What are the primary uses of colchicine. How does colchicine work in the body. What are the most common side effects of colchicine. When should caution be exercised when taking colchicine. How does colchicine interact with other medications.

Understanding Colchicine: An Overview of Its Uses and Mechanism of Action

Colchicine is a powerful medication with a wide range of applications in modern medicine. Its primary FDA-approved uses include the treatment and prevention of gout, as well as the management of familial Mediterranean fever. However, healthcare providers often prescribe colchicine off-label for various other conditions, showcasing its versatility in treating inflammatory and autoimmune disorders.

Primary Indications for Colchicine

• Gout prophylaxis
• Treatment of acute gout flares
• Familial Mediterranean fever

Off-Label Uses of Colchicine

• Acute and recurrent pericarditis
• Prevention of post-pericardial syndrome
• Primary biliary cirrhosis
• Hepatic cirrhosis
• Dermatitis herpetiformis
• Paget’s disease of bone
• Chronic immune thrombocytopenia
• Pseudogout
• Idiopathic pulmonary fibrosis

How does colchicine work in the body? Colchicine primarily acts as an anti-inflammatory agent. Its mechanism of action involves disrupting cytoskeletal functions by inhibiting beta-tubulin polymerization into microtubules. This process prevents the activation, degranulation, and migration of neutrophils, which are associated with mediating gout symptoms. Additionally, colchicine appears to interfere with the release of inflammatory glycoproteins from phagocytes, further contributing to its anti-inflammatory effects.

In the context of familial Mediterranean fever, colchicine’s mechanism is less understood. It is believed to interfere with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes, which mediates the activation of interleukin-1-beta, a key player in the inflammatory response.

Dosage and Administration: Ensuring Optimal Therapeutic Effects

Colchicine is available in various forms, including tablets, capsules, and gel. The most common route of administration is oral, with the topical gel form being rarely used. It’s crucial to note that due to toxicity concerns, the injectable form is no longer available in the United States.

Recommended Dosages for Different Conditions

1. Gout Prophylaxis:
   • Adults and adolescents over 16: 0.6 mg once or twice daily
   • Maximum dose: 1.2 mg per day
2. Treatment of Acute Gout Flare:
   • 1.2 mg at the first sign of a flare
   • Followed by 0.6 mg one hour later
3. Familial Mediterranean Fever:
   • Adults and children over 12: 1.2 mg to 2.4 mg daily
   • Administered in one or two doses

Why is proper dosing crucial when taking colchicine? Adhering to the recommended dosages is essential to maximize the therapeutic benefits while minimizing the risk of adverse effects. Colchicine has a narrow therapeutic window, meaning the difference between an effective dose and a toxic dose is relatively small. Therefore, patients should never adjust their dosage without consulting their healthcare provider.

Navigating the Side Effects: What Patients Need to Know

While colchicine can be highly effective in treating various conditions, it’s not without potential side effects. Understanding these adverse reactions is crucial for patients and healthcare providers alike to ensure safe and effective use of the medication.

Common Side Effects of Colchicine

• Gastrointestinal issues:
  • Diarrhea (23% of patients)
  • Vomiting (17% of patients)
  • Nausea (4% to 17% of patients)
• Central nervous system symptoms:
  • Fatigue
  • Headache
• Endocrine and metabolic conditions (e.g., gout)
• Pharyngolaryngeal pain

Are there any serious side effects associated with colchicine use? While less common, colchicine can cause more severe adverse reactions. These effects are generally reversible upon discontinuation of the medication or lowering the dose:

• Neurologic: Sensorimotor neuropathy
• Dermatologic: Alopecia, maculopapular rash, purpura
• Gastrointestinal: Abdominal cramping, abdominal pain, lactose intolerance
• Hematologic: Leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia
• Hepatobiliary: Elevated AST and ALT levels
• Musculoskeletal: Myopathy, elevated CPK, myotonia, muscle weakness, muscle pain, rhabdomyolysis
• Reproductive: Azoospermia, oligospermia

Patients should be vigilant and report any unusual symptoms to their healthcare provider promptly. Early detection and management of side effects can prevent more serious complications and ensure the continued benefits of colchicine therapy.

Drug Interactions: Ensuring Safe Use of Colchicine

Colchicine’s effectiveness and safety can be significantly affected by its interactions with other medications and substances. Understanding these interactions is crucial for healthcare providers and patients to prevent potential complications and ensure optimal therapeutic outcomes.

Key Mechanisms of Colchicine Interactions

• Substrate for P-glycoprotein efflux transporter
• Primarily metabolized by CYP3A4 enzyme

How do these mechanisms affect colchicine’s interactions with other drugs? The involvement of P-glycoprotein and CYP3A4 in colchicine’s metabolism means that medications or substances that inhibit or induce these pathways can significantly alter colchicine’s concentration in the body. This can lead to increased toxicity or reduced effectiveness, depending on the interaction.

Notable Drug Interactions with Colchicine

1. Strong CYP3A4 inhibitors:
   • Examples: Clarithromycin, ketoconazole, ritonavir
   • Effect: Can increase colchicine levels, potentially leading to toxicity
2. P-glycoprotein inhibitors:
   • Examples: Cyclosporine, verapamil
   • Effect: May increase colchicine absorption and decrease elimination
3. Statins:
   • Examples: Atorvastatin, simvastatin
   • Effect: Increased risk of myopathy and rhabdomyolysis when used concurrently with colchicine
4. Grapefruit juice:
   • Effect: Can inhibit CYP3A4, potentially increasing colchicine levels

What precautions should be taken when prescribing colchicine? Healthcare providers should conduct a thorough review of a patient’s current medications before prescribing colchicine. In some cases, dose adjustments or alternative treatments may be necessary to avoid potential interactions. Patients should be advised to inform their healthcare provider of all medications, supplements, and dietary habits to ensure safe use of colchicine.

Special Populations: Tailoring Colchicine Use for Specific Patient Groups

While colchicine is a versatile medication, its use requires special consideration in certain patient populations. Understanding these nuances is crucial for healthcare providers to ensure safe and effective treatment while minimizing risks.

Pediatric Patients

Is colchicine safe for use in children? The use of colchicine in pediatric patients is limited:

• Not recommended for gout prophylaxis or treatment of gout flares in children
• Approved for treating familial Mediterranean fever in children 4 years and older

When prescribing colchicine to children, healthcare providers must carefully consider the risk-benefit ratio and adjust dosages based on the child’s age, weight, and specific condition.

Elderly Patients

How should colchicine be used in older adults? Elderly patients may require special attention when taking colchicine:

• Increased risk of toxicity due to age-related changes in kidney and liver function
• Higher likelihood of drug interactions due to polypharmacy
• May require lower doses or less frequent administration

Healthcare providers should closely monitor elderly patients for signs of colchicine toxicity and adjust dosages accordingly.

Patients with Renal or Hepatic Impairment

Why is caution necessary when prescribing colchicine to patients with kidney or liver problems? Colchicine is primarily eliminated through the kidneys and metabolized in the liver. Therefore:

• Patients with renal impairment may have reduced colchicine clearance, increasing the risk of toxicity
• Those with hepatic impairment may have altered metabolism of colchicine, potentially leading to higher blood levels

Dose adjustments and close monitoring are essential for these patient populations to ensure safe and effective treatment.

Monitoring and Follow-up: Ensuring Long-term Safety and Efficacy

Proper monitoring and follow-up are crucial components of colchicine therapy, helping to ensure its long-term safety and efficacy. Healthcare providers should establish a comprehensive monitoring plan tailored to each patient’s specific needs and risk factors.

Key Aspects of Colchicine Monitoring

1. Regular blood tests:
   • Complete blood count (CBC) to monitor for hematologic effects
   • Liver function tests to assess hepatic impact
   • Kidney function tests to evaluate renal clearance
2. Symptom assessment:
   • Evaluate the effectiveness in managing the primary condition (e.g., gout flares, familial Mediterranean fever)
   • Monitor for potential side effects, particularly gastrointestinal symptoms
3. Drug interaction screening:
   • Regularly review patient’s medication list for potential interactions
   • Adjust colchicine dose or consider alternative treatments if necessary

How often should patients on long-term colchicine therapy be monitored? The frequency of monitoring may vary depending on the individual patient’s risk factors and overall health status. Generally, patients should have follow-up appointments and laboratory tests at least every 3-6 months, or more frequently if concerns arise.

Patient Education and Self-monitoring

Empowering patients with knowledge about their medication is crucial for safe and effective long-term use of colchicine. Healthcare providers should educate patients on:

• Recognizing signs of potential toxicity or adverse effects
• The importance of adherence to prescribed dosages
• Potential drug interactions, including over-the-counter medications and supplements
• The need to inform all healthcare providers about their colchicine use

Patients should be encouraged to keep a symptom diary and report any unusual changes or concerns promptly to their healthcare provider.

Future Directions: Expanding the Therapeutic Potential of Colchicine

As research into colchicine continues, new potential applications and improved formulations are emerging. These developments hold promise for expanding the therapeutic reach of this ancient yet versatile medication.

Emerging Research Areas

• Cardiovascular applications:
  • Potential role in preventing recurrent myocardial infarction
  • Investigating effects on atherosclerosis progression
• Neurodegenerative diseases:
  • Exploring anti-inflammatory effects in Alzheimer’s and Parkinson’s diseases
• Cancer research:
  • Investigating potential anti-tumor properties
  • Studying combinations with other cancer treatments

What challenges need to be overcome in expanding colchicine’s use? While the potential for new applications is exciting, several hurdles must be addressed:

• Optimizing dosing regimens for new indications
• Developing targeted delivery systems to reduce systemic side effects
• Conducting large-scale clinical trials to establish efficacy and safety in new therapeutic areas

Improving Formulations and Delivery Methods

Researchers are also working on enhancing colchicine’s formulation and delivery to improve its therapeutic index and patient compliance:

• Extended-release formulations to reduce dosing frequency
• Topical preparations for localized treatment of inflammatory conditions
• Nanoparticle-based delivery systems for targeted therapy

These advancements could potentially reduce side effects, improve efficacy, and expand the range of conditions treatable with colchicine.

As research progresses, healthcare providers should stay informed about the latest developments in colchicine therapy. This knowledge will be crucial in providing patients with the most up-to-date and effective treatment options, potentially expanding the role of this time-tested medication in modern medicine.

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

1.

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

2.

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

3.

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]

4.

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]

10.

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.

Colchicine side effects and how to avoid them

Colchicine is commonly prescribed to treat gout and other conditions such as Familial Mediterranean Fever (FMF). Colchicine is not recommended for long-term use and can have many side effects.

Glipizide side effects | Diarrhea | Serious side effects |
Colchicine toxicity | Kidney injury | How long do side effects last? | Warnings | Interactions | How to avoid side effects

If you are one of the 9.2 million Americans that have suffered from a gout attack this year, your healthcare provider may have prescribed an antigout medication named colchicine to help ease your symptoms. This medication has been around since the ninth century and remains a popular option for patients and healthcare professionals.   

Colchicine is a U.S. Food and Drug Administration (FDA) approved drug that is safe for use in both adults and children. It is a plant-based alkaloid from the autumn crocus and glory lily. Although most commonly used for gout management and prevention, the medication can also be used for the treatment of the genetic condition Familial Mediterranean Fever (FMF) and helps to manage the symptoms of Behcet’s syndrome, pseudogout, and pericarditis.

Currently, colchicine can only be acquired by a prescription from a healthcare provider. There are many forms of colchicine available.  It can be prescribed in either a capsule (Mitigare), tablet (Colcrys), or liquid form. It is important to note that colchicine cannot cure any of the medical conditions that it treats and is only used to manage symptoms. This medication also is not recommended for long-term use for pain management.

Common side effects of colchicine

There are quite a number of side effects associated with the use of colchicine. Luckily most are related to symptoms of gastrointestinal distress, but all are usually short-lived. The most common symptoms to be aware of when using colchicine include: 

• Diarrhea
• Nausea
• Vomiting
• Cramping
• Abdominal pain
• Fatigue
• Headache
• Sore throat

Diarrhea

As previously discussed, gastrointestinal symptoms are quite common with the use of colchicine. Diarrhea tends to be the most prevalent complication seen with its use. Although colchicine has been available for centuries, there are not many studies available that evaluate its use. A systematic review was performed in 2017 that found diarrhea could be seen in as many as 3 out of 4 patients prescribed with the original recommended dosage for colchicine.   This dosage has since been studied and adjusted. Because of the potential gastrointestinal concerns associated with colchicine, the lowest effective dose is always recommended.

Serious side effects of colchicine

Although colchicine is considered a safe drug, one must note that there are some serious adverse effects associated with its use. If any of the following symptoms below occur while using colchicine, your medical provider should be contacted immediately for further medical attention. 

• Myelosuppression (decreased bone marrow activity)
• Leukopenia (reduced white blood cells)
• Thrombocytopenia (reduced platelets)
• Granulocytopenia (reduced granulocytes)
• Pancytopenia (reduced red blood cells)
• Aplastic anemia
• Severe diarrhea
• Myopathy (disease of muscle tissue)
• Rhabdomyolysis (serious condition of muscle fibers entering the bloodstream)
• Neuropathy (nerve damage)
• Hepatotoxicity (liver damage)
• Nephrotoxicity (kidney damage)
• Multiple organ failure
• Disseminated intravascular coagulation (abnormal blood clotting in the body)
• Hypersensitivity reaction
• Reversible azoospermia (absence of viable sperm in semen)

Colchicine toxicity

Since there is minimal room for error when dosing colchicine safely, one must be aware of certain symptoms that may represent signs of toxicity. Gastrointestinal symptoms, the most common side effects with the use of colchicine, are usually the first symptoms of toxicity. When these symptoms (usually diarrhea and vomiting) occur, the medication is frequently stopped. This is because it may be hard to judge if the medication is continued that there will be more serious adverse effects that occur. Less common symptoms usually involve multiorgan failure and lastly death.  

Colchicine toxicity is commonly divided into three stages. Stage one involves the common and initial symptoms of diarrhea, nausea, and vomiting. These symptoms may cause severe dehydration resulting in low blood pressure and an irregular amount of blood cells in the body. This stage typically lasts anywhere from 1-12 hours. Stage two usually lingers for 1-7 days and involves more catastrophic complications such as bone marrow suppression, multi-organ failure, kidney failure, altered mental status, and heart attack. Finally, stage three includes hair loss and rebound elevated blood count that will last 1-2 weeks for those individuals that survive stage two.   

Because the stages of colchicine toxicity may overlap, close monitoring is vital if any symptoms begin to occur—even minor ones. Early intervention may be required to prevent fatalities associated with its use.

Kidney injury

Although not common, there are some studies showing direct toxicity of the kidneys due to the use of colchicine. They report kidney damage as well as the potential for kidney failure from the direct toxic effect of colchicine on the kidney tubules. Most studies show acute kidney damage from colchicine use is reversible. Typically kidney damage related to colchicine is a direct result of chronic use of the medication at high doses. Because kidney damage is always a concern with any medication, colchicine management should be monitored closely by a medical professional.

How long do side effects last?

The majority of side effects from colchicine are considered minor and short-lived. These usually include gastrointestinal side effects like abdominal pain, nausea, vomiting, and diarrhea that can start as early as two hours after initiating treatment. The symptoms may linger for a few days or up to a couple of weeks. Some of the more serious side effects like multiorgan failure may start around 8-72 hours after consumption. Symptoms may not fully go away for 7-10 days. Long-term side effects like numbness are less common with colchicine utilization. The quicker onset of symptoms appears to be found more with the use of intravenous colchicine versus the oral formulation.  

Colchicine contraindications & warnings

Abuse and dependence

Colchicine is not a habit-forming drug and does not pose any risk of dependency with the use of this medication. Additionally, there are no withdrawal symptoms documented with the discontinuation of the medicine.

Overdose

It is recommended that no more than 0.5 mg/kg of colchicine be prescribed to prevent a fatal overdose of the medication. Understanding how to properly use this medication is important as there is no antidote to reverse the effects of the medication. This may be fatal. Currently, activated charcoal and saline flushing is the traditional treatment for an overdose and should be started as quickly as possible.

Colchicine restrictions

 Do not use colchicine if you have:

• Known allergic reaction to the medication
• Known liver disease especially when preventative management is needed
• Known kidney disease especially when preventative management is needed

Colchicine should be avoided, if another option is available, in seniors and individuals with blocked bile ducts.

Pregnancy and breastfeeding

Colchicine has been shown to be safe for use during pregnancy with no adverse effects noted to the fetus or mother. However, it is advised that colchicine be avoided while breastfeeding. Currently, there is no human data to support damage to breast milk production or harm to the infant, so caution has been recommended at this time. When deciding to take colchicine under these circumstances, the potential benefits should always outweigh the risks.

Children

Colchicine has been approved for use in pediatric patients as young as four years old. This is only for the treatment of the genetic condition Familial Mediterranean Fever (FMF). Gout prophylaxis can be used only for those over the age of 16.

Seniors

Close monitoring is needed when prescribing colchicine to seniors. Kidney function may not work as well which causes colchicine to not be processed in the body adequately. This increases the risk for side effects with this medication. To counteract this possibility, a lower dose of colchicine may be considered or a different medication altogether.  

Colchicine interactions

There is a wide range of medications that should be monitored closely or avoided when there is a consideration for prescribing colchicine.

Contraindications

Colchicine is absolutely contraindicated with certain HIV/antivirals, macrolide antibiotics, cancer medications, antifungals, and heart prescription drugs. They have the potential to increase the amount of colchicine levels in the body which results in colchicine toxicity and other serious adverse effects. This is especially true if there is liver or kidney disease present. Some of these medications include:

• Atazanavir
• Clarithromycin
• Cyclosporine
• Itraconazole
• Ketoconazole
• Lopinavir/Ritonavir
• Ribociclib
• Ritonavir
• Saquinavir
• Voriconazole
• Voxilaprevir

Other drug interactions

• Statins. This includes popular cholesterol medications such as atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin.
• Antibiotics. Antibiotics such as ciprofloxacin and erythromycin should be avoided as they pose a risk of muscle pain and damage when combined with colchicine.
• NSAIDs. Certain anti-inflammatories should also be closely monitored. Examples include indomethacin and naproxen.

Other interactions

If supplements such as vitamin B12, turmeric, milk thistle, or ginkgo are being used, they should always be disclosed to your healthcare provider due to potential interactions when added with colchicine. Additionally, any products containing grapefruit should be avoided as they may cause unwanted side effects with colchicine use.

How to avoid colchicine side effects

1. Provide your healthcare provider with a current list of all medications 

Information should be provided that includes all prescription and over-the-counter medications, vitamins, and herbal supplements.

2. Supply your healthcare provider with a complete medical history 

Because colchicine toxicity poses a higher risk for those with certain medical conditions, a complete history should be provided so that it can be determined if you are a good candidate to take this medication. Disclosure of liver disease, kidney disease, pregnancy, or if you are breastfeeding is important.

3. Medication should only be given to those who are 4 years old and older. 

Colchicine has only been FDA approved for those who are 4 years old or older. Infants and toddlers should not be given colchicine.  

4. Always take your medication on time

Keep a record of when you should take your medication. If there is a missed dose, take it as soon as you remember. If the missed dose is close to your next scheduled dose, take that one instead.

5. Take medication as directed by your healthcare professional

Do not take more or less of this medication without the guidance of your physician. Even small increases of colchicine can be life-threatening and may not improve symptoms. Taking colchicine will vary based on your age, the medical condition being treated, medical history, and how you react to the medication. If your symptoms are not improving, do not take more medication or take them for longer than recommended.   

• Acute gout: When taking colchicine for an acute gout flare, usually larger doses are prescribed initially. The medication should be discontinued as soon as the pain has cleared up. If any acute symptoms of diarrhea, vomiting, nausea, or stomach pain occur, the medication should be discontinued immediately.
• Gout prevention: When taking colchicine for an extended time for gout prevention, smaller dosages will be given but for longer periods of time. This medication may be given in addition with other gout medications like allopurinol. Depending on other medical conditions that may need to be treated, colchicine may be prescribed for the rest of someone’s life. Close monitoring may be required in this scenario along with laboratory testing.  

6. Monitor symptoms closely

Overdose of colchicine can be fatal. Contact your physician immediately if you notice any of the following:

• Diarrhea
• Vomiting
• Stomach pain
• Muscle weakness
• Little or no urinating
• Numbness or tingling
• Weak pulse
• Slow heart rate
• Weak or shallow breathing
• Fainting

7. Avoid grapefruit juice

Grapefruit products of any kind should be avoided while taking colchicine as they may lead to some of the side effects discussed above by increasing the levels of colchicine in the body.

Related Resources for colchicine side effects

• Colchicine, Epocrates
• Colchicine Overdose-Induced Acute Renal Failure and Electrolyte Imbalance, Renal Failure
• Diarrhea in Adults, Merck Manual
• Diagnosis and Treatment of Colchicine Poisoning, California Poison Control System
• Gout and hyperuricaemia in the USA: prevalence and trends, Rheumatology
• Hepatotoxicity and nephrotoxicity of colchicine prolonged use in the rats, International Journal of Advanced Research
• Lessons from the Courtroom: Colchicine Toxicity, Emergency Medicine News
• Management of Gout: A Systematic Review in Support of an American College of Physicians Clinical Practice Guideline, Annals of Internal Medicine
• The Ugly Side of Colchicine,  Journal of Investigative Medicine High Impact Case Reports

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

Ph. Eur. European Pharmacopoeia drug interaction Included in preparations: list Pharmacological action Agent that affects the metabolism of uric acid. An alkaloid isolated from corms of Colchicum splendid (Colchicum Speciosum Stev.). It has a pronounced analgesic and anti-inflammatory effect in acute gout attacks. Suppresses the mitotic activity of granulocytes. Inhibits the formation of leukotriene B 4 . Reduces the migration of leukocytes to the focus of inflammation, inhibits phagocytosis of uric acid microcrystals and delays their deposition in tissues. It has an antimitotic effect, suppresses (fully or partially) cell division at the anaphase and metaphase stages, prevents neutrophil degranulation. By reducing the formation of amyloid fibrils, it prevents the development of amyloidosis. Pharmacokinetics After oral administration, it is well absorbed from the gastrointestinal tract. C max in plasma is reached within 2 hours. Excreted as metabolites by the kidneys and through the intestines. Indications of the active substance COLCHICIN Gout (treatment and prevention of attacks), gouty arthritis, periodic illness (familial Mediterranean fever), Behçet’s disease, chondrocalcinosis, scleroderma, phlebitis (some forms), inflammatory diseases in dentistry and ENT practice. Open list of ICD-10 codes E85.0 Hereditary familial amyloidosis without neuropathy I80 Phlebitis and thrombophlebitis M10 Gout M11 Other crystalline arthropathies M34 Systemic sclerosis M35. 2 Behçet’s disease Dosing regimen When taken orally, a single dose is 0.5-1.5 mg, the frequency of administration and the duration of the course depend on the indications and the treatment regimen used. The maximum daily dose of is 8 mg. Side effects From the digestive system: nausea, vomiting, abdominal pain, diarrhea. From the urinary system: impaired renal function. From the side of the hematopoietic system: leukopenia; with prolonged use – agranulocytosis. Dermatological reactions: with long-term use – alopecia. Contraindications for use Pregnancy, severe renal and/or hepatic insufficiency, hypersensitivity to colchicine. Use in pregnancy and lactation Contraindicated in pregnancy. No data are available on the safety of colchicine during lactation. Use in hepatic impairment Contraindicated in severe hepatic impairment. Use in impaired renal function Contraindicated in severe renal impairment. Use with caution in kidney disease. Use in elderly patients Use with caution in elderly patients. Special instructions Use with caution in elderly patients, with diseases of the kidneys, gastrointestinal tract, heart. When treating with colchicine, it is necessary to control the picture of peripheral blood. Drug interactions When used simultaneously with antibiotics of the macrolide group, the possibility of developing the toxic effect of colchicine cannot be excluded, especially in patients with previous impaired renal function. When used simultaneously with cyanocobalamin, its absorption from the gastrointestinal tract decreases. Verapamil increases the plasma concentration of colchicine, which increases the risk of its side effects.

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).