Note: This document contains side effect information about methotrexate. Some dosage forms listed on this page may not apply to the brand name Otrexup.

Applies to methotrexate: oral solution, oral tablet. Other dosage forms:

• powder for solution, solution

Serious side effects of Otrexup

Along with its needed effects, methotrexate (the active ingredient contained in Otrexup) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking methotrexate:

More common

• Black, tarry stools
• bleeding gums
• blood in the urine or stools
• bloody vomit
• diarrhea
• increased heartbeat
• itching, rash, reddening of the skin
• joint pain
• nausea
• pinpoint red spots on the skin
• sores in the mouth or lips
• stomach pain
• swelling of the eyelids, face, lips, hands, feet, or lower legs
• swelling or inflammation of the mouth
• trouble breathing
• unusual bleeding or bruising
• vomiting
• yellow eyes or skin

Less common

• Back pain
• bloody nose
• blurred vision
• body and muscle pain
• burning while urinating
• confusion
• continuing ringing, buzzing, or other unexplained noise in the ears
• cough or hoarseness
• cracked, dry, scaly skin
• dark urine
• dizziness
• drowsiness
• ear congestion
• fever or chills
• headache
• loss of appetite
• loss of hearing
• loss of voice
• lower back or side pain
• painful or difficult urination
• pale skin
• runny nose
• seizures
• sneezing
• sore throat
• stuffy or runny nose
• unusual tiredness or weakness
• weight loss
• white or brownish vaginal discharge

Incidence not known

• Anxiety
• blistering, peeling, or loosening of the skin
• bloating
• blurred or change in vision
• changes in skin color
• confusion
• constipation
• decreased interest in sexual intercourse
• difficulty in moving
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• dry mouth
• dryness or soreness of the throat
• eye pain
• fruit-like breath odor
• heartburn
• inability to have or keep an erection
• increased hunger or thirst
• indigestion
• irritation in the mouth
• large, flat, blue, or purplish patches in the skin
• loss in sexual ability, desire, drive, or performance
• loss of consciousness
• menstrual problem
• night blindness
• pain in the chest or groin
• pain, redness, swelling, or tenderness in the arm or leg
• red skin lesions, often with a purple center
• red, wart-like spots on the skin
• sudden loss of coordination
• sudden onset of slurred speech
• swelling or soreness of the breasts
• swollen, painful, or tender lymph glands in the neck or armpit
• tingling or numbness in the hands, feet, or lips

Other side effects of Otrexup

Some side effects of methotrexate may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Hair loss or thinning

Less common

• Blemishes on the skin
• hard, red, swollen skin irritation
• pimples

For Healthcare Professionals

Applies to methotrexate: compounding powder, injectable powder for injection, injectable solution, intramuscular solution, oral liquid, oral solution, oral tablet, subcutaneous solution.

Cardiovascular

Uncommon (0.1% to 1%): Vasculitis

Rare (less than 0.1%): Pericarditis, pericardial effusion, pericardial tamponade, hypotension, thromboembolic events (e.g., arterial thrombosis, cerebral thrombosis, thrombophlebitis, deep vein thrombosis, retinal vein thrombosis, pulmonary embolism), myocardial ischemia

Frequency not reported: Cerebral edema^[Ref]

Dermatologic

Common (1% to 10%): Exanthema, erythema, itching

Uncommon (0.1% to 1%): Urticaria, photosensitivity, depigmentation or hyperpigmentation of the skin, alopecia, increase of rheumatic nodules, painful lesions of psoriatic plaque, herpetiform eruption of the skin, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome)

Rare (0.01% to 0.1%): Increased pigmentary changes of nails, acne, petechiae, ecchymoses, erythema multiforme, cutaneous erythematous eruptions

Very rare (less than 0.01%): Furunculosis, telangiectasia

Frequency not reported: Exfoliative dermatitis, skin necrosis, skin ulceration, folliculitis, hidradenitis, allergic vasculitis^[Ref]

Endocrine

Uncommon (0.1% to 1%): Inflammation and ulceration of the vagina

Very rare (less than 0.01%): Loss of libido (males and females), impotence, impaired menstruation, vaginal discharge, infertility, abortion, fetal death, fetal defects, gynecomastia, defective oogenesis or spermatogenesis, transient oligospermia, vaginal bleeding^[Ref]

Gastrointestinal

Very common (10% or more): Anorexia, nausea, vomiting, abdominal pain, inflammation, ulcerations of the mucous membrane of mouth and throat (especially during the first 24 to 48 hours after administration), stomatitis, dyspepsia, dehydration

Common (1% to 10%): Diarrhea (especially during the first 24 to 48 hours after administration)

Uncommon (0.1% to 1%): GI bleeding and ulcers, pancreatitis

Rare (0.01% to 0.1%): Gingivitis, enteritis, melena, malabsorption

Very rare (less than 0.01%): Hematemesis, toxic megacolon

Frequency not reported: Glossitis^[Ref]

General

Generally, the incidence and severity of acute side effects are related to dose and frequency of administration. The most frequently reported adverse reactions include ulcerative stomatitis, leukopenia, nausea, abdominal distress, malaise, undue fatigue, chills and fever, dizziness, and decreased resistance to infection.^[Ref]

Genitourinary

Uncommon (0.1% to 1%): Dysuria

Rare (0.01% to 0.1%): Oliguria, anuria, azotemia

Very rare (less than 0.01%): Proteinuria

Frequency not reported: Cystitis, hematuria^[Ref]

Hematologic

Common (1% to 10%): Leukocytopenia, thrombocytopenia, anemia

Uncommon (0.1% to 1%): Pancytopenia, agranulocytosis, hematopoietic disorders

Rare (0.01% to 0.1%): Megaloblastic anemia

Very rare (less than 0.01%): Severe bone marrow depression, aplastic anemia, lymphadenopathy, lymphoproliferative disorders (partly reversible), eosinophilia, neutropenia

Frequency not reported: Hemorrhage, hematoma, myelosuppression^[Ref]

Hepatic

Very common (10% or more): Increase in liver related enzymes (ALAT, ASAT, alkaline phosphatase, bilirubin, and LDH levels) is commonly reported but usually resolves within one month after cessation of therapy

Uncommon (0.1% to 1%): Development of liver fattening, fibrosis and cirrhosis (occurs frequently despite regularly monitored, normal values of liver enzymes), drop of serum albumin

Rare (0.01% to 0.1%): Acute hepatitis, hepatotoxicity

Very rare (less than 0.01%): Reactivation of chronic hepatitis, acute liver degeneration, liver insufficiency, liver failure, liver atrophy, necrosis^[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Allergic vasculitis, severe allergic reactions progressing to anaphylactic shock^[Ref]

Immunologic

Common (1% to 10%): Disseminated herpes zoster, pneumocystis carinii pneumonia

Very rare (less than 0.01%): Immunosuppression, hypogammaglobulinemia, sepsis, opportunistic infections (may be fatal in some cases), infections caused by the cytomegalic virus, acute paronychia

Frequency not reported: Nocardiosis, cryptococcus mycosis, disseminated herpes simplex, listeria meningitis, mycobacterium avium, intracellular pneumonia, systemic fungal infections (e.g., cryptococcosis, nocardiosis, aspergillosis, histoplasmosis), sepsis, decreased resistance to infection, pneumocystis jiroveci, pneumonia (most common infection), respiratory tract infection, cutaneous bacterial infections, pneumonia, reactivation of hepatitis B infection, worsening of hepatitis C infection^[Ref]

Musculoskeletal

Uncommon (0.1% to 1%): Osteoporosis, arthralgia, myalgia

Rare (0.01% to 0.1%): Stress fracture, nodulosis

Very rare (less than 0.01%): Pain, muscular asthenia or paresthesia of the extremities

Frequency not reported: Osteoporosis, osteonecrosis (aseptic necrosis of the femoral head), soft tissue necrosis, abnormal tissue cell changes, arthralgia/myalgia, back pain^[Ref]

Nervous system

Common (1% to 10%): Headache, fatigue, drowsiness

Uncommon (0.1% to 1%): Vertigo, confusion, seizures, convulsion, encephalopathy

Very rare (less than 0.01%): Paresis, effect on speech including dysarthria and aphasia, myelopathy, changes in sense of taste (metallic taste), meningism, acute aseptic meningitis^[Ref]

Ocular

Rare (0.01% to 0.1%): Severely impaired vision, visual disturbances, blurred vision

Very rare (less than 0.01%): Conjunctivitis, retinopathy, transient blindness/loss of vision, periorbital edema, blepharitis, epiphora, photophobia, eye discomfort^[Ref]

Oncologic

Frequency not reported: Lymphomas and leukemias have been associated with this drug^[Ref]

Other

Very rare (less than 0.01%): Fever, impaired wound healing

Frequency not reported: Fetal death, fetal damage, abortion, tinnitus, chills, malaise, fatigue^[Ref]

Renal

Uncommon (0.1% to 1%): Inflammation and ulceration of the urinary bladder (possibly with hematuria)

Rare (0.01% to 0.1%): Renal failure, elevated serum creatinine and urea level

Frequency not reported: Renal insufficiency (usually with high doses), severe nephropathy^[Ref]

Respiratory

Common (1% to 10%): Pulmonary complications due to interstitial alveolitis pneumonitis (e.g., general illness, dry/nonproductive cough, shortness of breath progressing to rest dyspnea, chest pain, fever)

Uncommon (0.1% to 1%): Pulmonary fibrosis

Rare (0.01% to 0.1%): Pharyngitis, apnea, bronchial asthma

Very rare (less than 0.01%): Pneumocystis carinii pneumonia, chronic obstructive pulmonary disease, pleural effusion

Frequency not reported: Acute pulmonary edema, pleurisy, hypoxia, respiratory failure^[Ref]

Metabolic

Rare (0.01% to 0.1%): Diabetes mellitus, hyperuricemia

Frequency not reported: Metabolic disorder, tumor lysis syndrome^[Ref]

Psychiatric

Rare (0.01% to 0.1%): Mood alterations

Very rare (less than 0.01%): Insomnia, cognitive dysfunction

Frequency not reported: Psychosis, depression, confusion, irritability^[Ref]