Methotrexate
Generic: METHOTREXATE
Basic Information
Manufacturer
AvPAK
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
4992fdaa-b880-ee25-e063-6394a90af03b
Indications & Usage
1 INDICATIONS AND USAGE Methotrexate tablets are a dihydrofolate reductase inhibitor indicated for the: Treatment of adults and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen ( 1.1 ) Treatment of adults with mycosis fungoides ( 1.1 ) Treatment of adults with relapsed or refractory non-Hodgkin lymphoma as part of a metronomic combination regimen ( 1.1 ) Treatment of adults with rheumatoid arthritis ( 1.2 ) Treatment of pediatric patients with polyarticular juvenile idiopathic arthritis (pJIA) ( 1.3 ) Treatment of adults with severe psoriasis ( 1.4 ) 1.1 Neoplastic Diseases Methotrexate tablets are indicated for the: treatment of adults and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen treatment of adults with mycosis fungoides (cutaneous T-cell lymphoma) as a single agent or as part of a combination chemotherapy regimen.
treatment of adults with relapsed or refractory non-Hodgkin lymphomas as part of a metronomic combination chemotherapy regimen 1.2 Rheumatoid Arthritis Methotrexate tablets are indicated for the treatment of adults with rheumatoid arthritis.
1.3 Polyarticular Juvenile Idiopathic Arthritis Methotrexate tablets are indicated for the treatment of pediatric patients with polyarticular Juvenile Idiopathic Arthritis (pJIA).
1.4 Psoriasis Methotrexate tablets are indicated for the treatment of adults with severe psoriasis.
treatment of adults with relapsed or refractory non-Hodgkin lymphomas as part of a metronomic combination chemotherapy regimen 1.2 Rheumatoid Arthritis Methotrexate tablets are indicated for the treatment of adults with rheumatoid arthritis.
1.3 Polyarticular Juvenile Idiopathic Arthritis Methotrexate tablets are indicated for the treatment of pediatric patients with polyarticular Juvenile Idiopathic Arthritis (pJIA).
1.4 Psoriasis Methotrexate tablets are indicated for the treatment of adults with severe psoriasis.
Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.2 )] Myelosuppression [see Warnings and Precautions ( 5.3 )] Gastrointestinal Toxicity [see Warnings and Precautions ( 5.4 )] Hepatotoxicity [see Warnings and Precautions ( 5.5 )] Pulmonary Toxicity [see Warnings and Precautions ( 5.6 )] Dermatologic Reactions [see Warnings and Precautions ( 5.7 )] Renal Toxicity [see Warnings and Precautions ( 5.8 )] Serious Infections [see Warnings and Precautions ( 5.11 )] Neurotoxicity [see Warnings and Precautions ( 5.12 )] Secondary Malignancies [see Warnings and Precautions ( 5.13 )] Tumor Lysis Syndrome [see Warnings and Precautions ( 5.14 )] Increased Risk of Adverse Reactions Due to Third-Space Accumulation [see Warnings and Precautions ( 5.17 )] Common adverse reactions include ulcerative stomatitis, leukopenia, nausea, abdominal distress.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials and other studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Common adverse reactions were: ulcerative stomatitis, leukopenia, nausea, and abdominal distress.
Other clinically relevant adverse reactions were infection, malaise, fatigue, chills, fever, and dizziness.
Rheumatoid Arthritis The most common adverse reactions of methotrexate that exceeded the rate of placebo in 12 to 18 week double-blind studies in patients (n=128) with rheumatoid arthritis are listed below.
Patients received methotrexate 7.5 to 15 mg orally once weekly.
Most patients received concomitant nonsteroidal anti-inflammatory drugs (NSAIDs) and some also received corticosteroids.
Hepatic histology was not examined in these short-term studies.
Incidence ≥10%: Elevated liver tests 15%, nausea/vomiting 10% Incidence 3% to <10%: Stomatitis, thrombocytopenia (platelet count <100,000/mm 3 ) Incidence 1% to <3%: Rash/pruritus/dermatitis, diarrhea, alopecia, leukopenia (white blood cell count < 3000/mm 3 ), pancytopenia, dizziness Two other controlled trials of patients (n=680) with rheumatoid arthritis who received methotrexate 7.5 mg to 15 mg orally once weekly showed the following serious adverse reaction: Incidence 1%: Interstitial pneumonitis Other less common adverse reactions were: anemia, headache, upper respiratory infection, anorexia, arthralgias, chest pain, coughing, dysuria, eye discomfort, epistaxis, fever, infection, sweating, tinnitus, vaginal discharge.
Polyarticular Juvenile Idiopathic Arthritis (pJIA) The most common adverse reactions reported in patients 2 to 18 years of age with pJIA treated with methotrexate 5 mg/m 2 to 20 mg/m 2 orally once weekly or 0.1 to 0.65 mg/kg orally once weekly were as follows: elevated liver tests 14%; gastrointestinal reactions (e.g., nausea, vomiting, diarrhea) 11%; stomatitis 2%; leukopenia 2%; headache 1.2%; alopecia 0.5%; dizziness 0.2%; rash 0.2%.
Most patients received concomitant NSAIDs and some also received corticosteroids.
Psoriasis In two published series of adults with psoriasis (n=204, 248) who received methotrexate up to 25 mg per week for up to 4 years, adverse reaction rates were similar to those in patients with rheumatoid arthritis, except for alopecia, photosensitivity, and "burning of skin lesions" (3% to 10% each).
Painful plaque erosions have been reported.
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of methotrexate.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure Cardiovascular: Thromboembolic events (including arterial thrombosis, cerebral thrombosis, deep vein thrombosis, retinal vein thrombosis, thrombophlebitis, and pulmonary embolus), pericarditis, pericardial effusion, hypotension, sudden death Endocrine: Diabetes Eye: Optic neuropathy, blurred vision, ocular pain, conjunctivitis, xerophthalmia Gastrointestinal: Hemorrhagic enteritis, intestinal perforation, gingivitis, pancreatitis, pharyngitis, hematemesis, melena, gastrointestinal ulceration Hematology: Aplastic anemia, lymphadenopathy, hypogammaglobulinemia Hepatobiliary: Acute hepatitis, decreased serum albumin, fibrosis, cirrhosis Immune system: Anaphylaxis, anaphylactoid reactions, vasculitis Metabolism: Hyperglycemia Musculoskeletal: Stress fracture, soft tissue and bone necrosis, arthralgia, myalgia, osteoporosis Nervous system: Headaches, drowsiness, blurred vision, speech impairment (including dysarthria and aphasia), transient cognitive dysfunction, mood alteration, unusual cranial sensations, paresis, encephalopathy, and convulsions.
Renal: Azotemia, hematuria, proteinuria, cystitis Reproductive: Defective oogenesis or spermatogenesis, loss of libido, impotence, gynecomastia, menstrual dysfunction Respiratory: Pulmonary fibrosis, respiratory failure, chronic interstitial obstructive pulmonary disease, pleuritic pain and thickening, alveolitis Skin: Toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin necrosis, and erythema multiforme, erythematous rashes, pruritus, alopecia, skin ulceration, accelerated nodulosis, urticaria, pigmentary changes, ecchymosis, telangiectasia, photosensitivity, acne, furunculosis To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials and other studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Common adverse reactions were: ulcerative stomatitis, leukopenia, nausea, and abdominal distress.
Other clinically relevant adverse reactions were infection, malaise, fatigue, chills, fever, and dizziness.
Rheumatoid Arthritis The most common adverse reactions of methotrexate that exceeded the rate of placebo in 12 to 18 week double-blind studies in patients (n=128) with rheumatoid arthritis are listed below.
Patients received methotrexate 7.5 to 15 mg orally once weekly.
Most patients received concomitant nonsteroidal anti-inflammatory drugs (NSAIDs) and some also received corticosteroids.
Hepatic histology was not examined in these short-term studies.
Incidence ≥10%: Elevated liver tests 15%, nausea/vomiting 10% Incidence 3% to <10%: Stomatitis, thrombocytopenia (platelet count <100,000/mm 3 ) Incidence 1% to <3%: Rash/pruritus/dermatitis, diarrhea, alopecia, leukopenia (white blood cell count < 3000/mm 3 ), pancytopenia, dizziness Two other controlled trials of patients (n=680) with rheumatoid arthritis who received methotrexate 7.5 mg to 15 mg orally once weekly showed the following serious adverse reaction: Incidence 1%: Interstitial pneumonitis Other less common adverse reactions were: anemia, headache, upper respiratory infection, anorexia, arthralgias, chest pain, coughing, dysuria, eye discomfort, epistaxis, fever, infection, sweating, tinnitus, vaginal discharge.
Polyarticular Juvenile Idiopathic Arthritis (pJIA) The most common adverse reactions reported in patients 2 to 18 years of age with pJIA treated with methotrexate 5 mg/m 2 to 20 mg/m 2 orally once weekly or 0.1 to 0.65 mg/kg orally once weekly were as follows: elevated liver tests 14%; gastrointestinal reactions (e.g., nausea, vomiting, diarrhea) 11%; stomatitis 2%; leukopenia 2%; headache 1.2%; alopecia 0.5%; dizziness 0.2%; rash 0.2%.
Most patients received concomitant NSAIDs and some also received corticosteroids.
Psoriasis In two published series of adults with psoriasis (n=204, 248) who received methotrexate up to 25 mg per week for up to 4 years, adverse reaction rates were similar to those in patients with rheumatoid arthritis, except for alopecia, photosensitivity, and "burning of skin lesions" (3% to 10% each).
Painful plaque erosions have been reported.
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of methotrexate.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure Cardiovascular: Thromboembolic events (including arterial thrombosis, cerebral thrombosis, deep vein thrombosis, retinal vein thrombosis, thrombophlebitis, and pulmonary embolus), pericarditis, pericardial effusion, hypotension, sudden death Endocrine: Diabetes Eye: Optic neuropathy, blurred vision, ocular pain, conjunctivitis, xerophthalmia Gastrointestinal: Hemorrhagic enteritis, intestinal perforation, gingivitis, pancreatitis, pharyngitis, hematemesis, melena, gastrointestinal ulceration Hematology: Aplastic anemia, lymphadenopathy, hypogammaglobulinemia Hepatobiliary: Acute hepatitis, decreased serum albumin, fibrosis, cirrhosis Immune system: Anaphylaxis, anaphylactoid reactions, vasculitis Metabolism: Hyperglycemia Musculoskeletal: Stress fracture, soft tissue and bone necrosis, arthralgia, myalgia, osteoporosis Nervous system: Headaches, drowsiness, blurred vision, speech impairment (including dysarthria and aphasia), transient cognitive dysfunction, mood alteration, unusual cranial sensations, paresis, encephalopathy, and convulsions.
Renal: Azotemia, hematuria, proteinuria, cystitis Reproductive: Defective oogenesis or spermatogenesis, loss of libido, impotence, gynecomastia, menstrual dysfunction Respiratory: Pulmonary fibrosis, respiratory failure, chronic interstitial obstructive pulmonary disease, pleuritic pain and thickening, alveolitis Skin: Toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin necrosis, and erythema multiforme, erythematous rashes, pruritus, alopecia, skin ulceration, accelerated nodulosis, urticaria, pigmentary changes, ecchymosis, telangiectasia, photosensitivity, acne, furunculosis To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.