Clinical medicine profile
Colchicine
Alkaloid [EPC]
- Route
- See product SmPC
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
Contraindications
- CYP3A4 inhibitors (this includes all protease inhibitors except fosamprenavir).
- In these patients, life-threatening and fatal colchicine toxicity has been reported with colchicine taken in therapeutic doses.
- Patients with renal or hepatic impairment should not be given colchicine tablets in conjunction with P-gp or strong CYP3A4 inhibitors ( Error! Hyperlink reference not valid. ).
- In these patients, life-threatening and fatal colchicine toxicity has been reported with colchicine taken in therapeutic doses ( Error! Hyperlink reference not valid. ).
Precautions
- 5 WARNINGS AND PRECAUTIONS • Fatal overdoses have been reported with colchicine in adults and children.
- Keep colchicine tablets out of the reach of children ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). • Blood dyscrasias: myelosuppression, leukopenia, granulocytopenia, thrombocytopenia and aplastic anemia have been reported ( Error! Hyperlink reference not valid. ). • Monitor for toxicity and if present consider temporary interruption or discontinuation of colchicine ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). • Drug interaction P-gp and/or CYP3A4 inhibitors: Coadministration of colchicine with P-gp and/or strong CYP3A4 inhibitors has resulted in life-threatening interactions and death ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). • Neuromuscular toxicity: Myotoxicity including rhabdomyolysis may occur, especially in combination with other drugs known to cause this effect.
- Consider temporary interruption or discontinuation of colchicine tablets ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). 5.1 Fatal Overdose Fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine [see Error! Hyperlink reference not valid. ] .
- Colchicine tablets should be kept out of the reach of children. 5.2 Blood Dyscrasias Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia and aplastic anemia have been reported with colchicine used in therapeutic doses. 5.3 Drug Interactions Colchicine is a P-gp and CYP3A4 substrate.
- Life-threatening and fatal drug interactions have been reported in patients treated with colchicine given with P-gp and strong CYP3A4 inhibitors.
- If treatment with a P-gp or strong CYP3A4 inhibitor is required in patients with normal renal and hepatic function, the patient’s dose of colchicine may need to be reduced or interrupted [see Error! Hyperlink reference not valid. ] .
- Use of colchicine tablets in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors except fosamprenavir) is contraindicated in patients with renal or hepatic impairment [see Error! Hyperlink reference not valid. ]. 5.4 Neuromuscular Toxicity Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses.
- Patients with renal dysfunction and elderly patients, even those with normal renal and hepatic function, are at increased risk.
- Concomitant use of atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, gemfibrozil, fenofibrate, fenofibric acid or benzafibrate (themselves associated with myotoxicity) or cyclosporine with colchicine tablets may potentiate the development of myopathy [see Error! Hyperlink reference not valid. ] .
- Once colchicine is stopped, the symptoms generally resolve within one week to several months.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
flares, but the safety and efficacy of repeat treatment for gout flares has not been evaluated. The dosing regimens for colchicine tablets are different for each indication and must be individualized. The recommended dosage of colchicine tablets depends on the patient’s age, renal function, hepatic function and use of coadministered drugs [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . Colchicine tablets are administered orally without regard to meals. Colchicine tablets are not an analgesic medication and should not be used to treat pain from other causes. • Gout Flares: Prophylaxis of Gout Flares: 0.6 mg once or twice daily in adults and adolescents older than 16 years of age ( Error! Hyperlink reference not valid. ). Maximum dose 1.2 mg/day. Treatment of Gout Flares: 1.2 mg (two tablets) at the first sign of a gout flare followed by 0.6 mg (one tablet) one hour later ( Error! Hyperlink reference not valid. ). • FMF: Adults and children older than 12 years 1.2 - 2.4 mg; children 6 to 12 years 0.9 - 1.8 mg; children 4 to 6 years 0.3 - 1.8 mg ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). o Give total daily dose in one or two divided doses ( Error! Hyperlink reference not valid. ). o Increase or decrease the dose as indicated and as tolerated in increments of 0.3 mg/day, not to exceed the maximum recommended daily dose ( Error! Hyperlink reference not valid. ). • Colchicine tablets are administered orally without regard to meals. • See full prescribing information (FPI) for dose adjustment regarding patients with impaired renal function ( Error! Hyperlink reference not valid. ), impaired hepatic function ( Error! Hyperlink reference not valid. ), the patient’s age ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ) or use of coadministered drugs ( Error! Hyperlink reference not valid. ). 2.1 Gout Flares Prophylaxis of Gout Flares The recommended dosage of colchicine tablets for prophylaxis of gout flares for adults and adolescents older than 16 years of age is 0.6 mg once or twice daily. The maximum recommended dose for prophylaxis of gout flares is 1.2 mg/day. An increase in gout flares may occur after initiation of uric acid-lowering therapy, including pegloticase, febuxostat and allopurinol, due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. Colchicine tablets are recommended upon initiation of gout flare prophylaxis with uric acid-lowering therapy. Prophylactic therapy may be beneficial for at least the first six months of uric acid-lowering therapy. Treatment of Gout Flares The recommended dose of colchicine tablets for treatment of a gout flare is 1.2 mg (two tablets) at the first sign of the flare followed by 0.6 mg (one tablet) one hour later. Higher doses have not been found to be more effective. The maximum recommended dose for treatment of gout flares is 1.8 mg over a 1-hour period. Colchicine tablets may be administered for treatment of a gout flare during prophylaxis at doses not to exceed 1.2 mg (two tablets) at the first sign of the flare followed by 0.6 mg (one tablet) one hour later. Wait 12 hours and then resume the prophylactic dose. 2.2 FMF The recommended dosage of colchicine tablets for FMF in adults is 1.2 mg to 2.4 mg daily. Colchicine tablets should be increased 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, the dose should be decreased in increments of 0.3 mg/day. The total daily colchicine tablets dose may be administered in one to two divided doses. 2.3 Recommended Pediatric Dosage Prophylaxis and Treatment of Gout Flares Colchicine tablets are not recommended for pediatric use in prophylaxis or treatment of gout flares. FMF The recommended dosage of colchicine tablets for FMF in pediatric patients 4 years of age and older is based on age. The following daily doses may be given as a single or divided dose twice daily: • Children 4 to 6 years: 0.3 mg to 1.8 mg daily • Children 6 to 12 years: 0.9 mg to 1.8 mg daily • Adolescents older than 12 years: 1.2 mg to 2.4 mg daily 2.4 Dose Modification for Coadministration of Interacting Drugs Concomitant Therapy Coadministration of colchicine tablets with drugs known to inhibit CYP3A4 and/or P-glycoprotein (P-gp) increases the risk of colchicine-induced toxic effects (Table 1) . If patients are taking or have recently completed treatment with drugs listed in Table 1 within the prior 14 days, the dose adjustments are as shown in the table below [see Error! Hyperlink reference not valid. ] . Table 1. Colchicine Tablets Dose Adjustment for Coadministration with Interacting Drugs if No Alternative Available For magnitude of effect on colchicine plasma concentrations [see Error! Hyperlink reference not valid. ] Strong CYP3A4 Inhibitors Patients with renal or hepatic impairment should not be given colchicine tablets in conjunction with strong CYP3A4 or P-gp inhibitors [see Error! Hyperlink reference not valid. ] Gout Flares Noted or Anticipated Outcome Prophylaxis of Gout Flares Treatment of Gout Flares FMF Drug Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Atazanavir Clarithromycin Darunavir/ Ritonavir When used in combination with Ritonavir, see dosing recommendations for strong CYP3A4 inhibitors [see Error! Hyperlink reference not valid. ] Indinavir Itraconazole Ketoconazole Lopinavir/ Ritonavir Nefazodone Nelfinavir Ritonavir Saquinavir Telithromycin Tipranavir/ Ritonavir Significant increase in colchicine plasma levels; fatal colchicine toxicity has been reported with clarithromycin, a strong CYP3A4 inhibitor. Similarly, significant increase in colchicine plasma levels is anticipated with other strong CYP3A4 inhibitors 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day 1.2 mg (2 tablets) followed by 0.6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 1.2 mg - 2.4 mg Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) Moderate CYP3A4 Inhibitors Gout Flares Note or Anticipated Outcome Prophylaxis of Gout Flares Treatment of Gout Flares FMF Drug Original Intended Dosage Adjusted Dosage Original Intended Dosage Adjusted Dosage Original Intended Dosage Adjusted Dosage Amprenavir Aprepitant Diltiazem Erythromycin Fluconazole Fosamprenavir (prodrug of Amprenavir) Grapefruit juice Verapamil Significant increase in colchicine plasma concentration is anticipated. Neuromuscular toxicity has been reported with diltiazem and verapamil interactions. 0.6 mg twice a day 0.6 mg once a day 0.3 mg twice a day or 0.6 mg once a day 0.3 mg once a day 1.2 mg (2 tablets) followed by 0.6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. 1.2 mg (2 tablets) x 1 dose. Dose to be repeated no earlier than 3 days. Maximum daily dose of 1.2 mg - 2.4 mg Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day) P-gp Inhibitors Gout Flares Note or Anticipated Outcome Prophylaxis of Gout Flares Treatment of Gout Flares FMF Drug Original Intended Dosage Adjusted Dosage Original Intended Dosage Adjusted Dosage Original Intended Dosage Adjusted Dosage Cyclosporine Ranolazine Significant increase in colchicine plasma levels; fatal colchicine toxicity has been reported with cyclosporine, a P-gp inhibitor. Similarly, significant increase in colchicine plasma levels is anticipated with other P-gp inhibitors. 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day 1.2 mg (2 tablets) followed by 0.6 mg (1 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. 0.6 mg (1 tablet) x 1 dose. Dose to be repeated no earlier than 3 days. Maximum daily dose of 1.2 mg - 2.4 mg Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) Table 2. Colchicine Tablets Dose Adjustment for Coadministration with Protease Inhibitors Protease Inhibitor Clinical Comment w/ Colchicine - Prophylaxis of Gout Flares w/o Colchicine – Treatment of Gout Flares w/Colchicine – Treatment of FMF Atazanavir sulfate (Reyataz) Patients with renal or hepatic impairment should not be given colchicine with Reyataz. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Darunavir (Prezista) Patients with renal or hepatic impairment should not be given colchicine with Prezista/ritonavir. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Fosamprenavir (Lexiva) with Ritonavir Patients with renal or hepatic impairment should not be given colchicine with Lexiva/ritonavir. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Fosamprenavir (Lexiva) Patients with renal or hepatic impairment should not be given colchicine with Lexiva/ritonavir Original dose Adjusted dose 1.2 mg (2 tablets) x 1 dose. Dose to be repeated no earlier than 3 days. Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg twice a day or 0.6 mg once a day 0.3 mg once a day Indinavir (Crixivan) Patients with renal or hepatic impairment should not be given colchicine with Crixivan. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Lopinavir/ Ritonavir (Kaletra) Patients with renal or hepatic impairment should not be given colchicine with Kaletra. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Nelfinavir mesylate (Viracept) Patients with renal or hepatic impairment should not be given colchicine with Viracept. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Ritonavir (Norvir) Patients with renal or hepatic impairment should not be given colchicine with Norvir. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) 0.6 mg twice a day 0.6 mg once a day 0.3 mg once a day 0.3 mg once every other day Saquinavir mesylate (Invirase) Patients with renal or hepatic impairment should not be given colchicine with Invirase/ritonavir. Original dose Adjusted dose 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (1/2 tablet) 1 hour later. Dose to be repeated no earlier than 3 days. Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice…
8.4 Pediatric Use The safety and efficacy of colchicine in children of all ages with FMF has been evaluated in uncontrolled studies. There does not appear to be an adverse effect on growth in children with FMF treated long-term with colchicine. Safety and effectiveness of colchicine in pediatric patients with gout has not been established.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
Indications
- 1 INDICATIONS AND USAGE Colchicine tablets are an alkaloid indicated for: • Prophylaxis and treatment of gout flares in adults ( 1.1 ).
- • Familial Mediterranean fever (FMF) in adults and children 4 years or older ( Error!
- Hyperlink reference not valid.
- 1.1 Gout Flares Colchicine tablets are indicated for prophylaxis and the treatment of acute gout flares.
- • Prophylaxis of Gout Flares: Colchicine tablets are indicated for prophylaxis of gout flares.
- • Treatment of Gout Flares: Colchicine tablets are indicated for treatment of acute gout flares when taken at the first sign of a flare.
- 1.2 Familial Mediterranean Fever (FMF) Colchicine tablets are indicated in adults and children four years or older for treatment of familial Mediterranean fever (FMF).
Adverse effects
- Flares: The most commonly reported adverse reaction in clinical trials of colchicine for the prophylaxis of gout was diarrhea.
- Treatment of Gout Flares: The most common adverse reactions reported in the clinical trial with colchicine tablets for treatment of gout flares were diarrhea (23%) and pharyngolaryngeal pain (3%).
- FMF: Gastrointestinal tract adverse effects are the most frequent side effects in patients initiating colchicine tablets, usually presenting within 24 hours, and occurring in up to 20% of patients given therapeutic doses.
- Typical symptoms include cramping, nausea, diarrhea, abdominal pain and vomiting.
- These events should be viewed as dose-limiting if severe, as they can herald the onset of more significant toxicity. • Prophylaxis of Gout Flares: The most commonly reported adverse reaction in clinical trials for the prophylaxis of gout was diarrhea. • Treatment of Gout Flares: The most common adverse reactions reported in the clinical trial for gout were diarrhea (23%) and pharyngolaryngeal pain (3%). • FMF: Most common adverse reactions (up to 20%) are abdominal pain, diarrhea, nausea and vomiting.
- These effects are usually mild, transient and reversible upon lowering the dose ( Error! Hyperlink reference not valid. ).
- To report SUSPECTED ADVERSE REACTIONS, contact Dr.
- Reddy’s Laboratories Inc., at 1-888- 375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience in Gout Because clinical studies are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice.
- In a randomized, double-blind, placebo-controlled trial in patients with a gout flare, gastrointestinal adverse reactions occurred in 26% of patients using the recommended dose (1.8 mg over one hour) of colchicine tablets compared to 77% of patients taking a nonrecommended high dose (4.8 mg over six hours) of colchicine and 20% of patients taking placebo.
- Diarrhea was the most commonly reported drug-related gastrointestinal adverse event.
- As shown in Table 3, diarrhea is associated with colchicine tablets treatment.
- Diarrhea was more likely to occur in patients taking the high-dose regimen than the low-dose regimen.
- Severe diarrhea occurred in 19% and vomiting occurred in 17% of patients taking the nonrecommended high-dose colchicine regimen but did not occur in the recommended low-dose colchicine tablets regimen.
- Table 3.
Drug interactions
Open multi-drug checker ↗- Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
- Document allergy status and key interactions.
Mechanism & disposition
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-1β.
Read complete mechanism
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-1β. Additionally, colchicine disrupts cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules and consequently prevents the activation, degranulation and migration of neutrophils thought to mediate some gout symptoms.
Product-specific
Product-specific
See product SmPC
In healthy adults, colchicine tablets are absorbed when given orally, reaching a mean C max of 2.5 ng/mL (range 1.1 to 4.4 ng/mL) in one to two hours (range 0.5 to 3 hours) after a single dose administered under fasting conditions. Following oral administration of colchicine tabl...
The mean apparent volume of distribution in healthy young volunteers is approximately 5 to 8 L/kg. Colchicine binding to serum protein is low, 39 ± 5%, primarily to albumin regardless of concentration. Colchicine crosses the placenta (plasma levels in the fetus are reported to be...
Colchicine is demethylated to two primary metabolites, 2-O-demethylcolchicine and 3-O-demethylcolchicine (2- and 3-DMC, respectively) and one minor metabolite, 10-O-demethylcolchicine (also known as colchicine). In vitro studies using human liver microsomes have shown that CYP3A4...
In healthy volunteers (n = 12), 40 to 65% of 1 mg orally administered colchicine was recovered unchanged in urine. Enterohepatic recirculation and biliary excretion are also postulated to play a role in colchicine elimination. Following multiple oral doses (0.6 mg twice daily), t...
(hr) 24.92 ± 5.34 and 30.06 ± 10.78; and clearance (mL/min) 0.0321 ± 0.0091 and 0.0292 ± 0.0071. Clinical studies with colchicine for prophylaxis and treatment of gout flares and for treatment of FMF did not include sufficient numbers of patients aged 65 years and older to determ...
Pregnancy, lactation & diet
8.1 Pregnancy Risk Summary Available data from published literature on colchicine use in pregnancy over several decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Error! Hyperlink reference not valid. ). Colchicine crosses the human placenta. Although animal reproductive and developmental studies were not conducted with colchicine tablets, published animal reproduction and development studies indicate that colchicine causes embryofetal toxicity, teratogenicity and altered postnatal development at exposures within or above the clinical therapeutic range. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects or miscarriage in pregnant women with rheumatic diseases (such as rheumatoid arthritis, Behcet’s disease, or familial Mediterranean fever (FMF) treated with colchicine at therapeutic doses during pregnancy. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications.
• In the presence of mild to moderate renal or hepatic impairment, adjustment of dosing is not required for treatment of gout flare, prophylaxis of gout flare and FMF, but patients should be monitored closely ( Error! Hyperlink reference not valid. ). • In patients with severe renal impairment for prophylaxis of gout flares, the starting dose should be 0.3 mg/day for gout flares, no dose adjustment is required, but a treatment course should be repeated no more than once every two weeks. In FMF patients, start with 0.3 mg/day, and any increase in dose should be done with close monitoring ( Error! Hyperlink reference not valid. ). • In patients with severe hepatic impairment, a dose reduction may be needed in prophylaxis of gout flares and FMF patients; while a dose reduction may not be needed in gout flares, a treatment course should be repeated no more than once every two weeks ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). • For patients undergoing dialysis, the total recommended dose for prophylaxis of gout flares should be 0.3 mg given twice a week with close monitoring. For treatment of gout flares, the total recommended dose should be reduced to 0.6 mg (one tablet) x 1 dose and the treatment course should not be repeated more than once every two weeks. For FMF patients, the starting dose should be 0.3 mg/day and dosing can be increased with close monitoring ( Error! Hyperlink reference not valid. ). • Females and Males of Reproductive Potential: Advise males that colchicine tablets may transiently impair fertility ( Error! Hyperlink reference not valid. ). • Geriatric Use: The recommended dose of colchicine should be based on renal function ( Error! Hyperlink reference not valid. ). 8.1 Pregnancy Risk Summary Available data from published literature on colchicine use in pregnancy over several decades have not identified any drug associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Error! Hyperlink reference not valid. ). Colchicine crosses the human placenta. Although animal reproductive and developmental studies were not conducted with colchicine tablets, published animal reproduction and development studies indicate that colchicine causes embryofetal toxicity, teratogenicity and altered postnatal development at exposures within or above the clinical therapeutic range. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Available data from published observational studies, case series, and case reports over several decades do not suggest an increased risk for major birth defects or miscarriage in pregnant women with rheumatic diseases (such as rheumatoid arthritis, Behcet’s disease, or familial Mediterranean fever (FMF) treated with colchicine at therapeutic doses during pregnancy. Limitations of these data include the lack of randomization and inability to control for confounders such as underlying maternal disease and maternal use of concomitant medications. 8.2 Lactation Risk Summary Colchicine is present in human milk (see Error! Hyperlink reference not valid. ) . Adverse events in breastfed infants have not been reported in the published literature after administration of colchicine to lactating women. There are no data on the effects of colchicine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for colchicine tablets and any potential adverse effects on the breastfed child from colchicine tablets or from the underlying maternal condition. Data Limited published data from case reports and a small lactation study demonstrate that colchicine is present in breastmilk. A systematic review of literature reported no adverse effects in 149 breastfed children. In a prospective observational cohort study, no gastrointestinal or other symptoms were reported in 38 colchicine-exposed breastfed infants. 8.3 Females and Males of Reproductive Potential Infertility Case reports and epidemiology studies in human male subjects on colchicine therapy indicated that infertility from colchicine is rare and may be reversible. A case report indicated that azoospermia was reversed when therapy was stopped. Case reports and epidemiology studies in female subjects on colchicine therapy have not established a clear relationship between colchicine use and female infertility. However, since the progression of FMF without treatment may result in infertility, the use of colchicine needs to be weighed against the potential risks [see Error! Hyperlink reference not valid. ] . 8.4 Pediatric Use The safety and efficacy of colchicine in children of all ages with FMF has been evaluated in uncontrolled studies. There does not appear to be an adverse effect on growth in children with FMF treated long-term with colchicine. Safety and effectiveness of colchicine in pediatric patients with gout has not been established. 8.5 Geriatric Use Clinical studies with colchicine for prophylaxis and treatment of gout flares and for treatment of FMF did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient with gout should be cautious, reflecting the greater frequency of decreased renal function, concomitant disease or other drug therapy [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . 8.6 Renal Impairment Colchicine is significantly excreted in urine in healthy subjects. Clearance of colchicine is decreased in patients with impaired renal function. Total body clearance of colchicine was reduced by 75% in patients with end-stage renal disease undergoing dialysis. Prophylaxis of Gout Flares For prophylaxis of gout flares in patients with mild (estimated creatinine clearance Cl cr 50 to 80 mL/min) to moderate (Cl cr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. However, in patients with severe impairment, the starting dose should be 0.3 mg per day and any increase in dose should be done with close monitoring. For the prophylaxis of gout flares in patients undergoing dialysis, the starting doses should be 0.3 mg given twice a week with close monitoring [see Error! Hyperlink reference not valid. ] . Treatment of Gout Flares For treatment of gout flares in patients with mild (Cl cr 50 to 80 mL/min) to moderate (Cl cr 30 to 50 mL/min) renal function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine tablets. However, in patients with severe impairment, while the dose does not need to be adjusted for the treatment of gout flares, a treatment course should be repeated no more than once every two weeks. For patients with gout flares requiring repeated courses, consideration should be given to alternate therapy. For patients undergoing dialysis, the total recommended dose for the treatment of gout flares should be reduced to a single dose of 0.6 mg (one tablet). For these patients, the treatment course should not be repeated more than once every two weeks [see Error! Hyperlink reference not valid. ] . FMF Although pharmacokinetics of colchicine in patients with mild (Cl cr 50 to 80 mL/min) and moderate (Cl cr 30 to 50 mL/min) renal impairment is not known, these patients should be monitored closely for adverse effects of colchicine. Dose reduction may be necessary. In patients with severe renal failure (Cl cr less than 30 mL/min) and end-stage renal disease requiring dialysis, colchicine tablets may be started at the dose of 0.3 mg/day. Any increase in dose should be done with adequate monitoring of the patient for adverse effects of colchicine tablets [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] . 8.7 Hepatic Impairment The clearance of colchicine may be significantly reduced and plasma half-life prolonged in patients with chronic hepatic impairment compared to healthy subjects [see Error! Hyperlink reference not valid. ] . Prophylaxis of Gout Flares For prophylaxis of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended dose is not required, but patients should be monitored closely for adverse effects of colchicine. Dose reduction should be considered for the prophylaxis of gout flares in patients with severe hepatic impairment [see Error! Hyperlink reference not valid. ] . Treatment of Gout Flares For treatment of gout flares in patients with mild to moderate hepatic function impairment, adjustment of the recommended colchicine tablets dose is not required, but patients should be monitored closely for adverse effects of colchicine tablets. However, for the treatment of gout flares in patients with severe impairment, while the dose does not need to be adjusted, the treatment course should be repeated no more than once every two weeks. For these patients, requiring repeated courses for the treatment of gout flares, consideration should be given to alternate therapy [see Error! Hyperlink reference not valid. ] . FMF In patients with severe hepatic disease, dose reduction should be considered with careful monitoring [see Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ] .
Brands & loaded prices
| Brand | Manufacturer | Pack | Observed price |
|---|---|---|---|
| No reviewed brand listings are linked yet. | |||
Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.