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probenecid (Benemid, Probalan)
Tradenames: Benemid, Probalan.
Indications:
1) treatment of gout, hyperuricemia
2) NOT to be used for acute attacks of gout
3) used to prolong action of penicillins & some, but not all cephalosporins
Contraindications:
1) history of renal stones (nephrolithiasis)
2) ineffective in patients with renal failure
- eGFR < 30-60 mL/min/1.73 m2 [6,7]
Dosage:
1) gout:
a) 250 mg PO BID x 7 days, then 500 mg PO BID [1]
b) start 500 mg PO QD [2]
c) to prevent renal colic from uric acid stones, liberalize fluid intake & alkalinize urine with 3-7.5 g of NaHCO3 until urate levels normalize
d) use in conjunction with colchicine
2) adjunct to penicillin injection:
a) adults: 1 g PO X 1
b) children 2-14 years: 25 mg/kg (initial), then 10 mg/kg QID
Tabs: 500 mg
Pharmacokinetics:
1) 74-99% bound to plasma proteins
2) metabolized or conjugated
3) elimination displays Michaelis-Menton elimination
4) < 5% of drug is excreted unchanged
Adverse effects:
1) common (> 10%)
- gouty arthritis (acute), headache, anorexia, nausea/vomiting
2) less common (1-10%)
- dizziness, flushing of face, sore gums, rash, itching, urinary frequency & painful urination, renal calculi
3) uncommon (< 1%)
- urate nephropathy, nephrotic syndrome, leukopenia, hepatic necrosis, hemolytic anemia, aplastic anemia, anaphylaxis
Drug interactions:
1) salicylates block uricosuric effect of probenecid
2) acyclovir, dapsone, methotrexate, NSAIDs, rifampin, sulfonamides, zidovudine levels are increased by probenecid
3) benzodiazepines have a faster onset & prolonged effect
4) allopurinol is synergistic with probenecid in lowering uric acid
Mechanism of action:
1) inhibits renal tubular resorption of urate, increasing urate elimination
2) inhibits tubular excretion of many antibiotics
3) inhihits OAT3, which is used by viruses including SARS-CoV2, influenza & RSV to transport & package viral proteins in infected cells.
Comparative biology:
- probenecid inhibits replication of SARS-CoV2, influenza & RSV in animal models & human lung cells [8]
Interactions
drug interactions
drug adverse effects of sulfonamides
General
sulfonamide
uricosuric agent
Properties
MISC-INFO: elimination route KIDNEY
LIVER
pregnancy-category B
safety in lactation ?
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed)
Lippincott-Raven, Philadelphia, 1998, pg 860
- Drug Information & Medication Formulary, Veterans Affairs,
Central California Health Care System, 1st ed., Ravnan et al
eds, 1998
- Kaiser Permanente Northern California Regional Drug
Formulary, 1998
- Geriatrics Review Syllabus, American Geriatrics Society,
5th edition, 2002-2004
- Medical Knowledge Self Assessment Program (MKSAP) 18,
American College of Physicians, Philadelphia 2018
- A Pocket Guide to the 2019 Beer's Criteria.
American Geriatrics Society.
- Laday J
Prophylaxis, treatment with probenecid inhibits 'virus replication' in
COVID-19, flu, RSV.
Helios. 2021. Sept 13.
https://www.healio.com/news/rheumatology/20210910/prophylaxis-treatment-with-probenecid-inhibits-virus-replication-in-covid19-flu-rsv
Component-of
colchicine/probenecid (ColBENEMID)
probenecid/sulopenem etzadroxil