Colchicine

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Colchicine on Prescriptsy

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Colchicine is an anti-inflammatory alkaloid derived from the autumn crocus (Colchicum autumnale), used in the United Kingdom for the treatment of acute gout flares, prophylaxis of gout attacks during the initiation of urate-lowering therapy, and the prevention and treatment of familial Mediterranean fever (FMF).

It has been used in medicine for centuries and remains a cornerstone of acute gout management alongside non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids.

Gout is the most common inflammatory arthritis in the UK, affecting approximately 2.5% of adults, with higher prevalence in men and increasing incidence with age.

It results from the deposition of monosodium urate (MSU) crystals in joints and surrounding tissues when serum urate levels exceed the saturation threshold (approximately 360 micromol/L).

Acute flares cause sudden, severe joint pain, swelling, redness, and warmth, most frequently affecting the first metatarsophalangeal joint (big toe).

This page provides a comprehensive clinical overview of colchicine, including how it works, correct dosing, expected timelines, side effects, drug interactions, safety warnings, and how to obtain a prescription in the UK.

Important safety information about colchicine

Before reading further, note the following critical safety points. Colchicine is a prescription-only medicine (POM) in the UK and has a narrow therapeutic index, meaning the margin between an effective dose and a harmful dose is small.

• Never exceed the prescribed dose. The maximum dose for an acute gout flare is 6 mg per course, and courses must be separated by at least 3 days.
• If diarrhoea or vomiting develops during treatment, stop taking colchicine and contact your GP.
• Tell your prescriber about all medications you take, particularly statins, macrolide antibiotics (clarithromycin, erythromycin), antifungals (ketoconazole), ciclosporin, and HIV protease inhibitors, as these increase the risk of colchicine toxicity.
• Colchicine should be used with caution in elderly patients and those with renal or hepatic impairment. Dose reduction is usually necessary.
• Seek emergency medical attention if you develop profuse vomiting or diarrhoea, muscle weakness, numbness, unexplained bruising or bleeding, or signs of infection.

Understanding gout

Gout is caused by chronically elevated serum urate levels (hyperuricaemia), leading to the formation and deposition of MSU crystals in and around joints.

Urate is the end product of purine metabolism. Hyperuricaemia develops when urate production exceeds renal and gut excretion capacity.

Risk factors include male sex, increasing age, obesity, excessive alcohol intake (particularly beer and spirits), a diet rich in purine-containing foods (red meat, offal, shellfish), chronic kidney disease, diuretic use, and genetic predisposition.

An acute gout flare begins when MSU crystals activate the innate immune system.

Neutrophils engulf the crystals, triggering the NLRP3 inflammasome and massive release of interleukin-1-beta (IL-1-beta) and other pro-inflammatory cytokines.

This produces the hallmark intense pain, swelling, redness, and warmth of an acute attack, which typically peaks within 12 to 24 hours and resolves over 7 to 14 days without treatment.

Recurrent flares and chronic hyperuricaemia can lead to tophaceous gout, in which visible deposits of urate crystals (tophi) accumulate in joints, tendons, and soft tissues, causing chronic pain, joint destruction, and disability.

Long-term management aims to reduce serum urate below the target threshold using urate-lowering therapy (ULT) such as allopurinol or febuxostat, combined with anti-inflammatory prophylaxis to prevent the mobilisation flares that commonly occur when ULT is initiated.

How colchicine works: mechanism of action

Colchicine binds to intracellular tubulin, a structural protein that polymerises to form microtubules.

Microtubules are essential for cell division, intracellular transport, and the motility functions of white blood cells.

By disrupting microtubule assembly, colchicine inhibits several key steps in the inflammatory cascade triggered by MSU crystals.

First, colchicine impairs neutrophil chemotaxis and adhesion, reducing the migration of these inflammatory cells to the site of crystal deposition.

Second, it inhibits phagocytosis of MSU crystals by neutrophils and macrophages.

Third, colchicine suppresses activation of the NLRP3 inflammasome, blocking the processing and release of IL-1-beta, the central cytokine driving gouty inflammation.

Fourth, it reduces the expression of adhesion molecules on endothelial cells and neutrophils, further limiting inflammatory cell recruitment.

These actions are relatively specific to crystal-induced inflammation, which is why colchicine is effective in gout and FMF but is not a general-purpose analgesic or anti-inflammatory.

It does not lower serum urate and does not prevent crystal formation; it works solely by dampening the inflammatory response to crystals already present.

Clinical evidence and UK guidelines

The AGREE trial (2010) established the modern low-dose colchicine regimen for acute gout.

Patients randomised to low-dose colchicine (1.8 mg total over 1 hour: 1.2 mg initially, then 0.6 mg one hour later) achieved equivalent pain reduction to those receiving high-dose colchicine (4.8 mg over 6 hours), but with gastrointestinal adverse effects comparable to placebo.

This landmark study shifted prescribing practice away from the historic high-dose regimens that frequently caused debilitating diarrhoea and vomiting.

The British Society for Rheumatology (BSR) guidelines for the management of gout (2017) recommend colchicine as a first-line option for acute gout flares alongside NSAIDs and corticosteroids.

The choice between these agents depends on comorbidities, renal function, cardiovascular risk, and patient preference.

Colchicine is particularly useful when NSAIDs are contraindicated (for example, in patients with peptic ulcer disease, heart failure, or chronic kidney disease) and when corticosteroids are undesirable.

For flare prophylaxis, the BSR recommends low-dose colchicine (500 micrograms once or twice daily) for at least 6 months after the serum urate target has been achieved during ULT initiation.

NICE Clinical Knowledge Summaries on gout adopt similar recommendations, emphasising that prophylaxis substantially reduces the frequency and severity of mobilisation flares that can undermine patient adherence to ULT.

For familial Mediterranean fever, colchicine remains the established first-line treatment and prophylaxis, reducing the frequency and severity of febrile episodes and preventing secondary amyloidosis. Long-term or lifelong treatment is usually necessary.

Dosage and administration

Acute gout flares

The recommended low-dose regimen is colchicine 500 micrograms two to three times daily until symptoms resolve or the maximum course dose of 6 mg has been reached.

Treatment is most effective when started within 12 hours of flare onset and becomes progressively less effective if delayed beyond 36 hours.

A treatment course should not be repeated within 3 days. During an acute flare, continue any existing urate-lowering therapy; do not stop or adjust allopurinol or febuxostat.

Gout prophylaxis

When initiating or titrating allopurinol or febuxostat, prescribe colchicine 500 micrograms once or twice daily as prophylaxis.

Continue for at least 6 months after the serum urate target has been reached.

This duration allows existing crystal deposits to dissolve and reduces the inflammatory stimulus for mobilisation flares.

Familial Mediterranean fever

The usual adult dose for FMF is 1 to 2 mg daily, taken in one or two divided doses.

The dose is titrated to the minimum effective level that prevents febrile episodes while minimising gastrointestinal side effects. Most patients require lifelong treatment.

Dose adjustments

Colchicine is metabolised in the liver (CYP3A4) and excreted by the kidneys and via biliary routes.

Dose reduction is required in patients with an eGFR below 30 mL/min/1.73 m2, in those with hepatic impairment, and in patients taking drugs that inhibit CYP3A4 or P-glycoprotein.

The BNF provides specific dose adjustment recommendations for these populations.

In severe renal or hepatic impairment, colchicine may need to be avoided entirely due to the risk of accumulation and life-threatening toxicity.

Side effects of colchicine

Common side effects

Gastrointestinal effects are the most frequent adverse reactions. Nausea, vomiting, abdominal cramps, and diarrhoea are dose-dependent and occur most commonly with higher-dose regimens.

The development of diarrhoea should be regarded as a signal to stop treatment, as it may precede more serious toxicity.

The modern low-dose regimen significantly reduces the incidence of gastrointestinal side effects.

Uncommon and rare side effects

With prolonged use or in the context of renal or hepatic impairment, colchicine can cause bone marrow suppression, manifesting as leucopenia, thrombocytopenia, or, rarely, agranulocytosis and aplastic anaemia.

Peripheral neuropathy (numbness, tingling, weakness in hands and feet) and proximal myopathy (muscle weakness, elevated creatine kinase) are recognised complications of chronic use and may be potentiated by concurrent statin therapy.

Rare adverse effects include rhabdomyolysis, hepatotoxicity, alopecia (usually reversible), and hypersensitivity reactions. Colchicine overdose is a medical emergency with potential for multi-organ failure and death; even relatively modest overdoses can be fatal.

When to seek medical advice

Stop taking colchicine and contact your GP or NHS 111 if you develop persistent diarrhoea or vomiting, muscle pain or weakness, tingling or numbness in hands or feet, or unexplained bruising or bleeding.

Call 999 or attend A&E if you suspect an overdose, if you develop profuse vomiting and diarrhoea with dehydration, fever with sore throat, or dark urine, as these may indicate serious toxicity requiring hospital assessment.

Report adverse reactions via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk .

Warnings and precautions

Narrow therapeutic index

Colchicine has one of the narrowest therapeutic windows of any medicine in routine clinical use. Accidental or intentional overdose can be fatal.

Patients must understand the importance of not exceeding the prescribed dose and not repeating courses too soon.

Prescribers should ensure that patients receive clear written instructions on dosing and the circumstances in which to stop treatment.

Drug interactions

Potent CYP3A4 inhibitors (clarithromycin, erythromycin, ketoconazole, itraconazole, ritonavir, and other HIV protease inhibitors) and P-glycoprotein inhibitors (ciclosporin, verapamil, diltiazem) significantly increase colchicine plasma concentrations and the risk of toxicity, including fatal outcomes.

If co-administration is essential, the colchicine dose must be substantially reduced and the patient monitored closely. Grapefruit juice also inhibits CYP3A4 and should be avoided.

Statins (particularly simvastatin and atorvastatin) share a risk of myopathy with colchicine. Combined use requires vigilant monitoring for muscle symptoms and should prompt creatine kinase measurement if symptoms occur.

Renal and hepatic impairment

Reduced clearance in patients with kidney or liver disease increases the risk of accumulation and toxicity.

Dose reduction is essential for patients with an eGFR below 30 mL/min/1.73 m2 or significant hepatic impairment. In severe impairment of either organ, colchicine is generally contraindicated.

Fertility and pregnancy

Colchicine crosses the placenta and is present in breast milk.

It should be avoided in pregnancy and breastfeeding unless the clinical benefit clearly outweighs the risk (for example, in severe FMF where discontinuation would be hazardous).

Both men and women should use effective contraception during treatment and for at least 3 months after the last dose, as colchicine may impair spermatogenesis.

How to get a colchicine prescription in the UK

Colchicine is a prescription-only medicine in the UK. Your GP can prescribe it for acute gout flares and for prophylaxis when starting urate-lowering therapy.

Rheumatologists typically manage patients with complex, recurrent, or tophaceous gout and may prescribe colchicine as part of a comprehensive management plan.

Authorised online prescribers registered with the GPhC may also prescribe colchicine following a clinical assessment that confirms the diagnosis and reviews renal function, hepatic function, and concurrent medications.

The standard NHS prescription charge in England is currently 9.90 pounds per item; prescriptions are free in Scotland, Wales, and Northern Ireland.

Living with gout: long-term management

Colchicine treats the symptoms of gout but does not address the underlying cause.

Long-term management of gout requires lowering serum urate levels below the crystallisation threshold using allopurinol, febuxostat, or (rarely) uricosuric agents.

Lifestyle modifications including weight management, reducing alcohol intake (especially beer and spirits), limiting purine-rich foods, staying well hydrated, and avoiding sugar-sweetened drinks containing fructose all support lower urate levels and reduced flare frequency.

Regular monitoring of serum urate, renal function, and (during colchicine use) full blood count ensures safe and effective management. Your GP or rheumatologist will review your gout management at least annually and adjust treatment as needed.

When to seek urgent medical advice

Contact your GP or NHS 111 if you experience a gout flare that does not respond to treatment, recurrent flares despite prophylaxis, or joint swelling with fever (which may indicate septic arthritis requiring urgent exclusion).

Call 999 or attend A&E if you develop signs of colchicine toxicity (profuse vomiting and diarrhoea, muscle weakness, bloody stools, confusion) or if you suspect an overdose.

Report any adverse reactions via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk .

Sources

• Colchicine 500 microgram Tablets, Summary of Product Characteristics (EMC)
• Colchicine, British National Formulary (BNF)
• BSR Guideline for the Management of Gout
• NICE CKS: Gout
• Gout, NHS
• MHRA Yellow Card Scheme