SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Colchicine 500 micrograms Tablets

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Colchicine Ph Eur 535 micrograms (equivalent to Colchicine 500 micrograms on a dry weight basis).

For excipients, see 6.1

3    PHARMACEUTICAL FORM

Tablet - oral use

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Colchicine tablets may be used for the treatment of acute gout and for short term prophylaxis during initial therapy with allopurinol and uricosuric drugs.

4.2    Posology and method of administration

Adults only:

Gout:

1mg initially, followed by 500 micrograms every two to three hours until relief of pain is obtained or vomiting or diarrhoea occurs. A total dose of 6mg should not be exceeded. The course should not be repeated within three days.

Renal Impairment:

For mild/moderate renal impairment (creatinine clearance 10-50ml/minute), reduce dose or increase interval between doses (see section 4.3 Contraindications).

For use with allopurinol or uricosuric drugs:

500 micrograms two to three times daily.

Elderly:

To be given with great care.

Children:

Not recommended.

4.3    Contraindications

The use of colchicine is contraindicated in pregnancy.

Colchicine should not be used in patients undergoing haemodialysis since it cannot be removed by dialysis or exchange transfusion.

Colchicine should not be used in patients with severe renal impairment (creatinine clearance less than 10ml/minute).

Colchicine is contraindicated in patients with renal or hepatic impairment who are taking a P-glycoprotein or a strong CYP3A4 inhibitor (see section 4.5 Interaction with other medicinal products and other forms of interaction).

4.4 Special warnings and precautions for use

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 section

4.2 Posology and method of administration and section 4.3 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 section

4.5 Interaction with other medicinal products and other forms of interaction).

Contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

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 section 4.3 Contraindications). AS CYP3A4 inhibitors, macrolides should not be used to treat patients with renal or hepatic impairment who are taking colchicine (see section 4.3, 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 ketoconazole) (see section 4.3 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 section 4.4, 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.

4.6 Fertility, pregnancy and lactation

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.

4.7 Effects on ability to drive and use machines

None known

4.8    Undesirable effects

Colchicine frequently causes nausea, vomiting and abdominal pain. Larger doses may cause profuse diarrhoea, gastrointestinal haemorrhage, skin rashes and renal and hepatic damage. Rarely peripheral neuritis, myopathy, rhabdomyolysis, alopecia, inhibition of spermatogenesis and, with prolonged treatment, bone marrow suppression with agranulocytosis, thrombocytopenia and aplastic anaemia occur.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme www.mhra.gov.uk/yellowcard.

4.9    Overdose

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.

a) 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.

b) Treatment

Consider oral activated charcoal in adults who have ingested more than 0.1mg/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 0.3mg/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 0.3mg/kg. After this time, asymptomatic patients may be discharged with advice to return if gastrointestinal symptoms appear.

5    PHARMACOLOGICAL PROPERTIES

5.1    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.

5.2 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.

5.3 Preclinical safety data

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

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Lactose

Pregelatinised Maize Starch Stearic Acid Purified Talc Purified Water Ethanol 96%

6.2    Incompatibilities

None known

6.3    Shelf life

Three years in polypropylene or polyethylene tablet containers.

Two years in strip packs of opaque white or clear PVC film and 20p aluminium foil of 10 or 14 tablets.

6.4    Special precautions for storage

Do not store above 25°C Store in the original container

6.5    Nature and contents of container

Polypropylene or polyethylene containers containing 100 or 500 tablets. Strip packs of opaque white or clear PVC film and 20p aluminium foil of 10 or 14 tablets.

The tablets will be packed in multiple strips of 10 tablets i.e. 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 tablets.

The tablets will be packed in multiple strips of 14 tablets i.e. 14, 28, 56, 84 or 112 tablets.

6.6 Special precautions for disposal

None

7    MARKETING AUTHORISATION HOLDER

Wockhardt UK Limited Ash Road North Wrexham Industrial Estate Wrexham LL13 9UF United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 29831/0055

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

12/08/1982

10 DATE OF REVISION OF THE TEXT

26/08/2015