What are the common side effects of colchicine. How does colchicine work for gout and familial Mediterranean fever. What are the serious risks and drug interactions associated with colchicine use. How should colchicine be taken safely and effectively.

Understanding Colchicine: A Powerful Medication for Gout and Familial Mediterranean Fever

Colchicine is a prescription medication used primarily to treat and prevent gout attacks, as well as manage symptoms of familial Mediterranean fever (FMF). This drug belongs to a class of medications known as anti-gout agents, though its exact mechanism of action is not fully understood. Researchers believe it may work by inhibiting certain immune cells responsible for causing inflammation and pain in the body.

Available in both tablet and capsule forms, colchicine can be found under brand names such as Colcrys and Mitigare, as well as in generic versions. While it’s an effective treatment for many patients, it’s crucial to understand its proper use, potential side effects, and important warnings before starting this medication.

How Colchicine Works to Combat Gout and FMF Symptoms

Gout is a form of arthritis caused by the buildup of uric acid crystals in the joints, leading to severe pain and inflammation. Colchicine helps alleviate these symptoms by:

• Reducing the body’s inflammatory response to uric acid crystals
• Decreasing the migration of neutrophils (a type of white blood cell) to affected areas
• Potentially interfering with the formation of uric acid crystals

In the case of familial Mediterranean fever, colchicine works to prevent or reduce the frequency of inflammatory attacks that characterize this genetic condition. These attacks can affect various parts of the body, including joints, the abdomen, and the lungs.

Is colchicine effective for both acute gout attacks and prevention?

Yes, colchicine can be used for both purposes. For acute gout attacks, it’s typically administered as soon as symptoms appear to reduce pain and inflammation. As a preventive measure, lower doses may be prescribed to reduce the frequency and severity of future gout flares.

Common Side Effects of Colchicine: What Patients Should Expect

While colchicine can be highly effective, it’s not without potential side effects. The most common side effects reported by patients include:

1. Abdominal pain
2. Diarrhea
3. Nausea
4. Vomiting
5. Constipation

These side effects are often mild and may subside as the body adjusts to the medication. However, if they persist or become severe, it’s important to consult with a healthcare provider.

Can the gastrointestinal side effects of colchicine be managed?

In many cases, yes. Some strategies to minimize gastrointestinal discomfort include taking the medication with food, staying well-hydrated, and potentially adjusting the dosage under medical supervision. Your doctor may also recommend over-the-counter remedies to alleviate specific symptoms.

Serious Risks and Warnings: When Colchicine Requires Caution

While colchicine is generally safe when used as prescribed, there are several serious risks and warnings that patients and healthcare providers must be aware of:

• Overdose risk: Taking more colchicine than prescribed can lead to severe toxicity and even death.
• Blood disorders: Colchicine may affect blood cell production, potentially increasing the risk of infections or bleeding.
• Muscle damage: Long-term use (6 months or more) can cause muscle damage, particularly in older adults or those taking certain cholesterol medications.
• Interactions with other medications: Colchicine can interact dangerously with various drugs, including certain antifungals and HIV medications.

How can patients reduce the risk of serious colchicine side effects?

To minimize risks, patients should:
1. Never exceed the prescribed dose
2. Inform their doctor of all medications, supplements, and medical conditions
3. Undergo regular blood tests to monitor for potential blood disorders
4. Report any unusual symptoms promptly, especially muscle weakness or pain
5. Avoid grapefruit and grapefruit juice, which can increase colchicine levels in the body

Drug Interactions: Medications to Avoid While Taking Colchicine

Colchicine can interact with numerous medications, potentially leading to increased side effects or reduced effectiveness. Some key drug interactions to be aware of include:

• Antifungal medications (e.g., ketoconazole, itraconazole)
• HIV medications (e.g., indinavir, atazanavir, ritonavir)
• Certain antibiotics (e.g., clarithromycin, erythromycin)
• Cholesterol-lowering drugs (statins)
• Some blood pressure medications

This list is not exhaustive, and it’s crucial to inform your healthcare provider about all medications you’re taking, including over-the-counter drugs and supplements.

What should patients do if they are taking a medication that interacts with colchicine?

If you’re taking a medication that interacts with colchicine, don’t stop either medication without consulting your doctor. They may adjust dosages, recommend alternative treatments, or closely monitor you for potential side effects. In some cases, the benefits of combination therapy may outweigh the risks when managed carefully.

Proper Dosage and Administration: Maximizing Colchicine’s Benefits

The correct dosage of colchicine varies depending on the condition being treated and individual patient factors. For gout, typical dosing might include:

• For acute attacks: 1.2 mg at the first sign of a flare, followed by 0.6 mg one hour later
• For prevention: 0.6 mg once or twice daily

For familial Mediterranean fever, dosing is often based on age and body weight, with adults typically taking between 1.2 to 2.4 mg daily.

It’s crucial to follow your doctor’s instructions precisely and never adjust your dose without medical supervision.

Should colchicine be taken with food?

Colchicine can be taken with or without food. However, taking it with food may help reduce gastrointestinal side effects in some patients. If you experience nausea or stomach discomfort, try taking your dose with a meal and see if it helps alleviate these symptoms.

Special Populations: Considerations for Certain Patient Groups

Colchicine use requires special consideration in certain populations:

• Elderly patients: May be more susceptible to side effects and may require lower doses
• Patients with kidney or liver disease: May need dose adjustments due to altered drug metabolism
• Pregnant women: Should only use colchicine if the potential benefit justifies the potential risk to the fetus
• Breastfeeding mothers: Should discuss the risks and benefits with their healthcare provider

Can colchicine be used safely in patients with decreased kidney function?

Colchicine can be used in patients with kidney disease, but dose adjustments are often necessary. These patients may require lower doses or less frequent administration to prevent toxicity. Close monitoring by a healthcare provider is essential in these cases.

Long-Term Use of Colchicine: Benefits and Potential Risks

For many patients with chronic gout or familial Mediterranean fever, long-term use of colchicine may be necessary. While this can effectively manage symptoms and prevent flares, it also comes with potential risks:

• Increased risk of muscle damage (rhabdomyolysis)
• Potential for blood disorders
• Risk of drug interactions over time as patients’ medication regimens change

Regular check-ups and blood tests are crucial for patients on long-term colchicine therapy to monitor for these potential complications.

How often should patients on long-term colchicine therapy have follow-up appointments?

The frequency of follow-up appointments can vary based on individual patient factors, but generally, patients on long-term colchicine therapy should have check-ups at least every 3-6 months. These appointments may include physical examinations, blood tests, and discussions about any new symptoms or concerns.

Alternative Treatments: When Colchicine Isn’t the Right Choice

While colchicine is effective for many patients, it’s not the only option for managing gout or familial Mediterranean fever. Alternative treatments may include:

• For gout:
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Corticosteroids
  • Uric acid-lowering medications (e.g., allopurinol, febuxostat)
• For familial Mediterranean fever:
  • Anakinra
  • Canakinumab

The choice of treatment depends on various factors, including the patient’s medical history, other medications, and individual response to treatment.

When might a doctor recommend switching from colchicine to an alternative treatment?

A healthcare provider might suggest switching from colchicine to an alternative treatment if:
1. The patient experiences severe or persistent side effects
2. Colchicine proves ineffective in managing symptoms
3. There are concerning drug interactions with other necessary medications
4. Long-term use poses unacceptable risks for the individual patient
5. A different treatment approach might offer better symptom control or quality of life

Colchicine remains a valuable tool in the management of gout and familial Mediterranean fever. Its ability to reduce inflammation and prevent painful flares has made it a mainstay of treatment for these conditions. However, like all medications, it comes with potential risks and side effects that must be carefully weighed against its benefits.

Patients considering or currently taking colchicine should maintain open communication with their healthcare providers, report any unusual symptoms promptly, and adhere strictly to prescribed dosages. With proper use and monitoring, colchicine can significantly improve quality of life for many individuals suffering from gout or familial Mediterranean fever.

As research continues, our understanding of colchicine’s mechanisms and optimal use may evolve, potentially leading to even more effective and safer treatment strategies in the future. For now, this ancient yet powerful medication continues to play a crucial role in managing these challenging conditions, offering relief to countless patients worldwide.

Side Effects, Dosage, Uses & More

Highlights for colchicine

1. Colchicine oral tablet is available as both a generic and brand-name drug. Brand name Colcrys.
2. It also comes in capsules that are also available as both a generic and brand-name drug. Brand name: Mitigare.
3. Colchicine is used to prevent or treat the symptoms of gout. Gout is caused when a substance called uric acid forms painful crystals in the body, typically in the joints. This drug is also used to treat familial Mediterranean fever. This condition can cause inflammation (pain and swelling) in the joints, lungs, or abdomen (stomach area).

• Overdose warning: Taking too much colchicine can be serious enough to cause death. Never take more of this drug than your doctor prescribes.
• Blood disorders warning: Colchicine may cause your body to produce fewer blood cells of different types. This could raise your risk of infection or bleeding because some of these blood cells fight infection and help form blood clots. If you have any blood disorders, talk with your doctor about whether this drug is safe for you.
• Muscle damage warning: Colchicine can damage your muscles if you take it for 6 months or longer. Your risk is higher if you’re a senior. Taking other drugs that cause muscle damage, such as cholesterol medications, may increase this risk. Talk with your doctor before taking colchicine if you’re also taking cholesterol drugs.

Colchicine oral tablet is a prescription drug that’s available as the brand-name drug Colcrys. It’s also available as a generic drug. Generic drugs usually cost less. In some cases, they may not be available in every strength or form as the brand-name version.

Colchicine is also available in capsules. The capsules are available as the brand-name drug Mitigare. The capsules are also available as generic drugs.

Why it’s used

Colchicine is used to treat the symptoms of gout or familial Mediterranean fever. Familial Mediterranean fever is passed down in families. It can cause inflammation (pain and swelling) in the joints, lungs, or abdomen (stomach area).

Colchicine is also used to prevent the symptoms of gout. Gout is caused when a substance called uric acid forms painful crystals in the body, typically in the joints.

Colchicine may be used as part of a combination therapy. This means you may need to take it with other medications.

How it works

Colchicine belongs to a class of drugs called anti-gout medications. A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.

The way colchicine works is not fully understood. It may prevent some of the body’s immune cells from causing pain and inflammation.

Colchicine oral tablet doesn’t cause drowsiness. However, it may cause other side effects.

More common side effects

The more common side effects of colchicine can include:

• pain in the abdomen (stomach area)
• constipation
• diarrhea
• nausea
• vomiting

If these effects are mild, they may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk to your doctor or pharmacist.

Serious side effects

Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

• Rhabdomyolysis (muscle damage). This serious syndrome can cause kidney disease, and can be life-threatening. Symptoms can include:
  • muscle weakness
  • muscle pain

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information is not a substitute for medical advice. Always discuss possible side effects with a healthcare provider who knows your medical history.

Colchicine oral tablet can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Drugs you should not use with colchicine

Taking certain drugs with colchicine can cause dangerous effects in the body. Examples of drugs you should not use with colchicine include:

• Antifungal drugs, such as ketoconazole or itraconazole. Using these drugs with colchicine can result in very high levels of colchicine in your body. This raises your risk of side effects, such as severe muscle damage.
• HIV drugs, such as indinavir, atazanavir, nelfinavir, saquinavir, or ritonavir. Using these drugs with colchicine can result in very high levels of colchicine in your body. This raises your risk of side effects, such as severe muscle damage.
• Antibiotics, such as clarithromycin or telithromycin. Using these drugs with colchicine can result in very high levels of colchicine in your body. This raises your risk of side effects, such as severe muscle damage.
• Antidepressants, such as nefazodone. Using these drugs with colchicine can result in very high levels of colchicine in your body. This raises your risk of side effects, such as severe muscle damage.

Interactions that increase your risk of side effects

Taking colchicine with certain medications raises your risk of side effects from colchicine. Examples of these drugs include:

• Cholesterol drugs, such as atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin, fibrates, or gemfibrozil. Increased side effects can include serious muscle damage. Your doctor may reduce your dosage of colchicine to avoid this.
• Digoxin, an antiarrhythmic drug. Increased side effects can include serious muscle damage. Your doctor may reduce your dosage of colchicine to avoid this.
• Heart drugs, such as verapamil or diltiazem. Increased side effects can include stomach pain, constipation, diarrhea, nausea, or vomiting. Your doctor may reduce your dosage of colchicine to avoid these problems.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

Colchicine oral tablet comes with several warnings.

Allergy warning

Colchicine can cause a severe allergic reaction. Symptoms can include:

• trouble breathing
• swelling of your throat or tongue

If you have an allergic reaction, call your doctor or local poison control center right away. If your symptoms are severe, call 911 or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).

Food interactions

Grapefruit or grapefruit juice may make your body less able to process colchicine. This can increase levels of the drug in your body and result in more side effects. Don’t eat grapefruit or drink grapefruit juice if you’re taking this drug.

Warnings for people with certain health conditions

For people with kidney disease: Your kidneys clear this drug from your body. If they’re not working well, levels of this drug may build up in your body, raising your risk of side effects. To help avoid this, your doctor may lower your dose of colchicine.

For people with liver disease: Your liver processes this drug in your body. If it’s not working well, levels of this drug may build up in your body, raising your risk of side effects. To help avoid this, your doctor may lower your dose of colchicine.

Warnings for other groups

For pregnant women: Colchicine is a category C pregnancy drug. That means two things:

1. Research in animals has shown adverse effects to the fetus when the mother takes the drug.
2. There haven’t been enough studies done in humans to be certain how the drug might affect the fetus.

Talk to your doctor if you’re pregnant or planning to become pregnant. This drug should only be used if the potential benefit justifies the potential risk to the fetus. Call your doctor right away if you become pregnant while taking this drug.

For women who are breastfeeding: Colchicine may pass into breast milk and may cause side effects in a child who is breastfed. Talk to your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this medication.

For seniors: The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects.

For children: It hasn’t been established that colchicine is safe and effective in the treatment of gout in children.

This dosage information is for colchicine oral tablet. All possible dosages and drug forms may not be included here. Your dosage, drug form, and how often you take the drug will depend on:

• your age
• the condition being treated
• how severe your condition is
• other medical conditions you have
• how you react to the first dose

Forms and strengths

Brand: Colcrys

• Form: oral tablet
• Strengths: 0. 6 mg

Brand: Mitigare

• Form: oral capsule
• Strengths: 0.6 mg

Generic: colchicine

• Form: oral tablet
• Strengths: 0.6 mg

• Form: oral capsule
• Strengths: 0.6 mg

Dosage for the treatment of gout flares

Adult dosage (ages 16–64 years):

Oral tablet (Colcrys).Typical dosage is 1.2 mg taken at the first sign of a gout flare, followed by 0.6 mg one hour later.

Child dosage (ages 0–15 years):

This medication hasn’t been studied for the treatment or prevention of gout in children. It shouldn’t be used in people younger than 16 years for these purposes.

Senior dosage (ages 65 years and older):

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects.

Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Dosage for prevention of gout flares

Adult dosage (ages 16–64 years):

• Oral tablet (Colcrys): Typical dosage is 0.6 mg, taken once or twice per day.
• Oral capsule (Mitigare): Typical dosage is 0.6 mg, taken once or twice per day.

Child dosage (ages 0–15 years):

This medication hasn’t been studied for the treatment or prevention of gout in children. It shouldn’t be used in people younger than 16 years for these purposes.

Senior dosage (ages 65 years and older):

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects. Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Dosage for familial Mediterranean fever

Adult dosage (ages 16–64 years):

Oral tablet (Colcrys): Typical dosage is 1.2–2.4 mg taken once per day.

Child dosage (ages 12–15 years):

Oral tablet (Colcrys): Typical dosage is 1.2–2.4 mg taken once per day.

Child dosage (ages 6–11 years):

Oral tablet (Colcrys): Typical dosage is 0.9–1.8 mg taken once per day.

Child dosage (ages 4–5 years):

Oral tablet (Colcrys): Typical dosage is 0.3–1.8 mg, taken once per day.

Child dosage (ages 0–3 years):

This medication shouldn’t be used in children younger than 3 years.

Senior dosage (ages 65 years and older):

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects. Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always speak with your doctor or pharmacist about dosages that are right for you.

Colchicine oral tablet is used for long-term treatment of familial Mediterranean fever and prevention of gout flares. It is used for short-term treatment of gout flares. It comes with risks if you don’t take it as prescribed.

If you stop taking the drug or don’t take it at all: The symptoms of your condition may worsen.

If you miss doses or don’t take the drug on schedule: Your medication may not work as well or may stop working completely.

If you take too much: You could have dangerous levels of the drug in your body. Symptoms of an overdose of this drug can include:

• muscle pain
• muscle weakness
• nausea
• vomiting
• diarrhea

If you think you’ve taken too much of this drug, call your doctor or local poison control center. If your symptoms are severe, call 911 or go to the nearest emergency room right away.

What to do if you miss a dose: Take your dose as soon as you remember. But if you remember just a few hours before your next scheduled dose, take only one dose. Never try to catch up by taking two doses at once. This could result in dangerous side effects.

How to tell if the drug is working:

• For treatment of gout flares: You should have decreased pain, tenderness, or swelling.
• For prevention of gout flares: Your gout flares should occur less often.
• For treatment of familial Mediterranean fever: Your painful inflammation should be reduced.

Keep these considerations in mind if your doctor prescribes colchicine oral tablets for you.

General

• You can take colchicine with or without food.
• Take this drug at the time(s) recommended by your doctor.
• You can cut or crush the tablet (Colcrys).
• Not every pharmacy stocks this drug. When filling your prescription, be sure to call ahead.

Storage

• Store colchicine at room temperature between 68°F and 77°F (20°C and 25°C).
• Keep this drug away from light.
• Don’t store this medication in moist or damp areas, such as bathrooms.

Refills

A prescription for this medication is refillable. You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.

Travel

When traveling with your medication:

• Always carry your medication with you. When flying, never put it into a checked bag. Keep it in your carry-on bag.
• Don’t worry about airport x-ray machines. They can’t hurt your medication.
• You may need to show airport staff the pharmacy label for your medication. Always carry the original prescription-labeled box with you.
• Don’t put this medication in your car’s glove compartment or leave it in the car. Be sure to avoid doing this when the weather is very hot or very cold.

Clinical monitoring

Your doctor may monitor your uric acid level. This can help make sure it’s within the range your doctor feels is best for you. It can also help your doctor know if your medication is working.

Your doctor may also check for side effects. This can help make sure you stay safe while you take this drug. Your doctor may do blood tests to check your:

• Blood counts. Blood count tests can tell if colchicine is making your body less able to produce certain blood cells.
• Liver and muscle function. These tests will measure your blood levels of certain products from your liver and muscles. The results can help your doctor find out if colchicine is causing damage to your liver or muscles.

Hidden costs

You may need to have certain blood tests during your treatment with colchicine. The cost of these tests depends on your insurance coverage.

Insurance

Many insurance companies require a prior authorization for this drug. This means your doctor may need to get approval from your insurance company before your insurance company will pay for the prescription.

There are other drugs available to treat your condition. Some may be better suited for you than others. Talk to your doctor about other drug options that may work for you.

Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

Colchicine – StatPearls – NCBI Bookshelf

Continuing Education Activity

Colchicine has FDA approval for gout prophylaxis and treatment of acute gouty flares. It also has approval for the treatment of familial Mediterranean fever. Colchicine has been used off-label to treat several other conditions, including hepatic cirrhosis, primary biliary cirrhosis, and pseudogout. Colchicine has primarily anti-inflammatory properties. This activity reviews the mechanism of action, adverse event profile, toxicity, dosing, pharmacodynamics, and monitoring of colchicine for gout and other indications for interprofessional team members.

Objectives:

• Identify the various hypothesized mechanisms of action of colchicine.

• Outline the primary and secondary indications for colchicine.

• Review the potential adverse events profile of colchicine.

• Summarize the importance of interprofessional communication improving care coordination among the interprofessional team when initiating antibiotic therapy with colchicine.

Access free multiple choice questions on this topic.

Indications

Colchicine has FDA approval for gout prophylaxis and treatment of acute gouty flares. It also has approval for the treatment of familial Mediterranean fever.[1][2]

While not approved for the following conditions, colchicine has been used off-label to treat the following:

• Acute and recurrent pericarditis

• Prevention of post pericardial syndrome

• Primary biliary cirrhosis

• Hepatic cirrhosis

• Dermatitis herpetiformis

• Paget’s disease of bone

• Chronic immune thrombocytopenia and idiopathic thrombocytopenic purpura

• Pseudogout

• Idiopathic pulmonary fibrosis

Recommendations for colchicine do not include prophylaxis or treatment of gout flares in the pediatric population. It can be used to treat familial Mediterranean fever in children four years of age and older.

Mechanism of Action

Colchicine has primarily anti-inflammatory properties. It disrupts cytoskeletal functions by inhibiting beta-tubulin polymerization into microtubules, preventing activation, degranulation, and migration of neutrophils associated with mediating some gout symptoms. Colchicine does not inhibit phagocytosis of uric acid crystals, but it does seem to prevent the release of an inflammatory glycoprotein from phagocytes. Colchicine blocks metaphase due to two separate anti-mitotic effects; disruption of mitotic spindle formation and disruption of the sol-gel formation. The toxic effects of colchicine are related to this anti-mitotic activity within proliferating tissue such as skin, hair, and bone marrow.[3][4]

The mechanism of action of colchicine in the treatment of familial Mediterranean fever is less well understood; it may interfere with intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediate the activation or interleukin-1-beta.

Administration

Colchicine is available as a tablet, capsule, and gel.  In tablet form, it is available in a 0.6 mg tablet. It is available in a 0.6 mg capsule. There is a topical gel form of Colchicum autumnale.

Colchicine administration is usually via the oral route, and the use of the topical gel is rare. Due to toxicity, the injectable form is no longer available in the United States.

Dosing

Prophylaxis of gout: Colchicine dosing is 0.6 mg once or twice a day in adults and adolescents older than 16 years old; the maximum dose is 1.2 mg per day.

Treatment of acute gout flare: 1.2 mg at the first sign of a gout flare followed by 0.6 mg one hour later.

Familial Mediterranean fever: 1.2 mg to 2.4 mg for adults and children over 12 years old; the daily dose gets administered in one or two doses.

Adverse Effects

The most common adverse reactions are related to the gastrointestinal tract. Diarrhea is the most commonly reported symptom (23%), followed by vomiting (17%) and nausea (4% to 17%). There are reports of central nervous system symptoms such as fatigue and headache. Endocrine and metabolic conditions such as gout have been reported when using colchicine, as has pharyngolaryngeal pain.[5][6]

While less common, the following adverse reactions have been reported with colchicine and are thought to be reversible upon discontinuation of the medication or lowering the dose:

• Neurologic – sensorimotor neuropathy

• Dermatologic – alopecia, maculopapular rash, purpura, rash

• Gastrointestinal – abdominal cramping, abdominal pain, lactose intolerance

• Hematologic – leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia

• Hepatobiliary – elevated AST, elevated ALT

• Musculoskeletal – myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis.

• Reproductive – azoospermia, oligospermia

Drug Interactions

Colchicine is a substrate for the efflux transporter P-glycoprotein. Of the cytochrome P450 enzymes tested, CYP3A4 is the primary enzyme involved in the metabolism of colchicine. If administering colchicine with drugs that inhibit P-glycoprotein, most of which also inhibit CYP3A4 increased concentrations of colchicine are likely, and there are reports of fatal drug interactions.

When co-administered with drugs known to inhibit CYP3A4 and/or P-glycoprotein, the colchicine dose should be adjusted.

The following medications should be used with caution when co-administered with colchicine:

Potent CYP3A4 inhibitors – atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin

Moderate CYP3A4 inhibitors  – amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, and verapamil

P-glycoprotein inhibitors – cyclosporine, ranolazine

Food Interactions

Grapefruit juice may increase the serum concentration of colchicine.   Therefore, the dose of colchicine may require adjustment when taking grapefruit juice. Patients should avoid grapefruit juice if they have hepatic or renal impairment and are taking colchicine.

Contraindications

Contraindications

Colchicine metabolism is via the liver and other tissues and is dependent on the P-glycoprotein transport and CYP 384 isoenzymes. It is eliminated unchanged in the urine and via metabolism. P-glycoprotein and CYP3A4 inhibitors can decrease the metabolism of colchicine and therefore result in increased plasma levels of colchicine. Impairment of renal and hepatic function can decrease the metabolism and clearance of colchicine and result in elevated concentrations. These elevated levels can cause adverse reactions, including death.[7][8][9]

The concomitant use of a P-glycoprotein or CYP3A4 inhibitor and colchicine in the presence of renal or hepatic impairment is contraindicated. Dose adjustments or alternative therapies are considerations for patients with renal or hepatic impairment who are not taking a P-glycoprotein or CYP3A4 inhibitor.

Precautions

Biliary obstruction, renal impairment, hepatic disease, and renal disease

Dosage adjustments are necessary for patients with normal renal and hepatic function, taking interacting medications, and patients with either renal or hepatic impairment.  Patients with renal impairment or elevated plasma concentrations of colchicine due to renal disease can develop myeloneuropathy characterized by proximal weakness, elevated serum creatinine, and possibly rhabdomyolysis.  Colchicine gets eliminated through biliary pathways. Therefore, patients with hepatic disease or hepatic biliary obstruction should have alternate therapies considered.

Alcoholism, Gastrointestinal Disease

The risk for colchicine-induced gastrointestinal tissue damage may be higher in patients with preexisting alcoholism or gastrointestinal disease. Therefore, the clinician should consider adjustments in dosing.

Bone Marrow Suppression

Colchicine taken over an extended period has correlations with bone marrow suppression. Therefore, colchicine should be used cautiously in patients with preexisting bone marrow suppression. Therapeutic doses of colchicine have reportedly correlated with myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, and aplastic anemia. Also, colchicine may worsen these types of blood dyscrasias.

Dialysis

Dialysis does not remove colchicine; patients receiving dialysis required a dosage reduction secondary to their impaired renal function.

Dental Disease

Colchicine can cause myelosuppression, and therefore, its use requires caution with patients with dental disease. The recommendation is that the dental work is performed before initiating therapy with colchicine or delayed until blood count returned to normal.

Neuromuscular Toxicity

Reports exist of colchicine-induced neuromuscular toxicity and rhabdomyolysis with chronic treatment in therapeutic doses of colchicine. Patients with renal impairment and elderly patients, even those with normal renal and hepatic function, are at increased risk. Concomitant use of colchicine and atorvastatin, simvastatin, pravastatin, fluvastatin, gemfibrozil, and fenofibric acid or cyclosporine may potentiate the development of myopathy.

Geriatric

With or without preexisting renal or hepatic impairment, geriatric patients have an increased risk of neuromuscular toxicity and rhabdomyolysis when taking colchicine. Caution is necessary, and a dose adjustment may be appropriate when dosing colchicine in geriatric patients.

Pregnancy

Colchicine classifies as pregnancy category C. Colchicine use during pregnancy should only be if the potential benefit to the mother justifies the possible risk to the fetus.

Breast Feeding

Colchicine is excreted into human breast milk. Colchicine can alter gastrointestinal cell renewal and permeability; however, there are no reported adverse effects in breastfed human infants. The American Academy of Pediatrics considers colchicine usually compatible with breastfeeding.

Monitoring

There is no blood test available to determine colchicine serum concentration. In patients with hepatic or renal impairment or disease, or patients taking a P-glycoprotein or CYP3A4 inhibitor, parameters that require monitoring include a complete blood count and renal and hepatic function tests.

Toxicity

The precise dose of colchicine that results in significant toxicity is unknown. Toxicity has occurred after the ingestion of a dose as low as 7 mg over four days, while other patients survived after taking more than 60 mg. In a review of 150 patients with a colchicine overdose, there was 100% mortality in those who ingested over 0.8 mg/kg.

Acute colchicine toxicity usually begins within 24 hours of ingestion and includes gastrointestinal symptoms, eventually leading to significant fluid loss and volume depletion. In this initial phase, peripheral leukocytosis may also be present. Life-threatening complications often occur 24 to 72 hours after drug administration and are usually attributed to multi-organ failure. Death is typically a result of respiratory depression and cardiovascular collapse.

Treatment of colchicine poisoning should start with gastric lavage and measures to prevent shock.  Otherwise, treatment is symptomatic and supportive. There is no known specific antidote, and colchicine is not effectively removed by dialysis.

Enhancing Healthcare Team Outcomes

While the use of colchicine has declined over the past two decades, physicians, nurses, and pharmacists still need to know about the dosing requirements and restrictions. Before administering colchicine to any patient, one must be aware of the current dosing recommendations and the patient’s age, renal, and liver function. At least 30% of all colchicine-related medication errors are related to incorrect dosing regimens. Also, it is important to know what else the patient is taking to prevent lethal drug interactions. One should also ensure that the patient knows how to take colchicine and that it is not an analgesic agent. Many errors have occurred with colchicine simply because patients did not know that the drug effects might take 24 to 36 hours to develop, and the patient should avoid taking repeated doses within this period. Further,  patients should understand to discontinue colchicine if they develop gastrointestinal side effects or paresthesias. Finally, all patients require education on how to safely store colchicine in the home, away from the reach of children. Colchicine has a very high mortality rate within a short time when ingesting a high dose.[10][1]

Given the above, prescribers should work closely with the pharmacist and the nursing staff when initiating colchicine therapy. All three disciplines need to provide patient counseling so that the crucial points receive emphasis. The prescriber and pharmacist should review all patient parameters and make sure dose adjustments are not necessary. Nurses should be familiar with signs of toxicity or adverse events to monitor the patient and inform the prescriber should any issues arise. With an interprofessional team approach, colchicine can still be an effective agent in specific cases. [Level 5]

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References

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Thompson PL, Nidorf SM. Colchicine: an affordable anti-inflammatory agent for atherosclerosis. Curr Opin Lipidol. 2018 Dec;29(6):467-473. [PubMed: 30320614]

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Vaidya K, Martínez G, Patel S. The Role of Colchicine in Acute Coronary Syndromes. Clin Ther. 2019 Jan;41(1):11-20. [PubMed: 30185392]

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Sun M, Biggs R, Hornick J, Marko JF. Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold. Chromosome Res. 2018 Dec;26(4):277-295. [PMC free article: PMC6370136] [PubMed: 30143891]

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Schenone AL, Menon V. Colchicine in Pericardial Disease: from the Underlying Biology and Clinical Benefits to the Drug-Drug Interactions in Cardiovascular Medicine. Curr Cardiol Rep. 2018 Jun 14;20(8):62. [PubMed: 29904810]

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Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Feb 15, 2023. Colchicine. [PubMed: 30000272]

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Gürkan A, Oğuz MM, Boduroğlu Cengiz E, Şenel S. Dermatologic Manifestations of Colchicine Intoxication. Pediatr Emerg Care. 2018 Jul;34(7):e131-e133. [PubMed: 29912088]

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Pascart T, Lioté F. Gout: state of the art after a decade of developments. Rheumatology (Oxford). 2019 Jan 01;58(1):27-44. [PubMed: 29547895]

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Abhishek A. Managing Gout Flares in the Elderly: Practical Considerations. Drugs Aging. 2017 Dec;34(12):873-880. [PubMed: 29214511]

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Imazio M, Gaita F. Acute and Recurrent Pericarditis. Cardiol Clin. 2017 Nov;35(4):505-513. [PubMed: 29025542]

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Lazaros G, Imazio M, Brucato A, Vlachopoulos C, Lazarou E, Vassilopoulos D, Tousoulis D. The Role of Colchicine in Pericardial Syndromes. Curr Pharm Des. 2018;24(6):702-709. [PubMed: 29336245]

Disclosure: Nazia Sadiq declares no relevant financial relationships with ineligible companies.

Disclosure: Kenneth Robinson declares no relevant financial relationships with ineligible companies.

Disclosure: Jamie Terrell declares no relevant financial relationships with ineligible companies.

Description COLCHICIN indications, dosages, contraindications of the active substance COLCHICIN

Colchicine – description of the substance, pharmacology, use, contraindications, formula

Contents

• Structural formula

• Russian name

• English title

• Latin name

• chemical name

• Gross formula

• Pharmacological group of the substance Colchicine

• Nosological classification

• CAS code

• pharmachologic effect

• Characteristic

• Pharmacology

• The use of the substance Colchicine

• Contraindications

• Side effects of Colchicine

• Interaction

• Overdose

• Dosage and administration

• Precautionary measures

• special instructions

• Trade names with the active ingredient Colchicine

Structural formula

Russian name

Colchicine

English name

Colchicine

Latin name

77 Colchicini)

Chemical name

(S)-N-(5,6,7 ,9-Tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen- 7-yl)acetamide

Gross formula

C ₂₂ H ₂₅ NO ₆

Pharmacological group of the substance Colchicine

Drugs affecting the metabolism of uric acid

Nosological classification

ICD-10 code list

CAS code

64-86-8

Pharmacological action

Pharmacological action 90 229-

pain reliever , antigout .

Feature

Corm alkaloid of colchicum splendid (Colchicum Speciosum Stev.) of the lily family. White or white with a yellowish tint fine crystalline powder, darkening in the light. 1 g dissolves in 25 ml of water and 220 ml of ether, easily soluble in ethanol and chloroform.

Pharmacology

It has antimitotic activity, inhibits leukopoiesis and lymphopoiesis, reduces the utilization of glucose by phagocytic and non-phagocytic leukocytes, stabilizes the membranes of neutrophil lysosomes, prevents the formation of amyloid fibrils. Violates neuromuscular transmission, stimulates the functions of the gastrointestinal tract, depresses the respiratory center, constricts blood vessels and increases blood pressure, lowers body temperature.

Rapidly absorbed in the gastrointestinal tract, undergoes enterohepatic recirculation. It practically does not bind to plasma proteins and does not linger in the systemic circulation. In high concentrations accumulates in the kidneys, liver and spleen. Excreted mainly with bile and through the kidneys.

Highly effective for the relief of acute gouty attacks. The anti-gout effect depends on the level in leukocytes, and not in plasma, and is due to a decrease in the release of lysosomal enzymes from neutrophils, a decrease in lactate formation, stabilization of tissue fluid pH and limitation of uric acid crystallization. The anti-inflammatory effect is manifested only in gouty arthritis: it affects the primary inflammatory reaction, incl. local inflammatory infiltration with granulocytes that phagocytize urate crystals, so the best result is obtained when treatment is started early (shortly after the onset of symptoms). In the first 12 hours of therapy, the condition improves significantly in more than 75% of patients. In 80%, it causes adverse reactions from the gastrointestinal tract, which may occur before clinical improvement or simultaneously with it. With intravenous application, side effects from the gastrointestinal tract do not develop and the patient’s condition improves faster. After a single injection, the level in leukocytes increases and does not change for 24 hours. In a daily dose of 1–2 mg, taken daily in 3/4 patients with gout, it reduces the likelihood of recurrent acute attacks. Prevents acute attacks in patients with familial Mediterranean fever (decreased activity of dopamine-beta-hydroxylase). Increases the life expectancy of patients with primary AL-amyloidosis. It has a positive effect on the skin (softening, reducing dryness) with progressive systemic sclerosis (scleroderma). Effective in mild Behcet’s syndrome, primary biliary cirrhosis. Slows down the progression of neurological disorders in multiple sclerosis.

Use of the substance Colchicine

Acute gouty attack, prevention of recurrence of acute gouty attacks, especially in the first 2 years after the start of hypouricemic drugs, systemic scleroderma, amyloidosis, Behcet’s disease, familial Mediterranean fever.

Contraindications

Hypersensitivity, lesions of the gastrointestinal tract, bone marrow, neutropenia, impaired liver and kidney function, cardiovascular pathology, purulent infections, alcoholism, pregnancy, old age.

Side effects of the substance Colchicine

Dyspeptic symptoms (nausea, vomiting, anorexia, diarrhea, etc.) that occur when high doses are taken orally, myelosuppression (leukopenia, agranulocytosis, aplastic anemia, thrombocytopenia – usually with long-term treatment), temporary alopecia, liver failure, increased levels of alkaline phosphatase and gamma-glutamyl transpeptidase, impaired renal function, depression, myopathy, peripheral neuritis, reversible aspermia, malabsorption syndrome, manifested, in particular, by vitamin B deficiency ₁₂ , skin allergic reactions, local irritation with intravenous administration and extravasation – sharp pain, necrosis.

Interaction

Enhances the effect of depriming and sympathomimetic agents. Interferes with the absorption of vitamin B ₁₂ . NSAIDs and other drugs that cause myelodepression increase the risk of leukopenia and thrombocytopenia. Antigout activity is reduced by cytostatics (increase the concentration of uric acid).

Overdose

Symptoms: nausea, vomiting, severe diarrhea, abdominal and oral pain, hemorrhagic gastroenteritis, skin burning, severe dehydration with hypotension and hypovolemic shock, reduced myocardial contractility and ST segment elevation on ECG, hematuria, oliguria, convulsions, ascending paralysis, respiratory depression. Perhaps the development of hepatocellular damage, acute renal failure, pulmonary infiltrates. 5 days after an overdose, severe bone marrow suppression with leukopenia, thrombocytopenia, and coagulopathy may occur.

Treatment: carried out in a poison center. There is no specific antidote. Hemodialysis is ineffective. It is necessary to control the patency of the respiratory tract, assisted ventilation, monitor and maintain vital functions, normalize blood gas composition, electrolyte balance, and conduct anti-shock measures.

Dosage and administration

Inside. In acute attacks of gout and inflammatory processes: on the 1st day – 1 mg 3 times a day (morning, afternoon and evening), on the 2nd and 3rd day – 1 mg 2 times a day (morning and evening ), on the 4th and subsequent days – 1 mg per day (in the evening).