Cinited 0,5 Mg Tablets

CINITED 0.5 mg is indicated for the relief of acute attacks of gout in case of emergency.

Posology
In acute gout, the initial dose is 0,5 to 1 mg (1 to 2 tablets) by mouth immediately, followed by 0,5 mg (1 tablet) every 2 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 treatment course should not be repeated within 3 days.
Paediatric population:
The safety and efficacy of CINITED 0.5 mg in children under the age of 18 years has not been established.
Method of administration
Tablets are taken by mouth.

CINITED 0.5 mg is contraindicated in:
u2022 Hypersensitivity to colchicine or to any of the excipients listed in section 6.1.
u2022 Pregnancy
u2022 Patients with blood dyscrasia
u2022 In patients undergoing haemodialysis since colchicine cannot be removed by dialysis or exchange transfusion.
u2022 Patients with renal or hepatic impairment should not be given colchicine 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 in therapeutic doses.
u2022 Women of childbearing potential unless effective contraceptive measures are taken
u2022 Patients with severe renal dysfunction
u2022 Patients with severe hepatic dysfunction

CINITED 0.5 mg is potentially toxic; therefore, it is important that the dose as prescribed by a medical specialist with the necessary knowledge and experience is not exceeded. Colchicine has a narrow therapeutic range. Administration should be discontinued for toxic symptoms such as nausea, vomiting, abdominal pain, diarrhoea. If patients develop signs or symptoms that could indicate blood cell dyscrasias, such as fever, stomatitis, sore throat or prolonged bleeding, treatment with CINITED 0.5 mg should be discontinued immediately and a full haematological examination should be performed. Caution is advised in:
u2022 mild or moderate hepatic and renal impairment
u2022 cardiovascular disorders
u2022 gastrointestinal disorders
u2022 elderly and debilitated patients
u2022 patients with blood count abnormalities. CINITED 0.5 mg can cause severe bone marrow depression (agranulocytosis, aplastic anaemia, and thrombocytopenia). The change in the blood count can occur gradually, but also very suddenly. Aplastic anaemia in particular has a high risk of death. Periodic inspection of the blood count is necessary. When skin abnormalities develop, the blood count must be checked immediately. Macrolides, CYP3A4 inhibitors, ciclosporin, HIV protease inhibitors, calcium channel antagonists and statins may cause clinically important interactions with CINITED 0.5 mg leading to colchicine-induced toxicity (see section 4.5).

Interactions with other medicines are not or hardly documented. Due to the nature of the adverse reactions, caution should be exercised when co-administering medicinal products that may affect the blood count or adversely affect liver and / or kidney function. In addition, substances such as cimetidine, and tolbutamide can decrease the metabolism of CINITED 0.5 mg and thus increase plasma levels of CINITED 0.5 mg. CINITED 0.5 mg is a substrate for both CYP3A4 and the transport protein P-glycoprotein. Inhibitors of CYP3A4 and P-glycoprotein can increase the levels of CINITED 0.5 mg in the blood. Toxicity, including fatalities, has been reported during concomitant use of inhibitors such as macrolides (clarithromycin and erythromycin), ciclosporin, ketoconazole, itraconazole, voriconazole, HIV protease inhibitors, calcium channel antagonists such as verapamil and diltiazem and colchicine. If treatment with a P-glycoprotein inhibitor or a strong CYP3A4 inhibitor is necessary in patients with normal renal and hepatic function, the CINITED 0.5 mg dose may need to be adjusted. Concomitant use of these inhibitors with CINITED 0.5 mg should be avoided in patients with kidney or liver damage (see section 4.4). Grapefruit juice can increase the plasma level of CINITED 0.5 mg. Grapefruit juice should therefore not be taken with CINITED 0.5 mg. Reversible malabsorption of cyanocobalamin (vitamin B 12) can be induced by altered functioning of the intestinal mucosa. The risk of myopathy and rhabdomyolysis is increased when CINITED 0.5 mg is combined with statins, fibrates, ciclosporin or digoxin.

Women of childbearing potential/Contraception in males and female
Animal studies have shown that CINITED 0.5 mg is teratogenic. Women of childbearing potential should not take CINITED 0.5 mg unless effective contraceptive measures are taken.
Pregnancy
CINITED 0.5 mg is contraindicated in pregnancy.
Breastfeeding
CINITED 0.5 mg is widely excreted in breast milk. Therefore, CINITED 0.5 mg should not be used during breastfeeding.

No information is available on the influence of CINITED 0.5 mg on the ability to drive and use machines. However, the possibility of drowsiness and dizziness should be taken into account.

a. Summary of the safety profile
The most common side-effects are nausea, vomiting, abdominal pain and diarrhoea. CINITED 0.5 mg should be withdrawn or the dose reduced if adverse gastrointestinal effects occur. Burning of the skin and throat may also occur. Larger doses may cause profuse diarrhoea, gastrointestinal haemorrhage, skin rashes and renal damage.
b. Tabulated list of adverse reactions
The following side effects have been observed. The frequency is unknown, unless stated according to the classification below:
System Organ Class Frequency Adverse reaction
Blood and lymphatic system disorders Unknown Bone marrow depression with agranulocytosis and aplastic anaemia
Nervous system disorders Unknown Peripheral neuritis, neuropathy
Gastrointestinal disorders Frequent Abdominal pain, nausea, vomiting and diarrhoea
Skin and subcutaneous tissue disorders Unknown Alopecia, rash (rashes)
Musculoskeletal and connective tissue disorders Unknown Myopathy and rhabdomyolysis
Reproductive system and breast disorders Unknown Amenorrhoea, dysmenorrhoea, oligospermia, azoospermia
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 to SAHPRA via the u20186.04 Adverse Drug Reactions Reporting Formu2019. Found under SAHPRAu2019s publications: https://www/sahpra.org.za/Publications/Index/8

Symptoms
Symptoms of overdosage do not appear for at least several hours. The first symptoms are a feeling of burning and rawness in the mouth and throat and difficulty 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 also occur. Extensive vascular damage and acute renal toxicity with oliguria and haematuria have been reported. Bone marrow depression with leucopenia may be followed by rebound leucocytosis. Multiple organ failure may occur and may manifest as CNS toxicity, bone marrow depression, hepatocellular damage, muscle damage, respiratory distress, myocardial injury and renal damage. The patient may develop convulsions, delirium, muscle weakness, neuropathy and ascending paralysis of the nervous system. Death may be due to respiratory depression, cardiovascular collapse, bone marrow depression or sepsis. In surviving patients, alopecia, rebound leucocytosis and stomatitis may occur about 10 days after the acute overdosage.
Treatment
In cases of acute poisoning, patients should be carefully monitored for some time to take account of the delayed onset of symptoms. In acute poisoning the stomach should be emptied by administration of multiple dose activated charcoal. Treatment is symptomatic and supportive. Respiration may require assistance. The circulation and blood pressure should be maintained and fluid and electrolyte imbalance corrected. Haemodialysis or peritoneal dialysis may be of value when kidney function is compromised.