YSP Colchicine

A white to off-white color round tablet, one side impressed with a score, blank on the other side.
Each tablet contains: Colchicine 0.6 mg.

Pharmacology: Pharmacodynamics: Colchicine acts against the inflammatory response to urate crystals, by possibly inhibiting the migration of granulocytes into the inflamed area. This reduces the release of lactic acid and proinflammatory enzymes that occur during phagocytosis and breaks the cycle that leads to the inflammatory response.
Pharmacokinetics: Peak plasma concentrations of colchicine are reached within 2 hours of oral administration. Colchicine is partially deacetylated in the liver and unchanged drug and its metabolites are excreted in the bile and undergo intestinal reabsorption. Colchicine is found in high concentration in leucocytes, kidneys and the liver and spleen. Most of the drug is excreted in the faeces but 10% to 20% is excreted in the urine and this proportion rises in patients with liver disorders.

For the treatment of acute gout, and for the prophylaxis of recurrent gout and to prevent acute attacks during initial therapy with allopurinol and uricosuric drugs.

Recommended Dose: Patients vary widely in their ability to tolerate the drug.
Dosage should be varied according to body weight or individual reaction to colchicine toxicity.
Acute gout: 1-2 tablets every 2 hours until the pain is relieved or until nausea, vomiting and diarrhoea occur. The usual amount of colchicine required in a course of therapy may range from 4-8mg.
Pain and swelling usually abate within 12 hours and are usually gone within 48-72 hours.
Prophylaxis: Depending on the severity and patient's response and tolerance, the dosage varies from 1 tablet daily 1-4 times weekly to 1 tablet daily.
Pseudogout: To relieve acute attack, 1-2 tablets every 2 hours until the pain is relieved or until nausea, vomiting and diarrhea occur.
Prophylaxis: Depending on the severity and patient's response and tolerance, up to 2 tablets daily.
Route of Administration: For oral administration only.

Colchicine has a narrow therapeutic window and is extremely toxic in overdose. Patients at particular risk of toxicity are those with renal or hepatic impairment, gastro-intestinal or cardiac disease and patients at extremes of age.
Symptoms may be delayed (3 hours on average): nausea, vomiting, abdominal pain, hemorrhagic gastroenteritis, volume depletion, electrolyte abnormalities, leukocytosis, and hypotension in severe cases. The second phase with life threatening complications develops 24 to 72 hours after drug administration: multisystem organ dysfunction, acute renal function, and confusion, coma, ascending peripheral motor and sensory neuropathy, myocardial depression, pancytopenia, dysrhythmias, respiratory failure, and 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 available.
Elimination of toxins by gastric lavage within one hour of acute poisoning.
Consider oral activated charcoal in adults who have ingested more than 0.1 mg/kg bodyweight within 1 hour of presentation and in children who have ingested any amount within 1 hour of presentation.
Hemodialysis has no efficacy.
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 electrolyte imbalance.
The lethal dose varies widely (7-65mg single dose) for adults but is generally about 20mg.

The use of colchicine is contraindicated in: Pregnancy and lactation; People who are hypersensitive to colchicines; Children under 2 years of age; Blood dyscrasias; Uric acid kidney stones; Patients with renal or hepatic impairment who are taking a P-glycoprotein (P-gp) inhibitor or a strong CYP34A4 inhibitor.
Colchicine should not be used in patients undergoing haemodialysis since it cannot be removed by dialysis or exchange transfusion.

Colchicine is potentially toxic so it is important not to exceed the dose prescribed. Colchicine has a narrow therapeutic window. The administration should be discontinued if toxic symptoms such as nausea, vomiting, abdominal pain and diarrhea occur. Colchicine may cause severe bone marrow depression (agranulocytosis, aplastic anaemia, and thrombocytopenia). The change in blood count 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 sign and symptoms that could indicate a blood cell dyscrasia, such as fever, stomatitis, sore throat, prolonged bleeding, bruising, or skin disorders, treatment with colchicine 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.
Co-administration with P-gp inhibitors and/or moderate 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 moderate or strong CYP3A4 inhibitor is required in patients with normal renal and hepatic function, a reduction in colchicine dosage or interruption of colchicine treatment is recommended.
This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on Ability to Drive and Use Machine: 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.

It is contraindicated during pregnancy and lactation.

Blood and lymphatic system disorders: Not known: Bone marrow depression with agranulocytosis, aplastic anemia and thrombocytopenia.
Nervous system disorders: Not known: Peripheral neuritis, neuropathy.
Gastrointestinal system disorders: Common: Abdominal pain, nausea, vomiting, and diarrhea.
Not known: Gastrointestinal haemorrhage.
Hepatobiliary disorders: Not known: Hepatic damage.
Skin and subcutaneous tissue disorders: Not known: Alopecia, rash.
Musculoskeletal and connective tissue disorders: Not known: Myopathy and rhabdomyolysis.
Renal and urinary disorders: Not known: Renal damage.
Reproductive system and breast disorders: Not known: Amenorrhoea, dysmenorrhea, oligospermia, azoospermia.
Others: Angioneurotic oedema, epistaxis, chromosomal dysfunction.

Potential risk of severe drug interactions, including death, in certain patients treated with colchicine and concomitant P-glycoprotein or strong CYP3A4 inhibitors such as clarithromycin, cyclosporine, erythromycin, calcium channel antagonists (e.g. Verapamil and Diltiazem), telithromycin, ketoconazole, itraconazole, HIV protease inhibitors and nefazodone.
P-glycoprotein or strong CYP3A4 inhibitors are not to be used in patients with renal or hepatic impairment who are taking colchicine.
A dose reduction or interruption of colchicine treatment should be considered in patients with normal renal and hepatic function if treatment with a P-glycoprotein or a strong CYP3A4 inhibitor is required. Avoid consuming grapefruit and grapefruit juice while using colchicine.

Store at temperature below 30°C.
Protect from light.
Shelf Life: 3 years.

Hyperuricemia & Gout Preparations

M04AC01 - colchicine ; Belongs to the class of preparations with no effect on uric acid metabolism. Used in the treatment of gout.

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