Methotrexate - Warnings and Precautions
The following warnings and precautions are taken directly from the US FDA-approved drug label for Methotrexate. This is the same information dispensing pharmacists read.
\u26a0\ufe0f Boxed Warning (Highest FDA Alert)
WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, BENZYL ALCOHOL TOXICITY, and OTHER SERIOUS ADVERSE REACTIONS • Methotrexate Injection can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, Methotrexate Injection is contraindicated in pregnancy. Advise females and males of reproductive potential to use effective contraception [see Contraindications , Warnings and Precautions , and Use in Specific Populations (8.1 , 8.3) ] . • Methotrexate Injection is contraindicated in patients with a history of severe hypersensitivity reactions to methotrexate, including anaphylaxis [see Contraindications and Warnings and Precautions ]. • Formulations with benzyl alcohol can cause severe central nervous toxicity or metabolic acidosis. Use only preservative-free Methotrexate Injection for treatment of neonates or low birth weight infants and for intrathecal use. Do not use benzyl alcohol-containing formulations for high-dose regimens unless immediate treatment is required and preservative-free formulations are not available [see Dosage and Administration and Warnings and Precautions ]. • Other serious adverse reactions, including death, have been reported with methotrexate. Closely monitor for infections and adverse reactions of the bone marrow, kidneys, liver, nervous system, gastrointestinal tract, lungs, and skin. Withhold or discontinue Methotrexate Injection as appropriate [see Warnings and Precautions (5.4 , 5.5 , 5.6 , 5.7 , 5.8 , 5.9 , 5.10 ,
5 WARNINGS AND PRECAUTIONS • Secondary malignancies can occur. • Tumor lysis syndrome can occur in patients with rapidly growing tumors. • Immunizations and Risks associated with Live Vaccines: Immunizations may be ineffective.
Live vaccines are not recommended due to risk of disseminated infection. • Infertility: Can cause impairment of fertility, oligospermia, and menstrual dysfunction. ( 5.16 , 8.3 ) 5.1 Embryo-Fetal Toxicity Based on published reports and its mechanism of action, methotrexate can cause embryo-fetal toxicity, including fetal death when administered to a pregnant woman.
Methotrexate Injection is contraindicated for use in pregnant women with non-neoplastic diseases.
Advise pregnant women with neoplastic diseases of the potential risk to a fetus.
The preservative benzyl alcohol can cross the placenta; when possible, use the preservative-free formulation when Methotrexate Injection is needed during pregnancy to treat a neoplastic disease [see Warnings and Precautions ] .
Advise females of reproductive potential to use effective contraception during Methotrexate Injection treatment and for 6 months after the last dose.
Advise males with female partners of reproductive potential to use effective contraception during Methotrexate Injection treatment and for 3 months after the last dose [see Contraindications and Use in Specific Populations (8.1 , 8.3 , 8.4) ] .
5.2 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, can occur with methotrexate [see Adverse Reactions ].
If signs or symptoms of anaphylaxis or any other serious hypersensitivity reaction occurs, immediately discontinue Methotrexate Injection and institute appropriate therapy [see Contraindications ] .
5.3 Risks of Serious Adverse Reactions due to Benzyl Alcohol-Preservative Formulations with benzyl alcohol can cause severe central nervous toxicity or metabolic acidosis, if used in neonates or low birth weight infants, intrathecally, or in high-dose regimens.
Use only preservative-free Methotrexate Injection for treatment of neonates or low birth weight infants and for intrathecal use.
Do not use benzyl alcohol-containing formulations for high-dose regimens unless immediate treatment is required, and preservative-free formulations are not available.
The preservative benzyl alcohol can cross the placenta; when possible, use the preservative-free formulation when Methotrexate Injection is needed during pregnancy to treat a neoplastic disease [see Use in Specific Populations ] .
Serious and Fatal Adverse Reactions Including Gasping Syndrome in Neonates and Low Birth Weight Infants Serious and fatal adverse reactions including "gasping syndrome" can occur in neonates and low birth weight infants treated with drugs containing benzyl alcohol, including Methotrexate Injection with preservative.
The "gasping syndrome" is characterized by central nervous system (CNS) depression, metabolic acidosis, and gasping respirations.
When prescribing in infants (non-neonate, non-low birth weight), if a preservative-free formulation of Methotrexate Injection is not available and use of a benzyl alcohol-containing formulation is necessary, consider the combined daily metabolic load of benzyl alcohol from all sources including Methotrexate Injection (Methotrexate Injection contains 9.4 mg of benzyl alcohol per mL) and other drugs containing benzyl alcohol.
The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known [see Use in Specific Populations ].
Neurotoxicity Due to Intrathecal Administration Serious neurotoxicity can occur following the intrathecal administration of Methotrexate Injection containing the preservative benzyl alcohol.
Metabolic Acidosis with High-Dose Therapy Severe metabolic acidosis can occur with Methotrexate Injection that contains the preservative benzyl alcohol.
5.4 Myelosuppression Methotrexate suppresses hematopoiesis and can cause severe and life-threatening pancytopenia, anemia, aplastic anemia, leukopenia, neutropenia, and thrombocytopenia [see Adverse Reactions ].
Obtain blood counts at baseline and periodically during treatment.
Monitor patients for possible clinical complications of myelosuppression.
Provide supportive care and withhold, reduce dose, or discontinue Methotrexate Injection as needed.
5.5 Serious Infections Patients treated with methotrexate are at increased risk for developing life-threatening or fatal bacterial, fungal, or viral infections including opportunistic infections such as Pneumocystis jiroveci pneumonia, invasive fungal infections, hepatitis B reactivation, tuberculosis primary infection or reactivation, and disseminated Herpes zoster and cytomegalovirus infections.
Closely monitor patients for the development of signs and symptoms of infection during and after treatment with Methotrexate Injection.
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