Colchicine is indicated for the treatment of acute gout flares. It is also indicated for Familial Mediterranean Fever (FMF) in adults and in children aged 4 years and older.

Colchicine is approved for the prevention of gout and for the treatment of acute, severe gout attacks. In gout, uric acid crystals accumulate in certain joints, triggering an inflammatory response. White blood cells move to these affected areas and attempt to engulf the crystals, which leads to the release of lactic acid and pro-inflammatory enzymes. These processes cause the typical pain and swelling associated with gout. Colchicine works by inhibiting the migration of white blood cells to the inflamed sites, thereby reducing inflammation and relieving pain.

An acute gout attack occurs due to an inflammatory reaction triggered by the deposition of monosodium urate crystals in joint tissues, which originate from hyperuricemic body fluids. As more crystals accumulate, the inflammatory response intensifies. Leukocytes migrate to the affected areas and attempt to engulf these crystals through phagocytosis. This process leads to the release of lactic acid and pro-inflammatory enzymes, resulting in severe pain, redness, and swelling in the affected joint. The accumulation of lactic acid lowers the local pH, which further promotes uric acid deposition. Colchicine acts by inhibiting the phagocytosis of uric acid crystals by leukocytes and directly reducing lactic acid production. In this way, it interrupts the cycle of crystal deposition and the inflammatory response that sustains an acute gout attack.

Colchicine is well absorbed following oral administration, reaching an average maximum plasma concentration (Cmax) of approximately 2.5 ng/mL (range 1.1 to 4.4 ng/mL) within 1 to 2 hours under fasting conditions. It has a mean apparent volume of distribution of about 5 to 8 L/kg and shows low plasma protein binding (around 39 ± 5%), primarily to albumin. The drug is metabolized mainly by the CYP3A4 enzyme into 2-O-demethylcolchicine and 3-O-demethylcolchicine, although these metabolites are present in minimal amounts (less than 5% of the parent drug). After repeated oral dosing (0.6 mg twice daily), colchicine has an elimination half-life ranging from approximately 26.6 to 31.2 hours.

Acute gouty arthritis:

• First dose- 1 to 1.2 mg (two 0.5 mg or two 0.6 mg tablets) at a time every 2 hours until pain and inflammation aborted.
• The total amount of colchicine needed to control pain and inflammation during an attack usually ranges from 4 to 8 mg.
• Articular pain and swelling typically reduced within 12 hours and are usually gone in 24 to 48 hours, An interval of three days between colchicine courses is advised in order to minimize the possibility of cumulative toxicity.

For prophylaxis during intercritical periods:

• To reduce the frequency of their severity, colchicine may be administered continuously.
• In patients who have less than one attack per year, the usual dose is 0.5 or 0.6 mg per day, three or four days a week.
• For cases involving more than one attack per year, the usual dose is 0.5 or 0.6 mg daily.
• Severe cases may require two or three 0.5 mg or 0.6 mg tablets daily.

For prophylaxis against attacks of gout in patients undergoing surgery:

• In patients with gout, an attack may be precipitated by even a minor surgical procedure. One 0.5 mg tablet or one 0.6 mg tablet three times daily should be administered for three days before and three days after surgery.

Co-administration of P-glycoprotein (P-gp) and/or CYP3A4 inhibitors (such as clarithromycin or cyclosporine) has been shown to increase and alter the concentration of colchicine in the body.

Colchicine should not be used in patients with renal or hepatic impairment who are also receiving P-glycoprotein (P-gp) inhibitors or strong CYP3A4 inhibitors (such as clarithromycin or cyclosporine).

Hematologic side effects such as myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, and aplastic anemia have been reported. Gastrointestinal symptoms like diarrhea, as well as pharyngolaryngeal pain, may also occur.

Pregnancy Category C. There are no adequate and well-controlled studies of colchicine in pregnant women. Colchicine is known to be excreted into human breast milk; therefore, caution should be exercised when it is administered to breastfeeding women.

Use in Special Populations – Pediatric Use:

Gout is uncommon in pediatric patients. The safety and effectiveness of colchicine in children have not been established.

The exact dose of colchicine that causes significant toxicity is not clearly known. Fatal cases have been reported with doses as low as 7 mg taken over a 4-day period, while some individuals have survived after ingesting doses exceeding 60 mg. A review of 150 overdose cases showed that patients who consumed less than 0.5 mg/kg generally survived and experienced milder toxicity, mainly gastrointestinal symptoms. In contrast, those who ingested 0.5 to 0.8 mg/kg developed more severe toxic effects, including myelosuppression.

Drugs used in Gout

Store at a temperature below 30°C. Protect from light and moisture. Keep out of the reach of children.