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Indications and Important Safety Information Including Boxed Warning

INDICATIONS:

Otrexup 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).
in adults for the symptomatic control of severe, recalcitrant, disabling psoriasis that is 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 response.

Otrexup should not be used for the treatment of cancer.

Otrexup should not be used for the treatment of children with psoriasis.

This product includes the following Black Box Warning:

WARNING: SEVERE TOXIC REACTIONS, INCLUDING EMBRYO-FETAL TOXICITY AND DEATH

Otrexup 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), Otrexup 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 has been reported to cause fetal death and/or congenital anomalies. Therefore, Otrexup is not recommended for females of childbearing potential unless there is clear medical evidence that the benefits can be expected to outweigh the considered risks.

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 Otrexup 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 Otrexup 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.

Otrexup is contraindicated in the following:

Females and Males of Reproductive Potential: Contraception should be used by both females and males while taking Otrexup. Pregnancy should be avoided if either partner is receiving Otrexup:
- for a minimum of 3 months after treatment with Otrexup for males.
- during and for at least 1 menstrual cycle after treatment with Otrexup for females.
Pregnancy: Otrexup can cause fetal death or teratogenic effects when administered to a pregnant woman. Otrexup is contraindicated in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Nursing Mothers: Because of the potential for serious adverse reactions from methotrexate in breast fed infants, Otrexup is contraindicated in nursing mothers.
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 Otrexup. Advise males to avoid pregnancy for a minimum of three months after therapy and females to avoid pregnancy for at least one ovulatory cycle after therapy.
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.

Adverse Reactions

Common adverse reactions are: nausea, abdominal pain, dyspepsia, stomatitis/mouth sores, rash, nasopharyngitis, diarrhea, liver function test abnormalities, vomiting, headache, bronchitis, thrombocytopenia, alopecia, leucopenia, pancytopenia, dizziness, photosensitivity, and “burning of skin lesions”.

Drug Interactions

Aspirin, NSAIDs, and steroids: concomitant use may elevate and prolong serum methotrexate levels and cause increased toxicity.
Proton pump inhibitors: concomitant use may elevate and prolong serum methotrexate levels and cause increased toxicity.

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: Because of the potential for serious adverse reactions from methotrexate in breast fed infants, Otrexup is contraindicated in nursing mothers.
Females and Males of Reproductive Potential: Contraception should be used by both females and males while taking Otrexup. Pregnancy should be avoided if either partner is receiving Otrexup:
- for a minimum of 3 months after treatment with Otrexup for males.
- during and for at least 1 menstrual cycle after treatment with Otrexup for females.
Pediatric use: Safety and efficacy of methotrexate, including Otrexup, have not been established in pediatric patients with psoriasis. Safety and efficacy of Otrexup have not been established in pediatric patients with malignancy.
Geriatric use: Use caution in dose selection.

Dosage and Administration

Otrexup is for once weekly subcutaneous use only.

Administer Otrexup in the abdomen or thigh.

For full prescribing information including boxed warning, please click here.