colchicine

KOL-chi-seen

Therapeutic Classification: antigout agents

High Alert

Treatment of gout flares (Colcrys and generic tablets only).
Prophylaxis of gout flares (Gloperba, Mitigare, and generic capsules only).
Familial Mediterranean fever (Colcrys and generic tablets only).
To reduce the risk of MI, stroke, coronary revascularization, and cardiovascular death in patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease (Lodoco only).

Interferes with the functions of WBCs in initiating and perpetuating the inflammatory response to monosodium urate crystals.

Therapeutic effects:

Decreased pain and inflammation in acute attacks of gout.
Reduced number of attacks of gout and familial Mediterranean fever.
Reduction in risk of MI, stroke, coronary revascularization, and cardiovascular death in patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease.

Absorption: 45% absorbed from the GI tract, then re-enters GI tract from biliary secretions, when more absorption may occur.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Partially metabolized by the liver by the CYP3A4 isoenzyme; also a substrate for P-glycoprotein. Secreted in bile back into GI tract; eliminated in the feces. 40–65% excreted in the urine as unchanged drug.

Half-Life: 19–31 hr.

(anti-inflammatory activity)

ROUTE	ONSET	PEAK	DURATION
PO	12 hr	24–72 hr	unknown

Contraindicated in:

Hypersensitivity;
Concurrent use of P-glycoprotein (P-gp) inhibitors or strong CYP3A4 inhibitors in patients with renal or hepatic impairment (generic tablets or Colcrys only);
Concurrent use of drugs that inhibit both P-gp and CYP3A4 in patients with renal or hepatic impairment (Gloperba or Mitigare only);
Concurrent use of strong P-glycoprotein inhibitors or strong CYP3A4 inhibitors (Lodoco only);
Presence of both renal and hepatic impairment (Gloperba and Mitigare only);
Renal failure (CCr <15 mL/min) (Lodoco only);
Severe hepatic impairment (Lodoco only);
Pre-existing blood dyscrasias (Lodoco only).

Use Cautiously in:

Renal impairment (dose ↓ suggested if CCr <80 mL/min);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children (for gout or cardiovascular risk reduction);
Geri: risk of toxicity in older adults with renal impairment.

Derm: alopecia

GI: diarrhea, nausea, vomiting, abdominal pain

Hemat: AGRANULOCYTOSIS, APLASTIC ANEMIA, leukopenia, thrombocytopenia

MS: myalgia, RHABDOMYOLYSIS

Neuro: peripheral neuritis

Drug-drug:

Concurrent use of strong CYP3A4 inhibitors, including atazanavir, clarithromycin, darunavir/ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, ritonavir, or tipranavir/ritonavir, may ↑ levels and risk of toxicity; ↓ colchicine dose in patients with normal renal or hepatic function; concurrent use in patients with renal or hepatic impairment is contraindicated; concurrent use with Lodoco is contraindicated.
Concurrent use of strong P-gp inhibitors, including cyclosporine or ranolazine may ↑ levels and risk of toxicity; ↓ colchicine dose in patients with normal renal or hepatic function; concurrent use in patients with renal or hepatic impairment is contraindicated; concurrent use with Lodoco is contraindicated.
Moderate CYP3A4 inhibitors, including aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, or verapamil may ↑ levels and risk of toxicity; ↓ colchicine dose in patients with normal renal or hepatic function; avoid concurrent use of Lodoco in patients with renal or hepatic impairment.
Additive bone marrow depression may occur with bone marrow depressants or radiation therapy.
↑risk of rhabdomyolysis with HMG-CoA reductase inhibitors, gemfibrozil, fenofibrate, digoxin, or cyclosporine.
Additive adverse GI effects with NSAIDs.
May cause reversible malabsorption of vitamin B12.

Grapefruit juice may ↑ levels and risk of toxicity; ↓ colchicine dose (for all formulations, except Lodoco); avoid concurrent use with Lodoco.

Treatment of Gout Flares (Colcrys and Generic Tablets Only)

PO (Adults ): 1.2 mg initially, then 0.6 mg 1 hr later (maximum dose of 1.8 mg in 1 hr); Concomitant use of strong CYP3A4 inhibitors in patients with normal renal and hepatic function (atazanavir, clarithromycin, darunavir/ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, ritonavir, tipranavir/ritonavir): 0.6 mg initially, then 0.3 mg 1 hr later (do not repeat treatment course for ≥3 days); Concomitant use of moderate CYP3A4 inhibitors (aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, verapamil): 1.2 mg as single dose (do not repeat for ≥3 days); Concomitant use of strong P-gp inhibitors (cyclosporine, ranolazine) in patients with normal renal and hepatic function: 0.6 mg as single dose (do not repeat for ≥3 days).

Renal Impairment

PO (Adults ): CCr <30 mL/min: 1.2 mg initially, then 0.6 mg 1 hr later; do not repeat treatment course for ≥2 wk; Dialysis: 0.6 mg as single dose; do not repeat treatment course for ≥2 wk.

Prevention of Gout Flares (Gloperba, Mitigare, and Generic Capsules Only)

PO (Adults ): 0.6 mg once or twice daily; Concomitant use of strong CYP3A4 inhibitors (atazanavir, clarithromycin, darunavir/ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, ritonavir, tipranavir/ritonavir) or strong P-gp inhibitors (cyclosporine, ranolazine) in patients with normal renal and hepatic function: if original dose was 0.6 mg twice daily, ↓ to 0.3 mg once daily; if original dose was 0.6 mg once daily, ↓ to 0.3 mg every other day; Concomitant use of moderate CYP3A4 inhibitors (aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, verapamil): if original dose was 0.6 mg twice daily, ↓ to 0.3 mg twice daily or 0.6 mg once daily; if original dose was 0.6 mg once daily, ↓ to 0.3 mg once daily.

Renal Impairment

PO (Adults ): CCr <30 mL/min: 0.3 mg once daily; Dialysis: 0.3 mg twice weekly.

Familial Mediterranean Fever (Colcrys and Generic Tablets Only)

PO (Adults and Children >12 yr): 1.2–2.4 mg/day (in 1–2 divided doses); may ↑ or ↓ dose in 0.3-mg/day increments based on safety and efficacy; Concomitant use of strong CYP3A4 inhibitors (atazanavir, clarithromycin, darunavir/ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, ritonavir, tipranavir/ritonavir) or strong P-gp inhibitors (cyclosporine, ranolazine) in patients with normal renal and hepatic function: Do not exceed 0.6 mg/day (may be given as 0.3 mg twice daily); Concomitant use of moderate CYP3A4 inhibitors (aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, verapamil): Do not exceed 1.2 mg/day (may be given as 0.6 mg twice daily).
PO (Children 6–12 yr): 0.9–1.8 mg/day (in 1–2 divided doses).
PO (Children 4–6 yr): 0.3–1.8 mg/day (in 1–2 divided doses).

Renal Impairment

PO (Adults ): CCr 30–50 mL/min: dose ↓ may be necessary; CCr <30 mL/min or dialysis: 0.3 mg/day.

Reduction in Risk of MI, Stroke, Coronary Revascularization, and Cardiovascular Death

PO (Adults ): 0.5 mg once daily.

(Generic available)

Tablets (Colcrys): 0.6 mg
Tablets (Lodoco): 0.5 mg
Capsules (Mitigare): 0.6 mg
Oral solution cherry flavor (Gloperba): 0.6 mg/5 mL
In combination with: probenecid.

Monitor intake and output ratios. Fluids should be encouraged to promote a urinary output of at least 2000 mL/day.
Gout: Assess involved joints for pain, mobility, and edema throughout therapy. During initiation of therapy, monitor for drug response every 1–2 hr.
Familial Mediterranean fever: Assess for signs and symptoms of familial Mediterranean fever (abdominal pain, chest pain, fever, chills, recurrent joint pain, red and swollen skin lesions) periodically during therapy.

Lab Test Considerations:

In patients receiving prolonged therapy, monitor baseline and periodic CBC; report significant ↓ in values. May cause ↓ platelet count, leukopenia, aplastic anemia, and agranulocytosis.
- May cause ↑ in AST and alkaline phosphatase.
- May cause false-positive results for urine hemoglobin.
- May interfere with results of urinary 17-hydroxycorticosteroid concentrations.

Toxicity and Overdose:

Assess patient for toxicity (muscle pain or weakness, tingling or numbness in fingers or toes; pale or gray color to lips, tongue, or palms of hands; severe diarrhea or vomiting; unusual bleeding, bruising, sore throat, fatigue, malaise, or weakness or tiredness). If these symptoms occur, discontinue colchicine and treat symptomatically.

Do not confuse colchicine with Cortrosyn.
Intermittent therapy with 3 days between courses may be used to decrease risk of toxicity.
PO: Administer without regard to meals.
- Use an accurate measuring device for solution; a teaspoon is not accurate. Solution is slightly hazy, red liquid with a cherry odor.

Instruct patient to take colchicine as directed. Review medication administration schedule. Take missed doses as soon as remembered unless almost time for next dose. Do not double doses.
Instruct patients taking prophylactic doses not to increase to therapeutic doses during an acute attack to prevent toxicity. An NSAID or corticosteroid, preferably via intrasynovial injection, should be used to treat acute attacks.
Advise patient to avoid grapefruit and grapefruit juice during therapy; may increase risk of toxicity.
Advise patient to follow recommendations of health care professional regarding weight loss, diet, and alcohol consumption.
Instruct patient to report muscle pain or weakness, tingling or numbness in fingers or toes; pale or gray color to lips, tongue, or palms of hands; severe diarrhea or vomiting; unusual bleeding, bruising, sore throat, fatigue, malaise, or weakness or tiredness promptly. Hold colchicine if symptoms of toxicity occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to notify health care professional before taking any other Rx, OTC, or herbal products.
Surgery may precipitate an acute attack of gout. Advise patient to confer with health care professional regarding dose 3 days before surgical or dental procedures.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Monitor breastfed infants for diarrhea. Inform males that colchicine may cause infertility that reverses when colchicine is stopped.

Decrease in pain and swelling in affected joints within 12 hr.
- Relief of symptoms within 24–48 hr.
Prevention of acute gout attacks.
Reduced number of attacks of familial Mediterranean fever.
Reduction in risk of MI, stroke, coronary revascularization, and cardiovascular death in patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease.

Colcrys, Gloperba, Lodoco, Mitigare

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Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆