Kolcrys 0,5 mg Tablets

KOLCRYS is indicated for the relief of acute attacks of gout in cases of emergency.

Posology: The initial dose is 0,5 mg to 1 mg (1 to 2 tablets) orally immediately, followed by 0,5 mg (1 tablet) every two hours until pain relief is obtained or gastrointestinal symptoms like vomiting or diarrhoea occur. A maximum total treatment course of 6 mg must not be exceeded. The course should not be repeated within three days.

Renal impairment: Reduce the dose or increase the interval between doses when given to patients with mild to moderate renal impairment (see section 4.4).

• Hypersensitivity to colchicine or to any of the inactive ingredients of KOLCRYS (see section 6.1).
• Pregnancy (see section 4.6).
• Patients with hepatic or renal impairment requiring concomitant therapy with CYP3A4 or P-glycoprotein inhibitors (see section 4.5).
• Patients with severe renal impairment (creatinine clearance less than 30 mL/min).
• Patients with severe liver impairment.
• Patients with blood disorders should not use KOLCRYS.
• Patients undergoing haemodialysis, since it cannot be removed by dialysis or exchange transfusion.

KOLCRYS is potentially toxic, so it is important not to exceed the recommended dose. KOLCRYS should be given with care to elderly and debilitated patients, as there is a greater risk of cumulative toxicity. KOLCRYS has a narrow therapeutic window, and should be discontinued if toxic symptoms such as nausea, vomiting, abdominal pain and diarrhoea occur. KOLCRYS should be used with caution in patients with cardiovascular, mild and moderate hepatic, mild and moderate renal, or gastrointestinal diseases.

KOLCRYS is contraindicated in severe renal and hepatic impairment. A reduction of KOLCRYS dosage or interruption of KOLCRYS 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). If patients develop signs or symptoms that could indicate a blood cell dyscrasia, such as fever, stomatitis, sore throat, prolonged bleeding, bruising or skin disorders, treatment with KOLCRYS should be immediately discontinued and a full haematological investigation should be conducted straight away.

Excipient warning: KOLCRYS contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take KOLCRYS.

KOLCRYS is a substrate for P-glycoprotein and the cytochrome P450 isoenzyme CYP3A4. Inhibitors of these may increase blood concentration levels of KOLCRYS and the potential for toxicity. Life-threatening or fatal medicine interactions have been reported when KOLCRYS was given with the following medicines:

• Macrolides (e.g., erythromycin).
• Calcium channel antagonists (e.g., diltiazem).

KOLCRYS is contraindicated in patients with renal or hepatic impairment who are taking a P-glycoprotein inhibitor (e.g., ciclosporin, verapamil, quinidine) or a strong CYP3A4 inhibitor (e.g., ritonavir, atazanavir, clarithromycin, telithromycin, itraconazole, ketoconazole) (see section 4.3). If treatment with a P-glycoprotein inhibitor or a strong CYP3A4 inhibitor is required in patients with normal renal and hepatic function, a reduction in the KOLCRYS dose or an interruption of KOLCRYS treatment is recommended (see section 4.4). Myopathy and rhabdomyolysis have been reported when taking KOLCRYS with statins, fibrates, ciclosporin and digoxin. Hydrochlorothiazide may increase serum uric acid and interfere with activity of KOLCRYS. Caution is advised with concomitant administration of medicine that can affect the blood count or have a negative effect on hepatic and/or renal function, due to the nature of side effects. Substances such as cimetidine and tolbutamide reduce metabolism of KOLCRYS and thus plasma levels of KOLCRYS increase. Grapefruit juice may increase plasma levels of KOLCRYS. Grapefruit juice should therefore not be taken together with KOLCRYS. KOLCRYS may impair the absorption of vitamin B12.

Pregnancy: Colchicine, as in KOLCRYS, is genotoxic in vivo and in vitro and is teratogenic in animals. The use of KOLCRYS is contraindicated in pregnancy (see section 4.3).

Lactation: KOLCRYS is distributed into breast milk. KOLCRYS may be used with caution during breastfeeding.

KOLCRYS is not known to affect the ability to drive a vehicle and use machines. Caution is advised before performing tasks requiring attention until the effects of KOLCRYS are known.

System Organ Class Frequency Side effects

• Blood and the lymphatic system disorders Frequency unknown Bone marrow depression with agranulocytosis, aplastic anaemia, thrombocytopenia
• Nervous system disorders Frequency unknown Peripheral neuritis, neuropathy
• Respiratory disorders Frequency unknown Burning of the throat
• Gastrointestinal disorders Frequent Frequency unknown Abdominal pain, nausea, vomiting, diarrhoea Gastrointestinal haemorrhage
• Hepato-biliary disorders Frequency unknown Hepatotoxicity
• Skin and subcutaneous tissue disorders Frequency unknown Alopecia, rash, burning sensation of the skin
• Musculoskeletal, connective tissue and bone disorders Frequency unknown Myopathy, rhabdomyolysis
• Renal and urinary disorders Frequency unknown Renal damage
• Reproductive system and breast disorders Frequency unknown Amenorrhoea, dysmenorrhoea, oligospermia, azoospermia

Reporting of suspected adverse reactions: Reporting of suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

KOLCRYS has a narrow therapeutic window and is extremely toxic in overdose. Patients with renal or hepatic impairment, gastrointestinal or cardiac disease and elderly patients are at particular risk of toxicity. Overdose with KOLCRYS is complex and specialist advice should be promptly obtained. Symptoms of overdose may not appear for at least 6 hours. All patients, even in the absence of early symptoms, should be referred for immediate medical assessment.

Symptoms: The first symptoms of toxicity are a feeling of burning and rawness in the mouth and throat, and difficulty in swallowing. This is followed by nausea, vomiting, and diarrhoea. The diarrhoea may be severe and haemorrhagic, and can lead to metabolic acidosis, dehydration, hypotension and shock. A burning sensation of the throat, stomach and skin may occur. Extensive vascular damage and acute renal toxicity with oliguria and haematuria have been reported. Bone marrow depression with leukopenia may be followed by rebound leukocytosis. Multiple organ failure may occur and may manifest as central nervous system (CNS) toxicity, bone marrow depression, hepatocellular damage, muscle damage, respiratory distress, myocardial injury and renal damage. The patient may develop convulsions, delirium, neuropathy and ascending paralysis of the central nervous system. Death may be due to respiratory distress, cardiovascular collapse, bone marrow depression or sepsis. Alopecia, rebound leukocytosis and stomatitis may occur about 10 days after the acute overdose, in surviving patients.

Treatment: When treating KOLCRYS overdose or acute poisoning, patients should be carefully monitored for some time to take account of the delayed onset of symptoms. Multiple doses of activated charcoal should be given. Treatment is primarily symptomatic and supportive. Patients may require respiratory assistance, maintenance of blood pressure and circulation and correction of fluid and electrolyte imbalance. Haemodialysis has no efficacy (high apparent distribution volume).