Colchicine Probenecid

What is Colchicine Probenecid

Colchicine and probenecid are used together to treat chronic gouty arthritis complicated by frequent, acute attacks.

Low-dose colchicine is used as to reduce inflammation, pain, and the risk of acute flares along with the initiation of uric acid lowering treatments (ULTs); the duration of treatment (at least 8 weeks and up to 6 months) is dependent on patient-specific factors such as the presence of tophi.

The NSAIDs or corticosteroids are other options.

Probenecid is a uricosuric agent that inhibits the tubular reabsorption of uric acid but is not a first-line agent for gout prophylaxis.

Combination treatment with probenecid and colchicine should not be started until an acute gouty attack has subsided.

However, if an acute flare is precipitated during use, the combination may be continued while additional colchicine or other appropriate therapy are given to control the acute attack.

For chronic gout management, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) guidelines recommend ULT to achieve a target serum uric acid (sUA) level of less than 6 mg/dL to prevent the formation of crystals and to eliminate crystal deposition, thereby dissolving tophi; a lower target (less than 5 mg/dL) is recommended for patients with severe disease.

ULTs such as allopurinol, febuxostat, and lesinurad are considered more effective than probenecid at achieving treatment goals. Treatment guidelines recommend combination therapy with a uricosuric plus a xanthine oxidase inhibitor (XOI) when treatment goals are not met with an XOI alone; use of pegloticase is usually reserved for severe, refractory chronic gout.

Probenecid is considered an alternative agent when other medications are contraindicated or are not tolerated by the patient.

Care must be used in the chronic use of either colchicine or probenecid. Use of colchicine is limited by a significant risk of toxicity, which may be higher in patients taking inhibitors of P-glycoprotein (P-gp) or strong CYP3A4 inhibitors, and in those with significant renal or hepatic impairment.

Probenecid may also cause significant drug-drug interactions, may precipitate uric acid kidney stones in patients at risk, and is not effective in patients with severe renal dysfunction.

Indications

  • gout
  • gouty arthritis

For the treatment of chronic gouty arthritis complicated by frequent acute gout flares

Side Effects

  1. abdominal pain
  2. agranulocytosis
  3. alopecia
  4. anaphylactic shock
  5. anemia
  6. anorexia
  7. aplastic anemia
  8. atopic dermatitis
  9. azoospermia
  10. costovertebral pain
  11. diarrhea
  12. dizziness
  13. fever
  14. flushing
  15. gout
  16. headache
  17. hematuria
  18. hemolytic anemia
  19. hepatic necrosis
  20. increased urinary frequency
  21. leukopenia
  22. nausea
  23. nephrolithiasis
  24. nephrotic syndrome
  25. neuritis
  26. neutropenia
  27. oligospermia
  28. oliguria
  29. peripheral neuropathy
  30. pruritus
  31. purpura
  32. spermatogenesis inhibition
  33. urticaria
  34. vitamin B12 deficiency
  35. vomiting

Monitoring Parameters

  • CBC
  • LFTs
  • serum creatinine/BUN
  • serum uric acid
  • urinalysis

Contraindications

  • accidental exposure
  • aplastic anemia
  • biliary obstruction
  • bone marrow suppression
  • breast-feeding
  • children
  • dialysis
  • G6PD deficiency
  • geriatric
  • hematological disease
  • hemolytic anemia
  • hepatic disease
  • infants
  • infertility
  • laboratory test interference
  • myopathy
  • neonates
  • nephrolithiasis
  • peptic ulcer disease
  • potential for overdose or poisoning
  • pregnancy
  • probenecid hypersensitivity
  • renal failure
  • renal impairment
  • reproductive risk
  • rhabdomyolysis
  • sulfonamide hypersensitivity

Interactions

  • Abacavir; Lamivudine, 3TC; Zidovudine, ZDV
  • Acetaminophen; Aspirin, ASA; Caffeine
  • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
  • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
  • Acidifying Agents
  • Acyclovir
  • Aliskiren; Amlodipine
  • Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
  • Alkalinizing Agents
  • Allopurinol
  • Alprazolam
  • Aminosalicylate sodium, Aminosalicylic acid
  • Amiodarone
  • Amitriptyline; Chlordiazepoxide
  • Amlodipine
  • Amlodipine; Atorvastatin
  • Amlodipine; Benazepril
  • Amlodipine; Celecoxib
  • Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan
  • Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan
  • Amlodipine; Olmesartan
  • Amlodipine; Telmisartan
  • Amlodipine; Valsartan
  • Amoxicillin
  • Amoxicillin; Clarithromycin; Lansoprazole
  • Amoxicillin; Clarithromycin; Omeprazole
  • Amoxicillin; Clavulanic Acid
  • Ampicillin
  • Ampicillin; Sulbactam
  • Amprenavir
  • Aprepitant, Fosaprepitant
  • Aspirin, ASA
  • Aspirin, ASA; Butalbital; Caffeine
  • Aspirin, ASA; Butalbital; Caffeine; Codeine
  • Aspirin, ASA; Caffeine; Dihydrocodeine
  • Aspirin, ASA; Caffeine; Orphenadrine
  • Aspirin, ASA; Carisoprodol
  • Aspirin, ASA; Carisoprodol; Codeine
  • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
  • Aspirin, ASA; Dipyridamole
  • Aspirin, ASA; Omeprazole
  • Aspirin, ASA; Oxycodone
  • Aspirin, ASA; Pravastatin
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  • Carbidopa; Levodopa; Entacapone
  • Carvedilol
  • Cefaclor
  • Cefditoren
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  • Cefprozil
  • Ceftazidime; Avibactam
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  • Deferiprone
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  • Dextromethorphan; Quinidine
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  • Diclofenac; Misoprostol
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  • grapefruit juice
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  • Lovastatin; Niacin
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  • Lumateperone
  • Magnesium Salicylate
  • Maraviroc
  • Mecamylamine
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  • Mefenamic Acid
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  • Venetoclax
  • Verapamil
  • Voriconazole
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  • Zidovudine, ZDV
  • Zonisamide
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