Colchicine and Probenecid

Medically reviewed on March 25, 2018

Pronunciation

(KOL chi seen & proe BEN e sid)

Index Terms

• ColBenemid
• Probenecid and Colchicine

Dosage Forms

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

Tablet: Colchicine 0.5 mg and probenecid 0.5 g

Pharmacologic Category

• Anti-inflammatory Agent
• Antigout Agent
• Uricosuric Agent

Use: Labeled Indications

Treatment of chronic gouty arthritis when complicated by frequent, recurrent acute attacks of gout

Contraindications

Hypersensitivity to colchicine, probenecid, or any component of the formulation; children <2 years of age; small- or large-dose aspirin therapy; blood dyscrasias; uric acid kidney stones; initiation during an acute gout attack; concomitant use of a P-glycoprotein (P-gp) or strong CYP3A4 inhibitor in presence of renal or hepatic impairment

Dosing: Adult

Gout: Oral: Colchicine 0.5 mg and probenecid 0.5 g: One tablet once daily for 1 week, then 1 tablet twice daily thereafter

Note: Current prescribing information states a maximum dose of 4 tablets per day; however this exceeds the usual maximum dose of colchicine for gout prophylaxis (1.2 mg per day).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

GFR <30 mL/minute: Probenecid may not be effective in patients with chronic renal insufficiency.

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

No dosage adjustment provided in manufacturer's labeling; use with caution.

Administration

Do not initiate therapy until acute attack has subsided.

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

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

Antihepaciviral Combination Products: May increase the serum concentration of Colchicine. Avoid combination

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

Ceritinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of ceritinib with a narrow therapeutic index CYP3A substrate (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus) should be avoided when possible. Monitor therapy

Choline C 11: Colchicine may diminish the therapeutic effect of Choline C 11. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Cyanocobalamin: Colchicine may decrease the serum concentration of Cyanocobalamin. Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. See full monograph for details. Use extra caution in patients with impaired renal and/or hepatic function. Consider therapy modification

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details. Consider therapy modification

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

Digoxin: May increase the serum concentration of Colchicine. 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

Fibric Acid Derivatives: May enhance the myopathic (rhabdomyolysis) effect of Colchicine. Monitor therapy

Fosamprenavir: May increase the serum concentration of Colchicine. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are receiving ritonavir-boosted fosamprenavir. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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

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

Grapefruit Juice: May increase the serum concentration of Colchicine. Avoid combination

HMG-CoA Reductase Inhibitors (Statins): Colchicine may enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Consider therapy modification

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

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

Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

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

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

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

Multivitamins/Fluoride (with ADE): Colchicine may decrease the serum concentration of Multivitamins/Fluoride (with ADE). Specifically, colchicine may decrease absorption of cyanocobalamin (vitamin B12). Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): Colchicine may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, colchicine may decrease the serum concentration of Cyanocobalamin. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): Colchicine may decrease the serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, colchicine may decrease absorption of cyanocobalamin (vitamin B12). 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

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

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

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details. 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

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

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

Tacrolimus (Systemic): May increase the serum concentration of Colchicine. Monitor therapy

Telaprevir: May increase the serum concentration of Colchicine. Management: Colchicine should not be used with telaprevir in patients with impaired renal or hepatic function. In those with normal renal and hepatic function, reduced colchicine doses (as directed) are required if used with telaprevir. Consider therapy modification

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

Tipranavir: May increase the serum concentration of Colchicine. Management: Colchicine should not be used with tipranavir in patients with impaired renal or hepatic function. In those with normal renal and hepatic function, reduced colchicine doses (as directed) are required if used with tipranavir. Consider therapy modification

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

Adverse Reactions

See individual agents.

Warnings/Precautions

See individual agents.

Monitoring Parameters

CBC, renal function, serum uric acid, urinary uric acid, frequency of gout attacks (Khanna 2012).

Pregnancy Considerations

See individual agents.

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, flushing, lack of appetite, or hair loss. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), burning or numbness feeling, severe nausea, vomiting, severe diarrhea, signs of a kidney stone (back pain, abdominal pain, or hematuria), urinary retention, change in amount of urine passed, bruising, bleeding, severe loss of strength and energy, pale skin, muscle pain, or muscle weakness (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.

Further information

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