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Drug overview for PROBENECID-COLCHICINE (probenecid/colchicine):
Generic name: PROBENECID/COLCHICINE (proe-BEN-e-sid/KOL-chi-seen)
Drug class: Uricosurics
Therapeutic class: Gout and Hyperuricemia Therapy
Colchicine is an antigout and antimitotic agent. Probenecid, a sulfonamide derivative, is a uricosuric agent and inhibitor of tubular secretion of weak organic acids (e.g., penicillins and certain other beta-lactam antibacterials).
No enhanced Uses information available for this drug.
Generic name: PROBENECID/COLCHICINE (proe-BEN-e-sid/KOL-chi-seen)
Drug class: Uricosurics
Therapeutic class: Gout and Hyperuricemia Therapy
Colchicine is an antigout and antimitotic agent. Probenecid, a sulfonamide derivative, is a uricosuric agent and inhibitor of tubular secretion of weak organic acids (e.g., penicillins and certain other beta-lactam antibacterials).
No enhanced Uses information available for this drug.
DRUG IMAGES
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The following indications for PROBENECID-COLCHICINE (probenecid/colchicine) have been approved by the FDA:
Indications:
Chronic gouty arthritis
Professional Synonyms:
Chronic gouty arthropathy
Indications:
Chronic gouty arthritis
Professional Synonyms:
Chronic gouty arthropathy
The following dosing information is available for PROBENECID-COLCHICINE (probenecid/colchicine):
Dosage of colchicine depends on the patient's age, renal and hepatic function, and whether the drug is administered concomitantly with or within 14 days following therapy with drugs that affect hepatic metabolism or the P-glycoprotein transport system.
When probenecid is used for the treatment of hyperuricemia associated with gout and gouty arthritis in patients with renal impairment, increased dosage of the drug may be required. The manufacturer states that probenecid may not be effective in patients with chronic renal insufficiency, especially if the glomerular filtration rate is 30 mL/minute or less. It has been suggested that the drug should be avoided in patients with moderate to severe renal impairment (creatinine clearance of less than 50 mL/minute).
Use of colchicine in combination with a potent CYP3A4 inhibitor, such as atazanavir, boceprevir, clarithromycin, ritonavir-boosted darunavir, ritonavir-boosted fosamprenavir, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, telithromycin, ritonavir-boosted tipranavir, lopinavir/ritonavir, or the fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir, or with a P-glycoprotein inhibitor, such as cyclosporine or ranolazine, in patients with renal impairment is contraindicated.
Use of colchicine in combination with a potent CYP3A4 inhibitor, such as atazanavir, boceprevir, clarithromycin, ritonavir-boosted darunavir, ritonavir-boosted fosamprenavir, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, telithromycin, ritonavir-boosted tipranavir, lopinavir/ritonavir, the fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir, or with a P-glycoprotein inhibitor, such as cyclosporine or ranolazine, in patients with hepatic impairment is contraindicated.
When probenecid is used for the treatment of hyperuricemia associated with gout and gouty arthritis in patients with renal impairment, increased dosage of the drug may be required. The manufacturer states that probenecid may not be effective in patients with chronic renal insufficiency, especially if the glomerular filtration rate is 30 mL/minute or less. It has been suggested that the drug should be avoided in patients with moderate to severe renal impairment (creatinine clearance of less than 50 mL/minute).
Use of colchicine in combination with a potent CYP3A4 inhibitor, such as atazanavir, boceprevir, clarithromycin, ritonavir-boosted darunavir, ritonavir-boosted fosamprenavir, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, telithromycin, ritonavir-boosted tipranavir, lopinavir/ritonavir, or the fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir, or with a P-glycoprotein inhibitor, such as cyclosporine or ranolazine, in patients with renal impairment is contraindicated.
Use of colchicine in combination with a potent CYP3A4 inhibitor, such as atazanavir, boceprevir, clarithromycin, ritonavir-boosted darunavir, ritonavir-boosted fosamprenavir, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, telithromycin, ritonavir-boosted tipranavir, lopinavir/ritonavir, the fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir, or with a P-glycoprotein inhibitor, such as cyclosporine or ranolazine, in patients with hepatic impairment is contraindicated.
Colchicine is administered orally without regard to meals. Colchicine has been administered by IV injection; however, IV preparations of colchicine have been withdrawn from the US market because of safety concerns. (See Uses: Regulatory Actions Affecting Colchicine and see Cautions.) Patients receiving colchicine should be instructed on how to resume therapy in the event of a missed dose.
Patients with gout who are receiving colchicine for treatment of an acute flare but not for prophylaxis of recurrent flares should be instructed to take the missed dose as soon as possible. Those receiving the drug to treat an acute gout flare during colchicine prophylaxis should be instructed to take the missed dose immediately and then wait 12 hours before resuming the previous dosing schedule. Patients receiving colchicine for treatment of familial Mediterranean fever or for prophylaxis of recurrent gout flares (without treatment for an acute gout flare) should be instructed to take the missed dose as soon as possible and then resume their usual dosing schedule, but not to take a double dose to make up for the missed dose.
Probenecid is administered orally. Adverse GI effects may be minimized by taking the drug with food or antacids; dosage reduction may be required.
Patients with gout who are receiving colchicine for treatment of an acute flare but not for prophylaxis of recurrent flares should be instructed to take the missed dose as soon as possible. Those receiving the drug to treat an acute gout flare during colchicine prophylaxis should be instructed to take the missed dose immediately and then wait 12 hours before resuming the previous dosing schedule. Patients receiving colchicine for treatment of familial Mediterranean fever or for prophylaxis of recurrent gout flares (without treatment for an acute gout flare) should be instructed to take the missed dose as soon as possible and then resume their usual dosing schedule, but not to take a double dose to make up for the missed dose.
Probenecid is administered orally. Adverse GI effects may be minimized by taking the drug with food or antacids; dosage reduction may be required.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| PROBENECID-COLCHICINE TABLET | Maintenance | Adults take 1 tablet by oral route 2 times per day |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| PROBENECID-COLCHICINE TABLET | Maintenance | Adults take 1 tablet by oral route 2 times per day |
The following drug interaction information is available for PROBENECID-COLCHICINE (probenecid/colchicine):
There are 2 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Ketorolac/OAT3 Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Inhibitors of organic anion transporter 3 (OAT3) may inhibit the renal clearance of ketorolac. CLINICAL EFFECTS: Enhanced ketorolac toxicity including gastrointestinal and renal toxicity as well as increased risk of bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Concomitant administration of ketorolac and organic anion transporter 3 (OAT3) inhibitors are contraindicated by the manufacturer. If concurrent therapy is deemed medically necessary, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: Probenecid has been reported to increase serum concentrations and toxicity of nonsteroidal anti-inflammatory drugs (e.g., indomethacin, ketoprofen, naproxen).(1-3) Based upon material from the manufacturer of ketorolac, concurrent administration of probenecid and ketorolac also increases serum concentrations of the NSAID ketorolac and produces a 2-fold increase in the half-life of ketorolac and a 3-fold increase in the area under the plasma concentration-time curve.(4) Ketorolac is a potent NSAID analgesic and increasing the serum concentrations may increase the risk of occurrence of serious renal, GI and hematologic side effects. OAT3 inhibitors linked to this monograph include: leflunomide, probenecid, teriflunomide, and vadadustat.(5) |
BUPIVACAINE-KETOROLAC-KETAMINE, KETOROLAC TROMETHAMINE, R.E.C.K.(ROPIV-EPI-CLON-KETOR), ROPIVACAINE-CLONIDINE-KETOROLC, ROPIVACAINE-KETOROLAC-KETAMINE, SPRIX, TORONOVA II SUIK, TORONOVA SUIK |
| Irinotecan/UGT1A1 Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Inhibitors of UGT1A1 may inhibit the metabolism of SN-38, the active metabolite of irinotecan.(1) Atazanavir may inhibit the metabolism of irinotecan by UGT1A1.(1,2) This increases the system exposure to SN-38, the active metabolite of irinotecan.(3) CLINICAL EFFECTS: Concurrent use of UGT1A1 inhibitors may result in increased exposure to and toxicity from irinotecan.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of irinotecan states do not administer UGT1A1 inhibitors with irinotecan unless there are no therapeutic alternatives. The increased exposure to the active metabolite should be taken into consideration when co-administering these agents.(1) The US manufacturer of atazanavir states that concurrent use of irinotecan is contraindicated.(2) The Australian manufacturer of atazanavir states that irinotecan should not be administered with atazanavir.(3) DISCUSSION: Because atazanavir inhibits UGT1A1 at therapeutic concentrations, it is expected to interfere with the metabolism of irinotecan. Therefore, the manufacturer of atazanavir states that irinotecan should not be administered with atazanavir.(1,2) UGT1A1 inhibitors linked to this monograph include: atazanavir, capivasertib, belumosudil, erlotinib, gemfibrozil, lapatinib, nilotinib, pazopanib, probenecid, regorafenib, and sorafenib. One or more of the drug pairs linked to this monograph have been included in a list of interactions that should be considered "high-priority" for inclusion and should not be inactivated in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology. |
CAMPTOSAR, IRINOTECAN HCL, ONIVYDE |
There are 15 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Colchicine/Cyclosporine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Colchicine is metabolized and transported by CYP3A4 and P-glycoprotein (P-gp) respectively. Cyclosporine is an inhibitor of both of these pathways. Studies indicate that cyclosporine may inhibit renal secretion(4) of colchicine and decrease the hepatic secretion(5) of colchicine into the bile. CLINICAL EFFECTS: Concurrent use of cyclosporine may result in elevated levels of and toxicity from colchicine. Symptoms of colchicine toxicity include muscle weakness or pain; numbness or tingling in the fingers or toes; myelosuppression; abdominal pain; nausea; severe diarrhea or vomiting; feeling weak or tired; increased infections; and pale or gray color of the lips, tongue, or palms of hands.(1,2) Patients with familial Mediterranean fever (FMF) may experience a higher incidence of colchicine-related gastrointestinal effects. PREDISPOSING FACTORS: Serum colchicine levels and the risk of colchicine myopathy may be increased by renal dysfunction,(2) which may occur in renal transplant patients(3) and is common in gout.(2) This interaction is expected to be more severe in patients with renal and/or hepatic impairment(1,2) and may occur more frequently in patients with familial Mediterranean fever (FMF). PATIENT MANAGEMENT: The concurrent use of strong P-gp inhibitors such as cyclosporine is contraindicated in patients with renal or hepatic impairment.(6,7) In patients without renal or hepatic impairment who are currently taking or have taken strong P-gp inhibitors such as cyclosporine in the previous 14 days, the dosage of colchicine should be reduced. For gout flares, the recommended dosage is 0.6 mg (1 tablet) for one dose. This dose should be repeated no earlier than in 3 days. For gout prophylaxis, if the original dosage was 0.6 mg twice daily, use 0.3 mg daily. If the original dosage was 0.6 mg daily, use 0.3 mg every other day. For Familial Mediterranean fever (FMF), the recommended maximum daily dose is 0.6 mg (may be given as 0.3 mg twice a day).(6,7) Patients should be instructed to immediately report any signs of colchicine toxicity, such as abdominal pain; significant nausea or vomiting; diarrhea; muscle weakness/pain; numbness/tingling in fingers/toes; unusual bleeding or bruising, infections, unusual weakness/tiredness, or pale/gray color of the lips/tongue/palms of hands. DISCUSSION: In a study in 23 subjects, concurrent administration of a single dose of cyclosporine (100 mg) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of colchicine (0.6 mg) by 270% (range 62% to 606.9%) and by 259% (range 75.8% to 511.9%), respectively.(7) In a case report, a renal transplant patient's cyclosporine level increased more than 9-fold the day after the initiation of colchicine. The patient also developed renal dysfunction.(1) In another report, a renal transplant patient developed renal dysfunction and myopathy two weeks after a three-day course of colchicine.(8) In a case report, a renal transplant patient developed myopathy four weeks after the addition of colchicine to his cyclosporine regimen. Prior to his transplant, he had taken colchicine for almost five years with no adverse effects.(9) In another report, a renal transplant patient developed myopathy two weeks after the addition of colchicine to cyclosporine therapy.(10) Another report describes three cases of myopathy during concurrent cyclosporine and colchicine. The patients had taken the combination for six weeks, one year, and eight years prior to developing myopathy.(11) In a retrospective review, five of ten patients (50%) who received concurrent cyclosporine and colchicine developed myopathy. There were no differences in age, transplant duration, or serum creatinine between those patients who developed myopathy and those who did not.(12) In a study in four patients with familial Mediterranean fever (FMF) who were receiving colchicine, an attempt was made to convert azathioprine to cyclosporine. All four patients developed pronounced side effects, including diarrhea and elevated serum lactic acid; three had elevated serum alanine aminotransferase (ALT) and hyperbilirubinemia; two had elevated serum creatinines; and one was hospitalized with myopathy. No patients reached therapeutic levels of cyclosporine. The authors had previously converted three colchicine-treated FMF patients to cyclosporine.(13) Another article reported that only one of eight patients with FMF tolerated concurrent cyclosporine and colchicine following renal transplantation. Two subjects only had gastrointestinal side effects, the other five had myopathy in addition to gastrointestinal side effects.(14) In another case report, a 59 year-old male renal transplant patient maintained on cyclosporine developed rhabdomyolysis with progressive quadriparesis, hematologic toxicity, and acute renal failure following the addition of colchicine (3 mg daily for 7 days) to his regimen.(15) |
CYCLOSPORINE, CYCLOSPORINE MODIFIED, GENGRAF, NEORAL, SANDIMMUNE |
| Colchicine (for Gout & FMF)/Strong CYP3A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong CYP3A4 inhibitors may inhibit the metabolism of colchicine.(1,2) CLINICAL EFFECTS: Concurrent use of a strong CYP3A4 inhibitor may result in elevated levels of and toxicity from colchicine. Symptoms of colchicine toxicity include muscle weakness or pain; numbness or tingling in the fingers or toes; myelosuppression; abdominal pain; nausea; severe diarrhea or vomiting; feeling weak or tired; increased infections; and pale or gray color of the lips, tongue, or palms of hands.(1,2) PREDISPOSING FACTORS: This interaction is expected to be more severe in patients with renal and/or hepatic impairment(1,2) and in patients who receive concurrent therapy. PATIENT MANAGEMENT: The concurrent use of a strong CYP3A4 inhibitor with colchicine is contraindicated in patients with renal or hepatic impairment.(1-3) Avoid concurrent use in other patients, if possible.(3) In patients without renal or hepatic impairment who are currently taking or have taken strong CYP3A4 inhibitors in the previous 14 days, the dosage of colchicine should be reduced. For gout flares, the recommended colchicine dosage is 0.6 mg (1 tablet) for one dose, then 0.3 mg (half tablet) 1 hour later. This dose should be repeated no earlier than in 3 days.(1,2) For gout prophylaxis, if the original colchicine dosage was 0.6 mg twice daily, use 0.3 mg daily. If the original dosage was 0.6 mg daily, use 0.3 mg every other day.(3-11) For Familial Mediterranean fever (FMF), the recommended maximum daily dose of colchicine is 0.6 mg (may be given as 0.3 mg twice a day).(1,2) Patients should be instructed to immediately report any signs of colchicine toxicity, such as muscle weakness/pain, numbness/tingling in fingers/toes, unusual bleeding or bruising, infections, weakness/tiredness, pale/gray color of the lips/tongue/palms of hands, and/or severe diarrhea/vomiting. DISCUSSION: In a study in 21 subjects, pretreatment with azithromycin (500 mg Day 1, then 250 mg daily Days 2-5) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of colchicine (0.6 mg) by 21.6% (range -41.7% to 222%) and by 57.1% (range -24.3% to 241.1%), respectively.(1) There are several reports of colchicine toxicity(4-6) and death(7,8) following the addition of clarithromycin to therapy. In a retrospective review of 116 patients who received clarithromycin and colchicine during the same hospitalization, 10.2% (9/88) of patients who received simultaneous therapy died, compared to 3.6% (1/28) of patients who received sequential therapy.(9) An FDA review of 117 colchicine-related deaths that were not attributable to overdose found that 60 deaths (51%) involved concurrent use of clarithromycin.(2) In a study in 23 subjects, pretreatment with clarithromycin (250 mg twice daily for 7 days) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of colchicine (0.6 mg) by 227.2% (range 65.7% to 591.1%) and by 281.5% (range 88.7% to 851.6%), respectively.(1) In a study in 24 subjects, pretreatment with ketoconazole (200 mg twice daily for 5 days) increased the Cmax and AUC of a single dose of colchicine (0.6 mg) by 101.7% (range 19.6% to 219%) and by 212.2% (range 76.7% to 419.6%), respectively.(1) In a study in 18 subjects, pretreatment with ritonavir (100 mg twice daily for 5 days) increased the Cmax and AUC of a single dose of colchicine (0.6 mg) by 184.4% (range 79.2% to 447.4%) and by 296% (range 53.8% to 924.4%), respectively.(1) Colchicine toxicity has been reported with concurrent use of CYP3A4 and P-gp inhibitors such as clarithromycin, cyclosporine, diltiazem, erythromycin, and verapamil.(1,2) Strong inhibitors of CYP3A4 include: adagrasib, atazanavir, boceprevir, ceritinib, clarithromycin, cobicistat, darunavir, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, levoketoconazole, lonafarnib, lopinavir/ritonavir, mibefradil, mifepristone, nefazodone, nelfinavir, nirmatrelvir, posaconazole, ribociclib, ritonavir, saquinavir, telaprevir, telithromycin, tipranavir, tucatinib, and voriconazole.(1,10) |
APTIVUS, ATAZANAVIR SULFATE, CLARITHROMYCIN, CLARITHROMYCIN ER, DARUNAVIR, EVOTAZ, GENVOYA, ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KALETRA, KETOCONAZOLE, KISQALI, KORLYM, KRAZATI, LANSOPRAZOL-AMOXICIL-CLARITHRO, LOPINAVIR-RITONAVIR, MIFEPREX, MIFEPRISTONE, NEFAZODONE HCL, NORVIR, NOXAFIL, OMECLAMOX-PAK, PAXLOVID, POSACONAZOLE, PREZCOBIX, PREZISTA, RECORLEV, REYATAZ, RITONAVIR, SPORANOX, STRIBILD, SYMTUZA, TOLSURA, TUKYSA, TYBOST, VFEND, VFEND IV, VIRACEPT, VOQUEZNA TRIPLE PAK, VORICONAZOLE, ZOKINVY, ZYDELIG, ZYKADIA |
| Doripenem; Meropenem/OAT3 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of organic anion transporter 3 (OAT3) may inhibit the renal excretion of doripenem (1) and meropenem(2) by competing with them for active tubular secretion. CLINICAL EFFECTS: Concurrent use of organic anion transporter 3 (OAT3) inhibitors may result in elevated levels of and toxicity from doripenem(1) or meropenem.(2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of doripenem states that concurrent use of organic anion transporter 3 (OAT3) inhibitors is not recommended.(1) The US manufacturer of meropenem states that concurrent use of OAT3 inhibitors is not recommended.(2) DISCUSSION: Probenecid has been shown to increase doripenem half-life (T1/2) and area-under-curve (AUC) by 53% and 75%, respectively.(1) In a study in six subjects, concurrent probenecid increased meropenem T1/2 by 33%.(3) Other studies have shown probenecid to increase the T1/2 of meropenem by 38% and the extent of meropenem systemic exposure by 58%.(2) OAT3 inhibitors linked to this monograph include: leflunomide, probenecid, teriflunomide, and vadadustat.(4) |
MEROPENEM, MEROPENEM-0.9% NACL, VABOMERE |
| Colchicine (for Gout & FMF)/Moderate CYP3A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate CYP3A4 inhibitors may inhibit the metabolism of colchicine(1-3) CLINICAL EFFECTS: Concurrent use of moderate CYP3A4 inhibitors may result in elevated levels of and toxicity from colchicine. Symptoms of colchicine toxicity include muscle weakness or pain; numbness or tingling in the fingers or toes; myelosuppression; abdominal pain; nausea; severe diarrhea or vomiting; feeling weak or tired; increased infections; and pale or gray color of the lips, tongue, or palms of hands.(1-3) PREDISPOSING FACTORS: This interaction is expected to be more severe in patients with renal and/or hepatic impairment.(1-3) PATIENT MANAGEMENT: Avoid use of colchicine concurrently with or within 14 days of taking moderate CYP3A4 inhibitors (without ritonavir). If concurrent use is unavoidable, the dosage of colchicine should be reduced.(1-3) For gout flares, the recommended dosage is 1.2 mg (2 tablets) for one dose. This dose should be repeated no earlier than in 3 days.(1-4) For gout prophylaxis, if the original dosage was 0.6 mg twice daily, use 0.3 mg twice daily or 0.6 mg daily. If the original dosage was 0.6 mg daily, use 0.3 mg daily.(1-4) For Familial Mediterranean fever (FMF), the recommended maximum daily dose is 1.2 mg (may be given as 0.6 mg twice a day).(1-4) Patients should be instructed to immediately report any signs of colchicine toxicity, such as muscle weakness/pain, numbness/tingling in fingers/toes, unusual bleeding or bruising, infections, weakness/tiredness, pale/gray color of the lips/tongue/palms of hands, and/or severe diarrhea/vomiting. DISCUSSION: Fluconazole (400 mg loading dose followed by 200 mg daily for 4 days) increased the area-under-curve (AUC) of colchicine by 40%.(2) Moderate inhibitors of CYP3A4 include: amprenavir, aprepitant, avacopan, clofazimine, conivaptan, crizotinib, duvelisib, fedratinib, fluconazole, fosamprenavir, fosnetupitant, imatinib, isavuconazonium, ledipasvir, lenacapavir, letermovir, netupitant, nilotinib, and treosulfan.(1,5,6) |
AKYNZEO, APONVIE, APREPITANT, CINVANTI, CLOFAZIMINE, CONIVAPTAN-D5W, COPIKTRA, CRESEMBA, DANZITEN, DIFLUCAN, EMEND, FLUCONAZOLE, FLUCONAZOLE-NACL, FOSAMPRENAVIR CALCIUM, GLEEVEC, GRAFAPEX, IMATINIB MESYLATE, IMKELDI, INREBIC, NILOTINIB HCL, PREVYMIS, SUNLENCA, TASIGNA, TAVNEOS, VAPRISOL-5% DEXTROSE, XALKORI |
| Belinostat/UGT1A1 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of UGT1A1 may inhibit the metabolism of belinostat.(1) CLINICAL EFFECTS: Concurrent use of UGT1A1 inhibitor may result in increased exposure to and toxicity from belinostat. Toxicities from belinostat include thrombocytopenia, neutropenia, anemia, infections, hepatotoxicity, and gastrointestinal toxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of UGT1A1 inhibitors in patients receiving belinostat. If concurrent use cannot be avoided, a dose reduction by 25% is recommended as follows: -If starting dose is 1,000 mg/m2 - reduce dose to 750 mg/m2 -If starting dose is 750 mg/m2 - reduce dose to 562.5 mg/m2 -If starting dose is 500 mg/m2 - interrupt belinostat treatment for the duration of the UGT1A1 inhibitor. After discontinuation of the UGT1A1 inhibitor for 5 half-lives, resume belinostat at the dosage that was taken prior to the UGT1A1 inhibitor.(1) If concurrent use is required, the dose of belinostat may need to be reduced in response to dose-limiting toxicities. The manufacturer of belinostat recommends a 25% dose reduction (to 750 mg/m2) in patients who are homozygous for the UGT1A1*28 allele.(1) DISCUSSION: Belinostat is primarily metabolized by UGT1A1 and inhibitors of UGT1A1 are expected to increase belinostat levels and dose limiting toxicities.(1) In a PKPB model, belinostat half-life increased by 1.5-fold, area-under-curve (AUC) increased by 1.4-fold, concentration maximum (Cmax) decreased by 33%, and renal excretion increased by 2.5-fold following administration with atazanavir (UGT1A1 inhibitor).(1) UGT1A1 inhibitors linked include: atazanavir, belumosudil, capivasertib, erlotinib, gemfibrozil, indinavir, ketoconazole, lapatinib, nilotinib, pazopanib, probenecid, regorafenib, and sorafenib. |
BELEODAQ |
| Colchicine (for Gout & FMF)/P-glycoprotein (P-gp) Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: P-glycoprotein (P-gp) inhibitors may affect the transport of colchicine, a P-gp substrate.(1,2) CLINICAL EFFECTS: Concurrent use of a P-gp inhibitor may result in elevated levels of and toxicity from colchicine. Symptoms of colchicine toxicity include abdominal pain; nausea or vomiting; severe diarrhea; muscle weakness or pain; numbness or tingling in the fingers or toes; myelosuppression; feeling weak or tired; increased infections; and pale or gray color of the lips, tongue, or palms of hands.(1,2) PREDISPOSING FACTORS: This interaction is expected to be more severe in patients with renal and/or hepatic impairment(1,2) and in patients who receive concurrent therapy. PATIENT MANAGEMENT: The concurrent use of colchicine with P-gp inhibitors is contraindicated in patients with renal or hepatic impairment.(1-3) Avoid concurrent use in other patients, if possible.(3) In patients without renal or hepatic impairment who are currently taking or have taken a P-gp inhibitor in the previous 14 days, the dosage of colchicine should be reduced. For gout flares, the recommended dosage is 0.6 mg (1 tablet) for one dose. This dose should be repeated no earlier than in 3 days.(1,2) For gout prophylaxis, if the original dosage was 0.6 mg twice daily, use 0.3 mg daily. If the original dosage was 0.6 mg daily, use 0.3 mg every other day.(3-12) For Familial Mediterranean fever (FMF), the recommended maximum daily dose is 0.6 mg (may be given as 0.3 mg twice a day).(1,2) Patients should be instructed to immediately report any signs of colchicine toxicity, such as abdominal pain, nausea/significant diarrhea, vomiting; muscle weakness/pain; numbness/tingling in fingers/toes; unusual bleeding or bruising, infections, weakness/tiredness, or pale/gray color of the lips/tongue/palms of hands. DISCUSSION: There are several reports of colchicine toxicity(4-6) and death(7,8) following the addition of clarithromycin to therapy. In a retrospective review of 116 patients who received clarithromycin and colchicine during the same hospitalization, 10.2% (9/88) of patients who received simultaneous therapy died, compared to 3.6% (1/28) of patients who received sequential therapy.(9) An FDA review of 117 colchicine-related deaths that were not attributable to overdose found that 60 deaths (51%) involved concurrent use of clarithromycin.(2) There is one case report of colchicine toxicity with concurrent erythromycin.(10) In a study in 20 subjects, pretreatment with diltiazem (240 mg daily for 7 days) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of colchicine (0.6 mg) by 44.2% (range -46.6% to 318.3%) and by 93.4% (range -30.2% to 338.6%), respectively.(1) In a study in 24 subjects, pretreatment with verapamil (240 mg twice daily for 7 days) increased the Cmax and AUC of a single dose of colchicine (0.6 mg) by 40.1% (range -47.1% to 149.5%) and by 103.3% (range -9.8% to 217.2%), respectively.(1) Colchicine toxicity has been reported with concurrent use of CYP3A4 and P-gp inhibitors such as clarithromycin, cyclosporine, diltiazem, erythromycin, and verapamil.(1,2) P-gp inhibitors include abrocitinib, amiodarone, asciminib, asunaprevir, azithromycin, belumosudil, capmatinib, carvedilol, cimetidine, danicopan, daridorexant, diltiazem, diosmin, dronedarone, erythromycin, flibanserin, fluvoxamine, fostamatinib, glecaprevir/pibrentasvir, lapatinib, ledipasvir, mavorixafor, neratinib, osimertinib, pirtobrutinib, propafenone, quinidine, ranolazine, schisandra, selpercatinib, sotorasib, tepotinib, tezacaftor, valbenazine, velpatasvir, vemurafenib, verapamil, vimseltinib, and voclosporin.(1,11,12) |
ADDYI, ALYFTREK, AMIODARONE HCL, AMIODARONE HCL-D5W, ASPRUZYO SPRINKLE, AZITHROMYCIN, CARDIZEM, CARDIZEM CD, CARDIZEM LA, CARTIA XT, CARVEDILOL, CARVEDILOL ER, CIBINQO, CIMETIDINE, COREG, COREG CR, DILT-XR, DILTIAZEM 12HR ER, DILTIAZEM 24HR ER, DILTIAZEM 24HR ER (CD), DILTIAZEM 24HR ER (LA), DILTIAZEM 24HR ER (XR), DILTIAZEM HCL, DILTIAZEM HCL-0.7% NACL, DILTIAZEM HCL-0.9% NACL, DILTIAZEM HCL-NACL, DILTIAZEM-D5W, E.E.S. 200, E.E.S. 400, EPCLUSA, ERY-TAB, ERYPED 200, ERYPED 400, ERYTHROCIN LACTOBIONATE, ERYTHROCIN STEARATE, ERYTHROMYCIN, ERYTHROMYCIN ESTOLATE, ERYTHROMYCIN ETHYLSUCCINATE, ERYTHROMYCIN LACTOBIONATE, FLIBANSERIN, FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER, HARVONI, INGREZZA, INGREZZA INITIATION PK(TARDIV), INGREZZA SPRINKLE, JAYPIRCA, LAPATINIB, LEDIPASVIR-SOFOSBUVIR, LUMAKRAS, LUPKYNIS, MATZIM LA, MAVYRET, MULTAQ, NERLYNX, NEXTERONE, NUEDEXTA, PACERONE, PROPAFENONE HCL, PROPAFENONE HCL ER, QUINIDINE GLUCONATE, QUINIDINE SULFATE, QUVIVIQ, RANOLAZINE ER, RETEVMO, REZUROCK, ROMVIMZA, SCEMBLIX, SOFOSBUVIR-VELPATASVIR, SYMDEKO, TABRECTA, TAGRISSO, TAVALISSE, TEPMETKO, TIADYLT ER, TIAZAC, TRANDOLAPRIL-VERAPAMIL ER, TRIKAFTA, TYKERB, VERAPAMIL ER, VERAPAMIL ER PM, VERAPAMIL HCL, VERAPAMIL SR, VOSEVI, VOYDEYA, XOLREMDI, ZELBORAF, ZITHROMAX, ZITHROMAX TRI-PAK |
| Baricitinib/OAT3 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of organic anion transporter 3 (OAT3) may inhibit the renal elimination of baricitinib.(1,2) CLINICAL EFFECTS: Concurrent use of organic anion transporter 3 (OAT3) inhibitors may result in an increase in both the therapeutic and toxic effects of baricitinib.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If concurrent therapy with a strong organic anion transporter 3 (OAT3) inhibitor is warranted, and the recommended dosage is 4 mg once daily, reduce to 2 mg once daily. If the recommended dosage is 2 mg once daily, reduce dose to 1 mg once daily. If the recommended dosage is 1 mg once daily, consider discontinuing probenecid.(2) OAT3 inhibitors with less inhibitor potency are not expected to cause a clinically significant change in baricitinib levels.(1,2) DISCUSSION: In a clinical pharmacology study, dosing of probenecid (an OAT3 inhibitor with strong inhibition potential) resulted in approximately a 2-fold increase in area-under-curve (AUC) with no change in time maximum (Tmax) or concentration maximum (Cmax) of baricitinib.(1,2) OAT3 inhibitors linked to this monograph include: probenecid and vadadustat.(1-3) |
OLUMIANT |
| Sacituzumab Govitecan/UGT1A1 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of UGT1A1 may inhibit the metabolism of SN-38, the topoisomerase inhibitor which is the antineoplastic component of sacituzumab govitecan.(1) CLINICAL EFFECTS: Concurrent use of UGT1A1 inhibitors may result in increased exposure to and toxicity from sacituzumab govitecan. Toxicities from sacituzumab govitecan include neutropenia, severe diarrhea, nausea, and vomiting.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of inhibitors of UGT1A1 in patients receiving sacituzumab govitecan.(1) DISCUSSION: SN-38, the small molecule moiety of sacituzumab govitecan, is metabolized by UGT1A1, and inhibitors of UGT1A1 are expected to increase SN-38 levels and dose limiting toxicities.(1) In a clinical trial, patients homozygous for decreased function UGT1A1*28 allele had a 26% incidence of Grade 4 neutropenia, compared to 13% of patients heterozygous for the UGT1A1*28 allele and 11% of patients homozygous for the wild type allele.(1) Coadministration of ketoconazole (a CYP3A4 and UGT1A1 inhibitor) with irinotecan, has been reported to result in increased exposure to SN-38, an active metabolite of irinotecan.(2) UGT1A1 inhibitors linked to this monograph include: atazanavir, belumosudil, capivasertib, erlotinib, gemfibrozil, indinavir, ketoconazole, lapatinib, nilotinib, pazopanib, probenecid, regorafenib, and sorafenib. |
TRODELVY |
| Sodium Iodide I 131/Myelosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1) DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1) |
HICON, SODIUM IODIDE I-131 |
| Lorazepam Extended Release/UGT Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of UDP-glucuronosyltransferases (UGT) may inhibit the metabolism of lorazepam.(1) CLINICAL EFFECTS: Concurrent use of UGT inhibitors may result in increased exposure to and toxicity from lorazepam, including profound sedation, respiratory depression, and coma.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of lorazepam extended release capsules states the initiating a UGT inhibitor during therapy with lorazepam extended release capsules should be avoided. If a UGT inhibitor is initiated, discontinue lorazepam extended release capsules and switch patient to a reduced dose of lorazepam tablets during concurrent therapy.(1) DISCUSSION: In a study in 8 healthy males, pretreatment with valproate (250 mg twice daily for 3 days) decreased the total clearance of a single dose of lorazepam (2 mg intravenously) by 40% in 6 subjects. The formation rate of lorazepam glucuronide was decreased by 55% in these subjects. Lorazepam concentrations were about 2-fold higher for at least 12 hours post-dose during concurrent valproate.(2,4) In a randomized, double-blind, placebo-controlled study in 16 healthy males, concurrent divalproex (500 mg every 12 hours for 12 days) increased the area-under-curve (AUC), maximum concentration (Cmax), and minimum concentration (Cmin) of lorazepam (1 mg every 12 hours, Days 6-10) by 20%, 8%, and 31%, respectively. Lorazepam clearance was decreased by 31% during concurrent divalproex.(5) There is one case report of coma following the injection of 6 mg of lorazepam over 24 hours in a patient maintained on valproate (1000 mg). The patient remained in a coma for between 48 and 72 hours.(6) In a study in 9 healthy subjects, pretreatment with probenecid (500 mg every 6 hours) increased the half-life (T1/2) of a single intravenous dose of lorazepam (2 mg) by 130%. Lorazepam clearance was decreased by 45%. There was no change in lorazepam apparent volume of distribution.(2,7) UGT inhibitors linked to this monograph include: atazanavir, belumosudil, capivasertib, erlotinib, gemfibrozil, indinavir, ketoconazole, lapatinib, mefenamic acid, nilotinib, pazopanib, probenecid, regorafenib, sorafenib, and valproic acid. |
LOREEV XR |
| Pexidartinib/UGT1A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of UGT1A4 may inhibit the metabolism of pexidartinib.(1) CLINICAL EFFECTS: Concurrent use of a inhibitors of UGT1A4 may result in elevated levels and increased effects of pexidartinib, such as hepatotoxicity.(1,2) Symptoms can include nausea, vomiting, jaundice, dark urine, abdominal pain, and unexplained fatigue. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of pexidartinib states that pexidartinib coadministration with inhibitors of UGT1A4 should be avoided.(1) If coadministration with a UGT1A4 inhibitor cannot be avoided, reduce the pexidartinib dose according to the following recommendations. If the planned total daily dose is currently 500 mg, modify the total daily dose to 250 mg by administering 125 mg twice daily. If the planned total daily dose is currently 375 mg, modify the total daily dose to 250 mg by administering 125 mg twice daily. If the planned total daily dose is currently 250 mg, modify the total daily dose to 125 mg by administering 125 mg once daily. If concomitant use of a UGT1A4 inhibitor is discontinued, increase the pexidartinib dose to the dose that was used before starting the inhibitor after three plasma half-lives of the UGT1A4 inhibitor. Monitor liver tests, including AST, ALT, total bilirubin, direct bilirubin, ALP and gamma-glutamyltransferase (GGT) according to the recommendations in the Turalio package insert. Advise patients to immediately report any symptoms of hepatotoxicity. DISCUSSION: Coadministration of probenecid (UGT1A4 inhibitor) increased pexidartinib maximum concentration (Cmax) and area-under-the-curve (AUC) by 5% and 60%.(1) Inhibitors of UGT1A4 linked to this monograph include: probenecid.(1,2) |
TURALIO |
| Colchicine (for Gout & FMF)/Rifampin SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Colchicine is a substrate of CYP3A4 and P-glycoprotein (P-gp).(1) Rifampin is a P-gp inhibitor with short-term use (<7 days) and a CYP3A4 and P-gp inducer with longer use.(2-5) CLINICAL EFFECTS: The exact course of this interaction is undefined. The addition of rifampin to existing colchicine therapy may initially increase colchicine absorption, resulting in increased colchicine levels and side effects including GI distress, neuropathy, myopathy, and myelosuppression.(1,6) Continued use will cause P-gp and CYP3A4 induction, resulting in decreased colchicine levels and effectiveness.(1,2) The addition of colchicine to a patient already receiving rifampin or who has recently discontinued rifampin may result in induction of colchicine metabolism and decreased levels and efficacy of colchicine.(1,2) PREDISPOSING FACTORS: This interaction is expected to be more severe in patients with renal and/or hepatic impairment.(1,6) PATIENT MANAGEMENT: The use of colchicine in patients with renal or hepatic impairment on P-gp inhibitors, including patients starting rifampin therapy, is contraindicated. Avoid concurrent use in other patients, if possible. In patients without renal or hepatic impairment who are starting rifampin, the dosage of colchicine should be reduced. For gout flares, the recommended dosage is 0.6 mg (1 tablet) for one dose. This dose should be repeated no earlier than in 3 days. For gout prophylaxis, if the original dosage was 0.6 mg twice daily, use 0.3 mg daily. If the original dosage was 0.6 mg daily, use 0.3 mg every other day. For Familial Mediterranean fever (FMF), the recommended maximum daily dose is 0.6 mg (may be given as 0.3 mg twice a day).(1,6) Patients should be instructed to immediately report any signs of colchicine toxicity, such as abdominal pain, nausea, significant diarrhea or vomiting, muscle weakness or pain, numbness or tingling in the fingers or toes, unusual bleeding or bruising, infections, weakness, tiredness, or pale or gray color of the lips, tongue, or palms of hands. In patients who have been on rifampin for at least 1 week and require colchicine therapy, monitor for decreased colchicine response. DISCUSSION: The combination of colchicine and rifampin has not been studied. Colchicine is a known P-gp and CYP3A4 substrate and concurrent therapy with inhibitors of P-gp and/or CYP3A4 increases the risk for colchicine toxicity, including death.(1) An FDA review of 117 colchicine-related deaths that were not attributable to overdose found that 60 deaths (51%) involved concurrent use of clarithromycin (a P-gp and strong CYP3A4 inhibitor).(2) In a study of 11 healthy volunteers, digoxin administered 1 hour after the last dose of a 28-day course of rifampin increased the area-under-curve (AUC(0-3h)) and maximum concentration (Cmax) of digoxin by 45% and 49%, respectively, compared to digoxin administered in the absence of induction. These digoxin levels represent both acute and chronic effects of rifampin on digoxin disposition. Digoxin AUC(0-3h) and Cmax at 1 week after rifampin discontinuation were 68% and 69%, respectively, of the reference values, demonstrating induction effects.(3) A study of 45 healthy volunteers investigated the effects of single-dose rifampin on the pharmacokinetics of a probe-drug cocktail of digoxin, furosemide, metformin, and rosuvastatin. The AUC and Cmax of digoxin were increased by 31% and 118%, respectively.(4) In a physiologically-based pharmacokinetic (PBPK) model, the effects of rifampin on P-gp activity in the liver, intestine, and kidney were predicted. Single-dose rifampin 600 mg is expected to decrease P-gp activity to 28% in the liver, <=5% in the intestine, and 44% in the kidney. Rifampin 600 mg daily at steady state is predicted to increase P-gp activity in the liver to 321%, in the intestine to 276%-284%, and in the kidney to 266%.(5) |
RIFADIN, RIFAMPIN |
| Methotrexate(Oncology-Inj)/OAT3 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of organic anion transporter 3 (OAT3) may inhibit the renal elimination of methotrexate. CLINICAL EFFECTS: Concurrent use of organic anion transporter 3 (OAT3) inhibitors may result in an increase in both the therapeutic and toxic effects of methotrexate, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression, including neutropenia. PREDISPOSING FACTORS: Risk factors for methotrexate toxicity include: - High-dose oncology regimens - Impaired renal function, ascites, or pleural effusions PATIENT MANAGEMENT: If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions. DISCUSSION: Concomitant administration of methotrexate and probenecid has been shown to increase methotrexate plasma levels two to four times higher than when methotrexate is administered alone.(2-5) OAT3 inhibitors linked to this monograph include: probenecid and vadadustat.(7) |
METHOTREXATE, METHOTREXATE SODIUM |
| Seladelpar/OAT3 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of organic anion transporter 3 (OAT3) may inhibit the renal elimination of seladelpar.(1,2) CLINICAL EFFECTS: Concurrent use of organic anion transporter 3 (OAT3) inhibitors may result in an increase in both the therapeutic and toxic effects of seladelpar, such as hepatotoxicity.(1) Symptoms can include nausea, vomiting, jaundice, dark urine, abdominal pain, and unexplained fatigue. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of seladelpar states that concurrent administration of seladelpar with organic anion transporter 3 (OAT3) inhibitors should be avoided.(1) DISCUSSION: In a study in healthy subjects, concurrent administration of seladelpar (single 10 mg dose) with probenecid (500 mg) resulted in approximately a 2-fold increase in area-under-curve (AUC) and a 4.69-fold increase in concentration maximum (Cmax) of seladelpar.(1) OAT3 inhibitors linked to this monograph include: leflunomide, probenecid, teriflunomide, and vadadustat.(1,2) |
LIVDELZI |
| Pralatrexate/Probenecid SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of multidrug resistance-associated protein 2 (MRP2) such as probenecid may inhibit the renal elimination of pralatrexate.(1) CLINICAL EFFECTS: Concurrent use of probenecid with pralatrexate may result in an increase in both the therapeutic and toxic effects of pralatrexate, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression, including neutropenia. PREDISPOSING FACTORS: Patients with severe renal impairment (eGFR 15 to < 30 mL/min/1.73 m2) may be at greater risk for increased exposure and adverse reactions. PATIENT MANAGEMENT: Administration of probenecid with pralatrexate should be avoided.(1) If coadministration is unavoidable, monitor for increased risk of adverse reactions. DISCUSSION: Concurrent administration of probenecid resulted in delayed clearance of pralatrexate and increased pralatrexate exposure.(1) |
FOLOTYN, PRALATREXATE |
There are 11 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Methotrexate (low strength inj, oral)/OAT3 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Inhibitors of organic anion transporter 3 (OAT3) may inhibit the renal elimination of methotrexate. CLINICAL EFFECTS: Concurrent use of organic anion transporter 3 (OAT3) inhibitors may result in an increase in both the therapeutic and toxic effects of methotrexate, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression, including neutropenia. PREDISPOSING FACTORS: Risk factors for methotrexate toxicity include: - High-dose oncology regimens - Impaired renal function, ascites, or pleural effusions PATIENT MANAGEMENT: If concurrent use cannot be avoided, monitor methotrexate blood levels closely and adjust the dose accordingly. DISCUSSION: Concomitant administration of methotrexate and probenecid has been shown to increase methotrexate plasma levels two to four times higher than when methotrexate is administered alone. OAT3 inhibitors linked to this monograph include: probenecid and vadadustat.(7) |
METHOTREXATE, OTREXUP, RASUVO, TREXALL, XATMEP |
| Uricosurics/Aspirin (Greater Than 100 mg); Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Not clearly established. Protein binding displacement is a possibility. CLINICAL EFFECTS: May observe hyperuricemia and gout resulting from reduced uricosuric response. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid chronic, moderate to high doses of salicylates. DISCUSSION: This interaction is well documented. Occasional small doses of salicylates do not appear to inhibit the action of uricosurics. |
ACETYL SALICYLIC ACID, ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, ASPIRIN, BALSALAZIDE DISODIUM, BISMUTH SUBSALICYLATE, BUTALBITAL-ASPIRIN-CAFFEINE, CARISOPRODOL-ASPIRIN, CARISOPRODOL-ASPIRIN-CODEINE, CHOLINE MAGNESIUM TRISALICYLAT, COLAZAL, DISALCID, DURLAZA, MB CAPS, NORGESIC, NORGESIC FORTE, ORPHENADRINE-ASPIRIN-CAFFEINE, ORPHENGESIC FORTE, PHENYL SALICYLATE, SALSALATE, SODIUM SALICYLATE, URELLE, URETRON D-S, URIBEL TABS, URIMAR-T, URNEVA, URO-MP, URO-SP, YOSPRALA |
| Dyphylline/Probenecid SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: It appears that probenecid reduces the renal excretion rate of dyphylline. CLINICAL EFFECTS: Increased serum levels of dyphylline. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If both drugs are given, adjust the dyphylline dose as needed based on serum dyphylline levels and patient response. DISCUSSION: Additional documentation is necessary to confirm this potential interaction. Since theophylline is eliminated by hepatic metabolism rather than renal excretion, it is recommended as an alternative to dyphylline when probenecid is given concurrently. However, the benefits of using this combination may outweigh the risks, especially in cases of theophylline intolerance. Professional judgement should be exercised. |
DYPHYLLINE |
| Zidovudine/Probenecid SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Inhibition of zidovudine metabolism by probenecid. CLINICAL EFFECTS: Increased serum zidovudine levels and cutaneous reactions with systemic symptoms (eg, fever, malaise, myalgia,) have been reported. PREDISPOSING FACTORS: There may be an increased tendency of patients with disorders of the immune system to develop adverse reaction to these drugs. PATIENT MANAGEMENT: Observe patient for unexpected cutaneous reactions. It may be necessary to reduce the dosing frequency of zidovudine if probenecid is administered concurrently. DISCUSSION: Concomitant administration of zidovudine and probenecid may be therapeutically beneficial in reducing the daily dose of zidovudine. However, because of the narrow therapeutic index of zidovudine, the frequent need to treat patients with immune system disorders with various additional drugs, and the known ability of probenecid to inhibit metabolism or renal excretion of many drugs, would make combined zidovudine/probenecid treatment difficult to manage in many of these type of patients. Cutaneous reactions have been reported in many patients receiving zidovudine and probenecid concurrently. |
LAMIVUDINE-ZIDOVUDINE, RETROVIR, ZIDOVUDINE |
| Selected Cephalosporins & Penicillins/Probenecid SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Probenecid impairs the clearance of some cephalosporins and penicillins via inhibition of renal anion transporters in the proximal tubule.(49) It has also been hypothesized that probenecid may affect tissue distribution of cephalosporins.(1-5) CLINICAL EFFECTS: The concurrent administration of probenecid may result in increased maximum concentration (Cmax), area-under-curve (AUC), and half-life of the cephalosporin or penicillin.(49) While this may improve antibiotic efficacy,(46-48) increased levels may also increase the risk for antibiotic-associated nephrotoxicity.(4) PREDISPOSING FACTORS: Underlying renal dysfunction may increase the risk for nephrotoxicity. PATIENT MANAGEMENT: In patients receiving the combination to improve antibiotic efficacy, monitor for antibiotic adverse effects and consider monitoring renal function. In patients receiving probenecid therapy to prevent or treat hyperuricemia, exposure to the antibiotic will be increased. A decrease in antibiotic dose or frequency may be required. The US manufacturer of piperacillin-tazobactam states probenecid should not be coadministered with piperacillin-tazobactam unless the benefit outweighs the risk.(50) DISCUSSION: Concurrent use of probenecid with a cephalosporin or penicillin may cause an increase in the Cmax, AUC, and an increased elimination half life of the antibiotic.(6-8,49) This may be beneficial or necessary in difficult to treat infections,(46-48) but an increased risk for adverse effects should be expected. Antibiotics not dose adjusted for concurrent use with probenecid may be associated with an increased risk for adverse effects, such as nephrotoxicity. Probenecid administered concurrently with piperacillin-tazobactam prolongs the half-life of piperacillin by 21% and tazobactam by 71%. In a study in 8 healthy males, concurrent administration of probenecid (1 g) with piperacillin (1 g IM) increased piperacillin's Cmax and AUC by 30% and 60%. Renal clearance was reduced by 40%.(51) The cephalosporins affected by probenecid include cefazolin,(9-11) cephacetrile,(12,13) cephaloglycin,(14,15) cephalexin,(16-21) cephradine, (22-23) cefoxitin,(24-28) cefadroxil(29), cefaclor,(23) cefamandole,(30) ceftizoxime,(31,32) cefuroxime,(33,34) cefprozil,(35) cefonicid,(36) cefmetazole,(37) cefmenoxime,(38) and cefditoren.(39) Probenecid has been shown not to affect moxalactam,(4,40,41) ceforanide, (4,42), cefoperazone, ceftazidime(4,34,43) or ceftriaxone.(4) |
AMOXICILLIN, AMOXICILLIN TRIHYDRATE, AMOXICILLIN-CLAVULANATE POT ER, AMOXICILLIN-CLAVULANATE POTASS, AUGMENTIN, AUGMENTIN ES-600, AUGMENTIN XR, BICILLIN C-R, BICILLIN L-A, CEFACLOR, CEFACLOR ER, CEFADROXIL, CEFAZOLIN SODIUM, CEFAZOLIN SODIUM-0.9% NACL, CEFAZOLIN SODIUM-DEXTROSE, CEFAZOLIN SODIUM-STERILE WATER, CEFAZOLIN-D5W, CEFDINIR, CEFEPIME, CEFEPIME HCL, CEFEPIME-DEXTROSE, CEFOTAN, CEFOTAXIME SODIUM, CEFOTETAN, CEFOXITIN, CEFOXITIN SODIUM, CEFPODOXIME PROXETIL, CEFPROZIL, CEFUROXIME, CEFUROXIME SODIUM, CEPHALEXIN, DICLOXACILLIN SODIUM, EXTENCILLINE, LANSOPRAZOL-AMOXICIL-CLARITHRO, LENTOCILIN S, MOXATAG, OMECLAMOX-PAK, PENICILLIN G POTASSIUM, PENICILLIN G SODIUM, PENICILLIN GK-ISO-OSM DEXTROSE, PFIZERPEN, PIPERACILLIN-TAZOBACTAM, TALICIA, VOQUEZNA DUAL PAK, VOQUEZNA TRIPLE PAK, ZOSYN |
| Selected NSAIDs/Probenecid SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Probenecid may inhibit the renal tubular secretion of some NSAIDs. Probenecid may also prevent biliary clearance of NSAIDs. CLINICAL EFFECTS: The decreased clearance of NSAIDs may lead to increased blood levels and an increase in adverse effects. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for an increase in NSAID-related adverse effects, including renal insufficiency. The dose of the NSAID may need to be decreased or probenecid may need to be discontinued. DISCUSSION: Probenecid has been reported to increase the blood levels of indomethacin by 2-fold to 6-fold.(1,2) Probenecid has been reported to increase levels of oral ketoprofen by 93%;(3) however, no effect was seen on intramuscular ketoprofen in another study.(4) Probenecid has also been shown to increase naproxen levels.(5) Probenecid has been shown to increase the maximum concentration (Cmax) of tenoxicam. No other pharmacokinetic parameters were affected.(6) This interaction may result in clinical benefits in some patients. |
ANAPROX DS, ARTHROTEC 50, ARTHROTEC 75, CALDOLOR, CAMBIA, CELEBREX, CELECOXIB, COMBOGESIC, COMBOGESIC IV, CONSENSI, DICLOFENAC, DICLOFENAC POTASSIUM, DICLOFENAC SODIUM, DICLOFENAC SODIUM ER, DICLOFENAC SODIUM MICRONIZED, DICLOFENAC SODIUM-MISOPROSTOL, EC-NAPROSYN, ELYXYB, ETODOLAC, ETODOLAC ER, FELDENE, FENOPROFEN CALCIUM, FENOPRON, FLURBIPROFEN, HYDROCODONE-IBUPROFEN, IBU, IBUPAK, IBUPROFEN, IBUPROFEN LYSINE, IBUPROFEN-FAMOTIDINE, INDOCIN, INDOMETHACIN, INDOMETHACIN ER, INFLAMMACIN, INFLATHERM(DICLOFENAC-MENTHOL), KETOPROFEN, KETOPROFEN MICRONIZED, KIPROFEN, LODINE, LOFENA, LURBIPR, MECLOFENAMATE SODIUM, NABUMETONE, NABUMETONE MICRONIZED, NALFON, NAPRELAN, NAPROSYN, NAPROTIN, NAPROXEN, NAPROXEN SODIUM, NAPROXEN SODIUM CR, NAPROXEN SODIUM ER, NAPROXEN-ESOMEPRAZOLE MAG, NEOPROFEN, PHENYLBUTAZONE, PIROXICAM, RELAFEN DS, SULINDAC, SUMATRIPTAN SUCC-NAPROXEN SOD, TOLECTIN 600, TOLMETIN SODIUM, TOXICOLOGY SALIVA COLLECTION, TRESNI, TREXIMET, VIMOVO, ZIPSOR, ZORVOLEX |
| Lorazepam; Mexazolam/UGT Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Inhibitors of UDP-glucuronosyltransferases (UGT) may inhibit the metabolism of lorazepam.(1-4) One of the active metabolites of mexazolam is lorazepam. CLINICAL EFFECTS: Concurrent use of UGT inhibitors may increase levels of and clinical effects from lorazepam, including profound sedation, respiratory depression, and coma.(1-4) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturers of lorazepam state that the dosage of lorazepam should be reduced by 50% in patients receiving UGT inhibitors.(1,2) DISCUSSION: In a study in 9 healthy subjects, pretreatment with probenecid (500 mg every 6 hours) increased the half-life (T1/2) of a single intravenous dose of lorazepam (2 mg) by 130%. Lorazepam clearance was decreased by 45%. There was no change in lorazepam apparent volume of distribution.(1,4) In 7 patients given probenecid 1G orally one hour prior to induction anesthesia with midazolam, there was no significant change in plasma protein binding due to probenecid pretreatment. The mean free midazolam fractions were 3.31% prior and 3.34% following pretreatment.(5) UGT inhibitors linked to this monograph include: atazanavir, belumosudil, capivasertib, erlotinib, gemfibrozil, indinavir, ketoconazole, lapatinib, mefenamic acid, nilotinib, pazopanib, probenecid, regorafenib, and sorafenib. |
ATIVAN, LORAZEPAM, LORAZEPAM INTENSOL |
| Colchicine/HMG-CoA Reductase Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Colchicine and HMG-CoA Reductase Inhibitors(statins) each have a risk for myopathy and rhabdomyolysis; these risks may be additive.(1-3) CLINICAL EFFECTS: Concurrent use of the statin drugs and colchicine may increase the risk of myopathy or rhabdomyolysis, which is characterized by progressive muscle weakness and pain in the presence of a normal neurological exam.(1-8) PREDISPOSING FACTORS: Long term use of colchicine, generally from weeks to months in duration of use, may predispose patients to myopathy or rhabdomyolysis.(1) The risk for myopathy or rhabdomyolysis may also be greater in patients 65 years and older, inadequately treated hypothyroidism, renal impairment, carnitine deficiency, malignant hyperthermia, or in patients with a history of myopathy or rhabdomyolysis. Patients with a SLCO1B1 polymorphism that leads to decreased function of the hepatic uptake transporter OATP1B1 may have increased statin concentrations and be predisposed to myopathy or rhabdomyolysis. Patients on fluvastatin who are CYP2C9 intermediate or poor metabolizers may have increased fluvastatin concentrations and risk of myopathy. Patients on rosuvastatin with ABCG2 polymorphisms leading to decreased or poor BCRP transporter function may have increased rosuvastatin concentrations and risk of myopathy. PATIENT MANAGEMENT: Patients receiving concurrent therapy with colchicine and HMG-CoA reductase inhibitors should be carefully monitored for myopathy or rhabdomyolysis. Patients should be instructed to report any symptoms of myopathy such as unexplained muscle aches, tenderness, weakness, or the onset of tingling/numbness in the fingers or toes.(1-6) DISCUSSION: The development of myopathy and clinical rhabdomyolysis have been reported in several case reports with concurrent use of colchicine and atorvastatin,(4) fluvastatin,(5) pravastatin,(6) simvastatin(7,8), and rosuvastatin.(2) The incidence and frequency appear to increase in patients with mild to moderate renal insufficiency and length of colchicine therapy. |
ALTOPREV, AMLODIPINE-ATORVASTATIN, ATORVALIQ, ATORVASTATIN CALCIUM, CADUET, CRESTOR, EZALLOR SPRINKLE, EZETIMIBE-SIMVASTATIN, FLOLIPID, FLUVASTATIN ER, FLUVASTATIN SODIUM, LESCOL XL, LIPITOR, LIVALO, LOVASTATIN, PITAVASTATIN CALCIUM, PRAVASTATIN SODIUM, ROSUVASTATIN CALCIUM, ROSUVASTATIN-EZETIMIBE, ROSZET, SIMVASTATIN, VYTORIN, ZOCOR, ZYPITAMAG |
| Colchicine/Fibrates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism of action is not clear. Concurrent use of colchicine and fibrates may result in additive or synergistic risk for myopathy or rhabdomyolysis.(1-2) CLINICAL EFFECTS: Concurrent use of colchicine and fibrates have been associated with myopathy and rhabdomyolysis.(1-2) PREDISPOSING FACTORS: This interaction is expected to be more severe in the elderly and in patients with renal impairment.(1-3) PATIENT MANAGEMENT: The risks and benefits of colchicine should be carefully weighed in patients who are currently taking fibrates. Assure that colchicine dosage has been reduced in patients with a creatinine clearance < 30 mL/min. Patients should be monitored and instructed to report any signs or symptoms of unexpected muscle pain, tenderness or weakness.(1) DISCUSSION: Neuromyopathy was reported in a patient maintained on bezafibrate who received colchicine for recurrent gout.(4) Rhabdomyolysis was reported in a patient following the addition of gemfibrozil to colchicine therapy. The patient had pre-existing mild renal failure, hepatitis B-related chronic liver disease, and amyloidosis, which may have contributed.(3) |
FENOFIBRATE, FENOFIBRIC ACID, FIBRICOR, GEMFIBROZIL, LIPOFEN, LOPID, TRICOR, TRILIPIX |
| Colchicine/Tacrolimus SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tacrolimus may inhibit the metabolism of colchicine through inhibition of CYP3A4 metabolism. CLINICAL EFFECTS: Concurrent use of tacrolimus, a CYP3A4 inhibitor, may result in elevated levels of and toxicity from colchicine. Approximately 80% of colchicine is metabolized by CYP3A4. Symptoms of colchicine toxicity include abdominal pain; nausea or vomiting; severe diarrhea; muscle weakness or pain; numbness or tingling in the fingers or toes; myelosuppression; feeling weak or tired; increased infections; and pale or gray color of the lips, tongue, or palms of hands.(1-3) PREDISPOSING FACTORS: This interaction is expected to be more severe in patients with renal and/or hepatic impairment(1,2) and in patients who receive concurrent therapy. PATIENT MANAGEMENT: The concurrent use of colchicine and tacrolimus should be approached with caution.(3) When concurrent therapy is required, consider following the manufacturer recommendations for dose adjustments. In patients without renal or hepatic impairment who are currently taking or have taken strong CYP3A4 inhibitors in the previous 14 days, the dosage of colchicine should be reduced. For gout flares, the recommended dosage is 0.6 mg (1 tablet) for one dose, then 0.3 mg (half tablet) 1 hour later. This dose should be repeated no earlier than in 3 days. For gout prophylaxis, if the original dosage was 0.6 mg twice daily, use 0.3 mg daily. If the original dosage was 0.6 mg daily, use 0.3 mg every other day. For Familial Mediterranean fever (FMF), the recommended maximum daily dose is 0.6 mg (may be given as 0.3 mg twice a day).(1,2) Patients should be instructed to immediately report any signs of colchicine toxicity, such as abdominal pain, nausea, severe diarrhea/vomiting; muscle weakness/pain; numbness/tingling in fingers/toes; unusual bleeding or bruising, infections, weakness/tiredness, or pale/gray color of the lips/tongue/palms of hands. DISCUSSION: In a study of 21 patients, treatment with tacrolimus (minimum 4-maximum 10 mg/daily; trough levels minimum 5-maximum 8 ng/ml) in 6 of the kidney transplant recipients increased the maximum concentration (Cmax) 4-fold and area-under-curve (AUC) 3-fold after a single dose of colchicine (1 mg) than those patients with normal renal function.(3) A case report of colchicine-induced myopathy describes a 62-year-old patient on stable tacrolimus therapy for renal transplant immunosuppression who was started on colchicine (0.6 mg twice daily). A few days after initiation of colchicine, the patient reported myopathy and labs showed a 4-fold increase in aspartate aminotransferase and elevated creatine phosphokinase.(4) |
ASTAGRAF XL, ENVARSUS XR, PROGRAF, TACROLIMUS, TACROLIMUS XL |
| Probenecid/Pyrazinamide SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Pyrazinamide has been shown to inhibit urate secretion.(1) CLINICAL EFFECTS: May observe hyperuricemia and gout resulting from reduced probenecid response. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor patients receiving concurrent probenecid and pyrazinamide for signs and symptoms of gout flares. DISCUSSION: In a study in 18 males, pyrazinamide inhibited urate secretion, but had no effect on probenecid secretion.(1) |
PYRAZINAMIDE |
The following contraindication information is available for PROBENECID-COLCHICINE (probenecid/colchicine):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 5 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Hemolytic anemia from pyruvate kinase and g6PD deficiencies |
| Urate renal calculi |
| Uric acid nephropathy |
There are 7 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Aplastic anemia |
| Child-pugh class C hepatic impairment |
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Disease of liver |
| Peptic ulcer |
| Renal dialysis |
There are 7 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Bone marrow depression |
| Granulocytopenic disorder |
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
| Leukopenia |
| Myopathy |
| Rhabdomyolysis |
| Thrombocytopenic disorder |
The following adverse reaction information is available for PROBENECID-COLCHICINE (probenecid/colchicine):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 33 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. |
Urate renal calculi |
| Rare/Very Rare |
|---|
|
Agranulocytosis Allergic dermatitis Anaphylaxis Anemia Angioedema Aplastic anemia Back pain Bone marrow depression Chest tightness Disseminated intravascular coagulation Drug fever Dyspnea Erythema Hemolytic anemia Hepatic necrosis Increased alanine transaminase Increased aspartate transaminase Leukopenia Myopathy Nephrotic syndrome Pancytopenia Peripheral motor neuropathy Pruritus of skin Purpura Renal colic Rhabdomyolysis Rib pain Skin rash Thrombocytopenic disorder Uric acid nephropathy Urticaria Wheezing |
There are 22 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Abdominal pain with cramps Acute gouty arthritis Anorexia Diarrhea Headache disorder Nausea Sore throat Vomiting |
Abnormal hepatic function tests Dizziness Flushing Gingival pain Headache disorder Increased creatine kinase level Increased urinary frequency Muscle weakness Myalgia |
| Rare/Very Rare |
|---|
|
Alopecia Azoospermia Maculopapular rash Oligospermia Peripheral sensory neuropathy |
The following precautions are available for PROBENECID-COLCHICINE (probenecid/colchicine):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Probenecid crosses the placenta and has been detected in cord blood. The risks and benefits of probenecid should be evaluated when considering use of the drug in women of childbearing potential. Chromosomal aberrations have been reported in a limited number of patients receiving prolonged colchicine therapy.
Colchicine crosses the placenta in humans and has been shown in animal reproduction and development studies to cause embryofetal toxicity, teratogenic effects, and altered postnatal development at exposure levels within or above the therapeutic range. Although there are no adequate and controlled studies to date in humans, results of one study suggest that patients receiving prolonged colchicine therapy may have a greater risk of producing trisomic offspring if conception occurs during therapy with the drug. Other clinicians, however, contend that this study is inconclusive and at most merely suggestive of a probable increased risk to the offspring.
Data from a limited number of published studies indicate that use of colchicine for the treatment of familial Mediterranean fever in pregnant women was not associated with increased risk of miscarriage, stillbirth, or teratogenic effects. Colchicine should be used during pregnancy only if the potential benefits outweigh the risks. The effect of colchicine on labor and delivery is not known.
Colchicine crosses the placenta in humans and has been shown in animal reproduction and development studies to cause embryofetal toxicity, teratogenic effects, and altered postnatal development at exposure levels within or above the therapeutic range. Although there are no adequate and controlled studies to date in humans, results of one study suggest that patients receiving prolonged colchicine therapy may have a greater risk of producing trisomic offspring if conception occurs during therapy with the drug. Other clinicians, however, contend that this study is inconclusive and at most merely suggestive of a probable increased risk to the offspring.
Data from a limited number of published studies indicate that use of colchicine for the treatment of familial Mediterranean fever in pregnant women was not associated with increased risk of miscarriage, stillbirth, or teratogenic effects. Colchicine should be used during pregnancy only if the potential benefits outweigh the risks. The effect of colchicine on labor and delivery is not known.
Probenecid is expected to be distributed into human milk; possible effects on nursing infants are not known. The drug should be used with caution in breast-feeding women because of potential risks to nursing infants. Colchicine is distributed into milk.
(See Pharmacokinetics: Distribution.) Limited information suggests that exclusively breast-fed infants receive less than 10% of the maternal weight-adjusted dose. Although the drug can affect GI cell renewal and permeability, some experts state that the actual amounts of the drug distributed into breast milk are not high enough to warrant cessation of nursing. No adverse effects have been reported to date in breast-fed infants of women receiving colchicine therapy who were observed over periods of up to 10 months.
The American Academy of Pediatrics (AAP) states that the drug usually is compatible with breast-feeding. Some clinicians have suggested that exposure of the infant to the drug could be minimized by waiting 8-12 hours after a dose to breast-feed the infant. The manufacturer states that caution is advised; the infant should be observed for adverse effects.
(See Pharmacokinetics: Distribution.) Limited information suggests that exclusively breast-fed infants receive less than 10% of the maternal weight-adjusted dose. Although the drug can affect GI cell renewal and permeability, some experts state that the actual amounts of the drug distributed into breast milk are not high enough to warrant cessation of nursing. No adverse effects have been reported to date in breast-fed infants of women receiving colchicine therapy who were observed over periods of up to 10 months.
The American Academy of Pediatrics (AAP) states that the drug usually is compatible with breast-feeding. Some clinicians have suggested that exposure of the infant to the drug could be minimized by waiting 8-12 hours after a dose to breast-feed the infant. The manufacturer states that caution is advised; the infant should be observed for adverse effects.
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for PROBENECID-COLCHICINE (probenecid/colchicine):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for PROBENECID-COLCHICINE (probenecid/colchicine)'s list of indications:
| Chronic gouty arthritis | |
| M1A | Chronic gout |
| M1A.0 | Idiopathic chronic gout |
| M1A.00 | Idiopathic chronic gout, unspecified site |
| M1A.00x0 | Idiopathic chronic gout, unspecified site, without tophus (tophi) |
| M1A.00x1 | Idiopathic chronic gout, unspecified site, with tophus (tophi) |
| M1A.01 | Idiopathic chronic gout, shoulder |
| M1A.011 | Idiopathic chronic gout, right shoulder |
| M1A.0110 | Idiopathic chronic gout, right shoulder, without tophus (tophi) |
| M1A.0111 | Idiopathic chronic gout, right shoulder, with tophus (tophi) |
| M1A.012 | Idiopathic chronic gout, left shoulder |
| M1A.0120 | Idiopathic chronic gout, left shoulder, without tophus (tophi) |
| M1A.0121 | Idiopathic chronic gout, left shoulder, with tophus (tophi) |
| M1A.019 | Idiopathic chronic gout, unspecified shoulder |
| M1A.0190 | Idiopathic chronic gout, unspecified shoulder, without tophus (tophi) |
| M1A.0191 | Idiopathic chronic gout, unspecified shoulder, with tophus (tophi) |
| M1A.02 | Idiopathic chronic gout, elbow |
| M1A.021 | Idiopathic chronic gout, right elbow |
| M1A.0210 | Idiopathic chronic gout, right elbow, without tophus (tophi) |
| M1A.0211 | Idiopathic chronic gout, right elbow, with tophus (tophi) |
| M1A.022 | Idiopathic chronic gout, left elbow |
| M1A.0220 | Idiopathic chronic gout, left elbow, without tophus (tophi) |
| M1A.0221 | Idiopathic chronic gout, left elbow, with tophus (tophi) |
| M1A.029 | Idiopathic chronic gout, unspecified elbow |
| M1A.0290 | Idiopathic chronic gout, unspecified elbow, without tophus (tophi) |
| M1A.0291 | Idiopathic chronic gout, unspecified elbow, with tophus (tophi) |
| M1A.03 | Idiopathic chronic gout, wrist |
| M1A.031 | Idiopathic chronic gout, right wrist |
| M1A.0310 | Idiopathic chronic gout, right wrist, without tophus (tophi) |
| M1A.0311 | Idiopathic chronic gout, right wrist, with tophus (tophi) |
| M1A.032 | Idiopathic chronic gout, left wrist |
| M1A.0320 | Idiopathic chronic gout, left wrist, without tophus (tophi) |
| M1A.0321 | Idiopathic chronic gout, left wrist, with tophus (tophi) |
| M1A.039 | Idiopathic chronic gout, unspecified wrist |
| M1A.0390 | Idiopathic chronic gout, unspecified wrist, without tophus (tophi) |
| M1A.0391 | Idiopathic chronic gout, unspecified wrist, with tophus (tophi) |
| M1A.04 | Idiopathic chronic gout, hand |
| M1A.041 | Idiopathic chronic gout, right hand |
| M1A.0410 | Idiopathic chronic gout, right hand, without tophus (tophi) |
| M1A.0411 | Idiopathic chronic gout, right hand, with tophus (tophi) |
| M1A.042 | Idiopathic chronic gout, left hand |
| M1A.0420 | Idiopathic chronic gout, left hand, without tophus (tophi) |
| M1A.0421 | Idiopathic chronic gout, left hand, with tophus (tophi) |
| M1A.049 | Idiopathic chronic gout, unspecified hand |
| M1A.0490 | Idiopathic chronic gout, unspecified hand, without tophus (tophi) |
| M1A.0491 | Idiopathic chronic gout, unspecified hand, with tophus (tophi) |
| M1A.05 | Idiopathic chronic gout, hip |
| M1A.051 | Idiopathic chronic gout, right hip |
| M1A.0510 | Idiopathic chronic gout, right hip, without tophus (tophi) |
| M1A.0511 | Idiopathic chronic gout, right hip, with tophus (tophi) |
| M1A.052 | Idiopathic chronic gout, left hip |
| M1A.0520 | Idiopathic chronic gout, left hip, without tophus (tophi) |
| M1A.0521 | Idiopathic chronic gout, left hip, with tophus (tophi) |
| M1A.059 | Idiopathic chronic gout, unspecified hip |
| M1A.0590 | Idiopathic chronic gout, unspecified hip, without tophus (tophi) |
| M1A.0591 | Idiopathic chronic gout, unspecified hip, with tophus (tophi) |
| M1A.06 | Idiopathic chronic gout, knee |
| M1A.061 | Idiopathic chronic gout, right knee |
| M1A.0610 | Idiopathic chronic gout, right knee, without tophus (tophi) |
| M1A.0611 | Idiopathic chronic gout, right knee, with tophus (tophi) |
| M1A.062 | Idiopathic chronic gout, left knee |
| M1A.0620 | Idiopathic chronic gout, left knee, without tophus (tophi) |
| M1A.0621 | Idiopathic chronic gout, left knee, with tophus (tophi) |
| M1A.069 | Idiopathic chronic gout, unspecified knee |
| M1A.0690 | Idiopathic chronic gout, unspecified knee, without tophus (tophi) |
| M1A.0691 | Idiopathic chronic gout, unspecified knee, with tophus (tophi) |
| M1A.07 | Idiopathic chronic gout, ankle and foot |
| M1A.071 | Idiopathic chronic gout, right ankle and foot |
| M1A.0710 | Idiopathic chronic gout, right ankle and foot, without tophus (tophi) |
| M1A.0711 | Idiopathic chronic gout, right ankle and foot, with tophus (tophi) |
| M1A.072 | Idiopathic chronic gout, left ankle and foot |
| M1A.0720 | Idiopathic chronic gout, left ankle and foot, without tophus (tophi) |
| M1A.0721 | Idiopathic chronic gout, left ankle and foot, with tophus (tophi) |
| M1A.079 | Idiopathic chronic gout, unspecified ankle and foot |
| M1A.0790 | Idiopathic chronic gout, unspecified ankle and foot, without tophus (tophi) |
| M1A.0791 | Idiopathic chronic gout, unspecified ankle and foot, with tophus (tophi) |
| M1A.08 | Idiopathic chronic gout, vertebrae |
| M1A.08x0 | Idiopathic chronic gout, vertebrae, without tophus (tophi) |
| M1A.08x1 | Idiopathic chronic gout, vertebrae, with tophus (tophi) |
| M1A.09 | Idiopathic chronic gout, multiple sites |
| M1A.09x0 | Idiopathic chronic gout, multiple sites, without tophus (tophi) |
| M1A.09x1 | Idiopathic chronic gout, multiple sites, with tophus (tophi) |
| M1A.1 | Lead-induced chronic gout |
| M1A.10 | Lead-induced chronic gout, unspecified site |
| M1A.10x0 | Lead-induced chronic gout, unspecified site, without tophus (tophi) |
| M1A.10x1 | Lead-induced chronic gout, unspecified site, with tophus (tophi) |
| M1A.11 | Lead-induced chronic gout, shoulder |
| M1A.111 | Lead-induced chronic gout, right shoulder |
| M1A.1110 | Lead-induced chronic gout, right shoulder, without tophus (tophi) |
| M1A.1111 | Lead-induced chronic gout, right shoulder, with tophus (tophi) |
| M1A.112 | Lead-induced chronic gout, left shoulder |
| M1A.1120 | Lead-induced chronic gout, left shoulder, without tophus (tophi) |
| M1A.1121 | Lead-induced chronic gout, left shoulder, with tophus (tophi) |
| M1A.119 | Lead-induced chronic gout, unspecified shoulder |
| M1A.1190 | Lead-induced chronic gout, unspecified shoulder, without tophus (tophi) |
| M1A.1191 | Lead-induced chronic gout, unspecified shoulder, with tophus (tophi) |
| M1A.12 | Lead-induced chronic gout, elbow |
| M1A.121 | Lead-induced chronic gout, right elbow |
| M1A.1210 | Lead-induced chronic gout, right elbow, without tophus (tophi) |
| M1A.1211 | Lead-induced chronic gout, right elbow, with tophus (tophi) |
| M1A.122 | Lead-induced chronic gout, left elbow |
| M1A.1220 | Lead-induced chronic gout, left elbow, without tophus (tophi) |
| M1A.1221 | Lead-induced chronic gout, left elbow, with tophus (tophi) |
| M1A.129 | Lead-induced chronic gout, unspecified elbow |
| M1A.1290 | Lead-induced chronic gout, unspecified elbow, without tophus (tophi) |
| M1A.1291 | Lead-induced chronic gout, unspecified elbow, with tophus (tophi) |
| M1A.13 | Lead-induced chronic gout, wrist |
| M1A.131 | Lead-induced chronic gout, right wrist |
| M1A.1310 | Lead-induced chronic gout, right wrist, without tophus (tophi) |
| M1A.1311 | Lead-induced chronic gout, right wrist, with tophus (tophi) |
| M1A.132 | Lead-induced chronic gout, left wrist |
| M1A.1320 | Lead-induced chronic gout, left wrist, without tophus (tophi) |
| M1A.1321 | Lead-induced chronic gout, left wrist, with tophus (tophi) |
| M1A.139 | Lead-induced chronic gout, unspecified wrist |
| M1A.1390 | Lead-induced chronic gout, unspecified wrist, without tophus (tophi) |
| M1A.1391 | Lead-induced chronic gout, unspecified wrist, with tophus (tophi) |
| M1A.14 | Lead-induced chronic gout, hand |
| M1A.141 | Lead-induced chronic gout, right hand |
| M1A.1410 | Lead-induced chronic gout, right hand, without tophus (tophi) |
| M1A.1411 | Lead-induced chronic gout, right hand, with tophus (tophi) |
| M1A.142 | Lead-induced chronic gout, left hand |
| M1A.1420 | Lead-induced chronic gout, left hand, without tophus (tophi) |
| M1A.1421 | Lead-induced chronic gout, left hand, with tophus (tophi) |
| M1A.149 | Lead-induced chronic gout, unspecified hand |
| M1A.1490 | Lead-induced chronic gout, unspecified hand, without tophus (tophi) |
| M1A.1491 | Lead-induced chronic gout, unspecified hand, with tophus (tophi) |
| M1A.15 | Lead-induced chronic gout, hip |
| M1A.151 | Lead-induced chronic gout, right hip |
| M1A.1510 | Lead-induced chronic gout, right hip, without tophus (tophi) |
| M1A.1511 | Lead-induced chronic gout, right hip, with tophus (tophi) |
| M1A.152 | Lead-induced chronic gout, left hip |
| M1A.1520 | Lead-induced chronic gout, left hip, without tophus (tophi) |
| M1A.1521 | Lead-induced chronic gout, left hip, with tophus (tophi) |
| M1A.159 | Lead-induced chronic gout, unspecified hip |
| M1A.1590 | Lead-induced chronic gout, unspecified hip, without tophus (tophi) |
| M1A.1591 | Lead-induced chronic gout, unspecified hip, with tophus (tophi) |
| M1A.16 | Lead-induced chronic gout, knee |
| M1A.161 | Lead-induced chronic gout, right knee |
| M1A.1610 | Lead-induced chronic gout, right knee, without tophus (tophi) |
| M1A.1611 | Lead-induced chronic gout, right knee, with tophus (tophi) |
| M1A.162 | Lead-induced chronic gout, left knee |
| M1A.1620 | Lead-induced chronic gout, left knee, without tophus (tophi) |
| M1A.1621 | Lead-induced chronic gout, left knee, with tophus (tophi) |
| M1A.169 | Lead-induced chronic gout, unspecified knee |
| M1A.1690 | Lead-induced chronic gout, unspecified knee, without tophus (tophi) |
| M1A.1691 | Lead-induced chronic gout, unspecified knee, with tophus (tophi) |
| M1A.17 | Lead-induced chronic gout, ankle and foot |
| M1A.171 | Lead-induced chronic gout, right ankle and foot |
| M1A.1710 | Lead-induced chronic gout, right ankle and foot, without tophus (tophi) |
| M1A.1711 | Lead-induced chronic gout, right ankle and foot, with tophus (tophi) |
| M1A.172 | Lead-induced chronic gout, left ankle and foot |
| M1A.1720 | Lead-induced chronic gout, left ankle and foot, without tophus (tophi) |
| M1A.1721 | Lead-induced chronic gout, left ankle and foot, with tophus (tophi) |
| M1A.179 | Lead-induced chronic gout, unspecified ankle and foot |
| M1A.1790 | Lead-induced chronic gout, unspecified ankle and foot, without tophus (tophi) |
| M1A.1791 | Lead-induced chronic gout, unspecified ankle and foot, with tophus (tophi) |
| M1A.18 | Lead-induced chronic gout, vertebrae |
| M1A.18x0 | Lead-induced chronic gout, vertebrae, without tophus (tophi) |
| M1A.18x1 | Lead-induced chronic gout, vertebrae, with tophus (tophi) |
| M1A.19 | Lead-induced chronic gout, multiple sites |
| M1A.19x0 | Lead-induced chronic gout, multiple sites, without tophus (tophi) |
| M1A.19x1 | Lead-induced chronic gout, multiple sites, with tophus (tophi) |
| M1A.2 | Drug-induced chronic gout |
| M1A.20 | Drug-induced chronic gout, unspecified site |
| M1A.20x0 | Drug-induced chronic gout, unspecified site, without tophus (tophi) |
| M1A.20x1 | Drug-induced chronic gout, unspecified site, with tophus (tophi) |
| M1A.21 | Drug-induced chronic gout, shoulder |
| M1A.211 | Drug-induced chronic gout, right shoulder |
| M1A.2110 | Drug-induced chronic gout, right shoulder, without tophus (tophi) |
| M1A.2111 | Drug-induced chronic gout, right shoulder, with tophus (tophi) |
| M1A.212 | Drug-induced chronic gout, left shoulder |
| M1A.2120 | Drug-induced chronic gout, left shoulder, without tophus (tophi) |
| M1A.2121 | Drug-induced chronic gout, left shoulder, with tophus (tophi) |
| M1A.219 | Drug-induced chronic gout, unspecified shoulder |
| M1A.2190 | Drug-induced chronic gout, unspecified shoulder, without tophus (tophi) |
| M1A.2191 | Drug-induced chronic gout, unspecified shoulder, with tophus (tophi) |
| M1A.22 | Drug-induced chronic gout, elbow |
| M1A.221 | Drug-induced chronic gout, right elbow |
| M1A.2210 | Drug-induced chronic gout, right elbow, without tophus (tophi) |
| M1A.2211 | Drug-induced chronic gout, right elbow, with tophus (tophi) |
| M1A.222 | Drug-induced chronic gout, left elbow |
| M1A.2220 | Drug-induced chronic gout, left elbow, without tophus (tophi) |
| M1A.2221 | Drug-induced chronic gout, left elbow, with tophus (tophi) |
| M1A.229 | Drug-induced chronic gout, unspecified elbow |
| M1A.2290 | Drug-induced chronic gout, unspecified elbow, without tophus (tophi) |
| M1A.2291 | Drug-induced chronic gout, unspecified elbow, with tophus (tophi) |
| M1A.23 | Drug-induced chronic gout, wrist |
| M1A.231 | Drug-induced chronic gout, right wrist |
| M1A.2310 | Drug-induced chronic gout, right wrist, without tophus (tophi) |
| M1A.2311 | Drug-induced chronic gout, right wrist, with tophus (tophi) |
| M1A.232 | Drug-induced chronic gout, left wrist |
| M1A.2320 | Drug-induced chronic gout, left wrist, without tophus (tophi) |
| M1A.2321 | Drug-induced chronic gout, left wrist, with tophus (tophi) |
| M1A.239 | Drug-induced chronic gout, unspecified wrist |
| M1A.2390 | Drug-induced chronic gout, unspecified wrist, without tophus (tophi) |
| M1A.2391 | Drug-induced chronic gout, unspecified wrist, with tophus (tophi) |
| M1A.24 | Drug-induced chronic gout, hand |
| M1A.241 | Drug-induced chronic gout, right hand |
| M1A.2410 | Drug-induced chronic gout, right hand, without tophus (tophi) |
| M1A.2411 | Drug-induced chronic gout, right hand, with tophus (tophi) |
| M1A.242 | Drug-induced chronic gout, left hand |
| M1A.2420 | Drug-induced chronic gout, left hand, without tophus (tophi) |
| M1A.2421 | Drug-induced chronic gout, left hand, with tophus (tophi) |
| M1A.249 | Drug-induced chronic gout, unspecified hand |
| M1A.2490 | Drug-induced chronic gout, unspecified hand, without tophus (tophi) |
| M1A.2491 | Drug-induced chronic gout, unspecified hand, with tophus (tophi) |
| M1A.25 | Drug-induced chronic gout, hip |
| M1A.251 | Drug-induced chronic gout, right hip |
| M1A.2510 | Drug-induced chronic gout, right hip, without tophus (tophi) |
| M1A.2511 | Drug-induced chronic gout, right hip, with tophus (tophi) |
| M1A.252 | Drug-induced chronic gout, left hip |
| M1A.2520 | Drug-induced chronic gout, left hip, without tophus (tophi) |
| M1A.2521 | Drug-induced chronic gout, left hip, with tophus (tophi) |
| M1A.259 | Drug-induced chronic gout, unspecified hip |
| M1A.2590 | Drug-induced chronic gout, unspecified hip, without tophus (tophi) |
| M1A.2591 | Drug-induced chronic gout, unspecified hip, with tophus (tophi) |
| M1A.26 | Drug-induced chronic gout, knee |
| M1A.261 | Drug-induced chronic gout, right knee |
| M1A.2610 | Drug-induced chronic gout, right knee, without tophus (tophi) |
| M1A.2611 | Drug-induced chronic gout, right knee, with tophus (tophi) |
| M1A.262 | Drug-induced chronic gout, left knee |
| M1A.2620 | Drug-induced chronic gout, left knee, without tophus (tophi) |
| M1A.2621 | Drug-induced chronic gout, left knee, with tophus (tophi) |
| M1A.269 | Drug-induced chronic gout, unspecified knee |
| M1A.2690 | Drug-induced chronic gout, unspecified knee, without tophus (tophi) |
| M1A.2691 | Drug-induced chronic gout, unspecified knee, with tophus (tophi) |
| M1A.27 | Drug-induced chronic gout, ankle and foot |
| M1A.271 | Drug-induced chronic gout, right ankle and foot |
| M1A.2710 | Drug-induced chronic gout, right ankle and foot, without tophus (tophi) |
| M1A.2711 | Drug-induced chronic gout, right ankle and foot, with tophus (tophi) |
| M1A.272 | Drug-induced chronic gout, left ankle and foot |
| M1A.2720 | Drug-induced chronic gout, left ankle and foot, without tophus (tophi) |
| M1A.2721 | Drug-induced chronic gout, left ankle and foot, with tophus (tophi) |
| M1A.279 | Drug-induced chronic gout, unspecified ankle and foot |
| M1A.2790 | Drug-induced chronic gout, unspecified ankle and foot, without tophus (tophi) |
| M1A.2791 | Drug-induced chronic gout, unspecified ankle and foot, with tophus (tophi) |
| M1A.28 | Drug-induced chronic gout, vertebrae |
| M1A.28x0 | Drug-induced chronic gout, vertebrae, without tophus (tophi) |
| M1A.28x1 | Drug-induced chronic gout, vertebrae, with tophus (tophi) |
| M1A.29 | Drug-induced chronic gout, multiple sites |
| M1A.29x0 | Drug-induced chronic gout, multiple sites, without tophus (tophi) |
| M1A.29x1 | Drug-induced chronic gout, multiple sites, with tophus (tophi) |
| M1A.3 | Chronic gout due to renal impairment |
| M1A.30 | Chronic gout due to renal impairment, unspecified site |
| M1A.30x0 | Chronic gout due to renal impairment, unspecified site, without tophus (tophi) |
| M1A.30x1 | Chronic gout due to renal impairment, unspecified site, with tophus (tophi) |
| M1A.31 | Chronic gout due to renal impairment, shoulder |
| M1A.311 | Chronic gout due to renal impairment, right shoulder |
| M1A.3110 | Chronic gout due to renal impairment, right shoulder, without tophus (tophi) |
| M1A.3111 | Chronic gout due to renal impairment, right shoulder, with tophus (tophi) |
| M1A.312 | Chronic gout due to renal impairment, left shoulder |
| M1A.3120 | Chronic gout due to renal impairment, left shoulder, without tophus (tophi) |
| M1A.3121 | Chronic gout due to renal impairment, left shoulder, with tophus (tophi) |
| M1A.319 | Chronic gout due to renal impairment, unspecified shoulder |
| M1A.3190 | Chronic gout due to renal impairment, unspecified shoulder, without tophus (tophi) |
| M1A.3191 | Chronic gout due to renal impairment, unspecified shoulder, with tophus (tophi) |
| M1A.32 | Chronic gout due to renal impairment, elbow |
| M1A.321 | Chronic gout due to renal impairment, right elbow |
| M1A.3210 | Chronic gout due to renal impairment, right elbow, without tophus (tophi) |
| M1A.3211 | Chronic gout due to renal impairment, right elbow, with tophus (tophi) |
| M1A.322 | Chronic gout due to renal impairment, left elbow |
| M1A.3220 | Chronic gout due to renal impairment, left elbow, without tophus (tophi) |
| M1A.3221 | Chronic gout due to renal impairment, left elbow, with tophus (tophi) |
| M1A.329 | Chronic gout due to renal impairment, unspecified elbow |
| M1A.3290 | Chronic gout due to renal impairment, unspecified elbow, without tophus (tophi) |
| M1A.3291 | Chronic gout due to renal impairment, unspecified elbow, with tophus (tophi) |
| M1A.33 | Chronic gout due to renal impairment, wrist |
| M1A.331 | Chronic gout due to renal impairment, right wrist |
| M1A.3310 | Chronic gout due to renal impairment, right wrist, without tophus (tophi) |
| M1A.3311 | Chronic gout due to renal impairment, right wrist, with tophus (tophi) |
| M1A.332 | Chronic gout due to renal impairment, left wrist |
| M1A.3320 | Chronic gout due to renal impairment, left wrist, without tophus (tophi) |
| M1A.3321 | Chronic gout due to renal impairment, left wrist, with tophus (tophi) |
| M1A.339 | Chronic gout due to renal impairment, unspecified wrist |
| M1A.3390 | Chronic gout due to renal impairment, unspecified wrist, without tophus (tophi) |
| M1A.3391 | Chronic gout due to renal impairment, unspecified wrist, with tophus (tophi) |
| M1A.34 | Chronic gout due to renal impairment, hand |
| M1A.341 | Chronic gout due to renal impairment, right hand |
| M1A.3410 | Chronic gout due to renal impairment, right hand, without tophus (tophi) |
| M1A.3411 | Chronic gout due to renal impairment, right hand, with tophus (tophi) |
| M1A.342 | Chronic gout due to renal impairment, left hand |
| M1A.3420 | Chronic gout due to renal impairment, left hand, without tophus (tophi) |
| M1A.3421 | Chronic gout due to renal impairment, left hand, with tophus (tophi) |
| M1A.349 | Chronic gout due to renal impairment, unspecified hand |
| M1A.3490 | Chronic gout due to renal impairment, unspecified hand, without tophus (tophi) |
| M1A.3491 | Chronic gout due to renal impairment, unspecified hand, with tophus (tophi) |
| M1A.35 | Chronic gout due to renal impairment, hip |
| M1A.351 | Chronic gout due to renal impairment, right hip |
| M1A.3510 | Chronic gout due to renal impairment, right hip, without tophus (tophi) |
| M1A.3511 | Chronic gout due to renal impairment, right hip, with tophus (tophi) |
| M1A.352 | Chronic gout due to renal impairment, left hip |
| M1A.3520 | Chronic gout due to renal impairment, left hip, without tophus (tophi) |
| M1A.3521 | Chronic gout due to renal impairment, left hip, with tophus (tophi) |
| M1A.359 | Chronic gout due to renal impairment, unspecified hip |
| M1A.3590 | Chronic gout due to renal impairment, unspecified hip, without tophus (tophi) |
| M1A.3591 | Chronic gout due to renal impairment, unspecified hip, with tophus (tophi) |
| M1A.36 | Chronic gout due to renal impairment, knee |
| M1A.361 | Chronic gout due to renal impairment, right knee |
| M1A.3610 | Chronic gout due to renal impairment, right knee, without tophus (tophi) |
| M1A.3611 | Chronic gout due to renal impairment, right knee, with tophus (tophi) |
| M1A.362 | Chronic gout due to renal impairment, left knee |
| M1A.3620 | Chronic gout due to renal impairment, left knee, without tophus (tophi) |
| M1A.3621 | Chronic gout due to renal impairment, left knee, with tophus (tophi) |
| M1A.369 | Chronic gout due to renal impairment, unspecified knee |
| M1A.3690 | Chronic gout due to renal impairment, unspecified knee, without tophus (tophi) |
| M1A.3691 | Chronic gout due to renal impairment, unspecified knee, with tophus (tophi) |
| M1A.37 | Chronic gout due to renal impairment, ankle and foot |
| M1A.371 | Chronic gout due to renal impairment, right ankle and foot |
| M1A.3710 | Chronic gout due to renal impairment, right ankle and foot, without tophus (tophi) |
| M1A.3711 | Chronic gout due to renal impairment, right ankle and foot, with tophus (tophi) |
| M1A.372 | Chronic gout due to renal impairment, left ankle and foot |
| M1A.3720 | Chronic gout due to renal impairment, left ankle and foot, without tophus (tophi) |
| M1A.3721 | Chronic gout due to renal impairment, left ankle and foot, with tophus (tophi) |
| M1A.379 | Chronic gout due to renal impairment, unspecified ankle and foot |
| M1A.3790 | Chronic gout due to renal impairment, unspecified ankle and foot, without tophus (tophi) |
| M1A.3791 | Chronic gout due to renal impairment, unspecified ankle and foot, with tophus (tophi) |
| M1A.38 | Chronic gout due to renal impairment, vertebrae |
| M1A.38x0 | Chronic gout due to renal impairment, vertebrae, without tophus (tophi) |
| M1A.38x1 | Chronic gout due to renal impairment, vertebrae, with tophus (tophi) |
| M1A.39 | Chronic gout due to renal impairment, multiple sites |
| M1A.39x0 | Chronic gout due to renal impairment, multiple sites, without tophus (tophi) |
| M1A.39x1 | Chronic gout due to renal impairment, multiple sites, with tophus (tophi) |
| M1A.4 | Other secondary chronic gout |
| M1A.40 | Other secondary chronic gout, unspecified site |
| M1A.40x0 | Other secondary chronic gout, unspecified site, without tophus (tophi) |
| M1A.40x1 | Other secondary chronic gout, unspecified site, with tophus (tophi) |
| M1A.41 | Other secondary chronic gout, shoulder |
| M1A.411 | Other secondary chronic gout, right shoulder |
| M1A.4110 | Other secondary chronic gout, right shoulder, without tophus (tophi) |
| M1A.4111 | Other secondary chronic gout, right shoulder, with tophus (tophi) |
| M1A.412 | Other secondary chronic gout, left shoulder |
| M1A.4120 | Other secondary chronic gout, left shoulder, without tophus (tophi) |
| M1A.4121 | Other secondary chronic gout, left shoulder, with tophus (tophi) |
| M1A.419 | Other secondary chronic gout, unspecified shoulder |
| M1A.4190 | Other secondary chronic gout, unspecified shoulder, without tophus (tophi) |
| M1A.4191 | Other secondary chronic gout, unspecified shoulder, with tophus (tophi) |
| M1A.42 | Other secondary chronic gout, elbow |
| M1A.421 | Other secondary chronic gout, right elbow |
| M1A.4210 | Other secondary chronic gout, right elbow, without tophus (tophi) |
| M1A.4211 | Other secondary chronic gout, right elbow, with tophus (tophi) |
| M1A.422 | Other secondary chronic gout, left elbow |
| M1A.4220 | Other secondary chronic gout, left elbow, without tophus (tophi) |
| M1A.4221 | Other secondary chronic gout, left elbow, with tophus (tophi) |
| M1A.429 | Other secondary chronic gout, unspecified elbow |
| M1A.4290 | Other secondary chronic gout, unspecified elbow, without tophus (tophi) |
| M1A.4291 | Other secondary chronic gout, unspecified elbow, with tophus (tophi) |
| M1A.43 | Other secondary chronic gout, wrist |
| M1A.431 | Other secondary chronic gout, right wrist |
| M1A.4310 | Other secondary chronic gout, right wrist, without tophus (tophi) |
| M1A.4311 | Other secondary chronic gout, right wrist, with tophus (tophi) |
| M1A.432 | Other secondary chronic gout, left wrist |
| M1A.4320 | Other secondary chronic gout, left wrist, without tophus (tophi) |
| M1A.4321 | Other secondary chronic gout, left wrist, with tophus (tophi) |
| M1A.439 | Other secondary chronic gout, unspecified wrist |
| M1A.4390 | Other secondary chronic gout, unspecified wrist, without tophus (tophi) |
| M1A.4391 | Other secondary chronic gout, unspecified wrist, with tophus (tophi) |
| M1A.44 | Other secondary chronic gout, hand |
| M1A.441 | Other secondary chronic gout, right hand |
| M1A.4410 | Other secondary chronic gout, right hand, without tophus (tophi) |
| M1A.4411 | Other secondary chronic gout, right hand, with tophus (tophi) |
| M1A.442 | Other secondary chronic gout, left hand |
| M1A.4420 | Other secondary chronic gout, left hand, without tophus (tophi) |
| M1A.4421 | Other secondary chronic gout, left hand, with tophus (tophi) |
| M1A.449 | Other secondary chronic gout, unspecified hand |
| M1A.4490 | Other secondary chronic gout, unspecified hand, without tophus (tophi) |
| M1A.4491 | Other secondary chronic gout, unspecified hand, with tophus (tophi) |
| M1A.45 | Other secondary chronic gout, hip |
| M1A.451 | Other secondary chronic gout, right hip |
| M1A.4510 | Other secondary chronic gout, right hip, without tophus (tophi) |
| M1A.4511 | Other secondary chronic gout, right hip, with tophus (tophi) |
| M1A.452 | Other secondary chronic gout, left hip |
| M1A.4520 | Other secondary chronic gout, left hip, without tophus (tophi) |
| M1A.4521 | Other secondary chronic gout, left hip, with tophus (tophi) |
| M1A.459 | Other secondary chronic gout, unspecified hip |
| M1A.4590 | Other secondary chronic gout, unspecified hip, without tophus (tophi) |
| M1A.4591 | Other secondary chronic gout, unspecified hip, with tophus (tophi) |
| M1A.46 | Other secondary chronic gout, knee |
| M1A.461 | Other secondary chronic gout, right knee |
| M1A.4610 | Other secondary chronic gout, right knee, without tophus (tophi) |
| M1A.4611 | Other secondary chronic gout, right knee, with tophus (tophi) |
| M1A.462 | Other secondary chronic gout, left knee |
| M1A.4620 | Other secondary chronic gout, left knee, without tophus (tophi) |
| M1A.4621 | Other secondary chronic gout, left knee, with tophus (tophi) |
| M1A.469 | Other secondary chronic gout, unspecified knee |
| M1A.4690 | Other secondary chronic gout, unspecified knee, without tophus (tophi) |
| M1A.4691 | Other secondary chronic gout, unspecified knee, with tophus (tophi) |
| M1A.47 | Other secondary chronic gout, ankle and foot |
| M1A.471 | Other secondary chronic gout, right ankle and foot |
| M1A.4710 | Other secondary chronic gout, right ankle and foot, without tophus (tophi) |
| M1A.4711 | Other secondary chronic gout, right ankle and foot, with tophus (tophi) |
| M1A.472 | Other secondary chronic gout, left ankle and foot |
| M1A.4720 | Other secondary chronic gout, left ankle and foot, without tophus (tophi) |
| M1A.4721 | Other secondary chronic gout, left ankle and foot, with tophus (tophi) |
| M1A.479 | Other secondary chronic gout, unspecified ankle and foot |
| M1A.4790 | Other secondary chronic gout, unspecified ankle and foot, without tophus (tophi) |
| M1A.4791 | Other secondary chronic gout, unspecified ankle and foot, with tophus (tophi) |
| M1A.48 | Other secondary chronic gout, vertebrae |
| M1A.48x0 | Other secondary chronic gout, vertebrae, without tophus (tophi) |
| M1A.48x1 | Other secondary chronic gout, vertebrae, with tophus (tophi) |
| M1A.49 | Other secondary chronic gout, multiple sites |
| M1A.49x0 | Other secondary chronic gout, multiple sites, without tophus (tophi) |
| M1A.49x1 | Other secondary chronic gout, multiple sites, with tophus (tophi) |
| M1A.9 | Chronic gout, unspecified |
| M1A.9xx0 | Chronic gout, unspecified, without tophus (tophi) |
| M1A.9xx1 | Chronic gout, unspecified, with tophus (tophi) |
Formulary Reference Tool