RiteMED Colchicine

White, round, biconvex, uncoated tablets, plain on both sides.
Each uncoated tablet contains: Colchicine, USP 500 mcg.

Pharmacology: Pharmacodynamics: The mechanism by which colchicine exerts its beneficial effect in patients with Familial Mediterranean Fever (FMF) has not been fully elucidated; however, evidence suggests that colchicine may interfere with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-1β. Additionally, colchicine disrupts cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules and consequently prevents the activation, degranulation and migration of neutrophils thought to mediate some gout symptoms.
Pharmacokinetics: Colchicine is readily absorbed from the gastrointestinal tract and peak concentrations occur in plasma by half an hour to two hours.
The leukocytes, kidney, liver and the spleen also contain high concentrations of Colchicine. 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 disorder. Colchicine is distributed into breast milk.

Colchicine tablets may be used for the treatment of acute gout and for short term prophylaxis during initial therapy with allopurinol and uricosuric drugs.

Adults only: Gout: 1 mg initially, followed by 500 micrograms every two to three hours until relief of pain is obtained or vomiting or diarrhea occurs. A total dose of 6 mg should not be exceeded. The course should not be repeated within three days. Or as prescribed by the physician.
Renal Impairment: For mild/moderate renal impairment (creatinine clearance 10-50 mL/minute), reduce dose or increase interval between doses.
For use with allopurinol or uricosuric drugs: 500 mcg two to three times daily.
Elderly: To be given with great care.
Children: Not recommended.
Or as prescribed by the physician.

The exact dose of colchicine that produces significant toxicity is unknown. Fatalities have occurred after ingestion of a dose as low as 7 mg over a four-day period, while other patients have survived after ingesting more than 60 mg. A review of 150 patients who overdosed on colchicine found that those who ingested less than 0.5 mg/kg survived and tended to have milder toxicities such as gastrointestinal symptoms, whereas those who took 0.5 to 0.8 mg/kg had more severe reactions such as myelosuppression. There was 100% mortality in those who ingested more than 0.8 mg/kg. The first stage of acute colchicine toxicity typically begins within 24 hours of ingestion and includes gastrointestinal symptoms such as abdominal pain, nausea, vomiting, diarrhea and significant fluid loss, leading to volume depletion. Peripheral leukocytosis may also be seen. Life-threatening complications occur during the second stage, which occurs 24 to 72 hours after drug administration, attributed to multiorgan failure and its consequences. Death is usually a result of respiratory depression and cardiovascular collapse. If the patient survives, recovery of multiorgan injury may be accompanied by rebound leukocytosis and alopecia starting about one week after the initial ingestion.
Treatment of colchicine poisoning should begin with gastric lavage and measures to prevent shock. Otherwise, treatment is symptomatic and supportive. No specific antidote is known. Colchicine is not effectively removed by dialysis.

The use of Colchicine is contraindicated in pregnancy.
Colchicine should not be used in patients undergoing hemodialysis since it cannot be removed by dialysis or exchange transfusion.
Colchicine should not be used in patients with severe renal impairment (creatinine clearance less than 10 mL/minute).
Colchicine is contraindicated in patients with renal or hepatic impairment who are taking a P-glycoprotein or a strong CYP3A4 inhibitor.

Colchicine should be given with great care to elderly and debilitated patients as there is a greater risk of cumulative toxicity.
Care should also be exercised in those with cardiac, hepatic, gastrointestinal disease or if patients are breast-feeding.
Colchicine should be avoided in patients with blood disorders.
It should also generally be avoided in pregnancy since it is known to be teratogenic in animals.

Pregnancy: Do not use in pregnancy as there is a risk of fetal chromosome damage.
Lactation: Colchicine is distributed into breast milk. Colchicine may be used with caution during breastfeeding.

The following adverse reactions have been observed.
The frequencies are listed under one of the following classifications: Very common >1/10; Common >1/100 and <1/10; Uncommon >1/1000 and <1/100; Rare >1/10,000 and <1/1000; Very rare <1/10,000; Not known (cannot be estimated from the available data).
Blood and lymphatic system disorders: Not known: bone marrow depression with agranulocytosis, aplastic anaemia and thrombocytopenia.
Nervous system disorders: Not known: peripheral neuritis, neuropathy.
Gastrointestinal system disorders: Common: abdominal pain, nausea, vomiting and diarrhea.
Not known: gastrointestinal hemorrhage.
Hepatobiliary disorders: Not known: hepatotoxicity.
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, dysmenorrhoea, oligospermia, azoospermia.

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.
Concomitant administration of azithromycin and P-gp substrates such as colchicine has been reported to result in increased serum levels of P-gp substrate. Therefore, if colchicine and azithromycin are administered concomitantly, the possibility of elevated serum colchicine concentrations should be considered.
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).
A reduction in colchicine dosage or an interruption of colchicine 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. A 4-fold reduction in colchicine dosage is recommended when co-administered with a P-gp inhibitor and/or a strong CYP3A4 inhibitor. A 2-fold reduction in colchicine dosage is recommended when co-administered with a moderate CYP3A4 inhibitor.

Store at temperatures not exceeding 30°C.

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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