe BEN e sid)

Index Terms

  • Benemid [DSC]

Dosage Forms

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

Tablet, Oral:

Generic: 500 mg

Pharmacologic Category

  • Uricosuric Agent

Pharmacology

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

Absorption

Rapid and complete

Metabolism

Hepatic

Excretion

Urine

Onset of Action

Effect on penicillin levels: 2 hours

Time to Peak

Serum: 2-4 hours

Half-Life Elimination

Dose dependent: Normal renal function: 6-12 hours

Use: Labeled Indications

Treatment of hyperuricemia associated with gout or gouty arthritis; prolongation and elevation of beta-lactam plasma levels (eg, uncomplicated gonococcal infection)

Use: Unlabeled

Prolongation and elevation of beta-lactam plasma levels (eg, neurosyphilis, pelvic inflammatory disease)

Contraindications

Hypersensitivity to probenecid or any component of the formulation; small- or large-dose aspirin therapy; blood dyscrasias; uric acid kidney stones; children <2 years of age; initiation during an acute gout attack

Dosage

Oral:

Children:

<2 years: Contraindicated

2-14 years: Prolong penicillin serum levels: Initial: 25 mg/kg, then 40 mg/kg/day in 4 divided doses (maximum: 500 mg/dose)

Gonorrhea: >50 kg: Refer to adult dosing.

Adults:

Hyperuricemia with gout: 250 mg twice daily for 1 week; may increase to 500 mg twice daily; if needed, may increase to a maximum of 2 g/day (increase dosage in 500 mg increments every 4 weeks). If serum uric acid levels are within normal limits and gout attacks have been absent for 6 months, daily dosage may be reduced by 500 mg every 6 months.

Prolong penicillin serum levels: 500 mg 4 times/day. Note: Dosing per manufacturer, see indication-specific dosing.

Gonorrhea, uncomplicated infections of cervix, urethra, and rectum: Oral: 1 g once with cefoxitin 2 g IM (CDC, 2010)

Pelvic inflammatory disease (off-label use): Oral: 1 g once with cefoxitin 2 g IM plus doxycycline (CDC, 2010)

Neurosyphilis (off-label use): Oral: 500 mg 4 times/day with procaine penicillin 2.4 million units/day IM for 10-14 days (CDC, 2010). Note: Penicillin G aqueous IV is the preferred agent.

Dosing adjustment in renal impairment: CrCl <30 mL/minute: Avoid use.

Dosing adjustment in hepatic impairment: No dosage adjustment provided in manufacturer’s labeling.

Administration

Administer with food or antacids to minimize GI effects.

Dietary Considerations

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

Storage

Store at 20°C to 25°C (68°F to 77°F). Protect from light.

Drug Interactions

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. Consider therapy modification

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

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

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

Dapsone (Systemic): Probenecid may increase the serum concentration of Dapsone (Systemic). Monitor therapy

Deferiprone: UGT1A6 Inhibitors may increase the serum concentration of Deferiprone. Monitor therapy

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

Doripenem: Probenecid may increase the serum concentration of Doripenem. This effect is due to probenecid's ability to decrease the active tubular secretion of doripenem. Avoid combination

Ertapenem: Probenecid may increase the serum concentration of Ertapenem. Monitor therapy

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

Gemifloxacin: Probenecid may decrease the excretion of Gemifloxacin. Monitor therapy

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

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

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

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

Loop Diuretics: Probenecid may enhance the adverse/toxic effect of Loop Diuretics. Probenecid may diminish the diuretic effect of Loop Diuretics. Probenecid may increase the serum concentration of Loop Diuretics. Management: Monitor for decreased diuretic effects or increased adverse effects of loop diuretics with concomitant use of probenecid. Bumetanide prescribing information recommends against concomitant use of probenecid. Monitor therapy

LORazepam: Probenecid may increase the serum concentration of LORazepam. Consider therapy modification

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

Methotrexate: Probenecid may increase the serum concentration of Methotrexate. Management: Avoid concomitant use of probenecid and methotrexate if possible. If used together, consider lower methotrexate doses and monitor for evidence of methotrexate toxicity. Consider therapy modification

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

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

Nitrofurantoin: Probenecid may increase the serum concentration of Nitrofurantoin. Monitor therapy

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

Oseltamivir: Probenecid may increase serum concentrations of the active metabolite(s) of Oseltamivir. Management: Consider a change in therapy when using oseltamivir together with probenecid; reduced oseltamivir dose may be necessary. Increase monitoring for adverse events, such as thrombocytopenia. Consider therapy modification

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. Avoid combination

Penicillins: Probenecid may increase the serum concentration of Penicillins. Avoid combination

PRALAtrexate: Probenecid may increase the serum concentration of PRALAtrexate. Monitor therapy

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. Consider therapy modification

Quinolone Antibiotics: Probenecid may increase the serum concentration of Quinolone Antibiotics. Monitor therapy

Salicylates: May diminish the therapeutic effect of Probenecid. Monitor therapy

Sodium Benzoate: Probenecid may increase the serum concentration of Sodium Benzoate. Specifically, probenecid may inhibit the renal transport of the hippuric acid metabolite of sodium benzoate. Monitor therapy

Sodium Phenylacetate: Probenecid may increase the serum concentration of Sodium Phenylacetate. Specifically, probenecid may inhibit the renal transport of the phenylacetylglutamine metabolite of sodium phenylacetate. Monitor therapy

Sulfonylureas: Probenecid may decrease the protein binding of Sulfonylureas. Probenecid may increase the serum concentration of Sulfonylureas. Monitor therapy

Theophylline Derivatives: Probenecid may increase the serum concentration of Theophylline Derivatives. Exceptions: Aminophylline; Theophylline. 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. Monitor therapy

Zidovudine: Probenecid may decrease the metabolism of Zidovudine. Monitor therapy

Test Interactions

False-positive glucosuria with Clinitest®, a falsely high determination of theophylline has occurred and the renal excretion of phenolsulfonphthalein 17-ketosteroids and bromsulfophthalein (BSP) may be inhibited

Adverse Reactions

Frequency not defined.

Cardiovascular: Flushing

Central nervous system: Dizziness, fever, headache

Dermatologic: Alopecia, dermatitis, pruritus, rash

Gastrointestinal: Anorexia, dyspepsia, gastroesophageal reflux, nausea, sore gums, vomiting

Genitourinary: Hematuria, polyuria

Hematologic: Anemia, aplastic anemia, hemolytic anemia (in G6PD deficiency), leukopenia

Hepatic: Hepatic necrosis

Neuromuscular & skeletal: Costovertebral pain, gouty arthritis (acute)

Renal: Nephrotic syndrome, renal colic

Miscellaneous: Anaphylaxis, hypersensitivity

Warnings/Precautions

Concerns related to adverse effects:

• Allergic 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.

• Renal impairment: Monotherapy may not be effective in patients with a creatinine clearance <30 mL/minute. The American College of Rheumatology guidelines for the treatment of hyperuricemia do not recommend probenecid as first-line or an alternative first-line therapy in patients with a creatinine clearance <50 mL/minute (ACR guidelines [Khanna, 2012]).

Concurrent drug therapy issues:

• Methotrexate: Probenecid may increase the serum concentration of methotrexate. Avoid concomitant use of probenecid and methotrexate if possible. If used together, consider lower methotrexate doses and monitor for methotrexate toxicity.

• Penicillin: Use of probenecid with penicillin in patients with renal insufficiency is not recommended.

• Salicylates: Salicylates may diminish the therapeutic effect of probenecid; this effect may be more pronounced with high, chronic doses, however, the manufacturer recommends the use of an alternative analgesic even in place of small doses of aspirin.

Monitoring Parameters

Uric acid, renal function, CBC

Pregnancy Considerations

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

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, headache, lack of appetite, nausea, or alopecia. Have patient report immediately to prescriber back pain, dyspepsia, hematuria, urinary retention, oliguria, ecchymosis, hemorrhaging, or severe asthenia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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