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  • CLASSES

    Anti-Gout Agents

    DEA CLASS

    Rx

    DESCRIPTION

    Antigout anti-inflammatory agent
    Used primary for treatment and prevention of acute gout and for familial Mediterranean fever
    Concomitant renal or hepatic dysfunction and the use of P-glycoprotein or strong CYP3A4 inhibitors increase toxicity risk

    COMMON BRAND NAMES

    ColciGel, Colcrys, GLOPERBA, MITIGARE

    HOW SUPPLIED

    Colchicine/Colcrys Oral Tab: 0.6mg
    Colchicine/MITIGARE Oral Cap: 0.6mg
    ColciGel Topical Gel
    GLOPERBA Oral Sol: 0.6mg, 5mL

    DOSAGE & INDICATIONS

    For the prevention and treatment of gout flares (gouty arthritis).
    For the prevention of gout flares (gout prophylaxis).
    Oral dosage (capsules, oral solution, tablets)
    Adults

    0.6 mg PO once or twice daily. Max: Do not exceed 1.2 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Following an acute gout flare, guidelines state that prophylactic antiinflammatory treatment is recommended for at least 8 weeks and up to 6 months while uric acid lowering therapy (ULT) is initiated; the agent and duration is dependent on patient specific factors such as the presence of tophi; low-dose colchicine, NSAIDs, or corticosteroids are options.

    Adolescents†

    Gout is rare in pediatric patients; safety and efficacy for this indication have not been evaluated in pediatric patients. Use has been reported in case studies. The adult dose is 0.6 mg PO once or twice daily. Do not exceed 1.2 mg/day PO (adult Max). Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the treatment of acute gout flares.
    Oral dosage (tablets)
    Adults

    1.2 mg PO at the first sign of gout flare, followed by 0.6 mg PO 1 hour later. Max total dose: 1.8 mg PO over a 1-hour period. At least 3 days should elapse before repeating this gout flare dose. Higher doses have not been found to be more effective. Patients receiving colchicine prophylaxis: Give the flare regimen as described, but the patient should wait 12 hours after the flare treatment dose to resume the prophylactic dose. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the treatment of familial Mediterranean fever (FMF).
    Oral dosage (tablets)
    Adults

    1.2 mg to 2.4 mg PO daily in 1 to 2 divided doses. May increase as needed to control disease and as tolerated in increments of 0.3 mg/day to a maximum recommended daily dose. If intolerable side effects develop, decrease the dose in increments of 0.3 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions..

    Adolescents

    1.2 mg to 2.4 mg PO daily, in 1 to 2 divided doses. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Children 4 to 12 years

    Dose is based on age as follows: CHILDREN 4 to 6 years: 0.3 mg to 1.8 mg daily, in 1 to 2 divided doses. CHILDREN 6 to 12 years: 0.9 mg to 1.8 mg daily, in 1 to 2 divided doses. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the management of pseudogout†.
    For the treatment of pseudogout†.
    Oral dosage (tablets)
    Adults

    0.6 mg orally 3 to 4 times daily; however, reported efficacy is inconsistent in medical literature. In clinical practice, joint aspiration, intra-articular and/or oral glucocorticoids, and oral NSAIDs have been used alone or in combination. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For prevention of pseudogout†.
    Oral dosage (tablets)
    Adults

    0.6 mg PO twice daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Maximum dosages are dependent on indication for use. Do not exceed the maximum dose recommended for the indication for use.

    Adults

    1.8 mg PO per acute gout flare course (tablets); 1.2 mg/day PO for gout prophylaxis (tablets, capsules, oral solution); 2.4 mg/day PO for familial Mediterranean fever (tablets).

    Geriatric

    1.8 mg PO per acute gout flare course (tablets); 1.2 mg/day PO for gout prophylaxis (tablets, capsules, oral solution); 2.4 mg/day PO for familial Mediterranean fever (tablets).

    Adolescents

    2.4 mg/day PO for familial Mediterranean fever (tablets). Rare off-label use for gout prophylaxis has been described, do not exceed 1.2 mg/day PO.

    Children

    4 to 12 years: 1.8 mg/day PO for familial Mediterranean fever (tablets).
    4 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Use of colchicine is contraindicated in any patient with hepatic impairment who is receiving a P-glycoprotein (P-gp) inhibitor, a strong CYP3A4 inhibitor, or a combined P-gp/CYP3A4 inhibitor.
    Mild to Moderate hepatic impairment: Use with caution. Treatment of gout flares with colchicine is not recommended in patients with hepatic impairment who are already receiving colchicine for prophylaxis.
    Severe hepatic impairment: For prophylaxis of gout flares or treatment of FMF, consider dose adjustments; no quantitative recommendations are available. For treatment of acute gout flares, dose as usual for one course but do not repeat treatment course within 2 weeks; use is not recommended in patients with hepatic impairment who are already receiving colchicine for prophylaxis.

    Renal Impairment

    NOTE: Use of colchicine is contraindicated in any patient with renal impairment who is receiving a P-glycoprotein (P-gp) inhibitor, a strong CYP3A4 inhibitor, or a combined P-gp/CYP3A4 inhibitor.
    CrCl 30—80 mL/min: Although no quantitative recommendations are available, colchicine dosage reductions may be needed depending on clinical response; close monitoring for drug toxicity is advised. Treatment of gout flares with colchicine is not recommended in patients with renal impairment who are already receiving colchicine for prophylaxis.
    CrCl < 30 mL/min: For prophylaxis of gout flare or treatment of familial Mediterranean fever (FMF), 0.3 mg PO daily; any increase in dose requires close monitoring. For treatment of acute gout flares, dose as usual for one course but do not repeat dosage course within 2 weeks; use is not recommended in patients with renal impairment who are already receiving colchicine for prophylaxis.
     
    Intermittent hemodialysis
    Colchicine is not removed by hemodialysis. For prophylaxis of gout flares: 0.3 PO twice weekly. For treatment of acute gout flares: 0.6 mg PO for 1 dose, do not repeat dosage course within 2 weeks and do not increase dose; not recommended in patients already receiving colchicine for prophylaxis. For familial Mediterranean fever (FMF): initiate therapy at 0.3 mg PO daily; increase dosage only with adequate monitoring.
     
    Peritoneal dialysis
    Colchicine is not removed by peritoneal dialysis. For prophylaxis of gout flares: 0.3 PO twice weekly. For treatment of acute gout flares: 0.6 mg PO for 1 dose, do not repeat dosage course within 2 weeks and do not increase dose; not recommended in patients already receiving colchicine for prophylaxis. For familial Mediterranean fever: initiate therapy at 0.3 mg PO daily; increase dosage only with adequate monitoring.

    ADMINISTRATION

    Oral Administration

    Take without regard to meals. Administer with food to minimize gastric irritation.

    Oral Liquid Formulations

    Oral solution:
    For accurate dosage, use a calibrated oral syringe, spoon, or dosing cup.

    Injectable Administration

    NOTE: This formulation is discontinued in the U.S.
    Parenteral colchicine was for IV administration only. Colchicine should never be injected subcutaneously or intramuscularly due to severe local irritation.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration.
    Injectable colchicine has a narrow therapeutic index and potential for serious or fatal toxicity.

    STORAGE

    Generic:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    ColciGel:
    - Product should be used within 6 months after opening
    - Protect from light
    - Store and dispense in original container
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Colcrys :
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    GLOPERBA:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    MITIGARE:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Biliary obstruction, dialysis, hepatic disease, renal disease, renal failure, renal impairment

    Colchicine capsules and oral solution are contraindicated in patients with both hepatic and renal impairment and are contraindicated in patients with either hepatic or renal impairment who are taking dual inhibitors of CYP3A4 and P-glycoprotein (P-gp).[58111] [63965] Regardless of whether organ function impairment is secondary to renal disease, hepatic disease, or other etiology, colchicine tablets are contraindicated in patients with hepatic or renal impairment who are also taking P-gp inhibitors and/or strong CYP3A4 inhibitors.[36114] Elevated colchicine concentrations and related toxicities, including fatalities, have been reported after the administration of therapeutic doses in such patients. Dosage adjustments are needed in patients with normal renal and hepatic function taking interacting medications; prescribers are advised to carefully review drug-drug interactions and the potential need for colchicine dosage adjustment. Dosage adjustments are also recommended for patients who have either renal or hepatic impairment alone. Colchicine is eliminated through biliary pathways; consider alternative therapies in patients with extrahepatic biliary obstruction. Colchicine is not removed by dialysis; patients with renal failure receiving dialysis require a dosage reduction secondary to their impaired renal function.[36114] [58111] [63965]

    Myopathy, rhabdomyolysis

    Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses, especially in combination with other drugs known to cause this effect (e.g., statins, fibrates, cyclosporine). Patients with impaired renal function and elderly patients, even those with normal renal and hepatic function, are at increased risk. The myoneuropathy is characterized by myopathy (muscular pain or weakness), and an elevated serum creatine kinase and/or rhabdomyolysis may be present. Rhabdomyolysis may occur anytime during drug treatment. Colchicine-induced neuromuscular toxicity generally resolves within 1 week to several months following discontinuation of therapy. Colchicine toxicity and overdosage can result in life-threatening adverse events. The incidence of gastrointestinal (GI) adverse events to colchicine are dose-related across all patient populations; consider the development of severe GI symptoms dose-limiting, as these may precede more systemic toxicity.[36114] [58111] [63965]

    Aplastic anemia, bone marrow suppression

    Colchicine should be used cautiously in patients with preexisting bone marrow suppression. Prolonged administration of colchicine has been associated with bone marrow depression. Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia have been reported with colchicine used within therapeutic doses. These adverse reactions have been generally reversible upon interrupting treatment or lowering the dose of colchicine. 

    Geriatric

    Colchicine should be used cautiously in geriatric or debilitated patients because of susceptibility to colchicine toxicity. The risk of neuromuscular toxicity and rhabdomyolysis is increased in geriatric patients, even in those with normal renal or hepatic function. According to the Beers Criteria, the dose of colchicine should be reduced in geriatric patients with a creatinine clearance less than 30 mL/minute due to the potential for gastrointestinal, neuromuscular, or bone marrow toxicity; monitor treated patients closely for adverse effects.

    Infertility, reproductive risk

    Colchicine may pose a reproductive risk in males. Azoospermia and oligospermia have been observed during postmarketing surveillance with colchicine. Rare case reports and epidemiology studies suggest that infertility may be reversible. 

    Pregnancy

    Colchicine is known to cross the human placenta, and use during pregnancy for the treatment of gout flare or other conditions is not well documented. There have been no adequate and well-controlled studies of colchicine in pregnant women. While not studied in the treatment of gout flares, data from a limited number of published studies found no evidence of an increased risk of miscarriage, stillbirth or teratogenic effects among pregnant women using colchicine to treat familial Mediterranean fever (FMF). Colchicine can arrest cell division in animals and plants. Published animal reproduction and development studies with colchicine demonstrated embryofetal toxicity, teratogenicity, and altered postnatal development at exposures within or above the clinical therapeutic range. Colchicine should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. The effect of colchicine on labor and delivery is unknown.  

    Breast-feeding

    Caution is needed if colchicine is administered to a breast-feeding woman. Colchicine is excreted into human milk. Limited data from infants of mothers receiving prophylactic doses of colchicine suggests that exclusively breastfed infants receive less than 10% of the maternal weight-adjusted dose. While no adverse effects have been reported in nursing infants, colchicine can affect gastrointestinal cell renewal and permeability. If this drug is used during lactation, the breastfed infant should be monitored closely for colchicine-related adverse effects.

    Children, infants, neonates

    Safety and efficacy have not been evaluated in pediatric patients less than 16 years of age in the treatment or prevention of gout. Colchicine is approved for use in children 4 years and older for the treatment of familial Mediterranean fever (FMF). Safety and efficacy have not been evaluated in children less than 4 years of age, infants or neonates.[36114] [58111] [63965]

    Accidental exposure, potential for overdose or poisoning

    Colchicine has a potential for overdose or poisoning. Fatal overdoses and poisonings, both intentional or by accidental exposure, have been reported in adults and children who have ingested colchicine. Keep colchicine out of the reach of children. Of note, forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of colchicine. [63965]

    ADVERSE REACTIONS

    Severe

    disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    oliguria / Early / Incidence not known

    Moderate

    leukopenia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    myopathy / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    myasthenia / Delayed / Incidence not known
    hematuria / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    vitamin B12 deficiency / Delayed / Incidence not known

    Mild

    diarrhea / Early / 23.0-23.0
    nausea / Early / 4.0-4.0
    fatigue / Early / 1.0-1.0
    headache / Early / 1.0-1.0
    abdominal pain / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    lactose intolerance / Early / Incidence not known
    vomiting / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    weakness / Early / Incidence not known
    myalgia / Early / Incidence not known
    maculopapular rash / Early / Incidence not known
    purpura / Delayed / Incidence not known
    alopecia / Delayed / Incidence not known
    rash / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    spermatogenesis inhibition / Delayed / Incidence not known
    oligospermia / Delayed / Incidence not known
    azoospermia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acidifying Agents: (Moderate) Colchicine is an alkaloid that is inhibited by acidifying agents. The colchicine dose may need adjustment
    Aliskiren; Amlodipine: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with amlodipine is necessary, especially in patients with renal or hepatic impairment. Amlodipine is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with amlodipine is necessary, especially in patients with renal or hepatic impairment. Amlodipine is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Alkalinizing Agents: (Moderate) The action of colchicine is potentiated by alkalinizing agents. The colchicine dose may need adjustment.
    Amiodarone: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and amiodarone in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Amiodarone can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like amiodarone in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Amlodipine: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with amlodipine is necessary, especially in patients with renal or hepatic impairment. Amlodipine is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Amlodipine; Atorvastatin: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin). (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with amlodipine is necessary, especially in patients with renal or hepatic impairment. Amlodipine is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Amlodipine; Benazepril: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with amlodipine is necessary, especially in patients with renal or hepatic impairment. Amlodipine is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with amlodipine is necessary, especially in patients with renal or hepatic impairment. Amlodipine is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with amlodipine is necessary, especially in patients with renal or hepatic impairment. Amlodipine is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Amlodipine; Olmesartan: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with amlodipine is necessary, especially in patients with renal or hepatic impairment. Amlodipine is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Amlodipine; Telmisartan: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with amlodipine is necessary, especially in patients with renal or hepatic impairment. Amlodipine is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Amlodipine; Valsartan: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with amlodipine is necessary, especially in patients with renal or hepatic impairment. Amlodipine is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and clarithromycin in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Clarithromycin can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken clarithromycin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and clarithromycin in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Clarithromycin can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken clarithromycin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Amprenavir: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and amprenavir unless the use of both agents is imperative. Amprenavir can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken amprenavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Aprepitant, Fosaprepitant: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and 3-day oral regimens of aprepitant (125 mg/80 mg/80 mg) unless the use of both agents is imperative. Multi-day regimens of aprepitant can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive CYP3A4 substrate. If coadministration cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken aprepitant in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Aspirin, ASA; Pravastatin: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Atazanavir: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and atazanavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Atazanavir can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken atazanavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Atazanavir; Cobicistat: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and atazanavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Atazanavir can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken atazanavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day. (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and cobicistat in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Cobicistat can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp/strong CYP3A4 inhibitor like cobicistat in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Atorvastatin: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Atorvastatin; Ezetimibe: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Azithromycin: (Moderate) Caution is warranted with the concomitant use of colchicine and azithromycin as increased colchicine concentrations may occur. Monitor for colchicine toxicity. Colchicine accumulation may be greater in patients with renal or hepatic impairment. Coadministration with azithromycin resulted in an increase in colchicine Cmax of 21.6% and an increase in the AUC of 57.1%.
    Boceprevir: (Major) Coadministration of colchicine and boceprevir is not recommended in patients with renal or hepatic impairment due to an increased risk for fatal colchicine toxicity. In patients with normal renal and hepatic function, a reduction in colchicine dose or an interruption of colchicine treatment is recommended. When coadministered with boceprevir and used for treatment of gout flares, patients should be administered 0.6 mg of colchicine for one dose, followed by 0.3 mg one hour later. Wait at least 3 days before repeating colchicine therapy. If colchicine is administered with boceprevir for prophylaxis of gout flare and the original regimen with 0.6 mg twice day, the colchicine regimen should be adjusted to 0.3 mg once daily. If the original regimen was 0.6 mg daily, the adjusted regimen should be 0.3 mg every other day. If colchicine is used for treatment of familial Mediterranean fever and in conjunction with boceprevir, the maximum daily dose should not exceed 0.6 mg daily (may be given as 0.3 mg twice daily).
    Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like colchicine; the risk of peripheral neuropathy may be additive.
    Brigatinib: (Moderate) Monitor for an increase in colchicine-related adverse reactions if coadministration with brigatinib is necessary; the risk is higher in patients with renal or hepatic impairment. A dose reduction of colchicine may be necessary. Colchicine is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index. Brigatinib is a P-gp inhibitor in vitro and may have the potential to increase concentrations of P-gp substrates.
    Cabozantinib: (Minor) Monitor for an increase in colchicine-related adverse reactions if coadministration with cabozantinib is necessary. Colchicine is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
    Carvedilol: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and carvedilol in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Carvedilol can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp inhibitor like carvedilol in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Ceritinib: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and ceritinib in patients with normal renal and hepatic function unless the use of both agents is imperative; If unavoidable, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor like ceritinib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Colchicine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
    Chloramphenicol: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and chloramphenicol in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Chloramphenicol can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor like chloramphenicol in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Ciprofloxacin: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and ciprofloxacin unless the use of both agents is imperative. Ciprofloxacin can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate inhibitor like ciprofloxacin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Citric Acid; Potassium Citrate: (Moderate) Colchicine is an alkaloid and its action is potentiated by alkalinizing agents like potassium citrate. The colchicine dose may need adjustment.
    Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Colchicine is an alkaloid and its action is potentiated by alkalinizing agents like potassium citrate. The colchicine dose may need adjustment.
    Clarithromycin: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and clarithromycin in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Clarithromycin can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken clarithromycin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Cobicistat: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and cobicistat in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Cobicistat can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp/strong CYP3A4 inhibitor like cobicistat in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Conivaptan: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and conivaptan in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Treatment with colchicine may be initiated no sooner than 1 week after completion of conivaptan therapy. Conivaptan can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor/P-gp inhibitor like conivaptan in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Crizotinib: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and crizotinib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Crizotinib can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A inhibitor like crizotinib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Cyanocobalamin, Vitamin B12: (Minor) Colchicine has been shown to induce reversible malabsorption of vitamin B12. Patients receiving these agents concurrently should be monitored for the desired therapeutic response to vitamin B12.
    Cyclosporine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and cyclosporine in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Cyclosporine can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken cyclosporine in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Daclatasvir: (Moderate) Systemic exposure of colchicine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of colchicine; monitor patients for potential adverse effects.
    Dalfopristin; Quinupristin: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and dalfopristin; quinupristin in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Dalfopristin; quinupristin can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor like dalfopristin; quinupristin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Darunavir: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and darunavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Darunavir can inhibit colchicine's CYP3A4 metabolism, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken darunavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Darunavir; Cobicistat: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and cobicistat in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Cobicistat can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp/strong CYP3A4 inhibitor like cobicistat in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day. (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and darunavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Darunavir can inhibit colchicine's CYP3A4 metabolism, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken darunavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and cobicistat in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Cobicistat can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp/strong CYP3A4 inhibitor like cobicistat in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day. (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and darunavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Darunavir can inhibit colchicine's CYP3A4 metabolism, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken darunavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Severe) Coadministration of colchicine and dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir is contraindicated due to the potential for serious and life-threatening toxicity. Colchicine is a P-glycoprotein (P-gp) and CYP3A4 substrate, and ritonavir is a P-gp inhibitor and strong CYP3A4 inhibitor. Paritaprevir is also a P-gp inhibitor. When coadministered with P-gp/CYP3A4 inhibitors, patients with renal or hepatic impairment may experience a significant increase in colchicine serum concentration; thereby, increasing the risk for seroius toxicity. (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and ritonavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Ritonavir can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken ritonavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Delavirdine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and delavirdine in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Delavirdine can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor like delavirdine in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Dextromethorphan; Quinidine: (Major) Coadministration of colchicine and quinidine should be avoided due to the potential for serious and life-threatening toxicity. Colchicine is a substrate of P-glycoprotein (P-gp) and quinidine is an inhibitor of P-gp; increased concentrations of colchicine are expected with concurrent use. Colchicine accumulation may be greater in patients with renal or hepatic impairment; therefore the manufacturer of Colcrys contraindicates the use of colchicine and P-gp inhibitors in this population. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine either by reducing the daily dose or reducing the dose frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for coadministration with P-gp inhibitors are provided by the manufacturer of Colcrys.
    Diazoxide: (Moderate) Diazoxide can cause hyperuricemia. Dosages of concomitantly administered antigout medications, including colchicine, may require adjustment.
    Digoxin: (Major) According to the manufacturer of Colcrys, both digoxin and colchicine are substrates of P-glycoprotein (Pgp) and rhabdomyolysis has been reported in patients on concurrent therapy. If such agents are co-administered, advise patients to report signs and symptoms of myotoxicity including muscle tenderness, pain, or weakness; monitoring creatine phosphokinase may not predict the development of severe myopathy.
    Diltiazem: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and diltiazem in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Diltiazem can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken diltiazem in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as colchicine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Dronedarone: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and dronedarone in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Dronedarone can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like dronedarone in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) L-methylfolate and colchicine should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with colchicine. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Duvelisib: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and duvelisib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Duvelisib can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like duvelisib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as colchicine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as colchicine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Elagolix: (Major) Avoid use together if possible. Concomitant use of elagolix and colchicine may result in altered blood concentrations of colchicine. Elagolix is an inhibitor of P-glycoprotein (P-gp) and a weak to moderate inducer of CYP3A4. Colchicine is a substrate of P-gp and CYP3A4. Use caution and monitor patients for toxicity and efficacy. If colchicine is administered with drugs that inhibit P-gp, increased concentrations of colchicine are likely. Fatal drug interactions have been reported. It is not clear what the net effect of elagolix use on colchicine will be.
    Elbasvir; Grazoprevir: (Moderate) Administering colchicine with elbasvir; grazoprevir may result in elevated colchicine plasma concentrations. Colchicine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Elexacaftor; tezacaftor; ivacaftor: (Major) Use caution when administering ivacaftor and colchicine concurrently; increased monitoring and/or dose adjustment of colchine may be necessary. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as colchicine, can increase colchicine exposure leading to increased or prolonged therapeutic effects and adverse events. Fatal colchicine toxicity has been reported when given with strong CYP3A4 and Pgp inhibitors.
    Eliglustat: (Major) Coadministration of colchicine, a P-glycoprotein (P-gp) substrate, and eliglustat, a P-gp inhibitor, is contraindicated in patients with renal or hepatic impairment. Fatal colchicine toxicity has occurred with therapeutic doses of colchicine in these patients when other P-gp inhibitors have been coadministered. In patients with normal hepatic and renal function, colchicine's product labeling recommends colchicine dosage reduction in patients who are currently taking or have taken a P-gp inhibitor within the last 14 days. Similarly, eliglustat's product labeling recommends consideration of colchicine dosage reduction and titration to clinical effect.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and cobicistat in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Cobicistat can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp/strong CYP3A4 inhibitor like cobicistat in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and cobicistat in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Cobicistat can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp/strong CYP3A4 inhibitor like cobicistat in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day. (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as colchicine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as colchicine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as colchicine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Erythromycin: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and erythromycin in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Erythromycin can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken erythromycin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Erythromycin; Sulfisoxazole: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and erythromycin in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Erythromycin can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken erythromycin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) L-methylfolate and colchicine should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with colchicine. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Etravirine: (Moderate) Etravirine is a CYP3A4 inducer and a P-glycoprotein (PGP) inhibitor and colchicine is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
    Everolimus: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with everolimus is necessary, especially in patients with renal or hepatic impairment. Everolimus is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Ezetimibe; Simvastatin: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Fedratinib: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and fedratinib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. fedratinib can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like fedratinib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Fenofibrate: (Moderate) Concurrent administration of colchicine and fibric acid derivatives may result in the development of myotoxicity (i.e., muscle pain and weakness, rhabdomyolysis). The pharmacokinetic and/or pharmacodynamic mechanism of this interaction is not clear; however, both colchicine and fibric acid derivatives are associated with the development of myotoxicity and concurrent use may increase the risk of myotoxicity. If such agents are coadministered, advise patients to report signs and symptoms of myotoxicity including muscle tenderness, pain, or weakness; monitoring creatine phosphokinase may not predict the development of severe myopathy.
    Fenofibric Acid: (Moderate) Concurrent administration of colchicine and fibric acid derivatives may result in the development of myotoxicity (i.e., muscle pain and weakness, rhabdomyolysis). The pharmacokinetic and/or pharmacodynamic mechanism of this interaction is not clear; however, both colchicine and fibric acid derivatives are associated with the development of myotoxicity and concurrent use may increase the risk of myotoxicity. If such agents are coadministered, advise patients to report signs and symptoms of myotoxicity including muscle tenderness, pain, or weakness; monitoring creatine phosphokinase may not predict the development of severe myopathy.
    Fibric acid derivatives: (Moderate) Concurrent administration of colchicine and fibric acid derivatives may result in the development of myotoxicity (i.e., muscle pain and weakness, rhabdomyolysis). The pharmacokinetic and/or pharmacodynamic mechanism of this interaction is not clear; however, both colchicine and fibric acid derivatives are associated with the development of myotoxicity and concurrent use may increase the risk of myotoxicity. If such agents are coadministered, advise patients to report signs and symptoms of myotoxicity including muscle tenderness, pain, or weakness; monitoring creatine phosphokinase may not predict the development of severe myopathy.
    Fluconazole: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and fluconazole unless the use of both agents is imperative. Fluconazole can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken fluconazole in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Fluvastatin: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Fluvoxamine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and fluvoxamine if possible. Fluvoxamine can inhibit the metabolism of colchicine via CYP3A4 inhibition, resulting in increased colchicine exposure. If coadministration cannot be avoided, carefully monitor for colchicine toxicity; a dose reduction or discontinuation of colchicine may be required.
    Fosamprenavir: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and fosamprenavir unless the use of both agents is imperative. Fosamprenavir can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken fosamprenavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Fostamatinib: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and fostamatinib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Fostamatinib can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a CYP3A4 or P-gp inhibitor like fostamatinib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 0.6 mg/day.
    Gemfibrozil: (Moderate) Concurrent administration of colchicine and fibric acid derivatives may result in the development of myotoxicity (i.e., muscle pain and weakness, rhabdomyolysis). The pharmacokinetic and/or pharmacodynamic mechanism of this interaction is not clear; however, both colchicine and fibric acid derivatives are associated with the development of myotoxicity and concurrent use may increase the risk of myotoxicity. If such agents are coadministered, advise patients to report signs and symptoms of myotoxicity including muscle tenderness, pain, or weakness; monitoring creatine phosphokinase may not predict the development of severe myopathy.
    Glecaprevir; Pibrentasvir: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and glecaprevir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Glecaprevir can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp inhibitor like glecaprevir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day. (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and pibrentasvir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Pibrentasvir can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp inhibitor like pibrentasvir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Grapefruit juice: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, patients should avoid eating grapefruit or drinking grapefruit juice while taking colchicine. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Grapefruit juice can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken grapefruit juice in the past 14 days or require concurrent use: administer half of the original intended Colcrys dosage for prophylaxis of gout flares; 1.2 mg as a single dose for treatment of gout flares and do not repeat for at least 3 days; and do not exceed a maximum daily dose of 1.2 mg/day for familial Mediterranean fever.
    HMG-CoA reductase inhibitors: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Ibrutinib: (Major) Avoid the concurrent use of ibrutinib and colchicine; plasma concentrations of colchicine may increase resulting in serious and life-threatening toxicity. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Ibrutinib is a P-glycoprotein (P-gp) inhibitor in vitro; colchicine is a narrow therapeutic index drug and a P-gp substrate.
    Idelalisib: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and idelalisib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Idelalisib can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor like idelalisib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Imatinib: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and imatinib unless the use of both agents is imperative. Imatinib can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like imatinib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Indinavir: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and indinavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Indinavir can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken indinavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Isavuconazonium: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and isavuconazonium in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Isavuconazonium can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like isavuconazonium in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Isoniazid, INH: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with isoniazid is necessary, especially in patients with renal or hepatic impairment. Isoniazid is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with isoniazid is necessary, especially in patients with renal or hepatic impairment. Isoniazid is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index. (Minor) Because pyrazinamide can increase serum uric acid levels and precipitate gouty attacks, the dosages of antigout agents, including colchicine, may need to be adjusted.
    Isoniazid, INH; Rifampin: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with isoniazid is necessary, especially in patients with renal or hepatic impairment. Isoniazid is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Istradefylline: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with istradefylline 40 mg daily is necessary, especially in patients with renal or hepatic impairment. Colchicine is a CYP3A4 and P-gp substrate with a narrow therapeutic index; istradefylline administered as 40 mg daily is a weak CYP3A4 inhibitor and P-gp inhibitor. There was no effect on drug exposure when istradefylline 20 mg daily was coadministered with a sensitive CYP3A4 substrate.
    Itraconazole: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid use of colchicine during and 2 weeks after itraconazole in patients with normal renal and hepatic function unless the use of both agents is imperative. Use of colchicine during and for 2 weeks after itraconazole is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Itraconazole can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken itraconazole in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Ivacaftor: (Major) Use caution when administering ivacaftor and colchicine concurrently; increased monitoring and/or dose adjustment of colchine may be necessary. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as colchicine, can increase colchicine exposure leading to increased or prolonged therapeutic effects and adverse events. Fatal colchicine toxicity has been reported when given with strong CYP3A4 and Pgp inhibitors.
    Ixabepilone: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). Colchicine is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in colchicine concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate.
    Ketoconazole: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and ketoconazole in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Ketoconazole can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken ketoconazole in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as colchicine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Lapatinib: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and lapatinib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Colchicine is a CYP3A4 and P-glycoprotein (P-gp) substrate. Lapatinib is a weak CYP3A4 inhibitor and a P-gp inhibitor, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken lapatinib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Larotrectinib: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with larotrectinib is necessary, especially in patients with renal or hepatic impairment. Larotrectinib is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Ledipasvir; Sofosbuvir: (Major) Coadministration of colchicine and ledipasvir should be avoided due to the potential for serious and life-threatening toxicity. Colchicine is a substrate of P-glycoprotein (P-gp) and ledipsavir is an inhibitor of P-gp; increased concentrations of colchicine are expected with concurrent use. Colchicine accumulation may be greater in patients with renal or hepatic impairment; therefore the manufacturer of Colcrys contraindicates the use of colchicine and P-gp inhibitors in this population. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine either by reducing the daily dose or reducing the dose frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for coadministration with P-gp inhibitors are provided by the manufacturer of Colcrys.
    Lefamulin: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and oral lefamulin in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Oral lefamulin can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure; an interaction is not expected with intravenous lefamulin. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like oral lefamulin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Letermovir: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and letermovir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Letermovir, a moderate CYP3A4 inhibitor, can inhibit colchicine's metabolism, resulting in increased colchicine exposure. The magnitude of this interaction may be increased in patients who are also receiving cyclosporine; the combined effect of letermovir and cyclosporine may be similar to a strong CYP3A4 inhibitor. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor including letermovir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day. For patients who have taken a strong CYP3A4 inhibitor including letermovir plus cyclosporine in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Levomefolate: (Minor) L-methylfolate and colchicine should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with colchicine. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Lomitapide: (Moderate) Concomitant use of lomitapide and colchicine may result in increased serum concentrations of colchicine. According to the manufacturer of lomitapide, dose reduction of colchicine should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and colchicine is a P-gp substrate.
    Lopinavir; Ritonavir: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and lopinavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Lopinavir can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken lopinavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day. (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and ritonavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Ritonavir can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken ritonavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Lovastatin: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Lovastatin; Niacin: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of colchicine and lumacaftor; ivacaftor if possible. If concurrent use cannot be avoided, monitor the patient closely for both colchicine toxicity and therapeutic efficacy. Colchicine is a substrate of CYP3A4 and the P-glycoprotein (P-gp) efflux transporter. Lumacaftor is a strong CYP3A inducer; in vitro data suggests lumacaftor; ivacaftor may also induce and/or inhibit P-gp. While the induction of colchicine through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Caution is warranted as coadministration of P-gp inhibitors and colchicine have been reported to lead to colchicine toxicity.
    Lumacaftor; Ivacaftor: (Major) Use caution when administering ivacaftor and colchicine concurrently; increased monitoring and/or dose adjustment of colchine may be necessary. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as colchicine, can increase colchicine exposure leading to increased or prolonged therapeutic effects and adverse events. Fatal colchicine toxicity has been reported when given with strong CYP3A4 and Pgp inhibitors.
    Mifepristone: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and mifepristone in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Mifepristone can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like mifepristone in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Mitotane: (Major) Use caution if mitotane and colchicine are used concomitantly, and monitor for decreased efficacy of colchicine and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and colchicine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of colchicine.
    Nefazodone: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and nefazodone in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Nefazodone can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken nefazodone in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Nelfinavir: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and nelfinavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Nelfinavir can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken nelfinavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Neratinib: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and neratinib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Neratinib can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp inhibitor like neratinib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Netupitant, Fosnetupitant; Palonosetron: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and netupitant unless the use of both agents is imperative. Netupitant can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like netupitant in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Niacin; Simvastatin: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Nicardipine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and nicardipine in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Nicardipine can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like nicardipine in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Nilotinib: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and nilotinib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Nilotinib can inhibit colchicine's metabolism via and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like nilotinib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Ombitasvir; Paritaprevir; Ritonavir: (Severe) Coadministration of colchicine and dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir is contraindicated due to the potential for serious and life-threatening toxicity. Colchicine is a P-glycoprotein (P-gp) and CYP3A4 substrate, and ritonavir is a P-gp inhibitor and strong CYP3A4 inhibitor. Paritaprevir is also a P-gp inhibitor. When coadministered with P-gp/CYP3A4 inhibitors, patients with renal or hepatic impairment may experience a significant increase in colchicine serum concentration; thereby, increasing the risk for seroius toxicity. (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and ritonavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Ritonavir can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken ritonavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Oritavancin: (Moderate) Colchicine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of colchicine may be reduced if these drugs are administered concurrently.
    Osimertinib: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and osimertinib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Osimertinib can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken osimertinib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Palbociclib: (Moderate) Closely monitor for evidence of colchicine toxicity if coadministration with palbociclib is necessary. Consider adjusting the colchicine dose by either reducing the daily dose or reducing the dose frequency. Concurrent use may increase colchicine exposure resulting in serious colchicine toxicity including multi-organ failure and death. Colchicine is a CYP3A4 substrate and palbociclib is a weak CYP3A4 inhibitor.
    Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and colchicine, a CYP3A4 substrate, may cause an increase in systemic concentrations of colchicine. Use caution when administering these drugs concomitantly.
    Perindopril; Amlodipine: (Moderate) Monitor for an increase in colchicine-related adverse reactions including neuromuscular toxicity and other serious toxicities if coadministration with amlodipine is necessary, especially in patients with renal or hepatic impairment. Amlodipine is a weak inhibitor of CYP3A while colchicine is a CYP3A4 substrate with a narrow therapeutic index.
    Pitavastatin: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Ponatinib: (Major) Concomitant use of ponatinib, a P-gp inhibitor, and colchicine, a P-gp substrate, may increase the exposure of colchicine. Life-threatening and fatal drug interactions have been reported in patients treated with colchicine given with P-gp inhibitors. If treatment with a P-gp inhibitor is required in patients with normal renal and hepatic function, the colchicine dose may need to be reduced or interrupted. Use of colchicine with P-gp inhibitors is contraindicated in patients with renal or hepatic impairment.
    Posaconazole: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and posaconazole in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Posaconazole can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor/P-gp inhibitor like posaconazole in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day. The recommended dose of colchicine oral solution when co-administered with posaconazole is 0.24 mg.
    Potassium Bicarbonate: (Moderate) Colchicine is an alkaloid and its action is potentiated by alkalinizing agents like potassium citrate. The colchicine dose may need adjustment.
    Potassium Chloride: (Moderate) Colchicine is an alkaloid and its action is potentiated by alkalinizing agents like potassium citrate. The colchicine dose may need adjustment.
    Potassium Citrate: (Moderate) Colchicine is an alkaloid and its action is potentiated by alkalinizing agents like potassium citrate. The colchicine dose may need adjustment.
    Pravastatin: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Propafenone: (Major) Coadministration of colchicine and propafenone should be avoided due to the potential for serious and life-threatening toxicity. Colchicine is a substrate of P-glycoprotein (P-gp) and propafenone is an inhibitor of P-gp; increased concentrations of colchicine are expected with concurrent use. Colchicine accumulation may be greater in patients with renal or hepatic impairment; therefore the manufacturer of Colcrys contraindicates the use of colchicine and P-gp inhibitors in this population. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine either by reducing the daily dose or reducing the dose frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for coadministration with P-gp inhibitors are provided by the manufacturer of Colcrys.
    Pyrazinamide, PZA: (Minor) Because pyrazinamide can increase serum uric acid levels and precipitate gouty attacks, the dosages of antigout agents, including colchicine, may need to be adjusted.
    Quinidine: (Major) Coadministration of colchicine and quinidine should be avoided due to the potential for serious and life-threatening toxicity. Colchicine is a substrate of P-glycoprotein (P-gp) and quinidine is an inhibitor of P-gp; increased concentrations of colchicine are expected with concurrent use. Colchicine accumulation may be greater in patients with renal or hepatic impairment; therefore the manufacturer of Colcrys contraindicates the use of colchicine and P-gp inhibitors in this population. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine either by reducing the daily dose or reducing the dose frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for coadministration with P-gp inhibitors are provided by the manufacturer of Colcrys.
    Quinine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and quinine unless the use of both agents is imperative. Quinine can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a moderate CYP3A4 inhibitor like quinine in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Ranolazine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and ranolazine in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Ranolazine can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken ranolazine in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Ribociclib: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and ribociclib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Ribociclib can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor like ribociclib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Ribociclib; Letrozole: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and ribociclib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Ribociclib can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor like ribociclib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Ritonavir: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and ritonavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Ritonavir can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken ritonavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Rosuvastatin: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Rucaparib: (Moderate) Closely monitor for evidence of colchicine toxicity if coadministration with rucaparib is necessary. Consider adjusting the colchicine dose by either reducing the daily dose or reducing the dose frequency. Concurrent use may increase colchicine exposure resulting in serious colchicine toxicity including multi-organ failure and death. Colchicine is a CYP3A4 substrate and rucaparib is a weak CYP3A4 inhibitor.
    Sapropterin: (Major) Coadministration of sapropterin and colchicine should be avoided due to the potential for serious and life-threatening toxicity. Colchicine is a P-glycoprotein (P-gp) substrate and in vitro data show that sapropterin may inhibit P-gp; increased concentrations of colchicine are expected with concurrent use. Colchicine accumulation may be greater in patients with renal or hepatic impairment; therefore the manufacturer of Colcrys contraindicates the use of colchicine and P-gp inhibitors in this population. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine either by reducing the daily dose or reducing the dose frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for coadministration with P-gp inhibitors are provided by the manufacturer of Colcrys.
    Saquinavir: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and saquinavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Saquinavir can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken saquinavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Sarecycline: (Major) Coadministration of sarecycline and colchicine should be avoided due to the potential for serious and life-threatening toxicity. Colchicine is a P-glycoprotein (P-gp) substrate; sarecycline is a P-gp inhibitor. Increased concentrations of colchicine are expected with concurrent use. Colchicine accumulation may be greater in patients with renal or hepatic impairment; therefore, the manufacturer of Colcrys contraindicates the use of colchicine and P-gp inhibitors in this population. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine either by reducing the daily dose or reducing the dose frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for coadministration with P-gp inhibitors are provided by the manufacturer of Colcrys.
    Simeprevir: (Major) As colchicine is a CYP3A4 and P-glycoprotein (P-gp) substrate and simepriver is mild intestinal CYP3A4 inhibitor and P-gp inhibitor, increased concentrations of colchicine may occur with concurrent use. Dosage adjustments of colchicine may be required. The increase in colchicine concentrations may be greater in patients with renal or hepatic impairment. Use simeprivir with extreme care, if at all, concomitantly with colchicine.
    Simvastatin: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Simvastatin; Sitagliptin: (Major) Use caution and the lowest HMG-CoA reductase inhibitor dose necessary if coadministration with colchicine is necessary due to an increased risk of myopathy and rhabdomyolysis. Carefully weigh the potential benefits and risk of combined therapy. Closely monitor patients for signs and symptoms of muscle pain, tenderness, or weakness especially during the initial months of therapy and during upward titration of either drug. There is no assurance that period monitoring of creatinine phosphokinase (CPK) will prevent the occurrence of myopathy. Case reports exist describing the development of myotoxicity with the concurrent administration of colchicine and HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin).
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of colchicine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently.
    Sorafenib: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and sorafenib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Sorafenib can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken sorafenib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Streptogramins: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and dalfopristin; quinupristin in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Dalfopristin; quinupristin can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor like dalfopristin; quinupristin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Sulfinpyrazone: (Moderate) Blood dyscrasias have rarely been reported with the use of sulfinpyrazone or colchicine alone. Careful monitoring of patients receiving this combination is recommended during chronic use.
    Sympathomimetics: (Minor) The response to sympathomimetics may be enhanced by colchicine.
    Tacrolimus: (Major) Coadministration of colchicine and tacrolimus should be avoided due to the potential for serious and life-threatening toxicity. Colchicine is a substrate of P-glycoprotein (P-gp) and tacrolimus is an inhibitor of P-gp; increased concentrations of colchicine are expected with concurrent use. Colchicine accumulation may be greater in patients with renal or hepatic impairment; therefore the manufacturer of Colcrys contraindicates the use of colchicine and P-gp inhibitors in this population. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine either by reducing the daily dose or reducing the dose frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for coadministration with P-gp inhibitors are provided by the manufacturer of Colcrys.
    Telaprevir: (Major) Coadministration of colchicine and telaprevir should be avoided due to the potential for serious and life-threatening toxicity. Colchicine is a P-glycoprotein (P-gp) and CYP3A4 substrate and telaprevir is a mild P-gp inhibitor and strong CYP3A4 inhibitor; increased concentrations of colchicine are expected with concurrent use. Colchicine accumulation may be greater in patients with renal or hepatic impairment; therefore, the coadministration of colchicine and combined P-gp/CYP3A4 inhibitors is contraindicated in this population. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine either by reducing the daily dose or reducing the dose frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for patients who have received a strong CYP3A4 inhibitor within the prior 14 days are provided by the manufacturer of Colcrys.
    Telithromycin: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and telithromycin in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Telithromycin can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken telithromycin in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and colchicine is necessary, as the systemic exposure of colchicine may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of colchicine; consider increasing the dose of colchicine if necessary. Colchicine is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Temsirolimus: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and temsirolimus in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Temsirolimus can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken temsirolimus in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Tenofovir, PMPA: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as colchicine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
    Tetrahydrozoline: (Minor) The response to sympathomimetics may be enhanced by colchicine.
    Tezacaftor; Ivacaftor: (Major) Use caution when administering ivacaftor and colchicine concurrently; increased monitoring and/or dose adjustment of colchine may be necessary. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as colchicine, can increase colchicine exposure leading to increased or prolonged therapeutic effects and adverse events. Fatal colchicine toxicity has been reported when given with strong CYP3A4 and Pgp inhibitors.
    Tipranavir: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and tipranavir in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Tipranavir can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken tipranavir in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Trandolapril; Verapamil: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and verapamil in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Verapamil can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken verapamil in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Ulipristal: (Moderate) It is recommended that administration of ulipristal acetate and oral colchicine should be separated in time by at least 1.5 hours. Colchicine is a substrate of P-glycoprotein (P-gp), and ulipristal is an inhibitor of P-gp in the gastrointestinal (GI) wall at the time of its absorption. Thus, ulipristal may increase colchicine exposure (AUC) if administered orally at the same time. Administration of ulipristal with another orally-administered P-gp substrate in vivo showed that an interaction did not occur if administration of ulipristal was separated from the oral P-gp substrate by at least 1.5 hours.
    Vemurafenib: (Major) Concomitant use of vemurafenib and colchicine may result in altered concentrations of colchicine. Vemurafenib is an inhibitor of P-glycoprotein (P-gp) and an inducer of CYP3A4. Colchicine is a substrate of P-gp and CYP3A4. Use caution and monitor patients for toxicity and efficacy. If colchicine is administered with drugs that inhibit P-gp, increased concentrations of colchicine are likely. Fatal drug interactions have been reported. It is not clear what the net effect of vemurafenib use on colchicine will be.
    Venetoclax: (Major) Coadministration of colchicine and venetoclax should be avoided due to the potential for serious and life-threatening colchicine toxicity. Colchicine is a substrate of P-glycoprotein (P-gp) and venetoclax is an inhibitor of P-gp; increased concentrations of colchicine are expected with concurrent use. Colchicine accumulation may be greater in patients with renal or hepatic impairment; therefore, the manufacturer of Colcrys contraindicates the use of colchicine and P-gp inhibitors in this population. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine either by reducing the daily dose or reducing the dose frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations for coadministration with P-gp inhibitors are provided by the manufacturer of Colcrys.
    Verapamil: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and verapamil in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Verapamil can inhibit colchicine's metabolism via P-glycoprotein (P-gp) and CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken verapamil in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg twice daily or 0.6 mg once daily or if the original dose is 0.6 mg once daily, decrease the dose to 0.3 mg once daily; for treatment of gout flares, give 1.2 mg as a single dose and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed 1.2 mg/day.
    Voriconazole: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and voriconazole in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Voriconazole can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor like voriconazole in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and colchicine is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.

    PREGNANCY AND LACTATION

    Pregnancy

    Colchicine is known to cross the human placenta, and use during pregnancy for the treatment of gout flare or other conditions is not well documented. There have been no adequate and well-controlled studies of colchicine in pregnant women. While not studied in the treatment of gout flares, data from a limited number of published studies found no evidence of an increased risk of miscarriage, stillbirth or teratogenic effects among pregnant women using colchicine to treat familial Mediterranean fever (FMF). Colchicine can arrest cell division in animals and plants. Published animal reproduction and development studies with colchicine demonstrated embryofetal toxicity, teratogenicity, and altered postnatal development at exposures within or above the clinical therapeutic range. Colchicine should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. The effect of colchicine on labor and delivery is unknown.  

    Caution is needed if colchicine is administered to a breast-feeding woman. Colchicine is excreted into human milk. Limited data from infants of mothers receiving prophylactic doses of colchicine suggests that exclusively breastfed infants receive less than 10% of the maternal weight-adjusted dose. While no adverse effects have been reported in nursing infants, colchicine can affect gastrointestinal cell renewal and permeability. If this drug is used during lactation, the breastfed infant should be monitored closely for colchicine-related adverse effects.

    MECHANISM OF ACTION

    Colchicine downregulates multiple pro-inflammatory pathways and increases levels of antiinflammatory mediators associated with gouty arthritis. Colchicine prevents microtubule assembly and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis. Although it is highly effective in treating acute gouty arthritis, it is not effective for other types of pain. It is not an analgesic and does not affect uric acid clearance. The actions of colchicine consequently prevent the activation, degranulation, and migration of neutrophils, thereby interfering with the inflammatory response to urate crystal deposition. Although colchicine does not inhibit phagocytosis of uric acid crystals, it does appear to prevent the release of an inflammatory glycoprotein from phagocytes.
     
    The mechanism by which colchicine exerts its beneficial effect in patients with familial Mediterranean fever (FMF) has not been fully elucidated; however, evidence suggests that colchicine may interfere with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-1beta (IL-1beta).
     
    Toxic effects of colchicine are related to its antimitotic activity within proliferating tissues such as the skin, hair, and bone marrow. As a result, acute overdoses of colchicine are extremely serious and can be fatal. In man and certain other animals, colchicine can produce a temporary leukopenia that is followed by leukocytosis. Colchicine has other pharmacologic actions in animals: It alters neuromuscular function, intensifies gastrointestinal activity by neurogenic stimulation, increases sensitivity to central depressants, heightens response to sympathomimetic compounds, depresses the respiratory center, constricts blood vessels, causes hypertension by central vasomotor stimulation, and lowers body temperature.

    PHARMACOKINETICS

    Colchicine is administered orally. Enterohepatic recirculation occurs to a large extent and can lead to adverse GI effects with larger dosages. Plasma protein binding is low (34% to 44%). Colchicine distributes to the kidney, liver, spleen, and intestinal tissues, and concentrates primarily in the leukocytes. It can be found in leukocytes for 10 days after administration. Colchicine is metabolized by the liver and other tissues and is dependent on P-glycoprotein (P-gp) transport and CYP3A4 isoenzymes. The distribution half-life in plasma is 3 to 5 minutes. It is eliminated unchanged in urine and via metabolism with great inter-patient variability; the elimination half-life has ranged from 1.7 to 31.2 hours in patients with normal renal function. Drug accumulation and potentially fatal drug toxicity have been reported following use at therapeutic doses.[23524]
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp)
    Colchicine is metabolized by the liver and other tissues, and is dependent on P-glycoprotein (P-gp) transport and CYP3A4 isoenzymes. Medications which inhibit CYP3A4 or P-gp are known to increase colchicine concentrations and increase the risk for toxicity.[23524]

    Oral Route

    Colchicine is rapidly absorbed, with peak serum concentrations occurring 0.5 to 3 hours after administration in healthy adults under a fasted state; periprandial dosing does not have a clinically significant effect on colchicine pharmacokinetics. Intestinal absorption or biliary recirculation may result in a second serum concentration peak occurring 3 to 36 hours after administration. The absolute bioavailability of oral colchicine is approximately 45%. The onset of action is within 12 hours, with the peak anti-inflammatory effect occurring within 24 to 48 hours; however, relief of swelling may take several days.