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Methotrexate (Methotrexate) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

IN GENERAL, THE INCIDENCE AND SEVERITY OF ACUTE SIDE EFFECTS ARE RELATED TO DOSE AND FREQUENCY OF ADMINISTRATION. THE MOST SERIOUS REACTIONS ARE DISCUSSED ABOVE UNDER ORGAN SYSTEM TOXICITY IN THE PRECAUTION SECTION. THAT SECTION SHOULD ALSO BE CONSULTED WHEN LOOKING FOR INFORMATION ABOUT ADVERSE REACTIONS WITH METHOTREXATE.

The most frequently reported adverse reactions include ulcerative stomatitis, leukopenia, nausea, and abdominal distress. Other frequently reported adverse effects are malaise, undue fatigue, chills and fever, dizziness and decreased resistance to infection.

Other adverse reactions that have been reported with methotrexate are listed below by organ system. In the oncology setting, concomitant treatment and the underlying disease make specific attribution of a reaction to methotrexate difficult.

Alimentary System

Gingivitis, pharyngitis, stomatitis, anorexia, nausea, vomiting, diarrhea, hematemesis, melena, gastrointestinal ulceration and bleeding, enteritis, pancreatitis.

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.

Hepatobiliary Disorders

Hepatotoxicity, acute hepatitis, chronic fibrosis and cirrhosis, hepatic failure, decrease in serum albumin, liver enzyme elevations.

Infection

There have been case reports of sometimes fatal opportunistic infections in patients receiving methotrexate therapy for neoplastic and non-neoplastic diseases. Pneumocystis carinii 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, H. simplex hepatitis, and disseminated H. simplex.

Musculoskeletal System

Stress fracture.

Ophthalmic

Conjunctivitis, serious visual changes of unknown etiology.

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.

Adverse Reactions in Double-Blind Rheumatoid Arthritis Studies

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. (See PRECAUTIONS).

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).

Incidence 1% to 3%: Rash/pruritis/dermatitis, diarrhea, alopecia, leukopenia (WBC less than 3000/mm3), pancytopenia, dizziness.

Two other controlled trials of patients (n=680) with Rheumatoid Arthritis on 7.5 mg to 15 mg/wk oral doses showed an incidence of interstitial pneumonitis of 1%. (See PRECAUTIONS.)

Other less common reactions included decreased hematocrit, headache, upper respiratory infection, anorexia, arthralgias, chest pain, coughing, dysuria, eye discomfort, epistatix, fever, infection, sweating, tinnitus, and vaginal discharge.

Adverse Reactions in Psoriasis:

There are no recent placebo-controlled trials in patients with psoriasis. 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).

Adverse Reactions in JRA Studies

The approximate incidences of adverse reactions reported in pediatric patients with JRA 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 nosteroidal 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 JRA, the published data for doses above 20 mg/m2/wk are too limited to provide reliable estimates of adverse reaction rates.



REPORTS OF SUSPECTED METHOTREXATE SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Methotrexate. The information is not vetted and should not be considered as verified clinical evidence.

Possible Methotrexate side effects / adverse reactions in 17 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-03

Patient: 17 year old female

Reactions: Vomiting, Blood Phosphorus Increased, Nausea, Blood Potassium Increased, Fungaemia, Tumour Lysis Syndrome, Oesophagitis, Dehydration, Pulmonary Oedema, Upper Gastrointestinal Haemorrhage, Hypovolaemia, Cardiac Failure Congestive, Deep Vein Thrombosis, Renal Failure Acute

Adverse event resulted in: hospitalization

Suspect drug(s):
Methotrexate
    Indication: Choriocarcinoma

Etoposide
    Indication: Choriocarcinoma



Possible Methotrexate side effects / adverse reactions in 54 year old male

Reported by a health professional (non-physician/pharmacist) from United Kingdom on 2011-10-03

Patient: 54 year old male

Reactions: Fungal Infection, Pyrexia, Neutropenia, Septic Shock

Adverse event resulted in: death

Suspect drug(s):
Cytarabine
    Dosage: 30 mg, unk

Idarubicin HCL
    Dosage: unk ukn, unk

Hydrocortisone
    Dosage: 12.5 mg, unk

Methotrexate
    Dosage: 12.5 mg, unk

Etoposide
    Dosage: unk ukn, unk

Other drugs received by patient: Amphotericin B



Possible Methotrexate side effects / adverse reactions in 39 year old female

Reported by a health professional (non-physician/pharmacist) from France on 2011-10-03

Patient: 39 year old female

Reactions: Pneumonia Aspiration, Drug Ineffective, Progressive Multifocal Leukoencephalopathy

Adverse event resulted in: death, hospitalization

Suspect drug(s):
Mycophenolate Mofetil
    Indication: Polymyositis

Imuran
    Indication: Polymyositis
    Start date: 2002-11-01
    End date: 2005-02-01

Cyclosporine
    Indication: Polymyositis

Methotrexate
    Indication: Polymyositis
    Start date: 2001-12-01
    End date: 2002-11-01

Mabthera
    Indication: Polymyositis

Mabthera
    Dosage: form: infusion

Mabthera

Mabthera

Mabthera

Other drugs received by patient: Prednisone; Prednisone; Prednisone; Prednisone; Prednisone; Prednisone; Prednisone



See index of all Methotrexate side effect reports >>

Drug label data at the top of this Page last updated: 2012-04-23

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