Methods of colchicine administration

• US 9,555,029 B2
• Filed: 12/11/2014
• Issued: 01/31/2017
• Est. Priority Date: 08/20/2013
• Status: Active Grant

• Current Assignee: Hikma Pharmaceuticals LLC (Hikma Pharmaceuticals PLC)
• Original Assignee: Hikma Pharmaceuticals LLC (Hikma Pharmaceuticals PLC)
• Inventors: Ducharme, Murray
• Primary Examiner(s): Carter, Kendra D
• Assistant Examiner(s): MATOS NEGRON, TAINA DEL MAR
• Application Number:
  US14/567,005
• Publication Number:
  US 20150094375A1
• Time in Patent Office: 782 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/12 Ketones
• CPC Class Codes: A61K 31/133 having hydroxy groups, e.g. sphingosine
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings

Abstract

The invention provides improved methods for coadministration of colchicine with drugs metabolized by CYP3A4 (anciently referred to as cytochrome P450 isozyme 3A4) or the P-glycoprotein transporter, but not both. The method enables non-toxic coadministration of colchicine and the second drug at their ordinary levels safely and effectively without reducing the dose or frequency for either drug.

Claims

1. A method of treating a patient for an inflammatory disorder, wherein the inflammatory disorder is chronic gout, familial Mediterranean fever or Behcet'"'"'s disease, with colchicine while concomitantly administering a second drug that is not an inhibitor of the cytochrome P450 3A4 isoenzyme (CYP3A4) but is an inhibitor of P-glycoprotein 1 (P-gp), wherein the second drug is propafenone, wherein the method comprises:

a) administering to the patient a therapeutically effective fixed maintenance dose of colchicine in an amount of from about 0.6 to about 1.2 mg/day, for a maintenance period of a plurality of days, without administering propafenone;

b) after step (a), administering to the patient one or more therapeutically effective doses of propafenone; and

c) concomitantly with step (b), administering to the patient the fixed maintenance dose of colchicine of step (a) without dose reduction.

2. The method of claim 1, wherein propafenone is administered at a dose of from 300 mg/day to 900 mg/day.

3. The method of claim 1, wherein said fixed maintenance dose of colchicine is 0.6 mg/day.

4. The method of claim 1, wherein said fixed maintenance dose of colchicine is 1.2 mg/day.

5. The method of claim 1, wherein the inflammatory disorder is chronic gout.

6. The method of claim 1, wherein said plurality of days comprises at least 7 days.

7. The method of claim 1, wherein said fixed maintenance dose of colchicine is 0.6 mg/day, and said inflammatory disorder is chronic gout.

8. A method of treating a patient for an inflammatory disorder, wherein the inflammatory disorder is chronic gout, familial Mediterranean fever or Behcet'"'"'s disease, by administering colchicine while concomitantly administering an inhibitor of P-glycoprotein 1 (P-gp) that is not an inhibitor of the cytochrome P450 3A4 isoenzyme (CYP3A4), wherein the inhibitor of P-gp—

is propafenone, Wherein the method comprises;

a) administering to the patient a therapeutically effective fixed maintenance dose of colchicine in an amount of from about 0.6 to about 1.2 mg/day, for a maintenance period of a plurality of days;

without administering propafenone;

b) after step (a), administering to the patient one or more therapeutically effective doses of propafenone;

c) concomitantly with step (b), administering to the patient the fixed maintenance dose of colchicine of step (a) without dose reduction; and

d) after step (c), discontinuing administration of propafenone and continuing to administer the fixed maintenance doses of colchicine administered in step (b) without dose adjustment.

9. The method of claim 8, wherein said fixed maintenance dose of colchicine is 0.6 mg/day, and said inflammatory disorder is chronic gout.

10. The method of claim 8, wherein said fixed maintenance dose of colchicine is 0.6 mg/day, said inflammatory disorder is chronic gout, and said propafenone is administered at a dose of from 300 mg/day to 900 mg/day.

11. The method of claim 8, wherein said fixed maintenance dose of colchicine is 1.2 mg/day, and said inflammatory disorder is chronic gout.

12. The method of claim 8, wherein said fixed maintenance dose of colchicine is 1.2 mg/day, said inflammatory disorder is chronic gout, and said propafenone is administered at a dose of from 300 mg/day to 900 mg/day.