Colchicine and Probenecid

Medically reviewed by Drugs.com. Last updated on Aug 8, 2020.

• Overview
• Side Effects
• Dosage
• Professional
• Interactions
• More

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, Oral:

Generic: Colchicine 0.5 mg and probenecid 0.5 g

Pharmacologic Category

• Anti-inflammatory Agent
• Antigout Agent
• Uricosuric Agent

Use: Labeled Indications

Gouty arthritis: 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

Note: Urate-lowering therapy may be initiated during a gout flare or after the flare subsides (ACR [FitzGerald 2020]).

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

Maximum dose: 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/day).

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral: Administer with food if GI upset occurs. Maintain adequate fluid intake (at least 64 oz water/day).

Drug Interactions

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

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. Management: Consider limiting acetaminophen use in combination with probenecid. Probenecid may reduce clearance of acetaminophen to one of its non-toxic metabolities, increasing the risk for acetaminophen toxicity, even a lower doses. 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

Baricitinib: Probenecid may increase the serum concentration of Baricitinib. Management: Decrease the dose of baricitinib to 1 mg daily when combined with probenecid. Consider therapy modification

Betalactamase Inhibitors: Probenecid may increase the serum concentration of Betalactamase Inhibitors. Management: Coadministration of probenecid with amoxicillin/clavulanate is not recommended per official package labeling. Consider therapy modification

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

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

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

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

Dichlorphenamide: OAT1/3 Inhibitors may increase the serum concentration of Dichlorphenamide. Monitor therapy

Digoxin: May enhance the adverse/toxic effect 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

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

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Monitor therapy

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 increase the serum concentration 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). Monitor therapy

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

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

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). 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. Management: Reduce lorazaepam dose 50% during coadministration with probenecid. Monitor for increased and prolonged lorazepam effects, particularly CNS depressant effects. Consider therapy modification

Lumacaftor and Ivacaftor: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may decrease the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors or Inducers). Monitor therapy

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

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. Monitor therapy

Pexidartinib: UGT1A4 Inhibitors may increase the serum concentration of Pexidartinib. Management: Avoid use of UGT1A4 inhibitors and pexidartinib. If combined use is required, reduce the pexidartinib dose. If receving pexidartinib 800 mg or 600 mg daily, reduce to 200 mg twice daily. If receiving 400 mg per day, reduce to 200 mg once daily. Consider therapy modification

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-gp inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Consider therapy modification

Phenprocoumon [INT]: Probenecid may decrease the serum concentration of Phenprocoumon [INT]. Monitor therapy

PRALAtrexate: Probenecid may increase the serum concentration of PRALAtrexate. Management: Avoid coadministration of pralatrexate with probenecid. If coadministration cannot be avoided, closely monitor for increased pralatrexate serum concentrations or possible toxicity with concomitant use of probenecid. Consider therapy modification

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. 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

Theophylline Derivatives: Probenecid may increase the serum concentration of Theophylline Derivatives. 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.

Pregnancy Considerations

See individual agents.

Patient Education

What is this drug used for?

• It is used to prevent gouty arthritis.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness

• Headache

• Flushing

• Not hungry

• Diarrhea

• Stomach pain

• Upset stomach

• Throwing up

• Hair loss

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, feeling tired, not hungry, upset stomach, stomach pain, light-colored stools, throwing up, or yellow skin or eyes

• Kidney problems like not able to pass urine, change in amount of urine passed, blood in your urine, or a big weight gain

• Burning or numbness feeling

• Kidney stone like back pain, stomach pain, or blood in the urine

• Unable to pass urine or change in amount of urine passed

• Chills

• Sore throat

• Bruising

• Bleeding

• Feeling very tired or weak

• Pale skin

• Muscle pain or weakness

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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