Each tablet contains:

active ingredient: colchicine – 1 mg;

excipients: sucrose, povidone, sodium starch glycolate,magnesium stearate, color red E-129, microcrystalline cellulose.

Antigout. ATC code: M04AC01.

Pharmacodynamic properties

The anti-inflammatory effect of colchicine in acute gouty arthritis is selective for this disorder. Although its mode of action is not clearly understood, it is thought that colchicine causes the inhibition of the migration of granulocytes into the inflamed area. This reduces the release of lactic acid and proinflammatory enzymes that occurs during phagocytosis and breaks the cycle that leads to the inflammatory response.

Pharmacokinetic properties

Colchicine is readily absorbed from the gastrointestinal tract and peak concentrations occur in plasma by half an hour to two hours.
The kidney, liver and the spleen also contain high concentrations of colchicine, but it is apparently largely excluded from the heart, skeletal muscle and brain. It is partially deacetylated in the liver. Colchicine and its metabolites are excreted in the urine and faeces.

Preclinical safety data

There are no pre-clinical data of relevance to the prescriber which are additional to those already included in other sections.

Gout:
1mg initially, followed by 0.5 mg every two to three hours until relief of pain is obtained or
vomiting or diarrhoea occurs. A total dose of 6 mg should not be exceeded. The course should
not be repeated within three days.

For use with allopurinol or uricosuric drugs: 0.5 mg two to three times daily.

Familial Mediterranean fever

Adults
Take 0.5 – 2.0 mg of colchicine evening.

Children:
FMF (Familial mediterranean fever): The recommended dosage of colchicine for FMF in
pediatric patients under 5 years of age and older is based on age.
Children under the 5 years of age: 0.5 mg daily
Children 5 -10 years: 1.5 mg daily
Аdolescents 10 years of age and over: 1.5 mg daily
Maximum daily dose is not more than 2 mg daily

Elderly:
To be given with great care.

Renal Impairment:
For mild/moderate renal impairment (creatinine clearance 10-50 ml/minute), reduce dose or increase interval between doses (see “Contraindications”).

Colchicine has a narrow therapeutic window and is extremely toxic in overdose. Patients at
particular risk of toxicity are those with renal or hepatic impairment, gastrointestinal or
cardiac disease, and patients at extremes of age.
Colchicine overdose is complex and specialist advice should be promptly obtained. There is
often a delay of up to 6 hours before toxicity is apparent, and some features of toxicity may
be delayed by 1 week or longer. All patients, even in the absence of early symptoms, should
be referred for immediate medical assessment.

Symptoms

Early features (up to 1 day after ingestion) include a feeling of burning and rawness in the mouth and throat, difficulty in swallowing, nausea, vomiting, abdominal pain and diarrhoea. Diarrhoea may be profuse, bloody and accompanied by tenesmus, and the patient may present with electrolyte disturbances and hypovolaemic shock. These symptoms, coupled with vascular damage, may lead to dehydration, hypotension and shock.
Features after 1 to 7 days include confusion, decreased cardiac output, cardiac arrhythmias, renal and hepatic impairment, respiratory distress, hyperpyrexia and bone marrow depression. This can progress in severe cases to multiple organ failure with accompanying bone marrow aplasia, CNS toxicity, convulsions, coma, hepatocellular damage, rhabdomyolysis, respiratory distress, myocardial injury, renal damage and disseminated intravascular coagulation.
Death may be due to respiratory depression, cardiovascular collapse or sepsis.
In surviving patients, alopecia, rebound leucocytosis and stomatitis may occur about 10 days after the acute overdose.

Treatment

Consider oral activated charcoal in adults who have ingested more than 0.1 mg/kg bodyweight within 1 hour of presentation, and in children who have ingested any amount within 1 hour. Further doses of activated charcoal may enhance systemic elimination and may be considered in patients who have ingested more than 0.3 mg/kg
Haemodialysis and haemoperfusion do not enhance colchicine elimination.
Management should include general symptomatic and supportive measures as indicated by the patient’s clinical condition, including monitoring of vital signs, ECG, haematological and biochemical indices. Respiration may need assistance. Circulation should be maintained and fluid and electrolyte imbalance corrected.
Morphine sulphate 10mg, intramuscularly, may be given to relieve severe abdominal cramps.
To allow for the delayed onset of symptoms, patients should be carefully monitored for at least 6 hours after ingestion, or for 12 hours if they have taken more than 0.3 mg/kg. After this time, asymptomatic patients may be discharged with advice to return if gastrointestinal symptoms appear.

Antibacterials: increased risk of colchicine toxicity when given with clarithromycin or erythromycin, particularly in patients with pre-existing renal impairment.
Rare reports of fatalities (see “Contraindications”). AS CYP3A4 inhibitors, macrolides should not be used to treat patients with renal or hepatic impairment who are taking colchicine (see “Contraindications”).

P-glycoprotein or strong CYP3A4 inhibitors: Colchicine is contraindicated in patients with renal or hepatic impairment who are taking a P-glycoprotein inhibitor (e.g. ciclosporin, verapamil or quinidine) or a strong CYP3A4 inhibitor (e.g. ritonavir, atazanavir, indinavir, clarithromycin, telithromycin, itraconazole or ketaconazole) (see “Contraindications”).
A reduction in colchicine dosage or an interruption of colchicine treatment is recommended in patients with normal renal or hepatic function if treatment with a P-glycoprotein or strong CYP3A4 inhibitor is required (see “Special warnings and precautions for use”).

Ciclosporin: Colchicine should be used with caution with ciclosporin due to the possible increased risk of nephrotoxicity and myotoxicity.

Vitamins: the absorption of Vitamin B12 may be impaired by chronic administration or high doses of colchicine; requirement may be increased.

Statins: Acute myopathy has been reported in patients given colchicine with statins. Patients should be advised to report muscle pain or weakness.

Colchicine should be given with care to elderly and debilitated patients as there is a greater risk of cumulative toxicity.
Care should also be exercised in those with cardiac, hepatic, gastrointestinal disease or if patients are breast-feeding.
Colchicine should be avoided in patients with blood disorders.
Reduce dose in patients with mild to moderate renal impairment (see “Posology and Method of Administration” and “Contraindications”).
A reduction in colchicine dosage or interruption of colchicine treatment is recommended in patients with normal renal and hepatic function if treatment with a P-glycoprotein or a strong CYP3A4 inhibitor is required (see “Interaction with other medicinal products and other forms of interaction”).
Contains surcose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Effects on ability to drive and use machines
– None known.

Do not use in pregnancy as there is a risk of foetal chromosome damage.
Colchicine is distributed into breast milk. Colchicine may be used with caution during
breast-feeding.

96 tablets are packed into PVC-Aluminum blister packets (inside package).
4 blisters are packed with 24 tablets in each are inserted together with the leaflet into
cardboard boxes (outer package).

3 years. Do not use after the expiration date.

Store at a room temperature (15-25⁰C), in a dry place, out of the reach of children. Protect from light.