Colcrys (colchicine 0.6 MG) Oral Tablet
Generic Name: COLCHICINE
Brand Name: Colcrys
- Substance Name(s):
- COLCHICINE
DRUG INTERACTIONS
7 COLCRYS (colchicine) is a substrate of the efflux transporter P-glycoprotein (P-gp).
Of the cytochrome P450 enzymes tested, CYP3A4 was mainly involved in the metabolism of colchicine.
If COLCRYS is administered with drugs that inhibit P-gp, most of which also inhibit CYP3A4, increased concentrations of colchicine are likely.
Fatal drug interactions have been reported.
Physicians should ensure that patients are suitable candidates for treatment with COLCRYS and remain alert for signs and symptoms of toxicities related to increased colchicine exposure as a result of a drug interaction.
Signs and symptoms of COLCRYS toxicity should be evaluated promptly and, if toxicity is suspected, COLCRYS should be discontinued immediately.
Table 4 provides recommendations as a result of other potentially significant drug interactions.
Table 1 provides recommendations for strong and moderate CYP3A4 inhibitors and P-gp inhibitors.
Table 4.
Other Potentially Significant Drug Interactions Concomitant Drug Class or Food Noted or Anticipated Outcome Clinical Comment HMG-Co A Reductase Inhibitors: atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin Pharmacokinetic and/or pharmacodynamic interaction: the addition of one drug to a stable long-term regimen of the other has resulted in myopathy and rhabdomyolysis (including a fatality) P-gp substrate; rhabdomyolysis has been reported Weigh the potential benefits and risks and carefully monitor patients for any signs or symptoms of muscle pain, tenderness, or weakness, particularly during initial therapy; monitoring CPK (creatine phosphokinase) will not necessarily prevent the occurrence of severe myopathy.
Other Lipid-Lowering Drugs: fibrates, gemfibrozil Digitalis Glycosides: digoxin Coadministration of P-gp and/or CYP3A4 inhibitors (e.g., clarithromycin or cyclosporine) have been demonstrated to alter the concentration of colchicine.
The potential for drug-drug interactions must be considered prior to and during therapy.
See full prescribing information for a complete list of reported and potential interactions (2.4, 5.3, 7).
OVERDOSAGE
10 The exact dose of colchicine that produces significant toxicity is unknown.
Fatalities have occurred after ingestion of a dose as low as 7 mg over a four-day period, while other patients have survived after ingesting more than 60 mg.
A review of 150 patients who overdosed on colchicine found that those who ingested less than 0.5 mg/kg survived and tended to have milder toxicities such as gastrointestinal symptoms, whereas those who took 0.5 to 0.8 mg/kg had more severe reactions such as myelosuppression.
There was 100% mortality in those who ingested more than 0.8 mg/kg.
The first stage of acute colchicine toxicity typically begins within 24 hours of ingestion and includes gastrointestinal symptoms such as abdominal pain, nausea, vomiting, diarrhea and significant fluid loss, leading to volume depletion.
Peripheral leukocytosis may also be seen.
Life-threatening complications occur during the second stage, which occurs 24 to 72 hours after drug administration, attributed to multiorgan failure and its consequences.
Death is usually a result of respiratory depression and cardiovascular collapse.
If the patient survives, recovery of multiorgan injury may be accompanied by rebound leukocytosis and alopecia starting about one week after the initial ingestion.
Treatment of colchicine poisoning should begin with gastric lavage and measures to prevent shock.
Otherwise, treatment is symptomatic and supportive.
No specific antidote is known.
Colchicine is not effectively removed by dialysis [see Pharmacokinetics (12.3)].
DESCRIPTION
11 Colchicine is an alkaloid chemically described as (S)N- (5,6,7,9-tetrahydro- 1,2,3, 10-tetramethoxy-9-oxobenzo [alpha] heptalen-7-yl) acetamide with a molecular formula of C22H25NO6 and a molecular weight of 399.4.
The structural formula of colchicine is given below.
Colchicine occurs as a pale yellow powder that is soluble in water.
COLCRYS (colchicine, USP) tablets are supplied for oral administration as purple, film-coated, capsule-shaped tablets (0.1575″ × 0.3030″), debossed with “AR 374” on one side and scored on the other, containing 0.6 mg of the active ingredient colchicine USP.
Inactive ingredients: carnauba wax, FD&C blue #2, FD&C red #40, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, pregelatinized starch, sodium starch glycolate, titanium dioxide and triacetin.
Structural Formula of Colchicine
CLINICAL STUDIES
14 The evidence for the efficacy of colchicine in patients with chronic gout is derived from the published literature.
Two randomized clinical trials assessed the efficacy of colchicine 0.6 mg twice a day for the prophylaxis of gout flares in patients with gout initiating treatment with urate-lowering therapy.
In both trials, treatment with colchicine decreased the frequency of gout flares.
The efficacy of a low-dosage regimen of oral colchicine (COLCRYS total dose 1.8 mg over one hour) for treatment of gout flares was assessed in a multicenter, randomized, double-blind, placebo-controlled, parallel group, one-week, dose-comparison study.
Patients meeting American College of Rheumatology criteria for gout were randomly assigned to three groups: high-dose colchicine (1.2 mg, then 0.6 mg hourly × 6 hours [4.8 mg total]); low-dose colchicine (1.2 mg, then 0.6 mg in 1 hour [1.8 mg total] followed by five placebo doses hourly); or placebo (two capsules, then one capsule hourly × 6 hours).
Patients took the first dose within 12 hours of the onset of the flare and recorded pain intensity (11-point Likert scale) and adverse events over 72 hours.
The efficacy of colchicine was measured based on response to treatment in the target joint, using patient self-assessment of pain at 24 hours following the time of first dose as recorded in the diary.
A responder was one who achieved at least a 50% reduction in pain score at the 24 hour post-dose assessment relative to the pretreatment score and did not use rescue medication prior to the actual time of 24 hour post-dose assessment.
Rates of response were similar for the recommended low-dose treatment group (38%) and the nonrecommended high-dose group (33%) but were higher as compared to the placebo group (16%) as shown in Table 8.
Table 8.
Number (%) of Responders Based on Target Joint Pain Score at 24 Hours Post First Dose COLCRYS Dose Responders n (%) Placebo n (%) (n=58) % Differences in Proportion Low-Dose (n=74) High-Dose (n=52) Low-Dose vs Placebo (95% CI) High-Dose vs Placebo (95% CI) 28 (38%) 17 (33%) 9 (16%) 22 (8, 37) 17 (1, 33) Figure 1 shows the percentage of patients achieving varying degrees of improvement in pain from baseline at 24 hours.
Figure 1 Pain Relief on Low and High Doses of COLCRYS and Placebo (Cumulative) The evidence for the efficacy of colchicine in patients with FMF is derived from the published literature.
Three randomized, placebo-controlled studies were identified.
The three placebo-controlled studies randomized a total of 48 adult patients diagnosed with FMF and reported similar efficacy endpoints as well as inclusion and exclusion criteria.
One of the studies randomized 15 patients with FMF to a six-month crossover study during which five patients discontinued due to study noncompliance.
The 10 patients completing the study experienced five attacks over the course of 90 days while treated with colchicine compared to 59 attacks over the course of 90 days while treated with placebo.
Similarly, the second study randomized 22 patients with FMF to a four-month crossover study during which nine patients discontinued due to lack of efficacy while receiving placebo or study noncompliance.
The 13 patients completing the study experienced 18 attacks over the course of 60 days while treated with colchicine compared to 68 attacks over the course of 60 days while treated with placebo.
The third study was discontinued after an interim analysis of six of the 11 patients enrolled had completed the study; results could not be confirmed.
Open-label experience with colchicine in adults and children with FMF is consistent with the randomized, controlled trial experience and was utilized to support information on the safety profile of colchicine and for dosing recommendations.
Figure1
HOW SUPPLIED
16 /STORAGE AND HANDLING 16.1 How Supplied COLCRYS (colchicine, USP) tablets 0.6 mg are purple, film-coated, capsule-shaped tablets debossed with “AR 374” on one side and scored on the other side.
Bottles of 30 NDC 64764-119-07 Bottles of 60 NDC 64764-119-06 Bottles of 100 NDC 64764-119-01 Bottles of 250 NDC 64764-119-03 Bottles of 500 NDC 64764-119-05 Bottles of 1000 NDC 64764-119-10 NDC 69189-0119-1 single dose pack with 1 tablet as repackaged by Avera McKennan Hospital 16.2 Storage Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Protect from light.
DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.
GERIATRIC USE
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 Dose Modification for Coadministration of Interacting Drugs (2.4) and Pharmacokinetics (12.3)].
DOSAGE FORMS AND STRENGTHS
3 0.6 mg tablets — purple capsule-shaped, film-coated with “AR 374” debossed on one side and scored on the other side.
•0.6 mg tablets (3).
MECHANISM OF ACTION
12.1 Mechanism of Action The mechanism by which COLCRYS exerts its beneficial effect in patients with 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-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.
INDICATIONS AND USAGE
1 COLCRYS (colchicine, USP) 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 (1.2).
COLCRYS is not an analgesic medication and should not be used to treat pain from other causes.
1.1 Gout Flares COLCRYS (colchicine, USP) tablets are indicated for prophylaxis and the treatment of acute gout flares.
• Prophylaxis of Gout Flares: COLCRYS is indicated for prophylaxis of gout flares.
• Treatment of Gout Flares: COLCRYS tablets are indicated for treatment of acute gout flares when taken at the first sign of a flare.
1.2 Familial Mediterranean Fever (FMF) COLCRYS (colchicine, USP) tablets are indicated in adults and children 4 years or older for treatment of familial Mediterranean fever (FMF).
PEDIATRIC USE
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.
Gout is rare in pediatric patients; safety and effectiveness of colchicine in pediatric patients has not been established.
PREGNANCY
8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies with colchicine in pregnant women.
Colchicine crosses the human placenta.
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).
Although animal reproductive and developmental studies were not conducted with COLCRYS, 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.
COLCRYS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
NUSRING MOTHERS
8.3 Nursing Mothers Colchicine is excreted into human milk.
Limited information suggests that exclusively breastfed infants receive less than 10 percent of the maternal weight-adjusted dose.
While there are no published reports of adverse effects in breastfeeding infants of mothers taking colchicine, colchicine can affect gastrointestinal cell renewal and permeability.
Caution should be exercised, and breastfeeding infants should be observed for adverse effects when COLCRYS is administered to a nursing woman.
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS • Fatal overdoses have been reported with colchicine in adults and children.
Keep COLCRYS out of the reach of children (5.1, 10).
• Blood dyscrasias: myelosuppression, leukopenia, granulocytopenia, thrombocytopenia and aplastic anemia have been reported (5.2).
•Monitor for toxicity and if present consider temporary interruption or discontinuation of colchicine (5.2, 5.3, 5.4, 6, 10).
• 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 (5.3, 7).
• Neuromuscular toxicity: Myotoxicity including rhabdomyolysis may occur, especially in combination with other drugs known to cause this effect.
Consider temporary interruption or discontinuation of COLCRYS (5.4, 7).
5.1 Fatal Overdose Fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine [see Overdosage (10)].
COLCRYS 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 Drug Interactions (7)].
Use of COLCRYS 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 Contraindications (4)].
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 COLCRYS may potentiate the development of myopathy [see Drug Interactions (7) ].
Once colchicine is stopped, the symptoms generally resolve within one week to several months.
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide) Dosing Instructions Patients should be advised to take COLCRYS as prescribed, even if they are feeling better.
Patients should not alter the dose or discontinue treatment without consulting with their doctor.
If a dose of COLCRYS is missed: • For treatment of a gout flare when the patient is not being dosed for prophylaxis, take the missed dose as soon as possible.
• For treatment of a gout flare during prophylaxis, take the missed dose immediately, wait 12 hours, then resume the previous dosing schedule.
• For prophylaxis without treatment for a gout flare, or FMF, take the dose as soon as possible and then return to the normal dosing schedule.
However, if a dose is skipped the patient should not double the next dose.
Fatal Overdose Instruct patient that fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine.
COLCRYS should be kept out of the reach of children.
Blood Dyscrasias Patients should be informed that bone marrow depression with agranulocytosis, aplastic anemia and thrombocytopenia may occur with COLCRYS.
Drug and Food Interactions Patients should be advised that many drugs or other substances may interact with COLCRYS and some interactions could be fatal.
Therefore, patients should report to their healthcare provider all of the current medications they are taking and check with their healthcare provider before starting any new medications, particularly antibiotics.
Patients should also be advised to report the use of nonprescription medication or herbal products.
Grapefruit and grapefruit juice may also interact and should not be consumed during COLCRYS treatment.
Neuromuscular Toxicity Patients should be informed that muscle pain or weakness, tingling or numbness in fingers or toes may occur with COLCRYS alone or when it is used with certain other drugs.
Patients developing any of these signs or symptoms must discontinue COLCRYS and seek medical evaluation immediately.
DOSAGE AND ADMINISTRATION
2 The long-term use of colchicine is established for FMF and the prophylaxis of gout flares, but the safety and efficacy of repeat treatment for gout flares has not been evaluated.
The dosing regimens for COLCRYS are different for each indication and must be individualized.
The recommended dosage of COLCRYS depends on the patient’s age, renal function, hepatic function and use of coadministered drugs [see Dose Modification for Coadministration of Interacting Drugs (2.4)].
COLCRYS tablets are administered orally without regard to meals.
COLCRYS is 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 (2.1).
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 (2.1).
• 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 (2.2, 2.3).
oGive total daily dose in one or two divided doses (2.2).
oIncrease or decrease the dose as indicated and as tolerated in increments of 0.3 mg/day, not to exceed the maximum recommended daily dose (2.2).
Colchicine tablets are administered orally without regard to meals.
See full prescribing information for dose adjustment regarding patients with impaired renal function (2.5), impaired hepatic function (2.6), the patient’s age (2.3, 8.5) or use of coadministered drugs (2.4).
2.1 Gout Flares Prophylaxis of Gout Flares The recommended dosage of COLCRYS 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.
COLCRYS is 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 COLCRYS 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 one-hour period.
COLCRYS 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 COLCRYS for FMF in adults is 1.2 mg to 2.4 mg daily.
COLCRYS 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 COLCRYS dose may be administered in one to two divided doses.
2.3 Recommended Pediatric Dosage Prophylaxis and Treatment of Gout Flares COLCRYS is not recommended for pediatric use in prophylaxis or treatment of gout flares.
FMF The recommended dosage of COLCRYS 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 COLCRYS 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 Drug Interactions (7)].
Table 1.
COLCRYS Dose Adjustment for Coadministration with Interacting Drugs if no Alternative AvailableFor magnitude of effect on colchicine plasma concentrations [see Pharmacokinetics (12.3) ] Strong CYP3A4 Inhibitors When used in combination with Ritonavir, see dosing recommendations for strong CYP3A4 inhibitors [see Contraindications (4)] Drug Noted or Anticipated Outcome Gout Flares FMF Prophylaxis of Gout Flares Treatment of Gout Flares Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Atazanavir Clarithromycin Darunavir/ Ritonavir 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) × 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 – 2.4 mg Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) Moderate CYP3A4 Inhibitors Drug Noted or Anticipated Outcome Gout Flares FMF Prophylaxis of Gout Flares Treatment of Gout Flares Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Amprenavir Aprepitant Diltiazem Erythromycin Fluconazole Fosamprenavir (pro-drug 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) × 1 dose.
Dose to be repeated no earlier than 3 days.
Maximum daily dose of 1.2 – 2.4 mg.
Maximum daily dose of 1.2 mg (may be given as 0.6 mg twice a day) P-gp Inhibitors Patients with renal or hepatic impairment should not be given COLCRYS in conjunction with strong CYP3A4 or P-gp inhibitors [see Contraindications (4)] Drug Noted or Anticipated Outcome Gout Flares FMF Prophylaxis of Gout Flares Treatment of Gout Flares Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose Original Intended Dosage Adjusted Dose 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) × 1 dose.
Dose to be repeated no earlier than 3 days.
Maximum daily dose of 1.2 – 2.4 mg Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day) Table 2.
COLCRYS Dose Adjustment for Coadministration with Protease Inhibitors Protease Inhibitor Clinical Comment w/Colchicine – Prophylaxis of Gout Flares w/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) × 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) × 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) × 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) × 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) × 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) × 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) × 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) × 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) × 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 Tipranavir (Aptivus) Patients with renal or hepatic impairment should not be given colchicine with Aptivus/ritonavir.
Original dose Adjusted dose 0.6 mg (1 tablet) × 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 Treatment of gout flares with COLCRYS is not recommended in patients receiving prophylactic dose of COLCRYS and CYP3A4 inhibitors.
2.5 Dose Modification in Renal Impairment Colchicine dosing must be individualized according to the patient’s renal function [see Renal Impairment (8.6)].
Clcr in mL/minute may be estimated from serum creatinine (mg/dL) determination using the following formula: [140-age (years) × weight (kg)] Clcr = ————————————— 72 × serum creatinine (mg/dL) × 0.85 for female patients Gout Flares Prophylaxis of Gout Flares For prophylaxis of gout flares in patients with mild (estimated creatinine clearance [Clcr] 50 to 80 mL/min) to moderate (Clcr 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/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 Clinical Pharmacology (12.3) and Renal Impairment (8.6)].
Treatment of Gout Flares For treatment of gout flares in patients with mild (Clcr 50 to 80 mL/min) to moderate (Clcr 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, 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 Clinical Pharmacology (12.3) and Renal Impairment (8.6)].
Treatment of gout flares with COLCRYS is not recommended in patients with renal impairment who are receiving COLCRYS for prophylaxis.
FMF Caution should be taken in dosing patients with moderate and severe renal impairment and in patients undergoing dialysis.
For these patients, the dosage should be reduced [see Clinical Pharmacology (12.3)].
Patients with mild (Clcr 50 to 80 mL/min) and moderate (Clcr 30 to 50 mL/min) renal impairment should be monitored closely for adverse effects of COLCRYS.
Dose reduction may be necessary.
For patients with severe renal failure (Clcr less than 30 mL/min), start with 0.3 mg/day; any increase in dose should be done with adequate monitoring of the patient for adverse effects of colchicine [see Renal Impairment (8.6)].
For patients undergoing dialysis, the total recommended starting dose should be 0.3 mg (half tablet) per day.
Dosing can be increased with close monitoring.
Any increase in dose should be done with adequate monitoring of the patient for adverse effects of colchicine [see Clinical Pharmacology (12.3) and Renal Impairment (8.6)].
2.6 Dose Modification in Hepatic Impairment Gout Flares 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 Hepatic Impairment (8.7)].
Treatment of Gout Flares For treatment 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.
However, for the treatment of gout flares in patients with severe impairment, while the dose does not need to be adjusted, a 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 Hepatic Impairment (8.7)].
Treatment of gout flares with COLCRYS is not recommended in patients with hepatic impairment who are receiving COLCRYS for prophylaxis.
FMF Patients with mild to moderate hepatic impairment should be monitored closely for adverse effects of colchicine.
Dose reduction should be considered in patients with severe hepatic impairment [see Hepatic Impairment (8.7) ].