METHODS OF ADMINISTERING PIRFENIDONE THERAPY

1 . Pirfenidone for use in treating a patient in need of pirfenidone therapy, characterized in that the treating comprises (a) avoiding, contraindicating, discontinuing or using with caution concomitant use or co-administration of a cytochrome P450 1 A2 (CYP1A2) inhibitor that is a moderate to strong inhibitor of both (i) cytochrome P450 1A2 (CYP1A2) and (ii) another CYP enzyme selected from the group consisting of CYP3A4, CYP2C9, CYP2C19, CYP2B6 and/or CYP2D6, or (b) using with caution pirfenidone in patients receiving a strong inhibitor of CYP1A2, or (c) using with caution a strong CYP1A2 inhibitor in patients receiving pirfenidone.

2 . Use of pirfenidone in preparation of a medicament for treating a patient in need of pirfenidone therapy, characterized in that the treating comprises (a) avoiding, contraindicating, discontinuing or using with caution concomitant use or co-administration of a cytochrome P450 1A2 (CYP1A2) inhibitor that is a moderate to strong inhibitor of both (i) cytochrome P450 1A2 (CYP1A2) and (ii) another CYP enzyme selected from the group consisting of CYP3A4, CYP2C9, CYP2C19, CYP2B6 and/or CYP2D6, or (b) using with caution pirfenidone in patients receiving a strong inhibitor of CYP1A2, or (c) using with caution a strong CYP1A2 inhibitor in patients receiving pirfenidone.

3 . A method of administering pirfenidone therapy to a patient in need thereof, comprising administering an effective amount of pirfenidone, and (a) avoiding, contraindicating, discontinuing or using with caution a cytochrome P450 1A2 (CYP1A2) inhibitor that is a moderate to strong inhibitor of both (i) cytochrome P450 1A2 (CYP1A2) and (ii) another CYP enzyme selected from the group consisting of CYP3A4, CYP2C9, CYP2C19, CYP2B6 and/or CYP2D6, or (b) using with caution pirfenidone in patients receiving a strong inhibitor of CYP1A2, or (c) using with caution a strong CYP1A2 inhibitor in patients receiving pirfenidone.

4 . The pirfenidone, use or method of any of claims 1 - 3 wherein the CYP1A2 inhibitor is a moderate to strong inhibitor of CYP1A2 and another CYP enzyme selected from the group consisting of CYP2C9, CYP2C19 and/or CYP2D6.

5 . The pirfenidone, use or method of any of claims 1 - 3 wherein the CYP1A2 inhibitor is a strong CYP1A2 inhibitor.

6 . The pirfenidone, use or method of any of claims 1 - 4 wherein the CYP1A2 inhibitor is discontinued prior to starting pirfenidone therapy to avoid an adverse drug interaction with pirfenidone, or to avoid a reduced clearance of pirfenidone.

7 . The pirfenidone of any one of claims 1 - 6 wherein the CYP1A2 inhibitor is discontinued within 1 month prior to starting pirfenidone therapy.

8 . The pirfenidone of any one of claims 1 - 7 wherein the CYP1A2 inhibitor is discontinued within 2 weeks prior to starting pirfenidone therapy.

9 . The pirfenidone, use or method of any of claims 1 - 4 wherein the CYP1A2 inhibitor is avoided during pirfenidone therapy.

10 . The pirfenidone, use or method of any of claims 1 - 9 wherein the patient is in need of therapy with a CYP1A2 inhibitor.

11 . The pirfenidone, use or method of any of claims 1 - 5 wherein the CYP1 A2 inhibitor is used with caution.

12 . The pirfenidone of any one of claims 1 - 11 wherein the patient has idiopathic pulmonary fibrosis (IPF).

13 . The pirfenidone of any of claims 1 - 11 wherein the patient suffers from a disease selected from idiopathic pulmonary fibrosis, pulmonary fibrosis, idiopathic interstitial pneumonia, 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, scleroderma, Hermansky-Pudlak syndrome, neurofibromatosis, Alzheimer's disease, diabetic retinopathy, or skin lesions, lymph node fibrosis associated with HIV, chronic obstructive pulmonary disease (COPD), inflammatory pulmonary fibrosis, rheumatoid arthritis; rheumatoid spondylitis; osteoarthritis; gout, other arthritic conditions; 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; scleroderma; chronic thyroiditis; Grave's disease; Ormond's disease; autoimmune gastritis; myasthenia gravis; autoimmune hemolytic anemia; autoimmune neutropenia; thrombocytopenia; pancreatic fibrosis; chronic active hepatitis including hepatic fibrosis; acute or chronic renal disease; renal fibrosis; diabetic nephropathy; irritable bowel syndrome; pyresis; restenosis; cerebral malaria; stroke or ischemic injury; neural trauma; Alzheimer's disease; Huntington's disease; Parkinson's disease; acute or chronic pain; allergies, including allergic rhinitis or 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, such as osteoporosis or multiple myeloma-related bone disorders; cancer, including but not limited to metastatic breast carcinoma, colorectal carcinoma, malignant melanoma, gastric cancer, or non-small cell lung cancer; graft-versus-host reaction; or auto-immune diseases, such as multiple sclerosis, lupus or fibromyalgia; AIDS or other viral diseases such as Herpes Zoster, Herpes Simplex I or II, influenza virus, Severe Acute Respiratory Syndrome (SARS) or cytomegalovirus; or diabetes mellitus, proliferative disorders (including both benign or malignant hyperplasias), acute myelogenous leukemia, chronic myelogenous leukemia, Kaposi's sarcoma, metastatic melanoma, multiple myeloma, breast cancer, including metastatic breast carcinoma; colorectal, carcinoma; malignant melanoma; gastric cancer; non-small cell lung cancer (NSCLC); bone metastases; pain disorders including neuromuscular pain, headache, cancer pain, dental pain, or arthritis pain; angiogenic disorders including solid tumor angiogenesis, ocular neovascularization, or infantile hemangioma; conditions associated with the cyclooxygenase or lipoxygenase signaling pathways, including conditions associated with prostaglandin endoperoxide synthase-2 (including edema, fever, analgesia, or pain); organ hypoxia; thrombin-induced platelet aggregation; or protozoal diseases.

14 . The pirfenidone of any one of claims 1 through 13 wherein the pirfenidone is administered at a total daily dosage of at least 1800 mg.

15 . The pirfenidone of any one of claims 1 through 13 wherein the pirfenidone is administered at a total daily dosage of about 2400 mg or 2403 mg.

16 . The pirfenidone of any one of claims 1 through 13 wherein 800 or 801 mg of pirfenidone is administered to the patient three times per day, with food.

17 . The pirfenidone of any one of claims 1 through 16 wherein the CYP1A2 inhibitor is fluvoxamine.

18 . The pirfenidone of any one of claims 1 through 17 wherein the CYP1A2 inhibitor is ciprofloxacin, amiodarone or propafenone.

19 . The pirfenidone of any one of claims 1 through 16 wherein the CYP1A2 inhibitor is grapefruit juice.

20 . A package or kit comprising (a) pirfenidone, optionally in a container, and (b) a package insert, package label, instructions or other labeling comprising avoiding or discontinuing or contraindicating concomitant use of or co-administration of or using with caution (1) a strong inhibitor of CYP1 A2, or (2) a moderate to strong inhibitor of both (i) CYP1A2 and (ii) another CYP enzyme selected from the group consisting of CYP3A4, CYP2C9, CYP2C19, CYP2B6 and/or CYP2D6, optionally according to any of the embodiments of claims 1 - 19 .