Colcrys

Prophylaxis of Gout 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 COLCRYS 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 COLCRYS, 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.

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 COLCRYS 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 COLCRYS treatment. Diarrhea was more likely to occur in patients taking the high-dose regimen than the lowdose 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 COLCRYS regimen.

Table 3: Number (%) of Patients with at Least One Drug-Related Treatment-Emergent Adverse Event with an Incidence of ≥ 2% of Patients in Any Treatment Group

MedDRA System Organ Class MedDRA Preferred Term	COLCRYS Dose		Placebo (N=59) n (%)
	High (N=52) n (%)	Low (N=74) n (%)
Number of Patients with at Least One Drug-Related TEAE	40 (77)	27 (37)	16 (27)
Gastrointestinal Disorders	40 (77)	19 (26)	12 (20)
Diarrhea	40 (77)	17 (23)	8 (14)
Nausea	9 (17)	3 (4)	3 (5)
Vomiting	9 (17)	0	0
Abdominal Discomfort	0	0	2 (3)
General Disorders and Administration Site Conditions	4 (8)	1 (1)	1 (2)
Fatigue	2 (4)	1 (1)	1 (2)
Metabolic and Nutrition Disorders	0	3 (4)	2 (3)
Gout	0	3 (4)	1 (2)
Nervous System Disorders	1 (2)	1 (1.4)	2 (3)
Headache	1 (2)	1 (1)	2 (3)
Respiratory Thoracic Mediastinal Disorders	1 (2)	2 (3)	0
Pharyngolaryngeal Pain	1 (2)	2 (3)	0

Postmarketing Experience

Serious toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation and injury to cells in the renal, hepatic, circulatory and central nervous systems.

These most often occur with excessive accumulation or overdosage [see OVERDOSAGE].

The following adverse reactions have been reported with colchicine. These have been generally reversible upon temporarily interrupting treatment or lowering the dose of colchicine.

Neurological: sensory motor neuropathy

Dermatological: alopecia, maculopapular rash, purpura, rash

Digestive: abdominal cramping, abdominal pain, diarrhea, lactose intolerance, nausea, vomiting

Hematological: leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia

Hepatobiliary: elevated AST, elevated ALT

Musculoskeletal: myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis

Reproductive: azoospermia, oligospermia

Colcrys is a prescription medicine used to:

• prevent and treat gout flares in adults
• treat familial Mediterranean fever (FMF) in adults and children age four or older.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor about all the medicines you take, including ones that you may only be taking for a short time, such as antibiotics.  Especially tell your doctor if you are taking:

• atazanavir sulfate (Reyataz)
• clarithromycin (Biaxin)
• cyclosporine (Neoral, Gengraf, Sandimmune)
• darunavir (Prezista)
• fosamprenavir (Lexiva) with ritonavir
• fosamprenavir (Lexiva)
• indinavir (Crixivan)
• itraconazole (Sporanox)
• ketoconazole (Nizoral)
• Iopinavir/ritonavir (Kaletra)
• nefazodone (Serzone)
• nelfinavir mesylate(Viracept)
• ritonavir (Norvir)
• saquinavir mesylate (Invirase)
• telithromycin (Ketek)
• tipranavir (Aptivus)

Do not start a new medicine without talking to your doctor.

This is not a complete list of Colcrys drug interactions.  Ask your doctor or pharmacist for more information.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• muscle pain or weakness;

• numbness or tingly feeling in your fingers or toes;

• pale or gray appearance of your lips, tongue, or hands;

• severe or ongoing vomiting or diarrhea;

• fever, chills, body aches, flu symptoms; or

• easy bruising, unusual bleeding, feeling weak or tired.

Common side effects may include:

• nausea, vomiting, stomach pain; or

• diarrhea.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General

Gout

• Administer prophylactic doses of colchicine before initiation of allopurinol or uricosurics because sudden changes in serum urate concentrations may precipitate acute gout flare.124 125 127 129

• May discontinue colchicine and use urate-lowering agents alone after serum urate concentration is reduced to the desired level, and acute gout flares have not occurred for 3–6 months (some clinicians suggest 1–12 months).124 126 143

Administration

Administer orally.152 Has been administered IV; parenteral preparation no longer available in the US.144 145 (See Serious Adverse Effects Related to Colchicine Injection under Cautions.)

Oral Administration

Initiate therapy for acute gout flare at the first sign of an attack.152

Administer without regard to meals.152

Dosage

Dosage depends on the patient’s age, renal and hepatic function, and recent (within 14 days) or concomitant use of moderate or potent CYP3A4 inhibitors or inhibitors of the P-glycoprotein transport system.152

Pediatric Patients

Prophylactic Treatment of Recurrent Gout Flares Oral

Manufacturer states that adolescents ≥16 years of age may receive adult dosages.152

Familial Mediterranean Fever Oral

Recommended dosage in children not receiving concomitant therapy with a moderate or potent CYP3A4 inhibitor or a P-glycoprotein inhibitor depends on child’s age (see Table 1).152 Manufacturer makes no specific recommendations for children who are receiving or have recently received therapy with a moderate or potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system.152

Dosage can be increased in increments of 0.3 mg daily to the maximum recommended dosage or decreased in decrements of 0.3 mg daily in individuals who develop intolerable adverse effects.152

Table 1. Recommended Dosage of Colchicine for Chronic Prophylactic Therapy of Familial Mediterranean Fever in Children Not Receiving Concomitant Therapy with Moderate or Potent CYP3A4 Inhibitors or with P-glycoprotein Inhibitors

Child’s Age (years)	Recommended Colchicine Dosage
4–6	0.3–1.8 mg daily (given as 1 dose or 2 divided doses)152
6–12	0.9–1.8 mg daily (given as 1 dose or 2 divided doses)152
>12	1.2–2.4 mg daily (given as 1 dose or 2 divided doses)152

Adults

Treatment of Gout Flare Oral

Recommended dosage of colchicine depends on whether patient is receiving or has recently (within 14 days) received a moderate or potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system (see Table 2).152

Use of colchicine for treatment of gout flare is not recommended in patients receiving the drug for prevention of gout flare and also receiving a CYP3A4 inhibitor.152

Do not repeat courses of colchicine therapy (see Table 2) until 3 days have elapsed.152 154

Table 2. Recommended Adult Dosage of Colchicine for Treatment of Gout Flare

Recent (within 14 days) or Concomitant Therapy	Recommended Colchicine Dosage
No recent or concomitant therapy with a moderate or potent CYP3A4 inhibitor or a P-glycoprotein inhibitor	1.2 mg at first sign of flare followed by 0.6 mg one hour later;152 wait 12 hours before resuming prophylactic doses of colchicine152
Potent CYP3A4 inhibitor (e.g., atazanavir, boceprevir, clarithromycin, darunavir with low-dose ritonavir [ritonavir-boosted darunavir], ritonavir-boosted fosamprenavir, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, telithromycin, ritonavir-boosted tipranavir, the fixed combination of lopinavir and ritonavir [lopinavir/ritonavir], the fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir)	0.6 mg at first sign of flare followed by 0.3 mg one hour later152 154 155 163 164
Moderate CYP3A4 inhibitor (e.g., aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir [without ritonavir], grapefruit juice, verapamil)	1.2 mg at first sign of flare152 154
P-glycoprotein inhibitor (e.g., cyclosporine, ranolazine)	0.6 mg at first sign of flare152

Prophylactic Treatment of Recurrent Gout Flares Oral

Recommended dosage of colchicine depends on whether patient is receiving or has recently (within 14 days) received a moderate or potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system (see Table 3).152

Table 3. Recommended Adult Dosage of Colchicine for Prophylactic Treatment of Recurrent Gout Flares

Recent (within 14 days) or Concomitant Therapy	Recommended Colchicine Dosage
No recent or concomitant therapy with a moderate or potent CYP3A4 inhibitor or a P-glycoprotein inhibitor	0.6 mg once or twice daily (maximum 1.2 mg daily)152
Potent CYP3A4 inhibitor (e.g., atazanavir, boceprevir, clarithromycin, ritonavir-boosted darunavir, ritonavir-boosted fosamprenavir, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, telithromycin, ritonavir-boosted tipranavir, lopinavir/ritonavir, the fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir)	0.3 mg daily or every other day152 154 155 163 164
Moderate CYP3A4 inhibitor (e.g., aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir [without ritonavir], grapefruit juice, verapamil)	0.3 mg twice daily, 0.6 mg once daily, or 0.3 mg once daily152 154
P-glycoprotein inhibitor (e.g., cyclosporine, ranolazine)	0.3 mg once daily or every other day152

Colchicine/Probenecid Fixed-Combination Therapy Oral

Fixed-dosage preparation has limited usefulness for prophylactic therapy because colchicine present exceeds the amount required by most patients.a

Manufacturer recommends initial dosage of colchicine 0.5 mg in fixed combination with probenecid 500 mg (1 tablet) daily for 1 week, then 1 tablet twice daily.146 If gouty arthritis is not controlled or if 24-hour uric acid excretion is ≤700 mg, increase daily dosage by 1 tablet every 4 weeks as tolerated (generally not exceeding 4 tablets [colchicine 2 mg and probenecid 2 g] daily).146

If acute attacks have been absent ≥6 months and serum urate concentrations are controlled, manufacturer recommends reducing dosage by 1 tablet every 6 months as long as serum urate concentrations remain controlled.146

Familial Mediterranean Fever Oral

Recommended dosage of colchicine depends on whether patient is receiving or has recently (within 14 days) received a moderate or potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system (see Table 4).152

Dosage can be increased in increments of 0.3 mg daily to the maximum recommended dosage or decreased in decrements of 0.3 mg daily in individuals who develop intolerable adverse effects.152

Table 4. Recommended Adult Dosage of Colchicine for Chronic Prophylactic Therapy of Familial Mediterranean Fever

Recent (within 14 days) or Concomitant Therapy	Maximum Recommended Colchicine Dosage
No recent or concomitant therapy with a moderate or potent CYP3A4 inhibitor or a P-glycoprotein inhibitor	1.2–2.4 mg daily (given as 1 dose or 2 divided doses)152
Potent CYP3A4 inhibitor (e.g., atazanavir, boceprevir, clarithromycin, ritonavir-boosted darunavir, ritonavir-boosted fosamprenavir, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, telithromycin, ritonavir-boosted tipranavir, lopinavir/ritonavir, the fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir)	0.6 mg daily (may be given as 0.3 mg twice daily)152 154 155 163 164
Moderate CYP3A4 inhibitor (e.g., aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir [without ritonavir], grapefruit juice, verapamil)	1.2 mg daily (may be given as 0.6 mg twice daily)152 154
P-glycoprotein inhibitor (e.g., cyclosporine, ranolazine)	0.6 mg daily (may be given as 0.3 mg twice daily)152

Special Populations

Hepatic Impairment

Contraindicated in patients with hepatic impairment who are receiving or have recently received therapy with a potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system.152 (See Contraindications under Cautions.)

Treatment of Gout Flare Oral

Mild to moderate hepatic impairment: Dosage adjustment is not needed, but monitor for adverse effects.152

Severe hepatic impairment: Dosage adjustment is not needed, but do not repeat courses of colchicine therapy until 2 weeks have elapsed.152 Consider alternative therapy for patients requiring repeat courses of therapy.152

Prophylactic Treatment of Recurrent Gout Flares Oral

Mild to moderate hepatic impairment: Dosage adjustment is not needed, but monitor for adverse effects.152

Severe hepatic impairment: Consider dosage reduction.152

Familial Mediterranean Fever Oral

Mild to moderate hepatic impairment: Dosage adjustment is not needed, but monitor for adverse effects.152

Severe hepatic impairment: Consider dosage reduction.152

Renal Impairment

Contraindicated in patients with renal impairment who are receiving or have recently received therapy with a potent CYP3A4 inhibitor or an inhibitor of the P-glycoprotein transport system.152 (See Contraindications under Cautions.)

Treatment of Gout Flare Oral

Use of colchicine for treatment of gout flare is not recommended in patients with renal impairment who are receiving the drug for prevention of gout flares.152

Mild to moderate renal impairment (Clcr 50–80 or 30–50 mL/minute, respectively): Dosage adjustment is not needed, but monitor for adverse effects.152

Severe renal impairment (Clcr <30 mL/minute): Dosage adjustment is not needed, but do not repeat courses of colchicine therapy until 2 weeks have elapsed.152 Consider alternative therapy for patients requiring repeat courses of therapy.152

Dialysis: 0.6 mg at first sign of gout flare.152 Do not repeat courses of colchicine therapy until 2 weeks have elapsed.152

Prophylactic Treatment of Recurrent Gout Flares Oral

Mild to moderate renal impairment (Clcr 50–80 or 30–50 mL/minute, respectively): Dosage adjustment is not needed, but monitor for adverse effects.152

Severe renal impairment (Clcr <30 mL/minute): Initial dosage is 0.3 mg daily; monitor closely if dosage is increased.152

Dialysis: Initial dosage is 0.3 mg twice weekly; monitor closely.152

Familial Mediterranean Fever Oral

Mild to moderate renal impairment (Clcr 50–80 or 30–50 mL/minute, respectively): Monitor for adverse effects; dosage adjustment may be needed.152

Severe renal impairment (Clcr <30 mL/minute) or dialysis: Initial dosage is 0.3 mg daily; dosage can be increased with careful monitoring.152

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function and concomitant disease and drug therapy.152

• If you have an allergy to colchicine or any other part of this medicine (Colcrys).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Kidney disease or liver disease.
• If you have liver or kidney problems and you take certain other drugs. Very bad and sometimes deadly side effects have happened in these people. There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine (Colcrys) with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid grapefruit and grapefruit juice.
• This medicine may have unsafe effects on the bone marrow. The bone marrow may not be able to make cells found in the blood as well as it used to for a few weeks. This may raise the chance of bleeding or infection. Talk with the doctor.
• Deadly overdoses have happened with this medicine (Colcrys) in adults and children. Keep away from children. Do not take more than you were told. If this drug is taken by accident, call your poison control center or get medical care right away.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine (Colcrys) while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

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.

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).

Patients with renal or hepatic impairment should not be given Colcrys in conjunction with P-gp or strong 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.

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

Tolerance, abuse or dependence with colchicine has not been reported.

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.

MEDICATION GUIDE

Colcrys
(KOL-kris)

(colchicine) tablets

Read the Medication Guide that comes with Colcrys before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about Colcrys when you start taking it and at regular checkups.

What is the most important information that I should know about Colcrys?

Colcrys can cause serious side effects or death if levels of Colcrys are too high in your body.

• Taking certain medicines with Colcrys can cause your level of Colcrys to be too high, especially if you have kidney or liver problems. • Tell your healthcare provider about all your medical conditions, including if you have kidney or liver problems. Your dose of Colcrys may need to be changed. • Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements. • Even medicines that you take for a short period of time, such as antibiotics, can interact with Colcrys and cause serious side effects or death. • Talk to your healthcare provider or pharmacist before taking any new medicine. • Especially tell your healthcare provider if you take:

• atazanavir sulfate (Reyataz) • cyclosporine (Neoral, Gengraf, Sandimmune) • fosamprenavir (Lexiva) with ritonavir • indinavir (Crixivan) • ketoconazole (Nizoral) • nefazodone (Serzone) • ritonavir (Norvir) • telithromycin (Ketek)

• clarithromycin (Biaxin) • darunavir (Prezista) • fosamprenavir (Lexiva) • itraconazole (Sporanox) • lopinavir/ritonavir (Kaletra) • nelfinavir mesylate (Viracept) • saquinavir mesylate (Invirase) • tipranavir (Aptivus)

Ask your healthcare provider or pharmacist if you are not sure if you take any of the medicines listed above. This is not a complete list of all the medicines that can interact with Colcrys.

• Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine. • Keep Colcrys out of the reach of children.

What is Colcrys?

Colcrys is a prescription medicine used to:

• prevent and treat gout flares in adults • treat familial Mediterranean fever (FMF) in adults and children age 4 or older

Colcrys is not a pain medicine, and it should not be taken to treat pain related to other conditions unless specifically prescribed for those conditions.

Who should not take Colcrys?

Do not take Colcrys if you have liver or kidney problems and you take certain other medicines. Serious side effects, including death, have been reported in these patients even when taken as directed. See "What is the most important information that I should know about Colcrys?"

What should I tell my healthcare provider before starting Colcrys?

See "What is the most important information that I should know about Colcrys?"

Before you take Colcrys, tell your healthcare provider about all your medical conditions, including if you:

• have liver or kidney problems. • are pregnant or plan to become pregnant. It is not known if Colcrys will harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant. • are breastfeeding or plan to breastfeed. Colcrys passes into your breast milk. You and your healthcare provider should decide if you will take Colcrys or breastfeed. If you take Colcrys and breastfeed, you should talk to your child's healthcare provider about how to watch for side effects in your child.

Tell your healthcare provider about all the medicines you take, including ones that you may only be taking for a short time, such as antibiotics. See "What is the most important information that I should know about Colcrys?" Do not start a new medicine without talking to your healthcare provider.

Using Colcrys with certain other medicines, such as cholesterol-lowering medications and digoxin, can affect each other, causing serious side effects. Your healthcare provider may need to change your dose of Colcrys. Talk to your healthcare provider about whether the medications you are taking might interact with Colcrys and what side effects to look for.

How should I take Colcrys?

• Take Colcrys exactly as your healthcare provider tells you to take it. If you are not sure about your dosing, call your healthcare provider. • Colcrys can be taken with or without food. • If you take too much Colcrys, go to the nearest hospital emergency room right away. • Do not stop taking Colcrys even if you start to feel better, unless your healthcare provider tells you. • Your healthcare provider may do blood tests while you take Colcrys. • If you take Colcrys daily and you miss a dose, then take it as soon as you remember. If it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time. Do not take two doses at the same time. • If you have a gout flare while taking Colcrys daily, report this to your healthcare provider.

What should I avoid while taking Colcrys?

• Avoid eating grapefruit or drinking grapefruit juice while taking Colcrys. It can increase your chances of getting serious side effects.

What are the possible side effects of Colcrys?

Colcrys can cause serious side effects or even cause death. See "What is the most important information that I should know about Colcrys?"

Get medical help right away if you have:

• Muscle weakness or pain • Numbness or tingling in your fingers or toes • Unusual bleeding or bruising • Increased infections • Feel weak or tired • Pale or gray color to your lips, tongue or palms of your hands • Severe diarrhea or vomiting

Gout Flares: The most common side effect of Colcrys in people who have gout flares is diarrhea.

FMF: The most common side effects of Colcrys in people who have FMF are abdominal pain, diarrhea, nausea and vomiting.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all of the possible side effects of Colcrys. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Colcrys?

• Store Colcrys at room temperature between 68°F and 77°F (20°C and 25°C). • Keep Colcrys in a tightly closed container. • Keep Colcrys out of the light.

Keep Colcrys and all medicines out of the reach of children.

General Information about Colcrys

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Colcrys for a condition for which it was not prescribed. Do not give Colcrys to other people, even if they have the same symptoms that you have. It may harm them. This Medication Guide summarizes the most important information about Colcrys. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Colcrys that is written for healthcare professionals.

For more information, go to www.Colcrys.com or call 1-877-825-3327.

What are the ingredients in Colcrys?

Active Ingredient: colchicine.

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.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Distributed by:
Takeda Pharmaceuticals America, Inc.
Deerfield, IL 60015

Revised: November 2012

Colcrys is a trademark of Takeda Pharmaceuticals U.S.A., Inc., registered with the U.S. Patent and Trademark Office and used under license by Takeda Pharmaceuticals America, Inc.

All other trademarks are the property of their respective owners.

COL243 R2

PRINCIPAL DISPLAY PANEL - 0.6 mg Tablet Bottle Label

30 TABLETS
NDC 64764-119-07

Colcrys®
(colchicine, USP) tablets
0.6 mg

PHARMACIST:
PLEASE DISPENSE WITH
MEDICATION GUIDE ATTACHED

Takeda
Rx only

Colcrys  colchicine tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:64764-119 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Colchicine (Colchicine) Colchicine 0.6 mg

Inactive Ingredients Ingredient Name Strength carnauba wax   FD&C blue no. 2   FD&C red no. 40   hypromelloses   lactose monohydrate   magnesium stearate   cellulose, microcrystalline   polydextrose   polyethylene glycols   starch, corn   sodium starch glycolate type A potato   titanium dioxide   triacetin

Product Characteristics Color PURPLE (Film Coated) Score 2 pieces Shape CAPSULE (capsule-shaped) Size 8mm Flavor Imprint Code AR;374 Contains

Packaging # Item Code Package Description 1 NDC:64764-119-07 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC 2 NDC:64764-119-06 60 TABLET, FILM COATED in 1 BOTTLE, PLASTIC 3 NDC:64764-119-01 100 TABLET, FILM COATED in 1 BOTTLE, PLASTIC 4 NDC:64764-119-03 250 TABLET, FILM COATED in 1 BOTTLE, PLASTIC 5 NDC:64764-119-05 500 TABLET, FILM COATED in 1 BOTTLE, PLASTIC 6 NDC:64764-119-10 1000 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022352 09/01/2009

Labeler - Takeda Pharmaceuticals America, Inc. (830134016)

Revised: 12/2015   Takeda Pharmaceuticals America, Inc.

Serious drug interactions can occur when certain medicines are used together with Colcrys. Tell each of your healthcare providers about all medicines you use now, and any medicine you start or stop using.

Before taking Colcrys, tell your doctor if you have liver or kidney disease, heart disease, a stomach ulcer, ulcerative colitis, Crohn's disease, intestinal bleeding, or any other severe gastrointestinal disorder.

If you take Colcrys over a long period of time, your blood may need to be tested on a regular basis. Do not miss any scheduled appointments.

Call your doctor at once if you have a serious side effect such as muscle pain or weakness, numbness or tingly feeling in your fingers or toes, severe vomiting or diarrhea, easy bruising or bleeding, feeling weak or tired, flu symptoms, blood in your urine, urinating less than usual or not at all, or a pale or gray appearance of your lips, tongue, or hands.

Grapefruit and grapefruit juice may interact with colchicine and lead to unwanted side effects. Avoid the use of grapefruit products while taking Colcrys.

Get emergency medical help if you have signs of an allergic reaction to Colcrys: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• muscle pain or weakness;

• numbness or tingly feeling in your fingers or toes;

• pale or gray appearance of your lips, tongue, or hands;

• severe or ongoing vomiting or diarrhea;

• fever, chills, body aches, flu symptoms; or

• easy bruising, unusual bleeding, feeling weak or tired.

Common Colcrys side effects may include:

• nausea, vomiting, stomach pain; or

• diarrhea.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Applies to colchicine: oral capsule, oral tablet

Along with its needed effects, colchicine (the active ingredient contained in Colcrys) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking colchicine:

More common

• Diarrhea
• nausea or vomiting
• stomach pain

Rare

• Black, tarry stools
• blood in the urine or stools
• burning, "crawling", or tingling feeling in the skin
• difficulty with breathing when exercising
• fever with or without chills
• headache
• large, hive-like swellings on the face, eyelids, mouth, lips, or tongue
• muscle weakness
• numbness in the fingers or toes (usually mild)
• pain
• peeling of the skin
• pinpoint red spots on the skin
• redness
• skin rash or hives
• sores, ulcers, or white spots on the lips or in the mouth
• sore throat
• swelling
• tenderness
• unusual bleeding or bruising
• unusual tiredness or weakness

Get emergency help immediately if any of the following symptoms of overdose occur while taking colchicine:

Symptoms of overdose

• Bleeding
• burning feeling in the stomach, throat, or skin
• convulsions (seizures)
• diarrhea (severe or bloody)
• fast, shallow breathing
• muscle weakness (very severe)
• nausea, stomach pain, or vomiting (severe)

Some side effects of colchicine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• Hair loss
• loss of appetite