Source: Health Products Regulatory Authority (IE) Revision Year: 2022 Publisher: Tiofarma B.V., Benjamin Franklinstraat 5-10, 3261 LW Oud-Beijerland, Netherlands
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:
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.
Long-term use of colchicine may be associated with vitamin B12 deficiency.
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).
No long-term safety data are available in paediatric patients. The use of colchicine in children is primarily indicated for the indication FMF.
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.
Interactions with other drugs are not or scarcely documented. Given the nature of the side effects, caution is advised with concomitant administration of drugs that can affect the blood count or have a negative effect on hepatic and/or renal function.
In addition, substances such as cimetidine and tolbutamide may reduce metabolism of colchicine and thus increase plasma levels of colchicine.
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 may increase. Toxicity, including fatal cases, have been reported during concurrent use of inhibitors such as macrolides (clarithromycin and erythromycin), ciclosporin, ketoconazole, itraconazole, voriconazole, HIV protease inhibitors, calcium channel antagonists such as verapamil and diltiazem (see section 4.4).
Grapefruit juice may increase plasma levels of colchicine. Grapefruit juice should therefore not be taken together with colchicine.
If treatment with a P-gp inhibitor (e.g. ciclosporin, verapamil or quinidine) or strong CYP3A4 inhibitor (e.g. ritonavir, atazanavir, indinavir, clarithromycin, telithromycin, itraconazole or ketaconazole) is required in patients with normal renal or hepatic function, adjustment of colchicine dosage may be necessary. Concurrent use of such inhibitors and colchicine should be avoided in patients with renal or hepatic damage (see section 4.4).
Reversible malabsorption of cyanocobalamine (Vitamin B12) may be induced by an altered function of the intestinal mucosa.
The risk of myopathy and rhabdomyolysis is increased by a combination of colchicine with statins, fibrates, ciclosporin or digoxin.
Animal research has shown that administration of colchicine may negatively influence spermatogenesis (see section 5.3). Rare cases of reversible oligospermia and azoospermia in men are known from literature.
Since the course of FMF without treatment may also lead to infertility, the use of colchicine should be weighed against the potential risks and may be considered, if clinically needed.
Male patients should not father a child during and for at least 6 months following termination of colchicine therapy (see section 4.4). If, nevertheless, pregnancy occurs during this time period, genetic counselling should be tasked.
Animal studies denote reproductive toxicity (see section 5.3).
A moderate amount of data on pregnant women with FMF indicate no malformative or feto/neonatal toxicity of colchicine. Since the course of FMF without treatment may also negatively influence pregnancy, the use of colchicine during pregnancy should be weighed against the potential risks and may be considered, if clinically needed.
There is a limited amount of data from the use of colchicine in pregnant women with gout. As a precautionary measure, use of colchicine in this patient population and in women of childbearing potential not using effective contraception, should be avoided and may only be considered if other treatment options, including NSAIDs and glucocorticoids, are not applicable. Female patients have to use effective contraception during and for at least three months following termination of colchicine therapy (see section 4.4). If, nevertheless, pregnancy occurs during this time period, genetic counselling should be tasked.
Colchicine/metabolites is/are found in breastfed newborns/infants of treated women. There is insufficient information on the effects of colchicine in newborns/infants. Colchicine should not be used in breast-feeding women with gout. In lactating mothers with FMF, a decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Colchicine Tiofarma therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
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.
The following adverse reactions have been observed.
The frequencies are unknown, unless listed under one of the following classifications: Very common (≥1/10), Common (≥1/100, <1/10), Uncommon (≥1/1,000, <1/100), Rare (≥1/10,000, <1/1,000), Very rare (<1/10,000).
Blood and lymphatic system disorders: Bone marrow depression with agranulocytosis and aplastic anemia.
Nervous system disorders: Peripheral neuritis, neuropathy.
Gastrointestinal disorders: Common: abdominal pain, nausea, vomiting and diarrhea.
Hepatobiliary disorders: Hepatotoxicity.
Skin and subcutaneous tissue disorders: Alopecia, rash.
Musculoskeletal and connective tissue disorders: Myopathy and rhabdomyolysis.
Reproductive system and breast disorders: Amenorrhoea, dysmenorrhoea, oligospermia, azoospermia.
Respiratory, thoracic en mediastinal disorders: Pharyngolaryngeal pain.
Metabolism and nutrition disorders: Vitamin B12 deficiency.
No long-term safety data are available in paediatric patients.
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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.
Not applicable.
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