Generic

Colchicine

Indications

Colchicine is prescribed to treat acute gout flares. Also suggested in adults and children 4 years of age and older with Familial Mediterranean fever (FMF).

Pharmacology

An acute episode of gout appears to be caused by an inflammatory reaction to monosodium urate crystals formed in joint tissue by hyperuric bodily fluids; the reaction is exacerbated as more urate crystals accumulate. Leukocytes move to urate crystal deposit locations and attempt to swallow the crystals via phagocytosis. As a result, lactic acid and proinflammatory enzymes are produced, causing inflammation in the afflicted joint with significant pain, redness, and swelling. Lactic acid promotes a local drop in pH, which increases uric acid deposition. Colchicine inhibits leukocyte phagocytosis of uric acid and directly reduces lactic acid generation. As a result, the loop of urate crystal deposition and inflammatory response that maintains acute gout attacks is broken.

Colchicine is well absorbed when taken orally, with a mean Cmax of 2.5 ng/mL (range 1.1 to 4.4 ng/mL) in 1 to 2 hours following a single fasting dosage. The average apparent volume of distribution is 5 to 8 L/kg. Colchicine's binding to serum protein is modest (39 5%), predominantly to albumin, regardless of concentration. Colchicine is metabolized by CYP3A4 to 2-O-demethylcolchicine and 3-O-demethylcolchicine. These metabolites have very low plasma levels (less than 5 percent of parent drug). The mean elimination half-life after repeated oral dosages (0.6 mg twice day) is 26.6 to 31.2 hours.

Dosage & Administration

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.

Interaction

Co-administration with P-gp and/or CYP3A4 inhibitors (e.g., clarithromycin or cyclosporine) has been shown to affect Colchicine concentrations.

Contraindications

Colchicine should not be administered to patients with renal or hepatic impairment who are also taking Permeability glycoprotein (P-gp) inhibitors or strong CYP3A4 inhibitors (e.g., clarithromycin or cyclosporine).

Side Effects

Blood dyscrasias have been documented, including myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, and aplastic anemia. Diarrhea and pharyngolaryngeal discomfort are possible side effects.

Pregnancy & Lactation

Pregnancy Type C. There have been no appropriate or well-controlled studies of Colchicine in pregnant women. Colchicine is a drug that is excreted in human milk. When administering to a breastfeeding lady, use extreme caution.

Precautions & Warnings

Gout is seldom seen in pediatric patients. Colchicine's safety and efficacy in pediatric patients have not been demonstrated.

Therapeutic Class

Gout medications

Storage Conditions

Temperatures should be kept below 30°C. Keep out of direct sunlight and dampness. Keep the medication out of children's reach.

Pharmaceutical Name

Incepta Pharmaceuticals Ltd