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Rheumatrex Dose Pack Side Effects

Generic Name: methotrexate

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

In Summary

Common side effects of Rheumatrex Dose Pack include: increased liver enzymes. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to methotrexate: oral solution, oral tablet

Along with its needed effects, methotrexate (the active ingredient contained in Rheumatrex Dose Pack) 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
  • blood in the urine or stools
  • bloody vomit
  • diarrhea
  • joint pain
  • reddening of the skin
  • sores in the mouth or lips
  • stomach pain
  • swelling of the feet or lower legs

Less common

  • Back pain
  • blurred vision
  • confusion
  • convulsions (seizures)
  • cough or hoarseness
  • dark urine
  • dizziness
  • drowsiness
  • fever or chills
  • headache
  • lower back or side pain
  • painful or difficult urination
  • pinpoint red spots on the skin
  • shortness of breath
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • yellow eyes or skin

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

Less common

For Healthcare Professionals

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


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]


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]


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]


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]


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]


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]


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]


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]


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


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]


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]


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]


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


Very rare (less than 0.01%): Fever, impaired wound healing
Frequency not reported: Fetal death, fetal damage, abortion, tinnitus, chills, malaise, fatigue[Ref]


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]


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]


Rare (0.01% to 0.1%): Diabetes mellitus, hyperuricemia
Frequency not reported: Metabolic disorder, tumor lysis syndrome[Ref]


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]


1. "Product Information. Methotrexate Sodium (methotrexate)." Teva Pharmaceuticals (formerly IVAX), Miami, FL.

2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

3. Cerner Multum, Inc. "Australian Product Information." O 0

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.