colchicine, Colcrys, Mitigare

 Indications

Prophylaxis and treatment of acute attacks of gouty arthritis.

Familial Mediterranean fever. 

Action

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.

Pharmacokinetics

Absorption: 45% absorbed from the GI tract, then

re-enters GI tract from biliary secretions, when more

absorption may occur.

Distribution: Concentrates in WBCs.

Metabolism and Excretion: Partially metabolized

by the liver by CYP3A4; 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: 27–31 hr.

TIME/ACTION PROFILE (anti-inflammatory

activity)

ROUTE ONSET PEAK DURATION

PO 12 hr 24–72 hr unknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Use of P-glycoprotein

inhibitors or strong CYP3A4 inhibitors in patients

with renal or hepatic impairment; Renal and hepatic

impairment.

Use Cautiously in: Geri: Elderly or debilitated patients

(toxicity may be cumulative); Renal impairment

(dosepsuggested if CCr 80 mL/min); OB, Lactation,

Pedi: Safety not established for gout.

Adverse Reactions/Side Effects

GI: diarrhea, nausea, vomiting, abdominal pain.

Derm: alopecia. Hemat: AGRANULOCYTOSIS, APLASTIC

ANEMIA, leukopenia, thrombocytopenia. Neuro: peripheral

neuritis.

Interactions

Drug-Drug: Concurrent use of strong CYP3A4 inhibitors,

including atazanavir, clarithromycin, darunavir/

ritonavir, indinavir, itraconazole, ketoconazole,

lopinavir/ritonavir, nefazodone,

nelfinavir, ritonavir, saquinavir, or tipranavir/ritonavir,

mayqlevels and risk of toxicity;pcolchicine

dose in patients with normal renal or hepatic function;

concurrent use in patients with renal or hepatic impairment

is contraindicated. Concurrent use of P-glycoprotein

inhibitors, including cyclosporine or ranolazine

mayqlevels and risk of toxicity;pcolchicine

dose in patients with normal renal or hepatic function;

concurrent use in patients with renal or hepatic impairment

is contraindicated. Moderate CYP3A4 inhibitors,

including aprepitant, diltiazem, erythromycin,

fluconazole, fosamprenavir, or verapamil may

qlevels and risk of toxicity;pcolchicine dose. Additive

bone marrow depression may occur with bone marrow

depressants or radiation therapy.qrisk of

rhabdomyolysis with HMG-CoA reductase inhibitors,

gemfibrozil, fenofibrate, or digoxin. Additive

adverse GI effects with NSAIDs. May cause reversible

malabsorption of vitamin B12.

Drug-Food: Grapefruit juice mayqlevels and risk

of toxicity;pcolchicine dose.

Route/Dosage

Treatment of Acute Gout Attacks

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, indinavir, itraconazole,

ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir,

ritonavir, saquinavir, tipranavir/ritonavir)—

0.6 mg  1 dose, 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  1 dose (do

not repeat for 3 days); Concomitant use of P-glycoprotein

inhibitors (cyclosporine, ranolazine) in patients

with normal renal and hepatic function—0.6

mg  1 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  1 dose; do not repeat

treatment course for 2 wk.

Prevention of Acute Gout Attacks

PO (Adults): 0.6 mg once or twice daily; Concomitant

use of strong CYP3A4 inhibitors (atazanavir,

clarithromycin, darunavir/ritonavir, indinavir, itraconazole,

ketoconazole, lopinavir/ritonavir, nefazodone,

nelfinavir, ritonavir, saquinavir, tipranavir/

ritonavir) or P-glycoprotein inhibitors (cyclosporine,

ranolazine) in patients with normal renal and

hepatic function—if original dose was 0.6 mg twice

daily,pto 0.3 mg once daily; if original dose was 0.6

mg once daily,pto 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,pto 0.3 mg twice daily or 0.6

mg once daily; if original dose was 0.6 mg once daily,

pto 0.3 mg once daily.

Renal Impairment

PO (Adults): CCr 30 mL/min—0.3 mg/day; Dialysis—

0.3 mg twice weekly.

Familial Mediterranean Fever

PO (Adults and Children 12 yr): 1.2–2.4 mg daily

(in 1–2 divided doses); mayqorpdose in 0.3-mg/day

increments based on safety and efficacy; Concomitant

use of strong CYP3A4 inhibitors (atazanavir, clarithromycin,

darunavir/ritonavir, indinavir, itraconazole,

ketoconazole, lopinavir/ritonavir, nefazodone,

nelfinavir, ritonavir, saquinavir, tipranavir/ritonavir)

or P-glycoprotein 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 daily (in 1–2

divided doses).

PO (Children 4–6 yr): 0.3–1.8 mg daily (in 1–2 divided

doses).

Renal Impairment

PO (Adults): CCr 30–50 mL/min—dosepmay be

necessary; CCr 30 mL/min or dialysis—0.3 mg/day.

Availability (generic available)

Tablets: 0.6 mg, 1 mg. Capsules: 0.6 mg. In combination

with: probenecid (Col-Probenecid). See

Appendix B.