(proe BEN e sid)
- Benemid [DSC]
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Generic: 500 mg
- Uricosuric Agent
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
Rapid and complete
Onset of Action
Effect on penicillin levels: 2 hours; Uric acid renal clearance: 30 minutes
Time to Peak
Serum: 2 to 4 hours
Dose dependent: Normal renal function: 6 to 12 hours
85% to 95%
Use: Labeled Indications
Treatment of hyperuricemia associated with gout or gouty arthritis; prolongation and elevation of beta-lactam plasma levels
Gout: Uricosurics, such as probenecid, are recommended alone or in combination with allopurinol in patients without proper control with allopurinol alone (EULAR [Richette 2016]).
Off Label Uses
Neurosyphilis, including ocular syphilis
Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, probenecid in combination with procaine penicillin G is an effective and recommended alternative regimen in the treatment neurosyphilis, including ocular syphilis.
Pelvic inflammatory disease
Based on the CDC sexually transmitted diseases treatment guidelines, probenecid (in combination with cefoxitin plus doxycycline with or without metronidazole) is an effective and recommended regimen for the treatment of mild to moderately severe acute pelvic inflammatory disease.
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
Hyperuricemia with gout: Oral: 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: Oral: 500 mg 4 times/day. Note: Dosing per manufacturer, see indication-specific dosing.
Neurosyphilis, including ocular syphilis (alternative to preferred therapy) (off-label use): Oral: 500 mg 4 times/day plus procaine penicillin IM for 10 to 14 days (CDC [Workowski 2015]).
Pelvic inflammatory disease (off-label use): Oral: 1 g as a single dose in combination with cefoxitin IM as a single dose plus oral doxycycline (with or without oral metronidazole) to complete 14 days of therapy (CDC [Workowski 2015])
Refer to adult dosing.
Note: Contraindicated in children <2 years of age.
Prolong penicillin serum levels: Children ≥2 years and Adolescents: Oral:
Patient weight ≤50 kg: Initial: 25 mg/kg/dose or 700 mg/m2/dose as a single dose; maintenance: 40 mg/kg/day or 1,200 mg /m2/day in 4 divided doses; maximum dose: 500 mg
Patient weight >50 kg: 500 mg 4 times daily
Dosing: Renal Impairment
GFR <30 mL/minute: Avoid use (reduced efficacy with renal impairment)
Note: Probenecid is not recommended as first-line urate-lowering therapy (ULT) monotherapy in patients with renal impairment (CrCl <50 mL/minute) (Khanna 2012).
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer’s labeling.
Administer with food to minimize GI effects.
Drug may cause GI upset; take with food if GI upset. Drink plenty of fluids.
Store at 20°C to 25°C (68°F to 77°F). Protect from light.
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
Anagliptin: Probenecid may increase the serum concentration of Anagliptin. Monitor therapy
Avibactam: Probenecid may increase the serum concentration of Avibactam. Avoid combination
Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Monitor therapy
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. Management: Avoid the routine use of penicillins and probenecid, but this combination may be used advantageously in select cases with careful monitoring. Monitor for toxic effects of penicillins if probenecid is initiated or the dose is increased. Consider therapy modification
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
Quinolones: Probenecid may decrease the excretion of Quinolones. Specifically, probenecid may decreased the renal excretion of quinolone antibiotics. Probenecid may increase the serum concentration of Quinolones. Exceptions: Moxifloxacin (Systemic). 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
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
Frequency not defined.
Central nervous system: Dizziness, headache, pain (costovertebral)
Dermatologic: Alopecia, dermatitis, pruritus, skin rash
Endocrine & metabolic: Gouty arthritis (acute)
Gastrointestinal: Anorexia, dyspepsia, gastroesophageal reflux disease, gingival pain, nausea, vomiting
Genitourinary: Hematuria, nephrotic syndrome
Hematologic & oncologic: Anemia, aplastic anemia, hemolytic anemia (in G6PD deficiency), leukopenia
Hepatic: Hepatic necrosis
Hypersensitivity: Anaphylaxis, hypersensitivity reaction
Renal: Polyuria, renal colic
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.
• 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.
Serum uric acid, urinary uric acid, renal function, CBC, frequency of gout attacks (Khanna 2012)
Probenecid crosses the placenta. Based on available data, an increased risk of adverse fetal events have not been reported (Gutman, 2012).
• 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, flushing, nausea, vomiting, gum edema, gum soreness, or hair loss. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice, signs of a kidney stone (back pain, abdominal pain, or hematuria), pharyngitis, chills, bruising, bleeding, or severe loss of strength and energy (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 health care 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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- Drug class: antigout agents