"The US Food and Drug Administration (FDA) has approved tofacitinib citrate extended-release (Xeljanz XR, Pfizer Inc) 11-mg tablets for once-daily treatment of moderate to severe rheumatoid arthritis (RA) in patients who have not responde"...
Otrexup Side Effects Center
Medical Editor: John P. Cunha, DO, FACOEP
Otrexup (methotrexate) Injection is a folate analog metabolic inhibitor used in adults to manage severe, active rheumatoid arthritis (RA) (ACR criteria), or children with active polyarticular juvenile idiopathic arthritis (pJIA), who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose nonsteroidal anti-inflammatory agents (NSAIDs). Otrexup is also used for the symptomatic control of severe, recalcitrant, disabling psoriasis that is not adequately responsive to other forms of therapy. Common side effects of Otrexup include cold sores or ulcers in the mouth, low levels of white blood cells (leukopenia), nausea, abdominal pain or upset, general feeling of being unwell (malaise), fatigue, chills and fever, dizziness, decreased resistance to infection, or anemia (symptoms include unusual tiredness, pale skin).
The recommended starting dose of Otrexup to treat adult RA is a single oral dose of 7.5 mg weekly using an oral formulation of methotrexate. To treat pJIA, the dose is 10 mg/mē once weekly. To treat psoriasis, a single weekly oral, intramuscular, subcutaneous, or intravenous dose of 10-25 mg. Otrexup may interact with nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, proton pump inhibitors (PPIs), antibiotics, azathioprine, retinoids, sulfasalazine, theophylline, folic acid, mercaptopurine, phenylbutazone, phenytoin, sulfonamides, and probenecid. Tell your doctor all medications and supplements you use. Otrexup is not recommended for use during pregnancy. It can harm a fetus or cause fetal death. Breastfeeding while taking Otrexup is not recommended.
Our Otrexup (methotrexate) Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Otrexup FDA Prescribing Information: Side Effects
The following adverse reactions are discussed in more detail in other sections of the labeling.
- Organ System Toxicity [see WARNINGS AND PRECAUTIONS]
- Embryo-Fetal Toxicity [see WARNINGS AND PRECAUTIONS]
- Effects on Reproduction [see WARNINGS AND PRECAUTIONS]
- Malignant Lymphomas [see WARNINGS AND PRECAUTIONS]
The most frequently reported adverse reactions include ulcerative stomatitis, leukopenia, nausea, and abdominal distress. Other frequently reported adverse reactions are malaise, undue fatigue, chills and fever, dizziness and decreased resistance to infection.
Clinical Trials Experience
This section provides a summary of adverse reactions reported in subjects in clinical studies conducted with Otrexup as well as with methotrexate injection and oral methotrexate.
Because clinical trials 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.
The approximate incidences of methotrexate-attributed (i.e. placebo rate subtracted) adverse reactions in 12 to 18 week double-blind studies of patients (n=128) with rheumatoid arthritis treated with low-dose oral (7.5 to 15 mg/week) pulse methotrexate, are listed below. Virtually all of these patients were on concomitant nonsteroidal anti-inflammatory drugs and some were also taking low dosages of corticosteroids. Hepatic histology was not examined in these short-term studies.
Incidence greater than 10%: Elevated liver function tests 15%, nausea/vomiting 10%.
Incidence 3% to 10%: Stomatitis, thrombocytopenia (platelet count less than 100,000/mm³).
Other less common reactions included decreased hematocrit, headache, upper respiratory infection, anorexia, arthralgias, chest pain, coughing, dysuria, eye discomfort, epistaxis, fever, infection, sweating, tinnitus, and vaginal discharge.
Polyarticular Juvenile Idiopathic Arthritis
The approximate incidences of adverse reactions reported in pediatric patients with pJIA treated with oral, weekly doses of methotrexate (5 to 20 mg/m²/wk or 0.1 to 0.65 mg/kg/wk) were as follows (virtually all patients were receiving concomitant nonsteroidal anti-inflammatory drugs, and some also were taking low doses of corticosteroids): elevated liver function tests, 14%; gastrointestinal reactions (e.g., nausea, vomiting, diarrhea), 11%; stomatitis, 2%; leukopenia, 2%; headache, 1.2%; alopecia, 0.5%; dizziness, 0.2%; and rash, 0.2%. Although there is experience with dosing up to 30 mg/m²/wk in pJIA, the published data for doses above 20 mg/m²/wk are too limited to provide reliable estimates of adverse reaction rates.
There are two literature reports (Roenigk, 1969, and Nyfors, 1978) describing large series (n=204, 248) of psoriasis patients treated with methotrexate. Dosages ranged up to 25 mg per week and treatment was administered for up to four years. With the exception of alopecia, photosensitivity, and “burning of skin lesions” (each 3% to 10%), the adverse reaction rates in these reports were very similar to those in the rheumatoid arthritis studies. Rarely, painful plaque erosions may appear (Pearce, HP and Wilson, BB: Am Acad Dermatol 35: 835-838, 1996).
Other Adverse Reactions
Blood and Lymphatic System Disorders: suppressed hematopoiesis, anemia, aplastic anemia, pancytopenia, leukopenia, neutropenia, thrombocytopenia, agranulocytosis, eosinophilia, lymphadenopathy and lymphoproliferative disorders (including reversible). Hypogammaglobulinemia has been reported rarely.
Cardiovascular: pericarditis, pericardial effusion, hypotension, and thromboembolic events (including arterial thrombosis, cerebral thrombosis, deep vein thrombosis, retinal vein thrombosis, thrombophlebitis, and pulmonary embolus).
Central Nervous System: headaches, drowsiness, blurred vision, transient blindness, speech impairment including dysarthria and aphasia, hemiparesis, paresis and convulsions have also occurred following administration of methotrexate. Following low doses, there have been occasional reports of transient subtle cognitive dysfunction, mood alteration or unusual cranial sensations, leukoencephalopathy, or encephalopathy.
Infection: There have been case reports of sometimes fatal opportunistic infections in patients receiving methotrexate therapy for neoplastic and non-neoplastic diseases. Pneumocystis jiroveci pneumonia was the most common opportunistic infection. There have also been reports of infections, pneumonia, Cytomegalovirus infection, including cytomegaloviral pneumonia, sepsis, fatal sepsis, nocardiosis; histoplasmosis, cryptococcosis, Herpes zoster, Herpes simplex hepatitis, and disseminated Herpes simplex.
Musculoskeletal System: stress fracture.
Pulmonary System: respiratory fibrosis, respiratory failure, alveolitis, interstitial pneumonitis deaths have been reported, and chronic interstitial obstructive pulmonary disease has occasionally occurred.
Skin: erythematous rashes, pruritus, urticaria, photosensitivity, pigmentary changes, alopecia, ecchymosis, telangiectasia, acne, furunculosis, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, skin necrosis, skin ulceration and exfoliative dermatitis.
Urogenital System: severe nephropathy or renal failure, azotemia, cystitis, hematuria, proteinuria; defective oogenesis or spermatogenesis, transient oligospermia, menstrual dysfunction, vaginal discharge, and gynecomastia; infertility, abortion, fetal death, fetal defects.
Other rarer reactions related to or attributed to the use of methotrexate such as nodulosis, vasculitis, arthralgia/myalgia, loss of libido/ impotence, diabetes, osteoporosis, sudden death, lymphoma, including reversible lymphomas, tumor lysis syndrome, soft tissue necrosis and osteonecrosis. Anaphylactoid reactions have been reported.
Read the entire FDA prescribing information for Otrexup (Methotrexate Injection)
Additional Otrexup Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get the latest treatment options