Methods of administering pirfenidone therapy

• US 8,778,947 B2
• Filed: 08/30/2013
• Issued: 07/15/2014
• Est. Priority Date: 08/31/2012
• Status: Active Grant

• Current Assignee: Intermune Incorporated (Roche Holding AG)
• Original Assignee: Intermune Incorporated (Roche Holding AG)
• Inventors: Bradford, Williamson Z.
• Primary Examiner(s): HENLEY III, RAYMOND J
• Application Number:
  US14/015,857
• Publication Number:
  US 20140066484A1
• Time in Patent Office: 319 Days
• Field of Search: 514/253.07, 514/277
• US Class Current: 514/253.07
• 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 31/4412 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: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• 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 11/06 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 19/10 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 25/16 : 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 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• 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 31/16 : 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 35/04 : specific for metastasis
• 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 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• 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 disclosure relates to improved methods of administering pirfenidone therapy when ciprofloxacin is administered concomitantly.

Claims

1. An improved method of administering pirfenidone therapy to treat a patient suffering from a fibrotic disorder, inflammatory disorder, or autoimmune disorder comprising reducing the dosage of pirfenidone administered to the patient by about one-half to about one-third during concomitant administration of ciprofloxacin at a dose of 750 mg twice daily (1500 mg/day).

3. The method of claim 1 wherein the pirfenidone dosage is reduced from about 2403 mg/day to a dosage ranging from about 1400 mg/day to about 1650 mg/day, optionally 1602 mg/day, during ciprofloxacin administration.

4. The method of claim 1 wherein the pirfenidone dosage is reduced from about 1800 mg/day to a dosage ranging from about 1000 mg/day to about 1250 mg/day, optionally 1200 mg/day, during ciprofloxacin administration.

5. The method of claim 1 wherein the method is for avoiding the potential for a reduced clearance of pirfenidone or the potential for an increased exposure to pirfenidone.

6. The pirfenidone of claim 1 wherein the total daily dose of pirfenidone is administered to the patient in divided doses three times per day, with food.

7. The method of claim 1 wherein the pirfenidone is administered in unit dosage forms that are capsules or tablets.

8. The method of claim 7 wherein the amount of pirfenidone in the unit dosage form is 200 mg or 267 mg.

9. The method of claim 1 wherein during concomitant ciprofloxacin administration 534 mg of pirfenidone is administered to the patient three times per day, with food.

10. The method of claim 1 wherein during the concomitant administration of ciprofloxacin the pirfenidone is administered at a total daily dosage of 1602 mg.

11. The method of claim 1 wherein during concomitant ciprofloxacin administration the pirfenidone is administered at a total daily dosage of about 1600 mg.

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

14. The method of claim 10 wherein the patient has idiopathic pulmonary fibrosis (IPF).

15. The method of claim 10 wherein the patient suffers from a disease selected from idiopathic pulmonary fibrosis, pulmonary fibrosis, bronchiolitis obliterans, chronic lung transplant rejection, scleroderma, primary focal segmental glomerulosclerosis (FSGC) or membranoproliferative glomerulonephritis (MPGN), idiopathic interstitial pneumonia, interstitial lung disease in systemic sclerosis, a fibrosis condition of the lung, myocardiac fibrosis, musculoskeletal fibrosis, post-surgical adhesions, renal fibrotic disease, fibrotic vascular disease, Hermansky-Pudlak syndrome, neurofibromatosis, lymph node fibrosis associated with HIV, inflammatory pulmonary fibrosis, pancreatic fibrosis;

hepatic fibrosis;

or renal fibrosis.

16. The method of claim 14 wherein the total daily dose of pirfenidone is administered to the patient in divided doses three times per day.

17. The method of claim 16 wherein the pirfenidone is administered with food.

2. A method of administering pirfenidone therapy to treat a patient suffering from a fibrotic disorder, inflammatory disorder, or autoimmune disorder, comprising administering to the patient a therapeutically effective amount of pirfenidone, and avoiding concomitant administration of ciprofloxacin at a dose of 750 mg.

13. An improved method of administering pirfenidone therapy to treat a patient comprising reducing the dosage of pirfenidone administered to the patient by about one-half to about one-third during concomitant administration of ciprofloxacin at a dose of 750 mg twice daily (1500 mg/day), wherein the patient suffers from a disease selected from idiopathic pulmonary fibrosis, pulmonary fibrosis, bronchiolitis obliterans, chronic lung transplant rejection, scleroderma, primary focal segmental glomerulosclerosis (FSGC) or membranoproliferative glomerulonephritis (MPGN), idiopathic interstitial pneumonia, interstitial lung disease in systemic sclerosis, a fibrosis condition of the lung, autoimmune lung diseases, benign prostate hypertrophy, coronary or myocardial infarction, atrial fibrillation, cerebral infarction, myocardiac fibrosis, musculoskeletal fibrosis, post-surgical adhesions, liver cirrhosis, renal fibrotic disease, fibrotic vascular disease, Hermansky-Pudlak syndrome, neurofibromatosis, diabetic retinopathy, skin lesions, lymph node fibrosis associated with HIV, chronic obstructive pulmonary disease (COPD), inflammatory pulmonary fibrosis, rheumatoid arthritis;

rheumatoid spondylitis;

osteoarthritis;

gout;

sepsis;

septic shock;

endotoxic shock;

gram-negative sepsis;

toxic shock syndrome;

myofacial pain syndrome (MPS);

Shigellosis;

asthma;

adult respiratory distress syndrome;

inflammatory bowel disease;

Crohn'"'"'s disease;

psoriasis;

eczema;

ulcerative colitis;

glomerular nephritis;

chronic thyroiditis;

Grave'"'"'s disease;

Ormond'"'"'s disease;

autoimmune gastritis;

myasthenia gravis;

autoimmune hemolytic anemia;

autoimmune neutropenia;

thrombocytopenia;

pancreatic fibrosis;

chronic active hepatitis, hepatic fibrosis;

acute or chronic renal disease;

renal fibrosis;

diabetic nephropathy;

irritable bowel syndrome;

pyresis;

restenosis;

cerebral malaria;

stroke or ischemic injury;

neural trauma;

Huntington'"'"'s disease;

Parkinson'"'"'s disease;

acute or chronic pain;

allergic rhinitis, allergic conjunctivitis;

cardiac hypertrophy, chronic heart failure;

acute coronary syndrome;

cachexia;

malaria;

leprosy;

leishmaniasis;

Lyme disease;

Reiter'"'"'s syndrome;

acute synoviitis;

muscle degeneration, bursitis;

tendonitis;

tenosynoviitis;

herniated, ruptured, or prolapsed intervertebral disk syndrome;

osteopetrosis;

thrombosis;

silicosis;

pulmonary sarcosis;

bone resorption diseases, osteoporosis, multiple myeloma-related bone disorders;

metastatic breast carcinoma, colorectal carcinoma, graft-versus-host reaction;

multiple sclerosis, lupus, fibromyalgia;

AIDS, viral diseases, Herpes Zoster, Herpes Simplex I or II, influenza virus, Severe Acute Respiratory Syndrome (SARS) cytomegalovirus;

diabetes mellitus, acute myelogenous leukemia, chronic myelogenous leukemia, Kaposi'"'"'s sarcoma, metastatic melanoma, multiple myeloma, breast cancer, colorectal carcinoma;

gastric cancer;

non-small cell lung cancer (NSCLC);

bone metastases;

neuromuscular pain, headache, cancer pain, dental pain, or arthritis pain;

solid tumor angiogenesis, ocular neovascularization, infantile hemangioma;

organ hypoxia;

thrombin-induced platelet aggregation;

or protozoal diseases.

18. The method of claim 13 wherein during concomitant ciprofloxacin administration the pirfenidone is administered at a total daily dosage of 1602 mg.