Pirfenidone Therapy and Inducers of Cytochrome P450

• US 20120088801A1
• Filed: 12/15/2011
• Published: 04/12/2012
• Est. Priority Date: 12/04/2009
• Status: Active Grant

• Current Assignee: Intermune Incorporated (Roche Holding AG)
• Original Assignee: Intermune Incorporated (Roche Holding AG)
• Inventors: Bradford, Williamson Z., Szwarcberg, Javier
• Granted Patent: US 8,648,098 B2
• Time in Patent Office: Days
• US Class Current: 514/350
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/4418 having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/08 : for leprosy
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/14 : for RNA viruses
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to methods involving avoiding adverse drug interactions with pirfenidone and CYP inducers, such as smoking.

Claims

1. A method of administering pirfenidone therapy to a patient in need thereof, wherein the patient is a smoker, comprising discontinuing smoking to avoid an adverse drug reaction and administering a therapeutically effective amount of pirfenidone.

2. The method of claim 1, wherein the patient discontinues smoking within 4 weeks prior to the administration of pirfenidone.

3. The method of claim 1, wherein the patient discontinues smoking concurrent to administration of pirfenidone.

4. The method of claim 1, comprising discontinuing smoking to avoid an adverse drug reaction which is decreased exposure to pirfenidone.

5. The method of claim 1, further comprising advising the patient that administration of pirfenidone in patients that smoke results in a 50% decrease in pirfenidone exposure compared to patients that do not smoke.

6. The method of claim 1, wherein the patient has idiopathic pulmonary fibrosis.

7. The method of claim 1, wherein the therapeutically effective amount of pirfenidone is 2400 mg or 2403 mg per day.

8. A method of administering pirfenidone therapy to a patient in need thereof comprising administering to the patient a therapeutically effective amount of pirfenidone and avoiding use or administration of a strong inducer of a cytochrome P450 1A2 (CYP1A2) to avoid an adverse drug reaction.

9. The method of claim 8, comprising avoiding use or administration of a strong inducer of CYP1A2 to avoid an adverse drug reaction which is reduced exposure to pirfenidone.

10. The method of claim 8, wherein the patient is a smoker and avoids smoking when using pirfenidone.

11. The method of claim 8, wherein the patient has idiopathic pulmonary fibrosis.

12. The method of claim 8, wherein the therapeutically effective amount of pirfenidone is 2400 mg or 2403 mg per day.

13. A method of administering pirfenidone therapy to a patient in need thereof, comprising administering to the patient a therapeutically effective amount of pirfenidone, and one or more of the following:

(a) advising the patient that inducers of a cytochrome P450 (CYP) (CYP1A2) should be avoided or discontinued;

(b) advising the patient that smoking should be avoided when using pirfenidone due to the potential for smoking to induce CYP1A2 metabolism resulting in decreased exposure to pirfenidone;

(c) advising the patient that smoking should be discontinued before treatment with pirfenidone;

(d) advising the patient that administration of pirfenidone in patients that smoke results in a 50% decrease in pirfenidone exposure compared to patients that do not smoke; and

(e) advising the patient that smoking may result in decreased pirfenidone exposure due to the potential for smoking to induce CYP1A2 metabolism.

14. The method of claim 13, further comprising encouraging patients who smoke to stop smoking before treatment with pirfenidone.

15. The method of claim 13, expedient (a), comprising advising the patient that strong inducers of a CYP1A2 should be avoided or discontinued.

16. The method of claim 13, wherein the inducer of a CYP1A2 is one or more of carbamazepine, charbroiled food, cigarette smoke, cruciferous vegetables, esomeprazole, griseofulvin, insulin, lansprazole, marijuana smoke, moricizine, omeprazole, phenobarbital, phenytoin, primidone rifampin, ritonavir, smoking, and St. John'"'"'s wort.

17. The method of claim 16, wherein the CYP1A2 inducer is selected from the group consisting of carbamazepine, esomeprazole, griseofulvin, insulin, lansprazole, moricizine, omeprazole, rifampin, ritonavir, and smoking.

18. The method of claim 16, wherein the CYP1A2 inducer is selected from the group consisting of carbamazepine, lansoprazole, omeprazole, phenobarbital, phenytoin, primidone, rifampin, ritonavir, smoking, and St. John'"'"'s wort.

19. The method of claim 13, wherein the patient in need of pirfenidone therapy is treated for idiopathic pulmonary fibrosis.

20. The method of claim 13, wherein the therapeutically effective amount of pirfenidone is 2400 mg or 2403 mg per day.