Special Warning : אזהרת שימוש

4.4       Special warnings and precautions for use
Colchicine is potentially toxic so it is important not to exceed the dose prescribed by a medical specialist with the necessary knowledge and experience. Colchicine has a narrow therapeutic window. The administration should be discontinued if toxic symptoms such as nausea, vomiting, abdominal pain, diarrhea occur.

If patients develop signs or symptoms that could indicate a blood cell dyscrasia, such as fever, stomatitis, sore throat, or prolonged bleeding, treatment with colchicine should be immediately discontinued and a full haematological investigation should be conducted.

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 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 count are essential. If skin abnormalities (petechiae) occur, blood counts should be checked immediately.

Macrolides, CYP3A4 inhibitors, ciclosporin, HIV protease inhibitors, calcium channel blockers, and statins may cause clinically significant interactions with colchicine which may lead to colchicine-induced toxicity (see section 4.5).

Co-administration with P-gp inhibitors and/or strong CYP3A4 inhibitors will increase the exposure to colchicine, which may lead to colchicine-induced toxicity including fatalities. If treatment with a P-gp inhibitor or a strong CYP3A4 inhibitor is required in patients with normal renal and or hepatic function, a reduction in colchicine dosage is recommended (see sections 4.2 and 4.5) and patients should be carefully monitored for adverse effects of colchicine.
For patients with an impaired renal or hepatic function, the combined use of colchicine and P-gp inhibitors and/or strong CYP3A4 inhibitors should be avoided whenever possible, as it may be difficult to forecast and control systemic exposure to colchicine. In those exceptional cases where continuation of colchicine when starting P-gp inhibitors and/or strong CYP3A4 inhibitors is considered a benefit, despite the potential risk of overdose, significant dose reductions of colchicine dose and careful clinical monitoring should be applied.

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

Long-term use of colchicine may be associated with vitamin B12 deficiency.

In case colchicine is used for treatment of acute gout or for prophylaxis of a gout attack during initiation of urate-lowering therapy
Patients should be carefully informed about the potential risk of a possible pregnancy and about effective contraception measures to be followed. Female patients should use effective contraception during and for at least three months following termination of colchicine therapy (see section 4.6). Based on concerns about a potential damage to sperm cells (see section 5.3), male patients should not father a child during and for at least 6 months following termination of colchicine therapy (see section 4.6).

Paediatric population
No long-term safety data are available in paediatric patients. The use of colchicine in children is primarily indicated for the indication FMF.

Effects on Driving

4.7   Effects on ability to drive and use machines
No data are available regarding the influence of colchicine on the ability to drive and use machines. However, the possibility of drowsiness and dizziness should be taken into account.