Probenecid and colchicine are used together to treat chronic gouty arthritis complicated by frequent, acute attacks. Probenecid is a uricosuric agent that inhibits the tubular reabsorption of uric acid but is not a first-line agent for gout prophylaxis. 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. 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.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-Colchicine is classified as a hazardous drug.
-NIOSH 2016 List: Group 3
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; may require eye/face protection.
Route-Specific Administration
Oral Administration
-May administer with food to minimize gastric irritation.
Due to the probenecid component, use of probenecid; colchicine can increase the number of acute gouty attacks occurring in the first 6 to 12 months of continuous therapy. If an acute gout attack is precipitated during therapy, continue this medication, and consider additional colchicine or other appropriate therapy for control.
Use of probenecid; colchicine may lead to central nervous system (CNS) adverse events. Peripheral neuropathy, specifically peripheral neuritis, is associated with colchicine, while headache and dizziness are associated with probenecid. Colchicine-induced side effects appear to be dosage-dependent; consider the possibility of toxicity and the need for dosage reductions or drug discontinuation if necessary.
Use of probenecid; colchicine may lead to gastrointestinal adverse events. The following have been reported with colchicine use: nausea, vomiting, abdominal pain, and diarrhea. With colchicine toxicity, diarrhea may be severe. Probenecid may cause anorexia, nausea, vomiting, sore gums, and rarely, hepatic necrosis. Colchicine-induced side effects appear to be dosage-dependent consider the possibility of toxicity and the need for dosage reductions or drug discontinuation if necessary.
Probenecid is a uricosuric agent and causes increased uric acid renal clearance. This effect could lead to uric acid kidney stones (nephrolithiasis), renal colic, hematuria, costovertebral pain, and nephrotic syndrome. Consider increasing fluid intake and alkalizing urine to increase the solubility of uric acid and decrease the risk of developing nephrolithiasis during probenecid; colchicine treatment. Increased urinary frequency has been also reported during probenecid therapy. Renal damage with hematuria and oliguria has been reported in patients receiving toxic doses of colchicine. If symptoms of colchicine-induced nephrotoxicity appear, consider the possibility of toxicity and the need for drug discontinuation if necessary.
Hypersensitivity reactions, including anaphylactic shock (anaphylaxis), fever, urticaria, and pruritus have been reported during probenecid therapy. Urticaria has also occurred following the use of colchicine. Discontinue probenecid; colchicine therapy if such reactions occur.
Integumentary adverse events may occur following the use of probenecid; colchicine. Atopic dermatitis and alopecia have been reported with both colchicine and probenecid use, while purpura has been associated with colchicine and flushing with probenecid. Consider dosage reductions or drug discontinuation if necessary.
Use of probenecid; colchicine may lead to hematologic adverse events. Aplastic anemia has been reported with both colchicine and probenecid use. Agranulocytosis (severe neutropenia) has been associated with colchicine. Leukopenia, hemolytic anemia (which may be related to a genetic deficiency of glucose-6-phosphate dehydrogenase in red blood cells), and anemia have been reported with probenecid. Colchicine-induced side effects appear to be dosage-dependent; consider dosage reductions or drug discontinuation if necessary.
Colchicine has been reported to adversely affect spermatogenesis (spermatogenesis inhibition) in animals. Azoospermia and oligospermia have been observed during postmarketing surveillance with colchicine. Reversible azoospermia has been reported in one patient. Rare case reports and epidemiology studies suggest that infertility may be reversible.
Colchicine impairs absorption and metabolism of vitamin B12 and may lead to vitamin B12 deficiency. Vitamin B12 supplementation may be necessary as well as monitoring of high-risk patients during probenecid; colchicine therapy.
This monograph discusses the contraindications/precautions of probenecid; colchicine combination products. Clinicians may wish to consult the individual monographs for more information about each agent.
Therapy with probenecid; colchicine should not be started until an acute gouty attack has subsided. However, if an acute attack is precipitated during therapy, probenecid; colchicine may be continued without changing the dosage, and additional colchicine or other appropriate therapy should be given to control the acute attack.
Probenecid; colchicine is contraindicated in patients with known probenecid hypersensitivity and/or colchicine hypersensitivity. Rarely, severe allergic reactions and anaphylaxis have been reported with the use of probenecid and colchicine. Most of these events have been reported to occur within several hours after re-administration following prior usage of the drug. The appearance of hypersensitivity reactions requires cessation of probenecid; colchicine therapy. Although probenecid contains a sulfonamide side chain, it and other nonantibiotic sulfonamides do not contain the N4 aromatic amine or the N1-substituent that are present in sulfonamide antibiotics and thought to be responsible for hypersensitivity-type adverse reactions. The risk of cross-sensitivity in patients taking a nonantibiotic sulfonamide that have a history of sulfonamide hypersensitivity is low and has been confirmed by observational studies.
Probenecid; colchicine is contraindicated in patients with blood dyscrasia (hematological disease). Use with caution in patients with pre-existing bone marrow suppression. Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia have been reported with colchicine used in therapeutic doses. Rarely, aplastic anemia, leukopenia, and anemia have been reported with probenecid. Use probenecid with caution in patients with known glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency). Hemolytic anemia, which in some patients could be related to genetic deficiency of G6PD in red blood cells, has been reported with probenecid use.
Use of probenecid; colchicine is contraindicated in patients with uric acid kidney stones (nephrolithiasis) because probenecid increases uric acid excretion, which may contribute to stone formation. Consider alkalization of the urine and liberal fluid intake during probenecid; colchicine therapy to minimize risks of developing drug-associated hematuria, renal colic, costovertebral pain, and uric acid stones. When alkalization is used, the acid-base balance of the patient should be monitored.
The fixed dose product of probenecid; colchicine has been used in renal impairment, but doses of the drug may need adjustment. The product is not recommended in patients with a CrCl less than 30 mL/minute, including those with renal failure, due to loss of efficacy of probenecid as renal dysfunction increases. Clearance of colchicine is decreased in patients with impaired renal function or hepatic disease; dosages should be adjusted in those with severe impairment to avoid an increased risk for toxicity and these patients must be monitored closely for appropriate dosage and tolerance of therapy. Colchicine is not removed by dialysis. Patients with either hepatic disease or renal impairment who are taking dual inhibitors of CYP3A4 and P-glycoprotein (P-gp), P-gp inhibitors alone, or strong CYP3A4 inhibitors should not receive colchicine. Elevated colchicine concentrations and related toxicities, including fatalities, have been reported after the administration of therapeutic doses in such patients. Prescribers are advised to carefully review drug-drug interactions and the potential need for colchicine dosage adjustment in patients with or without hepatic or renal impairment. Colchicine is eliminated through biliary pathways; consider alternative therapies in patients with extrahepatic biliary obstruction.
Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses, especially in combination with other drugs known to cause this effect (e.g., statins, fibrates, cyclosporine). Patients with impaired renal function and elderly patients, even those with normal renal and hepatic function, are at increased risk. The myoneuropathy is characterized by myopathy (muscular pain or weakness), and an elevated serum creatine kinase and/or rhabdomyolysis may be present. Rhabdomyolysis may occur anytime during drug treatment. Colchicine-induced neuromuscular toxicity generally resolves within 1 week to several months following discontinuation of therapy. Colchicine toxicity and overdosage can result in life-threatening adverse events. The incidence of gastrointestinal (GI) adverse events to colchicine are dose-related across all patient populations; consider the development of severe GI symptoms dose-limiting, as these may precede more systemic toxicity.
Use probenecid; colchicine with caution in patients with a history of peptic ulcer disease. Uricosuric agents like probenecid can cause upper gastrointestinal irritation and aggravate peptic ulcer.
Probenecid; colchicine should be used cautiously in the older adult and debilitated patients because of susceptibility to cumulative colchicine toxicity. The risk of neuromuscular toxicity and rhabdomyolysis is increased in geriatric patients, even in those without renal or hepatic dysfunction. According to the Beers Criteria, the dose of colchicine should be reduced in geriatric patients with a creatinine clearance less than 30 mL/minute due to the potential for gastrointestinal, neuromuscular, or bone marrow toxicity; monitor treated patients closely for adverse effects. The Beers expert panel also recommends avoiding probenecid in geriatric patients with a creatinine clearance less than 30 mL/minute due to loss of effectiveness of the drug.
Probenecid; colchicine may pose a reproductive risk in males. Azoospermia and oligospermia have been observed during postmarketing surveillance with colchicine. Rare case reports and epidemiology studies suggest that infertility may be reversible.
Use of probenecid; colchicine is contraindicated during pregnancy due to the colchicine component. Probenecid crosses the placental barrier and appears in cord blood. Colchicine is also known to cross the human placenta. Colchicine can arrest cell division in animals and plants. In certain species of animals under certain conditions, colchicine has produced teratogenic effects at exposures within or above the clinical therapeutic range. The possibility of such effects in humans also has been reported. The use of any drug in women of childbearing potential requires that the anticipated benefit be weighed against the possible hazards.
Manufacturer recommendations about the use of probenecid; colchicine during breast-feeding are not available. Use with caution. Limited data are known from the study of the individual components of this medication. Colchicine appears to be excreted into human milk; information suggests that exclusively breastfed infants receive less than 10% of the maternal weight-adjusted dose of colchicine. One case report has documented probenecid excretion into human milk; the average probenecid milk concentration corresponded to a relative infant dose 0.7% of the maternal weight-adjusted dose. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. Monitor the breastfed infant for any untoward effects if this product must be administered.
Probenecid; colchicine is contraindicated in neonates, infants, and children less than 2 years of age. Fatal overdoses, both and intentional or from accidental exposure, have been reported in adults and children who have ingested colchicine. Due to the potential for overdose or poisoning, this product should be kept out of the reach of children.
Laboratory test interference has been reported with probenecid. Falsely high readings for theophylline have been reported in an in vitro study, using the Schack and Waxler technique, when therapeutic concentrations of theophylline and probenecid were added to human plasma. Also, a reducing substance may appear in the urine of patients receiving probenecid. This disappears with discontinuance of therapy. Suspected glycosuria should be confirmed by using a test specific for glucose.
For the treatment of chronic gouty arthritis complicated by frequent acute gout flares:
Oral dosage:
Adults: Initially, 1 tablet (probenecid 500 mg with colchicine 0.5 mg) PO once daily for 1 week, then 1 tablet PO twice daily. If tolerated and if symptoms are not controlled or the 24-hour uric acid excretion is not above 700 mg, increase the daily dose by 1 tablet/day every 4 weeks. Max: Usually not more than 4 tablets/day (probenecid 2 grams/day; colchicine 2 mg/day). Continue effective dose for 6 months or longer. Then, if serum uric acid (sUA) remains normal and no acute gouty attacks occur, may decrease by 1 tablet/day every 6 months. The sUA should remain within normal limits during maintenance. Do NOT reduce the dose to the point where sUA increases. GUIDELINES: Probenecid is not a first-line treatment for gout management. ACUTE FLARES: Do not initiate colchicine; probenecid until an acute gout attack has been resolved. If a patient is controlled on therapy, and an acute attack occurs, the maintenance dosage may be continued. DOSE ADJUSTMENT: Colchicine dosage reduction is required if CYP3A4 inhibitors or P-glycoprotein inhibitors are used. This fixed-dose combination medication may not be appropriate in such patients. Review drug interactions.
Maximum Dosage Limits:
-Adults
4 tablets/day PO of probenecid-colchicine (each tablet with 500 mg probenecid/0.5 mg colchicine) is the usual maximally tolerated dose.
-Geriatric
4 tablets/day PO of probenecid-colchicine (each tablet with 500 mg probenecid/0.5 mg colchicine) is the usual maximally tolerated dose.
-Adolescents
Safety and efficacy have not been established.
-Children
2 to 12 years: Safety and efficacy have not been established.
Less than 2 years: Use is contraindicated.
-Infants
Use is contraindicated.
Patients with Hepatic Impairment Dosing
Impaired hepatic function may increase the risk of colchicine-related toxicity. Patients should be monitored closely for adverse effects of colchicine. Dose reduction should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment.
Patients with Renal Impairment Dosing
CrCl 31 to 80 mL/minute: Do not exceed maximum recommended doses. Use with caution in patients with gout with renal impairment; adjust dosage to needed therapeutic response. Probenecid; colchicine has been used in patients with some renal impairment, as some degree of renal impairment may be present in patients with gout. Use a reduced initial dosage in patients with renal impairment and titrate to response. A daily dosage of 2 tablets (e.g., 1 tablet of probenecid 500mg/colchicine 0.5 mg PO twice daily) may be adequate. However, if necessary, the daily dosage may be increased by 1 tablet every 4 weeks within tolerance (and usually not above 4 tablets/day) if symptoms of gouty arthritis are not controlled or the 24-hour uric acid excretion is not above 700 mg.
CrCl 30 mL/minute or less: Avoid use of this combination. Probenecid may not be effective.
*non-FDA-approved indication
Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Major) Concomitant use of probenecid with zidovudine, ZDV may produce substantially higher serum concentrations of zidovudine.
Abrocitinib: (Major) Avoid concomitant use of colchicine and abrocitinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and abrocitinib is a P-gp inhibitor.
Acetaminophen; Aspirin, ASA; Caffeine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Acetaminophen; Aspirin: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Acetaminophen; Aspirin; Diphenhydramine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Acetaminophen; Ibuprofen: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Acyclovir: (Moderate) Probenecid decreases the renal tubular secretion of acyclovir and can increase serum and CSF concentrations of acyclovir, increasing the potential for toxicity. This interaction would appear to be more significant for parenteral acyclovir.
Adagrasib: (Major) Avoid concomitant use of colchicine and adagrasib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and adagrasib is a dual strong CYP3A and P-gp inhibitor. Concomitant use with other dual strong CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 3- to 4-fold.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Allopurinol: (Minor) Uricosuric agents are likely to increase the excretion of the active metabolite of allopurinol, oxypurinol. Although uricosuric agents increase the renal excretion of oxypurinol, the antihyperuricemic effects of allopurinol may be additive when administered with either probenecid or sulfinpyrazone.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Aminosalicylate sodium, Aminosalicylic acid: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Amiodarone: (Major) Avoid concomitant use of colchicine and amiodarone due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and amiodarone is a P-gp inhibitor.
Amlodipine; Atorvastatin: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
Amlodipine; Celecoxib: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Amoxicillin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concomitant use of colchicine and clarithromycin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and clarithromycin is a dual strong CYP3A and P-gp inhibitor. Concomitant use has been observed to increase colchicine overall exposure by 3.8-fold. (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Amoxicillin; Clavulanic Acid: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Ampicillin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Ampicillin; Sulbactam: (Moderate) Monitor for an increase in sulbactam-related adverse effects if concomitant use with probenecid is necessary. Concomitant use may increase sulbactam exposure. Sulbactam is an OAT1 substrate and probenecid is an OAT1 inhibitor. (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Aprepitant, Fosaprepitant: (Major) Avoid concomitant use of colchicine and aprepitant/fosaprepitant due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and aprepitant/fosaprepitant is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Asciminib: (Major) Avoid concomitant use of colchicine and asciminib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and asciminib is a P-gp inhibitor.
Aspirin, ASA: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Butalbital; Caffeine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Caffeine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Caffeine; Orphenadrine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Carisoprodol; Codeine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Dipyridamole: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Omeprazole: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Aspirin, ASA; Oxycodone: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Atazanavir: (Major) Avoid concomitant use of colchicine and atazanavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor..
Atazanavir; Cobicistat: (Major) Avoid concomitant use of colchicine and atazanavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor.. (Major) Avoid concomitant use of colchicine and cobicistat due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and cobicistat is a dual strong CYP3A and P-gp inhibitor. Concomitant use with other dual strong CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 3- to 4-fold.
Atenolol; Chlorthalidone: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Atorvastatin: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
Azilsartan; Chlorthalidone: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Azithromycin: (Moderate) Monitor for colchicine toxicity during concomitant azithromycin use. Concurrent use resulted in an increase in colchicine Cmax of 21.6% and an increase in the AUC of 57.1%.
Baricitinib: (Major) Reduce the recommended baricitinib dose by half in patients receiving concomitant therapy with probenecid. If the recommended dose is 4 mg daily, reduce to 2 mg daily. If the recommended dose is 2 mg daily, reduce to 1 mg daily. If the recommended dose is 1 mg daily, consider discontinuing probenecid. Coadministration of baricitinib and probenecid results in increased baricitinib exposure. In a drug interaction study, administration of probenecid increased baricitinib exposure by 2-fold. Baricitinib is an OAT3 substrate and probenecid is a strong OAT3 inhibitor.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Berotralstat: (Major) Avoid concomitant use of colchicine and berotralstat due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and berotralstat is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Bismuth Subsalicylate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like colchicine; the risk of peripheral neuropathy may be additive.
Brigatinib: (Major) Avoid concomitant use of colchicine and brigatinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and brigatinib is a P-gp inhibitor.
Bromocriptine: (Moderate) Bromocriptine is highly bound to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., probenecid), which may alter their effectiveness and risk for side effects.
Bumetanide: (Moderate) Probenecid can interfere with the natriuresis and plasma renin activity increases caused by diuretics such as bumetanide. Bumetanide can in turn increase the levels of serum uric acid, antagonizing the effects of probenecid.
Bupivacaine; Meloxicam: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Butalbital; Aspirin; Caffeine; Codeine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Cabozantinib: (Major) Avoid concomitant use of colchicine and cabozantinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and cabozantinib is a P-gp inhibitor. (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with probenecid is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and probenecid is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Caffeine; Sodium Benzoate: (Moderate) Renal excretion of phenylacetylglutamine and hippuric acid may be affected by probenecid through competitive inhibition. These competitive reactions could be significant, as the overall usefulness of sodium benzoate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. Use with caution.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Cannabidiol: (Major) Avoid concomitant use of colchicine and cannabidiol due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Capmatinib: (Major) Avoid concomitant use of colchicine and capmatinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and capmatinib is a P-gp inhibitor.
Captopril: (Moderate) Probenecid decreases the renal tubular secretion of captopril, resulting in higher captopril serum concentrations. If probenecid is given to a patient stabilized on captopril, hypotension may occur. This interaction would appear to be of lesser significance if captopril is added after probenecid therapy is in place.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Probenecid decreases the renal tubular secretion of captopril, resulting in higher captopril serum concentrations. If probenecid is given to a patient stabilized on captopril, hypotension may occur. This interaction would appear to be of lesser significance if captopril is added after probenecid therapy is in place. (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Carbacephems: (Minor) Renal tubular secretion of loracarbef is inhibited by probenecid, resulting in higher, approximately 80% increase in AUC, serum levels of loracarbef. The interaction also increases the normal half-life of loracarbef from 1 to 1.5 hours.
Carbidopa; Levodopa; Entacapone: (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation or intestinal beta-glucuronidation such as probenecid. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
Carvedilol: (Minor) Monitor for colchicine-related adverse effects during concomitant use of carvedilol. Although carvedilol is a P-gp inhibitor, drug interaction studies have shown no significant changes in colchicine systemic exposure with coadministration. Colchicine can be administered with carvedilol without a dose adjustment.
Cefaclor: (Minor) Probenecid competitively inhibits renal tubular secretion of cefaclor, thereby causing higher serum concentrations and prolonged elimination of cefaclor.
Cefotaxime: (Minor) Probenecid competitively inhibits renal tubular secretion of cefotaxime, thereby causing higher, prolonged serum levels of the drug.
Cefpodoxime: (Minor) Renal excretion of cefpodoxime is inhibited by probenecid.
Cefprozil: (Minor) Probenecid competitively inhibits renal tubular secretion of cefprozil, causing higher, prolonged serum levels of the drug. In the oral treatment of pediatric osteomyelitis, probenecid is intentionally administered with cefprozil to achieve higher serum concentrations.
Ceftazidime; Avibactam: (Major) Avoid concurrent administration of ceftazidime; avibactam with probenicid. Use of these medications together may decrease the renal clearance of avibactam; thereby resulting in prolonged drug exposures. Avibactam is a substrate of the renal organic anion transporters (OAT)1 and OAT3; probenecid is a potent inhibitor of these transporters. An in vitro study found probencid blocked 56% to 70% of avibactam uptake by these transporters.
Ceftolozane; Tazobactam: (Minor) Probenecid may prolong serum concentrations of tazobactam when coadministered with ceftolozane; tazobactam. Probenecid has been shown to prolong the half-life of tazobactam by 71% when coadministered. The clinical significance of this interaction has not been established.
Celecoxib: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Celecoxib; Tramadol: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Cephalexin: (Minor) Probenecid competitively inhibits renal tubular secretion of cephalexin, causing higher, prolonged serum levels of the drug.
Ceritinib: (Major) Avoid concomitant use of colchicine and ceritinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Chloramphenicol: (Major) Avoid concomitant use of colchicine and chloramphenicol due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Chlorothiazide: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Chlorthalidone: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Choline Salicylate; Magnesium Salicylate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Cidofovir: (Minor) Probenecid impairs the tubular secretion of cidofovir. While cidofovir serum concentrations are higher as a result of the effects of probenecid, probenecid is recommended for use in combination with cidofovir to offset cidofovir-induced nephrotoxicity.
Ciprofloxacin: (Minor) Monitor for colchicine-related adverse effects during concomitant use of ciprofloxacin. Although ciprofloxacin is a moderate CYP3A inhibitor, drug interaction studies have shown no significant changes in colchicine systemic exposure with coadministration. Colchicine can be administered with ciprofloxacin without a dose adjustment. (Minor) Probenecid decreases renal secretion of ciprofloxacin by 50%, resulting in elevated ciprofloxacin serum concentrations and prolonging its half-life.
Clarithromycin: (Major) Avoid concomitant use of colchicine and clarithromycin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and clarithromycin is a dual strong CYP3A and P-gp inhibitor. Concomitant use has been observed to increase colchicine overall exposure by 3.8-fold.
Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and probenecid, an inhibitor of OAT1 and OAT3, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g., hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OAT3 inhibitors.
Cobicistat: (Major) Avoid concomitant use of colchicine and cobicistat due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and cobicistat is a dual strong CYP3A and P-gp inhibitor. Concomitant use with other dual strong CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 3- to 4-fold.
Conivaptan: (Major) Avoid concomitant use of colchicine and conivaptan due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and conivaptan is a dual moderate CYP3A and P-gp inhibitor. Concomitant use with other dual moderate CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 2- to 3.6-fold.
Crizotinib: (Major) Avoid concomitant use of colchicine and crizotinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and crizotinib is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Cyclosporine: (Major) Avoid concomitant use of colchicine and cyclosporine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and cyclosporine is a dual moderate CYP3A and P-gp inhibitor. Concomitant use has been observed to increase colchicine overall exposure by 3.6-fold.
Daclatasvir: (Major) Avoid concomitant use of colchicine and daclatasvir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and daclatasvir is a P-gp inhibitor.
Danazol: (Major) Avoid concomitant use of colchicine and danazol due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Danicopan: (Major) Avoid concomitant use of colchicine and danicopan due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and danicopan is a P-gp inhibitor.
Dapsone: (Minor) Current evidence suggests that probenecid can inhibit the renal excretion of dapsone, resulting in elevated plasma concentrations. Dapsone toxicity as a result of this interaction has not been studied, so patients receiving these agents concurrently should be monitored for hemolytic anemia, methemoglobinemia, and/or peripheral neuropathy with muscle weakness. This interaction may, however, be beneficial in treating organisms that are resistant to dapsone.
Daridorexant: (Major) Avoid concomitant use of colchicine and daridorexant due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and daridorexant is a P-gp inhibitor.
Darunavir: (Major) Avoid concomitant use of colchicine and darunavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat: (Major) Avoid concomitant use of colchicine and cobicistat due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and cobicistat is a dual strong CYP3A and P-gp inhibitor. Concomitant use with other dual strong CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 3- to 4-fold. (Major) Avoid concomitant use of colchicine and darunavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of colchicine and cobicistat due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and cobicistat is a dual strong CYP3A and P-gp inhibitor. Concomitant use with other dual strong CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 3- to 4-fold. (Major) Avoid concomitant use of colchicine and darunavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Deferiprone: (Major) Avoid the concomitant use of deferiprone and probenecid. Deferiprone is a UDP glucuronosyltransferase (UGT) 1A6 substrate, and probenecid inhibits this enzyme. The in vitro glucuronidation of deferiprone is reduced by 78% in the presence of phenylbutazone, another UGT1A6 inhibitor. Similar results may be seen when deferiprone and probenecid are administered concomitantly.
Delavirdine: (Major) Avoid concomitant use of colchicine and delavirdine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor.
Desogestrel; Ethinyl Estradiol: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Dextromethorphan; Quinidine: (Major) Avoid concomitant use of colchicine and quinidine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and quinidine is a P-gp inhibitor.
Diazoxide: (Moderate) Diazoxide can cause hyperuricemia. Dosages of concomitantly administered antigout medications, including probenecid, may require adjustment.
Dichlorphenamide: (Moderate) Monitor for increased toxicity of dichlorphenamide, including hypokalemia and hyperchloremic metabolic acidosis, if probenecid and dichlorphenamide are coadministered. Dichlorphenamide is a substrate for OAT1 and OAT3. Probenecid may increase exposure to dichlorphenamide through OAT1 and OAT3 inhibition. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Diclofenac; Misoprostol: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Dicloxacillin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Dienogest; Estradiol valerate: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Diflunisal: (Major) Probenecid can affect the pharmacokinetics of diflunisal. In healthy males, probenecid inhibits both renal and biliary excretion of and slightly decreases the protein binding of diflunisal. It has been proposed that the decreased clearance of diflunisal may result in an increased concentration of the glucuronide metabolites. Diflunisal does have uricosuric effects; however, it is not known whether diflunisal affects the activity of probenicid. Reduction of the diflunisal dose may be necessary when it is used together with probenecid.
Digoxin: (Major) According to the manufacturer of Colcrys, both digoxin and colchicine are substrates of P-glycoprotein (Pgp) and rhabdomyolysis has been reported in patients on concurrent therapy. If such agents are co-administered, advise patients to report signs and symptoms of myotoxicity including muscle tenderness, pain, or weakness; monitoring creatine phosphokinase may not predict the development of severe myopathy.
Diltiazem: (Major) Avoid concomitant use of colchicine and diltiazem due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and diltiazem is a moderate CYP3A inhibitor. Concomitant use increased colchicine overall exposure by 1.9-fold.
Diphenhydramine; Ibuprofen: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Diphenhydramine; Naproxen: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Doripenem: (Moderate) Probenecid inhibits the renal excretion of doripenem by competing with doripenem for active tubular secretion. The elimination half-life of doripenem is increased by 53% and the extent of systemic exposure (AUC) to doripenem is increased by 75%. Concurrent administration of doripenem with probenecid is not recommended.
Dronedarone: (Major) Avoid concomitant use of colchicine and dronedarone due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and dronedarone is a dual moderate CYP3A and P-gp inhibitor. Concomitant use with other dual moderate CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 2- to 3.6-fold.
Drospirenone: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Drospirenone; Estetrol: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Drospirenone; Estradiol: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Drospirenone; Ethinyl Estradiol: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Duvelisib: (Major) Avoid concomitant use of colchicine and duvelisib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Elacestrant: (Major) Avoid concomitant use of colchicine and elacestrant due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and elacestrant is a P-gp inhibitor.
Elagolix: (Major) Avoid concomitant use of colchicine and elagolix due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and elagolix is a P-gp inhibitor.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of colchicine and elagolix due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and elagolix is a P-gp inhibitor. (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Elexacaftor; tezacaftor; ivacaftor: (Major) Avoid concomitant use of colchicine and ivacaftor due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and ivacaftor is a P-gp inhibitor.
Eliglustat: (Major) Avoid concomitant use of colchicine and eliglustat due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and eliglustat is a P-gp inhibitor.
Eluxadoline: (Minor) Systemic exposure (AUC) and maximum plasma concentration of eluxadoline are increased by 35% and 31%, respectively, when administered concurrently with probenecid. According to the manufacturer, the increase in exposure is not expected to be clinically meaningful; no dosage adjustments are required during coadministration with probenecid.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of colchicine and cobicistat due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and cobicistat is a dual strong CYP3A and P-gp inhibitor. Concomitant use with other dual strong CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 3- to 4-fold. (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of colchicine and cobicistat due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and cobicistat is a dual strong CYP3A and P-gp inhibitor. Concomitant use with other dual strong CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 3- to 4-fold. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Enasidenib: (Major) Avoid concomitant use of colchicine and enasidenib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and enasidenib is a P-gp inhibitor.
Entacapone: (Moderate) Entacapone should be given cautiously with drugs known to interfere with biliary excretion, glucuronidation or intestinal beta-glucuronidation such as probenecid. Decreased biliary excretion of entacapone may occur if these agents are given concurrently.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Erdafitinib: (Major) Avoid concomitant use of colchicine and erdafitinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and erdafitinib is a P-gp inhibitor.
Ertapenem: (Minor) Probenecid inhibits the renal excretion of ertapenem by competing with them for active tubular secretion. In some instances, this effect is used therapeutically to increase availability of the antimicrobial agent. However, the elimination half-life of ertapenem is increased only from 4 to 4.8 hours. Concurrent administration of ertapenem with probenecid is not recommended.
Erythromycin: (Major) Avoid concomitant use of colchicine and erythromycin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and erythromycin is a dual moderate CYP3A and P-gp inhibitor. Concomitant use with other dual moderate CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 2- to 3.6-fold.
Estradiol; Levonorgestrel: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Estradiol; Norethindrone: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Estradiol; Norgestimate: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Ethacrynic Acid: (Moderate) Probenecid has uricosuric actions. Ethacrynic acid can also cause hyperuricemia. Although this effect represents a pharmacodynamic interaction, dosage adjustments of probenecid may be necessary if ethacrynic acid is administered to patients being treated with probenecid.
Ethambutol: (Moderate) Probenecid has uricosuric actions. Ethambutol can also cause hyperuricemia. Although this effect represents a pharmacodynamic interaction, dosage adjustments of probenecid may be necessary if ethambutol is administered to patients being treated with probenecid.
Ethinyl Estradiol; Norelgestromin: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Ethinyl Estradiol; Norgestrel: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Etodolac: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Etonogestrel; Ethinyl Estradiol: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Etravirine: (Major) Avoid concomitant use of colchicine and etravirine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and etravirine is a P-gp inhibitor.
Ezetimibe; Simvastatin: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
Famciclovir: (Moderate) Probenecid undergoes both renal tubular secretion and renal tubular reabsorption. Concomitant administration of probenecid with famciclovir may impair clearance of the active metabolite, penciclovir. Probenecid should be avoided during therapy with famciclovir.
Fedratinib: (Major) Avoid concomitant use of colchicine and fedratinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and fedratinib is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Fenofibrate: (Moderate) Monitor for myopathy during concomitant colchicine and fibric acid derivative use. Cases of myopathy, including rhabdomyolysis, have been reported with fibric acid derivatives coadministered with colchicine.
Fenofibric Acid: (Moderate) Monitor for myopathy during concomitant colchicine and fibric acid derivative use. Cases of myopathy, including rhabdomyolysis, have been reported with fibric acid derivatives coadministered with colchicine.
Fenoprofen: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Fibric acid derivatives: (Moderate) Monitor for myopathy during concomitant colchicine and fibric acid derivative use. Cases of myopathy, including rhabdomyolysis, have been reported with fibric acid derivatives coadministered with colchicine.
Flibanserin: (Major) Avoid concomitant use of colchicine and flibanserin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and flibanserin is a P-gp inhibitor.
Fluconazole: (Major) Avoid concomitant use of colchicine and fluconazole due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. Concomitant use increased colchicine overall exposure by 1.4-fold.
Flurbiprofen: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Fluvastatin: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
Fluvoxamine: (Major) Avoid concomitant use of colchicine and fluvoxamine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and fluvoxamine is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Fosamprenavir: (Major) Avoid concomitant use of colchicine and fosamprenavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Fostamatinib: (Major) Avoid concomitant use of colchicine and fostamatinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and fostamatinib is a P-gp inhibitor.
Furosemide: (Moderate) Probenecid can interfere with the natriuresis and plasma renin activity increases caused by diuretics such as furosemide. Furosemide can in turn increase the levels of serum uric acid, antagonizing the effects of probenecid.
Futibatinib: (Major) Avoid concomitant use of colchicine and futibatinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and futibatinib is a P-gp inhibitor.
Ganciclovir: (Moderate) Ganciclovir should be used with probenecid with caution. Probenecid can inhibit renal tubular secretion of ganciclovir, possibly potentiating ganciclovir toxicity. Patients should be monitored for increased ganciclovir toxicity when taking probenecid with ganciclovir.
Gemfibrozil: (Moderate) Monitor for myopathy during concomitant colchicine and fibric acid derivative use. Cases of myopathy, including rhabdomyolysis, have been reported with fibric acid derivatives coadministered with colchicine.
Gemifloxacin: (Minor) Probenecid, 4.5 g total dose, reduced the mean renal clearance of a single 320-mg dose of gemifloxacin by approximately 50%, increased the AUC by 45%, increased the Cmax by 8%, and prolonged the mean half by 1.6 hours.
Gilteritinib: (Major) Avoid concomitant use of colchicine and gilteritinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and gilteritinib is a P-gp inhibitor.
Glecaprevir; Pibrentasvir: (Major) Avoid concomitant use of colchicine and glecaprevir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and glecaprevir is a P-gp inhibitor. (Major) Avoid concomitant use of colchicine and pibrentasvir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and pibrentasvir is a P-gp inhibitor.
Glimepiride: (Moderate) Probenecid is highly protein bound, and the hypoglycemic effect of sulfonylureas made be potentiated if these drugs are coadministered.
Glipizide: (Moderate) Probenecid is highly protein bound, and the hypoglycemic effect of sulfonylureas made be potentiated if these drugs are coadministered.
Glipizide; Metformin: (Moderate) Probenecid is highly protein bound, and the hypoglycemic effect of sulfonylureas made be potentiated if these drugs are coadministered.
Glyburide: (Moderate) Probenecid is highly protein bound, and the hypoglycemic effect of sulfonylureas made be potentiated if these drugs are coadministered.
Glyburide; Metformin: (Moderate) Probenecid is highly protein bound, and the hypoglycemic effect of sulfonylureas made be potentiated if these drugs are coadministered.
Glycerol Phenylbutyrate: (Moderate) Probenecid may inhibit renal excretion of glycerol phenylbutyrate metabolites, including phenylacetate (PAA) and phenylacetylglutamine (PAGN). PAA has been associated with neurotoxicity. If probenecid must be used in combination with glycerol phenylbutyrate, monitor the patient closely for signs and symptoms of neurotoxicity. In addition, because probenecid alters PAGN excretion, use caution when interpreting urinary PAGN concentrations for the purpose of dosage adjustments.
Grapefruit juice: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, patients should avoid eating grapefruit or drinking grapefruit juice while taking colchicine. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Grapefruit juice can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken grapefruit juice in the past 14 days or require concurrent use: administer half of the original intended Colcrys dosage for prophylaxis of gout flares; 1.2 mg as a single dose for treatment of gout flares and do not repeat for at least 3 days; and do not exceed a maximum daily dose of 1.2 mg/day for familial Mediterranean fever.
HMG-CoA reductase inhibitors: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Hydrocodone; Ibuprofen: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Hydroxyurea: (Major) Hydroxyurea may raise the serum uric acid concentration, so dosage adjustment of uricosuric medications such as probenecid may be necessary.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Ibrutinib: (Major) Avoid concomitant use of colchicine and ibrutinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and ibrutinib is a P-gp inhibitor.
Ibuprofen: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Ibuprofen; Famotidine: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Ibuprofen; Oxycodone: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Ibuprofen; Pseudoephedrine: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Idelalisib: (Major) Avoid concomitant use of colchicine and idelalisib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Imatinib: (Major) Avoid concomitant use of colchicine and imatinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Imipenem; Cilastatin: (Major) Concomitant use of imipenem and probenecid is not recommended. Probenecid competitively inhibits renal tubular secretion and causes increased serum concentrations of imipenem and prolonged half-life.
Imipenem; Cilastatin; Relebactam: (Major) Concomitant use of imipenem and probenecid is not recommended. Probenecid competitively inhibits renal tubular secretion and causes increased serum concentrations of imipenem and prolonged half-life.
Indinavir: (Major) Avoid concomitant use of colchicine and indinavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and indinavir is a strong CYP3A inhibitor.
Indomethacin: (Major) Probenecid reduces the clearance of indomethacin, and a lower dosage of indomethacin may be required to produce a therapeutic effect.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Isavuconazonium: (Major) Avoid concomitant use of colchicine and isavuconazonium due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and isavuconazonium is a dual moderate CYP3A and P-gp inhibitor. Concomitant use with other dual moderate CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 2- to 3.6-fold.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Concomitant use of rifampin and probenecid may result in increased serum concentrations of rifampin. Monitor for increased rifampin toxicity during coadministration. (Minor) Because pyrazinamide can increase serum uric acid levels and precipitate gouty attacks, the dosages of antigout agents, including probenecid, may need to be adjusted.
Isoniazid, INH; Rifampin: (Moderate) Concomitant use of rifampin and probenecid may result in increased serum concentrations of rifampin. Monitor for increased rifampin toxicity during coadministration.
Istradefylline: (Major) Avoid concomitant use of colchicine and istradefylline due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and istradefylline is a P-gp inhibitor.
Itraconazole: (Major) Avoid concomitant use of colchicine and itraconazole due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and itraconazole is a dual strong CYP3A and P-gp inhibitor. Concomitant use with other dual strong CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 3- to 4-fold.
Ivacaftor: (Major) Avoid concomitant use of colchicine and ivacaftor due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and ivacaftor is a P-gp inhibitor.
Ketoconazole: (Major) Avoid concomitant use of colchicine and ketoconazole due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and ketoconazole is a dual strong CYP3A and P-gp inhibitor. Concomitant use has been observed to increase colchicine overall exposure by 3.1-fold.
Ketoprofen: (Major) Concomitant administration of ketoprofen with probenecid can increase plasma concentrations of ketoprofen. Simultaneous use of these agents is not recommended.
Ketorolac: (Contraindicated) Simultaneous use of ketorolac and probenecid is contraindicated. Concomitant administration of ketorolac with probenecid can result in substantially increased plasma concentrations of ketorolac through decreased clearance. The elimination half-life of ketorolac is approximately doubled.
Lamivudine, 3TC; Zidovudine, ZDV: (Major) Concomitant use of probenecid with zidovudine, ZDV may produce substantially higher serum concentrations of zidovudine.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of colchicine and clarithromycin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and clarithromycin is a dual strong CYP3A and P-gp inhibitor. Concomitant use has been observed to increase colchicine overall exposure by 3.8-fold. (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Lapatinib: (Major) Avoid concomitant use of colchicine and lapatinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and lapatinib is a P-gp inhibitor.
Lasmiditan: (Major) Avoid concomitant use of colchicine and lasmiditan due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Ledipasvir; Sofosbuvir: (Major) Avoid concomitant use of colchicine and ledipasvir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and ledipasvir is a P-gp inhibitor.
Lefamulin: (Major) Avoid concomitant use of colchicine and oral lefamulin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and oral lefamulin is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Lenacapavir: (Major) Avoid concomitant use of colchicine and lenacapavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and lenacapavir is a dual moderate CYP3A and P-gp inhibitor. Concomitant use with other dual moderate CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 2- to 3.6-fold.
Letermovir: (Major) Avoid concomitant use of colchicine and letermovir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. In patients who are also receiving treatment with cyclosporine, this combination is contraindicated in patients with renal or hepatic impairment or if being used for cardiovascular risk reduction. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. Additionally, dosage recommendations vary based on whether letermovir is used alone or with cyclosporine. For gout prophylaxis when used without cyclosporine, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For gout prophylaxis when used with cyclosporine, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For gout treatment when used without cyclosporine, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For gout treatment when used with cyclosporine, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For Familial Mediterranean Fever, the maximum daily dose is 1.2 mg if used without cyclosporine and 0.6 mg if used with cyclosporine. Colchicine is a CYP3A substrate and letermovir is a moderate CYP3A inhibitor; combination letermovir plus cyclosporine is a strong CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Leuprolide; Norethindrone: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Levetiracetam: (Minor) The renal clearance of the major metabolite of levetiracetam, UCB L057, is decreased by 60 percent in the presence of probenecid. This is probably related to competitive inhibition of tubular secretion of UCB L057. The clinical significance of this is unknown.
Levoketoconazole: (Major) Avoid concomitant use of colchicine and ketoconazole due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and ketoconazole is a dual strong CYP3A and P-gp inhibitor. Concomitant use has been observed to increase colchicine overall exposure by 3.1-fold.
Levonorgestrel: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Levonorgestrel; Ethinyl Estradiol: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Lomitapide: (Major) Avoid concomitant use of colchicine and lomitapide due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and lomitapide is a P-gp inhibitor.
Lonafarnib: (Major) Avoid concomitant use of colchicine and lonafarnib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and lonafarnib is a dual strong CYP3A and P-gp inhibitor. Concomitant use with other dual strong CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 3- to 4-fold.
Lopinavir; Ritonavir: (Major) Avoid concomitant use of colchicine and ritonavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and ritonavir is a dual strong CYP3A and P-gp inhibitor. Concomitant use has been observed to increase colchicine overall exposure by 4-fold.
Lorazepam: (Moderate) Monitor for an increase in lorazepam-related adverse reactions and consider reducing the dose of lorazepam if concomitant use of lorazepam and probenecid is necessary. Avoid lorazepam extended-release capsules and utilize lorazepam immediate-release dosage forms that can be easily titrated. Coadministration of lorazepam with probenecid may cause a more rapid onset or prolonged effect of lorazepam due to increased half-life and decreased total clearance. Lorazepam is an UGT substrate and probenecid is an UGT inhibitor.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Lovastatin: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of colchicine and ivacaftor due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and ivacaftor is a P-gp inhibitor. (Major) Avoid concomitant use of colchicine and lumacaftor due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and lumacaftor is a P-gp inhibitor.
Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of colchicine and lumacaftor due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and lumacaftor is a P-gp inhibitor.
Mafenide: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Magnesium Salicylate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and probenecid as increased maraviroc concentrations may occur. Maraviroc is a substrate of multidrug resistance-associated protein (MRP2); probenecid is an inhibitor of MRP2. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
Maribavir: (Major) Avoid concomitant use of colchicine and maribavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and maribavir is a P-gp inhibitor.
Mecamylamine: (Moderate) Probenecid has uricosuric actions. Mecamylamine can also cause hyperuricemia. Although this effect represents a pharmacodynamic interaction, dosage adjustments of probenecid may be necessary if mecamylamine is administered to patients being treated with probenecid.
Meclofenamate Sodium: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Mefenamic Acid: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Mefloquine: (Major) Avoid concomitant use of colchicine and mefloquine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and mefloquine is a P-gp inhibitor.
Meloxicam: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Meropenem: (Major) Avoid concomitant use of meropenem and probenecid due to the risk for increased meropenem exposure which may increase the risk for meropenem-related adverse effects. Concurrent use has been observed to increase the mean systemic exposure and half-life of meropenem by 56% and 38%, respectively.
Meropenem; Vaborbactam: (Major) Avoid concomitant use of meropenem and probenecid due to the risk for increased meropenem exposure which may increase the risk for meropenem-related adverse effects. Concurrent use has been observed to increase the mean systemic exposure and half-life of meropenem by 56% and 38%, respectively.
Methenamine; Sodium Salicylate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Methotrexate: (Contraindicated) Probenecid inhibits renal elimination of methotrexate, which can cause increased plasma levels and toxicity of methotrexate. In addition, methotrexate can increase uric acid production. Probenecid has also been associated with decreased clearance of methotrexate from the CSF. Concomitant use of methotrexate and probenecid is not recommended because of the increased risk of uric acid neuropathy. If coadministration is necessary, patients receiving this combination should be closely monitored.
Metolazone: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Mifepristone: (Major) Avoid concomitant use of colchicine and mifepristone due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Mitapivat: (Major) Avoid concomitant use of colchicine and mitapivat due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and mitapivat is a P-gp inhibitor.
Mycophenolate: (Minor) Probenecid is a known inhibitor of renal tubular secretion, and the inactive metabolite, MPAG undergoes tubular secretion. Increased MPAG concentrations can cause increased mycophenolic acid systemic exposure and thus, adverse effects. Patients receiving both drugs should be monitored carefully.
Nabumetone: (Major) The effects of probenecid on the elimination of nabumetone has not been studied, but probenecid decreases the elimination of other NSAIDs such as naproxen, potentially increasing the effectiveness and/or toxicity. Caution should be exercised when administering probenecid with nabumetone; nabumetone and naproxen are chemically similar, and probenecid has been shown to affect the pharmacokinetics of naproxen.
Nafcillin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Naproxen: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance.
Naproxen; Esomeprazole: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance.
Naproxen; Pseudoephedrine: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance.
Nefazodone: (Major) Avoid concomitant use of colchicine and nefazodone due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor.
Nelfinavir: (Major) Avoid concomitant use of colchicine and nelfinavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and nelfinavir is a dual strong CYP3A and P-gp inhibitor. Concomitant use with other dual strong CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 3- to 4-fold.
Neratinib: (Major) Avoid concomitant use of colchicine and neratinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and neratinib is a P-gp inhibitor.
Netupitant, Fosnetupitant; Palonosetron: (Major) Avoid concomitant use of colchicine and netupitant due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and netupitant is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Nilotinib: (Major) Avoid concomitant use of colchicine and nilotinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and nilotinib is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Nirmatrelvir; Ritonavir: (Major) Avoid concomitant use of colchicine and ritonavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and ritonavir is a dual strong CYP3A and P-gp inhibitor. Concomitant use has been observed to increase colchicine overall exposure by 4-fold. (Major) Concomitant use of ritonavir-boosted nirmatrelvir and colchicine is contraindicated in patients with renal and/or hepatic impairment. Consider temporary discontinuation of colchicine during treatment with ritonavir-boosted nirmatrelvir and for at least 2 to 3 days after treatment completion; if not feasible, consider alternative COVID-19 therapy. Coadministration may increase colchicine exposure resulting in increased toxicity. Colchicine is a CYP3A substrate and nirmatrelvir is a CYP3A inhibitor.
Nirogacestat: (Major) Avoid concomitant use of colchicine and nirogacestat due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and nirogacestat is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Nitrofurantoin: (Moderate) High doses of probenecid can inhibit the renal tubular secretion of nitrofurantoin, leading to a decrease in renal clearance. Nitrofurantoin serum concentrations can increase, elevating the risk of toxicity. Lower doses of nitrofurantoin should be used when probenecid is used.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Norethindrone: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Norethindrone; Ethinyl Estradiol: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Norgestimate; Ethinyl Estradiol: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Norgestrel: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Oral Contraceptives: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Oseltamivir: (Minor) Coadministration of oseltamivir and probenecid results in a two-fold increase in exposure to oseltamivir carboxylate due to a decrease in active anionic tubular secretion in the kidney. However, due to the safety margin of oseltamivir carboxylate, no dosage adjustments are required when oseltamivir is given concomitantly with probenecid.
Osimertinib: (Major) Avoid concomitant use of colchicine and osimertinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and osimertinib is a P-gp inhibitor.
Oxacillin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Oxaprozin: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents. Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Pacritinib: (Major) Avoid concomitant use of colchicine and pacritinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and pacritinib is a P-gp inhibitor.
Pegloticase: (Major) Oral urate-lowering medications, including allopurinol, febuxostat, probenecid, and sulfinpyrazone may potentially blunt the rise of serum uric acid levels in patients taking pegloticase. Since patients who have lost therapeutic response to pegloticase are at higher risk of developing anaphylaxis and infusion reactions, oral urate-lowering therapy should be discontinued prior to pegloticase initiation and withheld during the course of treatment.
Penicillin G Benzathine: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Penicillin G Benzathine; Penicillin G Procaine: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Penicillin G Procaine: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Penicillin G: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Penicillin V: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Penicillins: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and probenecid due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If probenecid is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of probenecid. Pexidartinib is a UGT substrate; probenecid is a UGT inhibitor. Coadministration of probenecid increased pexidartinib exposure by 60%.
Phentermine; Topiramate: (Minor) Probenecid may increase the renal clearance of topiramate resulting in lower topiramate concentrations. Although not evaluated in humans, animal studies using probenecid along with topiramate showed a significant increase in renal clearance of topiramate. This suggests that topiramate may undergo renal tubular reabsorption. Probenecid may block renal tubular reabsorption of topiramate, thus increasing the renal clearance of the drug.
Pioglitazone; Glimepiride: (Moderate) Probenecid is highly protein bound, and the hypoglycemic effect of sulfonylureas made be potentiated if these drugs are coadministered.
Piperacillin; Tazobactam: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed. (Minor) Probenecid may prolong serum concentrations of tazobactam when coadministered with ceftolozane; tazobactam. Probenecid has been shown to prolong the half-life of tazobactam by 71% when coadministered. The clinical significance of this interaction has not been established.
Piroxicam: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Pirtobrutinib: (Major) Avoid concomitant use of colchicine and pirtobrutinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and pirtobrutinib is a P-gp inhibitor.
Pitavastatin: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
Posaconazole: (Major) Avoid concomitant use of colchicine and posaconazole due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and posaconazole is a dual strong CYP3A and P-gp inhibitor. Concomitant use has been observed to increase colchicine overall exposure by 3-fold.
Pralatrexate: (Major) Coadministration of increasing doses of probenecid, a uricosuric drug, and pralatrexate resulted in a delayed clearance of pralatrexate and a commensurate increase in systemic exposure of pralatrexate.
Pravastatin: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
Pretomanid: (Major) Avoid concomitant use of colchicine and pretomanid due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and pretomanid is a P-gp inhibitor.
Propafenone: (Minor) Monitor for colchicine-related adverse effects during concomitant use of propafenone. Although propafenone is a P-gp inhibitor, drug interaction studies have shown no significant changes in colchicine systemic exposure with coadministration. Colchicine can be administered with propafenone without a dose adjustment.
Pyrazinamide, PZA: (Minor) Because pyrazinamide can increase serum uric acid levels and precipitate gouty attacks, the dosages of antigout agents, including probenecid, may need to be adjusted.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Quinidine: (Major) Avoid concomitant use of colchicine and quinidine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and quinidine is a P-gp inhibitor.
Quinine: (Major) Avoid concomitant use of colchicine and quinine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and quinine is a P-gp inhibitor.
Ranolazine: (Major) Avoid concomitant use of colchicine and ranolazine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and ranolazine is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Ribociclib: (Major) Avoid concomitant use of colchicine and ribociclib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Ribociclib; Letrozole: (Major) Avoid concomitant use of colchicine and ribociclib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Rifampin: (Moderate) Concomitant use of rifampin and probenecid may result in increased serum concentrations of rifampin. Monitor for increased rifampin toxicity during coadministration.
Ritlecitinib: (Major) Avoid concomitant use of colchicine and ritlecitinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Ritonavir: (Major) Avoid concomitant use of colchicine and ritonavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and ritonavir is a dual strong CYP3A and P-gp inhibitor. Concomitant use has been observed to increase colchicine overall exposure by 4-fold.
Rolapitant: (Major) Avoid concomitant use of colchicine and rolapitant due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and rolapitant is a P-gp inhibitor.
Rosuvastatin: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
Rosuvastatin; Ezetimibe: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
Salicylates: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Salsalate: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates.
Saquinavir: (Major) Avoid concomitant use of colchicine and saquinavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and saquinavir is a dual strong CYP3A and P-gp inhibitor. Concomitant use with other dual strong CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 3- to 4-fold.
Sarecycline: (Major) Avoid concomitant use of colchicine and sarecycline due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and sarecycline is a P-gp inhibitor.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Concomitant use of colchicine and oral contraceptives may increase the risk of adverse effects such as diarrhea, nausea, upper abdominal pain, and cold sweats. Concomitant use studies have demonstrated that hormone concentrations are unlikely to be affected.
Selpercatinib: (Major) Avoid concomitant use of colchicine and selpercatinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and selpercatinib is a P-gp inhibitor.
Silodosin: (Major) KMD-3213G, the primary metabolite of silodosin, is formed from direct conjugation of silodosin by UDP-glucuronosyltransferase 2B7 (UBT2B7). In theory, coadministration of silodosin with UBT2B7 inhibitors such as probenecid may increase silodosin plasma concentrations.
Simvastatin: (Moderate) Concomitant use of colchicine and HMG-CoA reductase inhibitors (statins) may increase the risk for myopathy and rhabdomyolysis. If concomitant use is necessary, monitor for signs and symptoms of muscle pain, tenderness, or weakness especially following therapy initiation and upward dose titration. The use of low dose colchicine may further reduce the risk for myopathy.
Sodium Benzoate; Sodium Phenylacetate: (Moderate) Renal excretion of phenylacetylglutamine and hippuric acid may be affected by probenecid through competitive inhibition. These competitive reactions could be significant, as the overall usefulness of sodium benzoate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. Use with caution.
Sodium Phenylbutyrate: (Major) Avoid coadministration of probenecid and sodium phenylbutyrate. Coadministration may increase the risk for potential for neurotoxicity. Probenecid may inhibit renal excretion of the metabolites of sodium phenylbutyrate, including phenylacetate and phenylacetylglutamine.
Sodium Phenylbutyrate; Taurursodiol: (Major) Avoid coadministration of probenecid and sodium phenylbutyrate. Coadministration may increase the risk for potential for neurotoxicity. Probenecid may inhibit renal excretion of the metabolites of sodium phenylbutyrate, including phenylacetate and phenylacetylglutamine. (Major) Avoid concomitant use of colchicine and taurursodiol due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and taurursodiol is a P-gp inhibitor.
Sofosbuvir; Velpatasvir: (Major) Avoid concomitant use of colchicine and velpatasvir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and velpatasvir is a P-gp inhibitor.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concomitant use of colchicine and velpatasvir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and velpatasvir is a P-gp inhibitor. (Major) Avoid concomitant use of colchicine and voxilaprevir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and voxilaprevir is a P-gp inhibitor.
Sorafenib: (Major) Avoid concomitant use of colchicine and sorafenib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and sorafenib is a P-gp inhibitor.
Sotorasib: (Major) Avoid concomitant use of colchicine and sotorasib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and sotorasib is a P-gp inhibitor.
Sparsentan: (Major) Avoid concomitant use of colchicine and sparsentan due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and sparsentan is a P-gp inhibitor.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Stavudine, d4T: (Minor) Stavudine undergoes active tubular secretion, and renal elimination may be affected by probenecid, a drug known to interfere with tubular secretion. Resultant increases in serum levels can lead to toxicity.
Stiripentol: (Major) Avoid concomitant use of colchicine and stiripentol due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and stiripentol is a P-gp inhibitor.
Sulbactam; Durlobactam: (Moderate) Monitor for an increase in sulbactam-related adverse effects if concomitant use with probenecid is necessary. Concomitant use may increase sulbactam exposure. Sulbactam is an OAT1 substrate and probenecid is an OAT1 inhibitor.
Sulfadiazine: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Sulfasalazine: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Sulfonamides: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
Sulfonylureas: (Moderate) Probenecid is highly protein bound, and the hypoglycemic effect of sulfonylureas made be potentiated if these drugs are coadministered.
Sulindac: (Major) Increases in the plasma concentration of sulindac and the inactive sulfone metabolite have been observed following concomitant administration with probenecid; however, the plasma concentration of the active sulfide metabolite was only slightly affected. The mechanism of this interaction may be through the inhibition of renal clearance. Concurrent use of probenecid and sulindac also modestly reduced the uricosuric action of probenecid. Monitor patients for signs and symptoms of sulindac toxicity if probenecid and sulindac are used concurrently.
Sumatriptan; Naproxen: (Major) Substantial increases in the plasma concentration of naproxen anion have been observed following concomitant administration with probenecid. Plasma concentrations of naproxen can be increased by 50% and its half-life increased to 37 hours. The mechanism of this interaction may be through the inhibition of the formation of naproxen's glucuronide metabolite as well as inhibition of renal clearance.
Tacrolimus: (Minor) Monitor for colchicine-related adverse effects during concomitant use of tacrolimus. Concomitant use may increase colchicine exposure.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Temsirolimus: (Major) Avoid concomitant use of colchicine and temsirolimus due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and temsirolimus is a P-gp inhibitor.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as probenecid. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as probenecid; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
Tepotinib: (Major) Avoid concomitant use of colchicine and tepotinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and tepotinib is a P-gp inhibitor.
Tezacaftor; Ivacaftor: (Major) Avoid concomitant use of colchicine and ivacaftor due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and ivacaftor is a P-gp inhibitor.
Thiazide diuretics: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Ticagrelor: (Major) Avoid concomitant use of colchicine and ticagrelor due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and ticagrelor is a P-gp inhibitor.
Tipranavir: (Major) Avoid concomitant use of colchicine and tipranavir due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and tipranavir is a dual strong CYP3A and P-gp inhibitor. Concomitant use with other dual strong CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 3- to 4-fold.
Tolmetin: (Major) Probenecid can decrease the renal clearance of nonsteroidal antiinflammatory agents (NSAIDs). Reduction of the NSAID dose may be necessary when it is used together with probenecid.
Topiramate: (Minor) Probenecid may increase the renal clearance of topiramate resulting in lower topiramate concentrations. Although not evaluated in humans, animal studies using probenecid along with topiramate showed a significant increase in renal clearance of topiramate. This suggests that topiramate may undergo renal tubular reabsorption. Probenecid may block renal tubular reabsorption of topiramate, thus increasing the renal clearance of the drug.
Trandolapril; Verapamil: (Major) Avoid concomitant use of colchicine and verapamil due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and verapamil is a dual moderate CYP3A and P-gp inhibitor. Concomitant use has been observed to increase colchicine overall exposure by 2-fold.
Triamterene: (Moderate) Probenecid has uricosuric actions. Triamterene can also cause hyperuricemia. Although this effect represents a pharmacodynamic interaction, dosage adjustments of probenecid may be necessary if triamterene is administered to patients being treated with probenecid.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Probenecid has uricosuric actions. Triamterene can also cause hyperuricemia. Although this effect represents a pharmacodynamic interaction, dosage adjustments of probenecid may be necessary if triamterene is administered to patients being treated with probenecid. (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Tucatinib: (Major) Avoid concomitant use of colchicine and tucatinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and tucatinib is a dual strong CYP3A and P-gp inhibitor. Concomitant use with other dual strong CYP3A and P-gp inhibitors has been observed to increase colchicine overall exposure by 3- to 4-fold.
Valacyclovir: (Moderate) Probenecid can reduce the renal tubular secretion of valacyclovir when these agents are coadministered, causing an increase in the serum concentration and elimination half-life of valacyclovir.
Valganciclovir: (Moderate) Probenecid may inhibit renal tubular secretion of valganciclovir, possibly potentiating valganciclovir toxicity. Patients should be monitored for increased valganciclovir toxicity when taking probenecid.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can cause hyperuricemia. Although this effect represents a pharmacodynamic interaction and not a pharmacokinetic one, dosage adjustments of probenecid may be necessary if these agents are administered concurrently to patients being treated with probenecid.
Vemurafenib: (Major) Avoid concomitant use of colchicine and vemurafenib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and vemurafenib is a P-gp inhibitor.
Venetoclax: (Major) Avoid concomitant use of colchicine and venetoclax due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and venetoclax is a P-gp inhibitor.
Verapamil: (Major) Avoid concomitant use of colchicine and verapamil due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and verapamil is a dual moderate CYP3A and P-gp inhibitor. Concomitant use has been observed to increase colchicine overall exposure by 2-fold.
Voclosporin: (Major) Avoid concomitant use of colchicine and voclosporin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and voclosporin is a P-gp inhibitor.
Vonoprazan; Amoxicillin: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of colchicine and clarithromycin due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A and P-gp substrate and clarithromycin is a dual strong CYP3A and P-gp inhibitor. Concomitant use has been observed to increase colchicine overall exposure by 3.8-fold. (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed.
Voriconazole: (Minor) Monitor for colchicine-related adverse effects during concomitant use of voriconazole. Although voriconazole is a strong CYP3A inhibitor, drug interaction studies have shown no significant changes in colchicine systemic exposure with coadministration. Colchicine can be administered with voriconazole without a dose adjustment.
Voxelotor: (Major) Avoid concomitant use of colchicine and voxelotor due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Zidovudine, ZDV: (Major) Concomitant use of probenecid with zidovudine, ZDV may produce substantially higher serum concentrations of zidovudine.
Zonisamide: (Major) Avoid concomitant use of colchicine and zonisamide due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and zonisamide is a P-gp inhibitor.
Probenecid; colchicine are used together in the treatment of gouty arthritis.
-Probenecid: Probenecid is an uricosuric and renal tubular blocking agent. It inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits. Probenecid also competitively inhibits the active reabsorption of uric acid at the proximal convoluted tubule, facilitating urinary excretion of uric acid and decreasing plasma urate concentrations. The drug does not affect the glomerular filtration rate or reabsorption of glucose, arginine, urea, sodium, potassium, and chloride. The tubular reabsorption of phosphorus is inhibited in hypoparathyroid but not in euparathyroid individuals.
-Colchicine: Colchicine downregulates multiple pro-inflammatory pathways and increases levels of antiinflammatory mediators associated with gouty arthritis. Colchicine prevents microtubule assembly and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis. Although it is highly effective in treating acute gouty arthritis, it is not effective for other types of pain. It is not an analgesic and does not affect uric acid clearance. The actions of colchicine consequently prevent the activation, degranulation, and migration of neutrophils, thereby interfering with the inflammatory response to urate crystal deposition. Although colchicine does not inhibit phagocytosis of uric acid crystals, it does appear to prevent the release of an inflammatory glycoprotein from phagocytes. Toxic effects of colchicine are related to its antimitotic activity within proliferating tissues such as the skin, hair, and bone marrow. As a result, acute overdoses of colchicine are extremely serious and can be fatal.
Probenecid; colchicine is administered orally. The pharmacokinetics of the combination has not been well studied; the following is known from the study of the individual agents.
-Probenecid: Probenecid distributes throughout the body tissues and is 75% to 95% plasma protein-bound, predominantly to albumin. Probenecid undergoes hepatic metabolism resulting in active metabolites. Both parent drug and active metabolites are eliminated renally, mainly by tubular secretion. Small amounts of unchanged probenecid are filtered at the glomeruli. The parent drug is nearly completely reclaimed via tubular reabsorption; minor amounts of metabolites undergo tubular reabsorption. The plasma half-life of probenecid is dose-dependent. Half-life ranges from 3 to 8 hours for a 500 mg dose and 6 to 12 hours for larger doses. Both unchanged drug and its metabolites are excreted in the urine; the unchanged drug is reabsorbed.
-Colchicine: Enterohepatic recirculation occurs to a large extent and can lead to adverse GI effects with larger dosages. Plasma protein binding is low (34% to 44%). Colchicine distributes to the kidney, liver, spleen, and intestinal tissues, and concentrates primarily in the leukocytes. Colchicine can be found in leukocytes for 10 days after administration. The drug is dependent on P-glycoprotein transport and CYP3A4 isoenzyme metabolism. Colchicine is eliminated unchanged in urine and via metabolism with great inter-patient variability; the elimination half-life has ranged from 1.7 to 31.2 hours in patients with normal renal function.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp)
Probenecid does not affect CYP enzymes. At the level of the proximal and distal tubules, probenecid inhibits the secretion of weak acids, thereby increasing plasma concentrations. Some of the medications affected by this action of probenecid include most cephalosporins and penicillins, and other beta-lactam-related antibiotics such as aztreonam and imipenem; indomethacin; and methotrexate. In some cases, probenecid administration can more than double the serum concentrations of the affected drug. Elimination half-life is prolonged correspondingly.
Colchicine is metabolized by the liver and other tissues and is dependent on P-glycoprotein (P-gp) transport and CYP3A4 isoenzymes. Medications which inhibit CYP3A4 or P-gp are known to increase colchicine concentrations and increase the risk for toxicity.
-Route-Specific Pharmacokinetics
Oral Route
-Probenecid: Probenecid is completely absorbed following an oral dose. The onset of uricosuric effect can be measured within 30 minutes of oral administration and appears to reach maximal effect after 1 to 3 hours. Further, a measurable drop in plasma uric acid concentrations may occur within 45 minutes and persist for 24 to 72 hours following a single-dose of oral probenecid 2 grams.
-Colchicine: Colchicine reaches maximal plasma concentrations within a range of 0.5 to 3 hours following single-dose administration to fasting subjects. Administration with food may decrease the extent of absorption by up to 15% but not the rate of absorption; this change in absorption is not expected to have clinical effect. Absolute oral bioavailability is reported to be approximately 45%.
-Special Populations
Hepatic Impairment
Dose modifications of colchicine are recommended in some patients with hepatic impairment. Published reports on the pharmacokinetics of IV colchicine in patients with severe chronic liver disease, as well as those with alcoholic or primary biliary cirrhosis, and normal renal function suggest wide inter-patient variability. In some subjects with mild to moderate cirrhosis, the clearance of colchicine is significantly reduced and plasma half-life prolonged compared to healthy subjects. In subjects with primary biliary cirrhosis, no consistent trends were noted. No pharmacokinetic data are available for patients with severe hepatic impairment (Child-Pugh C). Renal elimination is expected to increase in patients with hepatic disease.
Renal Impairment
Probenecid has been used in patients with some renal impairment, but dosage requirements may be increased. Probenecid may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is 30 mL/minute or less.
Dose modifications of colchicine are recommended in some patients with renal impairment. Pharmacokinetics of colchicine in patients with mild and moderate renal impairment is not known. A published report described the disposition of colchicine (1 mg) in young adult men and women who had normal renal function or end-stage renal disease requiring dialysis. Patients with end-stage renal disease had 75% lower colchicine clearance (0.17 vs. 0.73 L/hour/kg) and prolonged plasma elimination half-life (18.8 hours vs. 4.4 hours) as compared to subjects with normal renal function. Colchicine is not removed by hemodialysis. Renal elimination is expected to increase in patients with hepatic disease.
Other
Pregnancy and Lactation
In pregnant women, colchicine crosses the placenta; fetal plasma concentrations of colchicine are approximately 15% of maternal concentrations. Breast milk concentrations approximate those of the maternal plasma concentrations with limited information suggesting that exclusively breast-fed infants receive less than 10% of the maternal weight-adjusted dose.