RediTrex (methotrexate) Injection
This product includes the following Boxed Warning:
WARNING: SEVERE TOXIC REACTIONS, INCLUDING EMBRYO-FETAL TOXICITY AND DEATH
RediTrex should be used only by physicians whose knowledge and experience include the use of antimetabolite therapy. Because of the possibility of serious toxic reactions (which can be fatal), RediTrex should be used only in patients with psoriasis or rheumatoid arthritis with severe, recalcitrant, disabling disease which is not adequately responsive to other forms of therapy. Deaths have been reported with the use of methotrexate in the treatment of malignancy, psoriasis, and rheumatoid arthritis.
Patients should be closely monitored for bone marrow, liver, lung, skin, and kidney toxicities. Patients should be informed by their physician of the risks involved and be under a physician’s care throughout therapy.
- Methotrexate can cause embryo-fetal toxicity, including fetal death. Use is contraindicated during pregnancy. Verify the pregnancy status of females of reproductive potential prior to initiating therapy.
- Methotrexate elimination is reduced in patients with impaired renal functions, ascites, or pleural effusions. Such patients require especially careful monitoring for toxicity, and require dose reduction or, in some cases, discontinuation of RediTrex administration.
- Unexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and gastrointestinal toxicity have been reported with concomitant administration of methotrexate (usually in high dosage) along with some nonsteroidal anti-inflammatory drugs (NSAIDs).
- Methotrexate causes hepatotoxicity, fibrosis and cirrhosis, but generally only after prolonged use. Acutely, liver enzyme elevations are frequently seen. These are usually transient and asymptomatic, and also do not appear predictive of subsequent hepatic disease. Liver biopsy after sustained use often shows histologic changes, and fibrosis and cirrhosis have been reported; these latter lesions may not be preceded by symptoms or abnormal liver function tests in the psoriasis population. For this reason, periodic liver biopsies are usually recommended for psoriatic patients who are under long-term treatment. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in the rheumatoid arthritis population.
- Methotrexate-induced lung disease, including acute or chronic interstitial pneumonitis, is a potentially dangerous lesion, which may occur acutely at any time during therapy and has been reported at low doses. It is not always fully reversible and fatalities have been reported. Pulmonary symptoms (especially a dry, nonproductive cough) may require interruption of treatment and careful investigation.
- Diarrhea and ulcerative stomatitis require interruption of therapy: otherwise, hemorrhagic enteritis and death from intestinal perforation may occur.
- Malignant lymphomas, which may regress following withdrawal of methotrexate, may occur in patients receiving low-dose methotrexate and, thus, may not require cytotoxic treatment. Discontinue RediTrex first and, if the lymphoma does not regress, appropriate treatment should be instituted.
- Like other cytotoxic drugs, methotrexate may induce “tumor lysis syndrome” in patients with rapidly growing tumors.
- Severe, occasionally fatal, skin reactions have been reported following single or multiple doses of methotrexate. Reactions have occurred within days of oral, intramuscular, intravenous, or intrathecal methotrexate administration. Recovery has been reported with discontinuation of therapy.
- Potentially fatal opportunistic infections, especially Pneumocystis jiroveci pneumonia, may occur with methotrexate therapy.
- Methotrexate given concomitantly with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis.
Indications: RediTrex is indicated in:
- the management of selected adults with 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 non-steroidal anti-inflammatory agents (NSAIDs).
- the symptomatic control of severe, recalcitrant, disabling psoriasis in adults who are not adequately responsive to other forms of therapy, but only when the diagnosis has been established, as by biopsy and/or after dermatologic consultation. It is important to ensure that a psoriasis “flare” is not due to an undiagnosed concomitant disease affecting immune responses.
RediTrex should not be used for the treatment of neoplastic diseases.
IMPORTANT SAFETY INFORMATION
RediTrex is contraindicated in the following:
- Pregnancy: RediTrex can cause embryo-fetal toxicity and fetal death when administered during pregnancy.
- Alcoholism or Liver Disease: Patients with alcoholism, alcoholic liver disease or other chronic liver disease.
- Immunodeficiency Syndromes: Patients who have overt or laboratory evidence of immunodeficiency syndromes.
- Preexisting Blood Dyscrasias: Patients who have preexisting blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia.
- Hypersensitivity: Patients with a known hypersensitivity to methotrexate. Severe hypersensitivity reactions have been observed with methotrexate use.
WARNINGS AND PRECAUTIONS
- Organ system toxicity: Potential for serious toxicity. Only for use by physicians experienced in antimetabolite therapy.
- Embryo-fetal toxicity: Exclude pregnancy before treatment. Avoid pregnancy if either partner is receiving RediTrex. Contraception should be used by females of reproductive potential during treatment and for 6 months after the final dose. Males of reproductive potential should use contraception during treatment and for at least 3 months after the final dose.
- Effects on reproduction: May cause impairment of fertility, oligospermia and menstrual dysfunction.
- Laboratory tests: Monitor complete blood counts, renal function and liver function tests.
- Risks from improper dosing: Mistaken daily use has led to fatal toxicity.
- Patients with impaired renal function, ascites, or pleural effusions: Elimination is reduced.
- Dizziness and fatigue: May impair ability to drive or operate machinery.
- Malignant Lymphomas: Malignant lymphoma may arise during treatment with low-dose oral methotrexate.
- Tumor Lysis Syndrome: Methotrexate may induce “tumor lysis syndrome” in patients with rapidly growing tumors.
- Concomitant Radiation Therapy: Methotrexate given with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis.
Common 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.
- Aspirin, NSAIDs, and steroids: concomitant use may elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity.
- Proton pump inhibitors: concomitant use may elevate and prolong serum levels of methotrexate and cause increased toxicity.
- Oral Antibiotics: certain oral antibiotics may decrease intestinal absorption of methotrexate or interfere with enterohepatic circulation. Use of RediTrex with penicillins should be carefully monitored.
- Hepatotoxins: patients receiving RediTrex and other potential hepatotoxins should be closely monitored for possible increased risk of hepatotoxicity.
- Theophylline: methotrexate may decrease the clearance of theophylline, theophylline levels should be monitored.
- Folic Acid and Antifolates: Folate deficiency states may increase methotrexate toxicity.
- Mercaptopurine: methotrexate increases the plasma levels of mercaptopurine, dose adjustment may be required.
- Other Drugs: Monitor patients when methotrexate is given with probenecid.
USE IN SPECIAL POPULATIONS
- Pregnancy: Methotrexate has been reported to cause embryotoxicity, fetal death, congenital anomalies, and abortion in humans and is contraindicated in pregnant women.
- Nursing Mothers: RediTrex is contraindicated in nursing mothers.
- Females and Males of Reproductive Potential: Contraception should be used by both females and males while taking RediTrex.
- Pediatric use: Safety and efficacy of methotrexate, including RediTrex, have not been established in pediatric patients with psoriasis or in pediatric patients with neoplastic diseases.
- Geriatric use: Use caution in dose selection.
- Renal Impairment: Elimination is reduced.
- Hepatic Impairment: Contraindicated in patients with alcoholic liver disease or other chronic liver disease.
DOSAGE AND ADMINISTRATION
RediTrex is for once weekly subcutaneous use only. Administer RediTrex in the abdomen or thigh.
Please see complete Full Prescribing Information, including Boxed Warning.