Colnova 0.5 0,5 mg Tablet

COLNOVA 0,5 is indicated for the relief of acute attacks of gout.

Acute attacks of gout in adult patients: Take 0,5 to 1 mg (1 to 2 tablets) by mouth immediately, followed by 0,5 mg (1 tablet) 2 hourly until pain relief is obtained or until vomiting or diarrhoea occur. A maximum dosage of 6 mg (six tablets) must not be exceeded. A minimum of 3 days, but preferably 7 days, should elapse between courses of gout treatment with COLNOVA 0,5 to avoid cumulative toxicity. Creatinine clearance: GFR 10 to 50 mL/minute, 50 % of normal dose. GFR less than 10 mL/minute, treatment with COLNOVA 0,5 must be avoided (see section 4.3). Special populations Elderly: COLNOVA 0,5 should be given with caution to the elderly (see section 4.4). Paediatric population There are no data available. COLNOVA 0,5 is not an analgesic medication and should not be used to treat pain from other causes. Method of administration For oral use.

• Hypersensitivity to colchicine or to any of the excipients listed in section 6.1.
• COLNOVA 0,5 should not be used in patients undergoing haemodialysis since it cannot be removed by dialysis or exchange transfusion.
• In patients with severe renal impairment (creatinine clearance less than 10 mL/minute).
• Patients with severe hepatic impairment.
• In patients with blood disorders: myelosupression, leucopenia, granulocytopenia, thrombocytopenia and aplastic anaemia.
• Patients with renal or hepatic impairment should not be given COLNOVA 0,5 in conjunction with P-gp (e.g., ciclosporin, verapamil or quinidine) or potent CYP3A4 inhibitors (e.g., ritonavir, atazanavir, indinavir, clarithromycin, telithromycin, itraconazole or ketoconazole). In these patients, life-threatening and fatal colchicine toxicity has been reported with COLNOVA 0,5 in therapeutic doses (see sections 4.5 and 4.4).
• Pregnancy and lactation. (see section 4.6)
• Women of childbearing potential unless using effective contraceptive measures.

Fatal overdoses COLNOVA 0,5 potentially toxic, so it is important not to exceed the dose prescribed by a medical practitioner with the necessary knowledge and experience. (see section 4.2) Colchicine as contained in COLNOVA 0,5 has a narrow therapeutic window. The administration should be discontinued if toxic symptoms such as nausea, vomiting, abdominal pain, diarrhoea occur. (see section 4.8) Blood dyscrasias COLNOVA 0,5 may cause severe bone marrow depression (agranulocytosis, aplastic anaemia, thrombocytopenia). The change in blood counts may be gradual or very sudden. Aplastic anaemia in particular has a high mortality rate. Periodic checks of the blood picture are essential. 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 COLNOVA 0,5 should be immediately discontinued and a full haematological investigation should be conducted straight away. Caution is advised in case of:

• liver or renal impairment;
• cardiovascular disease;
• gastrointestinal disorders;
• elderly and debilitated patients;
• patients with abnormalities in blood counts.

Colchicine is a substrate for both CYP3A4 and the transport protein P-gp. In the presence of CYP3A4 or P-gp inhibitors, the concentrations of colchicine in the blood increase. Toxicity, including fatal cases, have been reported during concurrent use of CYP3A4 or P-gp inhibitors such as macrolides (clarithromycin and erythromycin), ciclosporin, ketoconazole, itraconazole, voriconazole, HIV protease inhibitors, calcium channel blockers (verapamil and diltiazem) and disulfiram (see section 4.4). Colchicine is contraindicated in patients with renal or hepatic impairment who are taking a P-gp 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). A reduction in COLNOVA 0,5 dosage or an interruption of COLNOVA 0,5 treatment is recommended in patients with normal renal or hepatic function if treatment with a P-gp inhibitor or moderate or strong CYP3A4 inhibitor is required (see section 4.4). A 4-fold reduction in COLNOVA 0,5 dosage is recommended when co-administered with a P-gp inhibitor and/or a strong CYP3A4 inhibitor. A 2-fold reduction in COLNOVA 0,5 dosage is recommended when co-administered with a moderate CYP3A4 inhibitor. Given the nature of the side effects, caution is advised with concomitant administration of medicines that can affect the blood count or have a negative effect on hepatic and/or renal function.

Women of child-bearing potential Women of childbearing potential have to use effective contraception during treatment. Pregnancy Colchicine is genotoxic in vitro and in vivo and is teratogenic in animal studies (see section 5.3). COLNOVA 0,5 is therefore contraindicated in pregnancy (see section 4.3). Breastfeeding COLNOVA 0,5 is excreted in breast milk. Therefore, the use of COLNOVA 0,5 is contraindicated in women who are breastfeeding (see section 4.3). Fertility Colchicine administration in animals induces significant reductions in fertility.

No details are available regarding the influence of COLNOVA 0,5 on the ability to drive and use machines. However, patients should not drive, use machinery or perform any tasks that require concentration until they are certain that COLNOVA 0,5 do not adversely affect their ability to do so safely (see section 4.8).

a) Summary of safety profile COLNOVA 0,5 frequently causes nausea, vomiting, abdominal pain and diarrhoea. Tabulated summary of adverse reactions:
System organ class Adverse reaction Frequency
a. Blood and lymphatic system disorders Bone marrow suppression with, agranulocytosis, aplastic anaemia, thrombocytopenia, leucopenia, neutropenia* Unknown frequency Nervous system disorders Peripheral neuritis, peripheral neuropathy Unknown frequency Vascular disorders Hypotension (with large doses) Unknown frequency Gastrointestinal system disorders Abdominal pain, nausea, vomiting and diarrhoea** Frequent
Burning of the throat Less frequent Profuse diarrhoea, gastrointestinal haemorrhage Unknown frequency Hepato-biliary disorders Hepatic damage, hepatotoxicity Unknown frequency Skin and subcutaneous tissue disorders Urticaria, morbilliform eruptions Less frequent Burning of the skin, skin rashes, alopecia Unknown frequency Musculoskeletal and connective tissue disorders Myopathy and rhabdomyolysis Unknown frequent Renal and urinary disorders Renal damage and dehydration Unknown frequency Reproductive system and breast disorders Amenorrhoea, dysmenorrhoea, oligospermia, reversible azoospermia Unknown frequency
Description of selected adverse reactions * Larger doses may cause profuse diarrhoea, gastrointestinal haemorrhage, skin rashes and renal damage. Bone marrow depression with agranulocytosis, thrombocytopenia and aplastic anaemia have occurred on prolonged treatment, as well as peripheral neuritis, myopathy, rashes, and alopecia. ** COLNOVA 0,5 should be withdrawn or the dose reduced if gastrointestinal side effects occur. Reporting of suspected adverse reactions Reporting 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 Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Colchicine such as COLNOVA 0,5 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. Following COLNOVA 0,5 overdose, all patients, even in the absence of early symptoms, should be referred for immediate medical assessment. Clinical: Symptoms of acute overdosage may be delayed (3 hours on average): nausea, vomiting, abdominal pain, hemorrhagic gastroenteritis, volume depletion, electrolyte abnormalities, leukocytosis, hypotension in severe cases. The second phase with life threatening complications develops 24 to 72 hours after medicine administration: multisystem organ dysfunction, acute renal failure, confusion, coma, ascending peripheral motor and sensory neuropathy, myocardial depression, pancytopenia, dysrhythmias, respiratory failure, consumption coagulopathy. Death is usually a result of respiratory depression and cardiovascular collapse. If the patient survives, recovery may be accompanied by rebound leukocytosis and reversible alopecia starting about one week after the initial ingestion. Treatment: No antidote is available. 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 of presentation. Doses may be repeated every 4 hours in both adults and children, for those who ingested more than 300 microgram/kg, provided they are not vomiting. Haemodialysis has no efficacy (high apparent distribution volume). Close clinical and biological monitoring in hospital environment. Symptomatic and supportive treatment: control of respiration, maintenance of blood pressure and circulation, correction of fluid and electrolytes imbalance. Patients should be monitored for at least 6 hours after ingestion, or 12 hours if they have taken more than 300 microgram/kg. Asymptomatic patients may then be discharged, with advice to return if gastrointestinal symptoms appear. The lethal dose varies widely (7 - 65 mg single dose) for adults but is generally about 20 mg.