Methods of administering pirfenidone therapy

• US 7,816,383 B1
• Filed: 01/08/2010
• Issued: 10/19/2010
• 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 Ziegler, Szwarcberg, Javier
• Primary Examiner(s): Padmanabhan; Sreeni
• Assistant Examiner(s): MCMILLIAN, KARA RENITA
• Application Number:
  US12/684,879
• Time in Patent Office: 284 Days
• Field of Search: 514/350, 514/354, 514/640, 514/646
• US Class Current: 514/350
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/15 Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4418 having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
• CPC Class Codes: A61K 36/752 Citrus, e.g. lime, orange or lemon
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• 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 1/12 Antidiarrhoeals
• 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 17/06 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 19/10 : 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 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• 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 27/14 : Decongestants or antiallergics
• 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 29/02 : without antiinflammatory effect
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• 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 31/20 : for DNA viruses
• 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 35/04 : specific for metastasis
• 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 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• 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 fluvoxamine and pirfenidone or other moderate to strong inhibitors of CYP enzymes.

Claims

1. 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 co-administration of fluvoxamine, wherein said patient is also in need of fluvoxamine therapy.

2. The method of claim 1 wherein the patient has idiopathic pulmonary fibrosis (IPF).

3. The method of claim 1 wherein the therapeutically effective amount of pirfenidone is a daily dosage of 2400 mg or 2403 mg per day.

4. The method of claim 1 wherein 800 or 801 mg of pirfenidone is administered to the patient three times per day, with food.

5. A method of administering pirfenidone therapy to a patient in need thereof, comprising first discontinuing administration of fluvoxamine to avoid an adverse drug interaction with pirfenidone, and then administering to the patient a therapeutically effective amount of pirfenidone.

6. The method of claim 5 wherein the patient has idiopathic pulmonary fibrosis (IPF).

7. The method of claim 5 wherein the therapeutically effective amount of pirfenidone is a daily dosage of 2400 mg or 2403 mg per day.

8. The method of claim 5 wherein 800 or 801 mg of pirfenidone is administered to the patient three times per day, with food.

9. The method of claim 5 wherein the fluvoxamine is discontinued within 1 month prior to starting pirfenidone therapy.

10. The method of claim 5 wherein the fluvoxamine is discontinued within 2 weeks prior to starting pirfenidone therapy.

11. A method of administering pirfenidone therapy to a patient with IPF, wherein said patient is also in need of fluvoxamine therapy, comprising administering to the patient a daily dosage of 2400 mg or 2403 mg pirfenidone per day while avoiding fluvoxamine co-administration, and any one or more of the following:

(a) advising the patient that fluvoxamine should be avoided or discontinued,

(b) advising the patient that co-administration of pirfenidone with drugs that are moderate to strong inhibitors of both CYP1A2 and another CYP enzyme selected from the group consisting of CYP2C9, CYP2C19 and CYP3A4 can alter the therapeutic effect or adverse reaction profile of pirfenidone,

(c) advising the patient that co-administration of pirfenidone with fluvoxamine can alter the therapeutic effect or adverse reaction profile of pirfenidone,

(d) advising the patient that use of pirfenidone in patients being treated with fluvoxamine is contraindicated,

(e) advising the patient that co-administration of pirfenidone and fluvoxamine resulted in a 6-fold increase in exposure to pirfenidone, or

(f) advising the patient that strong CYP1A2 inhibitors should be used with caution in patients receiving pirfenidone due to the potential for reduced pirfenidone clearance.

12. The method of claim 11 wherein the patient is advised that fluvoxamine should be avoided or discontinued.

13. The method of claim 11 wherein the patient is advised that co-administration of pirfenidone with drugs that are moderate to strong inhibitors of both CYP1A2 and another CYP enzyme selected from the group consisting of CYP2C9, CYP2C19 and CYP3A4 can alter the therapeutic effect or adverse reaction profile of pirfenidone.

14. The method of claim 11 wherein the patient is advised that co-administration of pirfenidone with fluvoxamine can alter the therapeutic effect or adverse reaction profile of pirfenidone.

15. The method of claim 11 wherein the patient is advised that use of pirfenidone in patients being treated with fluvoxamine is contraindicated.

16. The method of claim 11 wherein the patient is advised that co-administration of pirfenidone and fluvoxamine resulted in a 6-fold increase in exposure to pirfenidone.

17. The method of claim 16 further comprising advising the patient that co-administration of pirfenidone and fluvoxamine resulted in a 2-fold increase in average peak serum concentration of pirfenidone (Cmax).

18. The method of claim 11 wherein the patient is advised that strong CYP1A2 inhibitors should be used with caution in patients receiving pirfenidone due to the potential for reduced pirfenidone clearance.

19. The method of claim 18 further comprising avoiding administering a strong CYP1A2 inhibitor.

20. The method of claim 18 further comprising discontinuing administration of a strong CYP1A2 inhibitor.