Jylamvo

• Methotrexate can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, Jylamvo is contraindicated in pregnancy. For neoplastic diseases, advise females and males of reproductive potential to use effective contraception during and after treatment with Jylamvo

  [see

  4 CONTRAINDICATIONS

  JYLAMVO is contraindicated in:

  • Pregnant women for treatment of non-neoplastic diseases
    [see Warnings and Precautions (5.1),and Use in Specific Populations (8.1, 8.3)]
    .
  • Patients with a history of a severe hypersensitivity reactions, including anaphylaxis, to methotrexate
    [see Warnings and Precautions (5.2)]
    .

  • Pregnant patients with non-neoplastic diseases
  • History of severe hypersensitivity to methotrexate

  5.1 Embryo-Fetal Toxicity

  Based on published reports and its mechanism of action, methotrexate can cause fetal harm, including fetal death, when administered to a pregnant woman. JYLAMVO is contraindicated for use in pregnant women receiving JYLAMVO for the treatment of non-malignant diseases. Advise pregnant women with neoplastic diseases of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with JYLAMVO and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during JYLAMVO treatment and for at least 3 months after the final dose

  [see Contraindications (4), Use in Specific Populations (8.1, 8.3)]

  .

  8.1 Pregnancy

  Risk Summary

  Based on published reports and methotrexate’s mechanism of action, methotrexate can cause embryo-fetal toxicity and fetal death when administered to a pregnant woman

  [see Clinical Pharmacology (12.1)]

  . There are no animal data that meet current standards for nonclinical developmental toxicity studies. In pregnant women with non-malignant disease, JYLAMVO is contraindicated. Consider the benefits and risks of JYLAMVO and risks to the fetus when prescribing JYLAMVO to a pregnant patient with a neoplastic disease.

  The background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

  Data

  Human Data

  Published data from case reports, literature reviews, and observational studies report that methotrexate exposure during pregnancy is associated with an increased risk of embryo-fetal toxicity and fetal death. Methotrexate exposure during the first trimester of pregnancy is associated with an increased incidence of spontaneous abortions and multiple adverse developmental outcomes, including skull anomalies, facial dysmorphism, central nervous system abnormalities, limb abnormalities, and sometimes cardiac anomalies and intellectual impairment. Adverse outcomes associated with exposure during second and third trimesters of pregnancy include intrauterine growth restriction and functional abnormalities. Because methotrexate is widely distributed and persists in the body for a prolonged period, there is a potential risk to the fetus from preconception methotrexate exposure.

  A prospective multicenter study evaluated pregnancy outcomes in women taking methotrexate less than or equal to 30 mg/week after conception. The rate of spontaneous abortion and miscarriage in pregnant women exposed to methotrexate was 42% (95% confidence interval [95% CI] 29, 59), which was higher than in unexposed patients with autoimmune disease (22%; 95% CI: 17, 30) and unexposed patients with nonautoimmune disease (17%; 95% CI: 13, 23). Of the live births, the rate of major birth defects in pregnant women exposed to methotrexate after conception was higher than in unexposed patients with autoimmune disease (adjusted odds ratio (OR) 1.8 [95% CI: 0.6, 6]) and unexposed patients with non-autoimmune disease (adjusted OR 3.1 [95% CI: 1, 10]) (2.9%). Major birth defects associated with pregnancies exposed to methotrexate after conception were not always consistent with methotrexate-associated adverse developmental outcomes.

  8.3 Females and Males of Reproductive Potential

  Methotrexate can cause malformations and fetal death at doses less than or equal to the recommended clinical doses

  [ Use in Specific Populations (8.1)]

  .

  Pregnancy Testing

  Verify the pregnancy status of females of reproductive potential prior to initiating JYLAMVO

  [see Contraindications (4), Use in Specific Populations (8.1)]

  .

  Contraception

  Females

  JYLAMVO can cause fetal harm when administered to a pregnant woman

  [see Use in Specific Populations (8.1)].

  Advise females of reproductive potential to use effective contraception during treatment with JYLAMVO and for 6 months after the final dose of JYLAMVO.

  Males

  Methotrexate can cause chromosomal damage to sperm cells. Advise males with female partners of reproductive potential to use effective contraception during treatment with JYLAMVO and for at least 3 months after the final dose of JYLAMVO.

  Infertility

  Females

  Based on published reports of female infertility after treatment with methotrexate, advise females of reproductive potential that methotrexate can cause impairment of fertility and menstrual dysfunction during treatment with JYLAMVO and after the final dose. It is not known if the infertility may be reversed in all affected females.

  Males

  Based on published reports of male infertility after treatment with methotrexate, advise males of reproductive potential that methotrexate can cause oligospermia or infertility during treatment with JYLAMVO and after the final dose. It is not known if the infertility may be reversed in all affected males.

  ]

  .
• Jylamvo is contraindicated in patients with a history of severe hypersensitivity reactions to methotrexate, including anaphylaxis

  [

  4 CONTRAINDICATIONS

  JYLAMVO is contraindicated in:

  • Pregnant women for treatment of non-neoplastic diseases
    [see Warnings and Precautions (5.1),and Use in Specific Populations (8.1, 8.3)]
    .
  • Patients with a history of a severe hypersensitivity reactions, including anaphylaxis, to methotrexate
    [see Warnings and Precautions (5.2)]
    .

  • Pregnant patients with non-neoplastic diseases
  • History of severe hypersensitivity to methotrexate

  5.2 Hypersensitivity Reactions

  Hypersensitivity reactions, including anaphylaxis, can occur with methotrexate

  [see Contraindications (4), Adverse Reactions (6.1)]

  .

  If anaphylaxis or other serious hypersensitivity reaction occurs, immediately and permanently discontinue JYLAMVO

  [see Dosage and Administration (2.6)]

  .

  ]

  .
• Serious adverse reactions, including death, have been reported with methotrexate. Closely monitor for infections and adverse reactions of the bone marrow, gastrointestinal tract, liver, lungs, skin, and kidneys. Withhold or discontinue Jylamvo as appropriate

  [

  5.3 Myelosuppression

  Methotrexate suppresses hematopoiesis and can cause severe and life-threatening pancytopenia, anemia, leukopenia, neutropenia, and thrombocytopenia

  [see Adverse Reactions (6.1)]

  .

  Obtain blood counts at baseline, periodically during treatment, and as clinically indicated. Monitor patients for clinical complications of myelosuppression. Withhold, dose reduce, or discontinue JYLAMVO taking into account the importance of JYLAMVO treatment in the context of the severity of the disease being treated, the severity of the adverse drug reaction, and availability of alternative therapy

  [see Dosage and Administration (2.6)]

  .

  5.4 Gastrointestinal Toxicity

  Diarrhea, vomiting, nausea, and stomatitis occurred in up to 10% of patients receiving methotrexate for treatment of non-neoplastic diseases. Hemorrhagic enteritis and fatal intestinal perforation have been reported

  [see Adverse Reactions (6.1, 6.2)]

  . Patients with peptic ulcer disease or ulcerative colitis are at a greater risk of developing severe gastrointestinal adverse reactions

  [see Drug Interactions (7.1)]

  .

  Withhold or discontinue JYLAMVO for severe gastrointestinal toxicity taking into account the importance of JYLAMVO treatment in the context of the severity of the disease being treated, the severity of the adverse drug reaction, and availability of alternative therapy

  [see Dosage and Administration (2.6)]

  .

  5.5 Hepatotoxicity

  Methotrexate can cause severe and potentially irreversible hepatotoxicity, including fibrosis, cirrhosis, and fatal liver failure

  [see Adverse Reactions (6.1)]

  . The safety of JYLAMVO in patients with hepatic disease is unknown.

  The risk of hepatotoxicity is increased with heavy alcohol consumption. In patients with psoriasis, fibrosis or cirrhosis may occur in the absence of symptoms or abnormal liver tests; the risk of hepatotoxicity appears to increase with total cumulative dose and generally occurs after receipt of a total cumulative dose of 1.5 g or more.

  Monitor liver tests at baseline, periodically during treatment and as clinically indicated. Withhold or discontinue JYLAMVO taking into account the importance of JYLAMVO treatment in the context of the severity of the disease being treated, the severity of the adverse drug reaction, and availability of alternative therapy

  [see Dosage and Administration (2.6)]

  .

  5.6 Pulmonary Toxicity

  Pulmonary toxicity, including acute or chronic interstitial pneumonitis and irreversible or fatal cases, can occur with methotrexate

  [see Adverse Reactions (6.1, 6.2)]

  .

  Monitor patients for pulmonary toxicity and withhold or discontinue JYLAMVO taking into account the importance of JYLAMVO treatment in the context of the severity of the disease being treated, the severity of the adverse drug reaction, and availability of alternative therapy

  [see Dosage and Administration (2.6)]

  .

  5.7 Dermatologic Reactions

  Severe, including fatal dermatologic reactions, such as toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin necrosis, and erythema multiforme, can occur with methotrexate

  [see Adverse Reactions (6.1, 6.2)]

  .

  Exposure to ultraviolet radiation while taking methotrexate may aggravate psoriasis.

  Methotrexate can cause radiation recall dermatitis and photodermatitis (sunburn) reactivation.

  Monitor patients for dermatologic toxicity and withhold or permanently discontinue JYLAMVO for severe dermatologic reactions taking into account the importance of JYLAMVO treatment in the context of the severity of the disease being treated, the severity of the adverse drug reaction, and availability of alternative therapy

  [see Dosage and Administration (2.6)]

  . Advise patients to avoid excessive sun exposure and use sun protection measures.

  5.8 Renal Toxicity

  Methotrexate can cause renal toxicity, including irreversible acute renal failure

  [see Adverse Reactions (6.2)]

  .

  Monitor renal function at baseline, periodically during treatment and as clinically indicated. Withhold or discontinue JYLAMVO for severe renal toxicity taking into account the importance of JYLAMVO treatment in the context of the severity of the disease being treated, the severity of the adverse drug reaction, and availability of alternative therapy

  [see Dosage and Administration (2.6)]

  .

  Administer glucarpidase in patients with toxic plasma methotrexate concentrations (> 1 micromole per liter) and delayed methotrexate clearance due to impaired renal function. Refer to the glucarpidase prescribing information for additional information.

  5.11 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

  [see Adverse Reactions (6.2)]

  .

  Monitor patients for infection during and after treatment with JYLAMVO. Withhold or discontinue JYLAMVO for serious infections taking into account the importance of JYLAMVO treatment in the context of the severity of the disease being treated, the severity of the adverse drug reaction, and availability of alternative therapy

  [see Dosage and Administration (2.6)]

  .

  ]

  .

JYLAMVO is a folate analog metabolic inhibitor indicated for the:

• Treatment of adults and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen (
  1.1 Neoplastic Disease

  JYLAMVO is indicated for the:

  • treatment of adults and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen.
  • treatment of adults with mycosis fungoides (cutaneous T-cell lymphoma) as a single agent or as part of a combination chemotherapy regimen.
  • treatment of adults with relapsed or refractory non-Hodgkin lymphomas as part of a metronomic combination chemotherapy regimen.
  )
• Treatment of adults with mycosis fungoides (
  1.1 Neoplastic Disease

  JYLAMVO is indicated for the:

  • treatment of adults and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen.
  • treatment of adults with mycosis fungoides (cutaneous T-cell lymphoma) as a single agent or as part of a combination chemotherapy regimen.
  • treatment of adults with relapsed or refractory non-Hodgkin lymphomas as part of a metronomic combination chemotherapy regimen.
  )
• Treatment of adults with relapsed or refractory non-Hodgkin lymphoma as part of a metronomic combination regimen (
  1.1 Neoplastic Disease

  JYLAMVO is indicated for the:

  • treatment of adults and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen.
  • treatment of adults with mycosis fungoides (cutaneous T-cell lymphoma) as a single agent or as part of a combination chemotherapy regimen.
  • treatment of adults with relapsed or refractory non-Hodgkin lymphomas as part of a metronomic combination chemotherapy regimen.
  )
• Treatment of adults with rheumatoid arthritis (
  1.2 Rheumatoid Arthritis

  JYLAMVO is indicated for the treatment of adults with rheumatoid arthritis.
  )
• Treatment of pediatric patients with polyarticular juvenile idiopathic arthritis (pJIA) (
  1.4 Psoriasis

  JYLAMVO is indicated for the treatment of adults with severe psoriasis.
  )
• Treatment of adults with severe psoriasis
  1.4 Psoriasis

  JYLAMVO is indicated for the treatment of adults with severe psoriasis.
  )

• Verify pregnancy status in females of reproductive potential before starting JYLAMVO. (
  2.1 Important Dosage and Safety Information

  Verify pregnancy status in females of reproductive potential before starting JYLAMVO

  [see Contraindications (4), Warnings and Precautions (5.1)].

  Instruct patients and caregivers on how to measure and administer the recommended dosage using the copackaged syringe and bottle adaptor as directed, because medication errors have led to deaths

  [see Warnings and Precautions (5.9)].

  Ensure patients and caregivers understand the instructions provided in the Patient Information on proper dosing of JYLAMVO based on volume (mL) utilizing the copackaged syringe before use.

  Advise patients and caregivers to only use the copackaged syringe to measure JYLAMVO and that a teaspoon is not an appropriate measuring device. The dosing syringe utilizes mL as the unit of measure; ensure that the correct dose expressed in volume (mL) is prescribed. JYLAMVO contains 2 mg of methotrexate in each mL of solution.

  JYLAMVO is intended for oral use only. When switching the patient’s dosing regimen from a methotrexate product for oral administration to a methotrexate product for intravenous, intramuscular, or subcutaneous administration, an alternative dosing regimen may be necessary due to potential differences in bioavailability.

  JYLAMVO is a hazardous drug. Follow applicable special handling and disposal procedures¹.
  4 CONTRAINDICATIONS

  JYLAMVO is contraindicated in:

  • Pregnant women for treatment of non-neoplastic diseases
    [see Warnings and Precautions (5.1),and Use in Specific Populations (8.1, 8.3)]
    .
  • Patients with a history of a severe hypersensitivity reactions, including anaphylaxis, to methotrexate
    [see Warnings and Precautions (5.2)]
    .

  • Pregnant patients with non-neoplastic diseases
  • History of severe hypersensitivity to methotrexate
  5.1 Embryo-Fetal Toxicity

  Based on published reports and its mechanism of action, methotrexate can cause fetal harm, including fetal death, when administered to a pregnant woman. JYLAMVO is contraindicated for use in pregnant women receiving JYLAMVO for the treatment of non-malignant diseases. Advise pregnant women with neoplastic diseases of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with JYLAMVO and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during JYLAMVO treatment and for at least 3 months after the final dose

  [see Contraindications (4), Use in Specific Populations (8.1, 8.3)]

  .
  )
• Instruct patients and caregivers to take the recommended dosage as directed, because medication errors have led to deaths. (
  2.1 Important Dosage and Safety Information

  Verify pregnancy status in females of reproductive potential before starting JYLAMVO

  [see Contraindications (4), Warnings and Precautions (5.1)].

  Instruct patients and caregivers on how to measure and administer the recommended dosage using the copackaged syringe and bottle adaptor as directed, because medication errors have led to deaths

  [see Warnings and Precautions (5.9)].

  Ensure patients and caregivers understand the instructions provided in the Patient Information on proper dosing of JYLAMVO based on volume (mL) utilizing the copackaged syringe before use.

  Advise patients and caregivers to only use the copackaged syringe to measure JYLAMVO and that a teaspoon is not an appropriate measuring device. The dosing syringe utilizes mL as the unit of measure; ensure that the correct dose expressed in volume (mL) is prescribed. JYLAMVO contains 2 mg of methotrexate in each mL of solution.

  JYLAMVO is intended for oral use only. When switching the patient’s dosing regimen from a methotrexate product for oral administration to a methotrexate product for intravenous, intramuscular, or subcutaneous administration, an alternative dosing regimen may be necessary due to potential differences in bioavailability.

  JYLAMVO is a hazardous drug. Follow applicable special handling and disposal procedures¹.
  5.9 Risk of Serious Adverse Reactions with Medication Error

  Deaths occurred in patients as a result of medication errors. Most commonly, these errors occurred in patients who were taking methotrexate daily when a weekly dosing regimen was prescribed.

  For patients prescribed a once weekly dosing regimen, instruct patients and caregivers to take the recommended dosage as directed, because medication errors have led to death.

  Instruct patients and caregivers on how to measure, dose, and administer the recommended dosage as directed

  [see Dosage and Administration (2)]

  .
  )
• ALL
  :
  The recommended dosage is 20 mg/m² orally once weekly as a part of a combination chemotherapy maintenance regimen. (
  2.2 Recommended Dosage for Neoplastic Diseases

  Acute Lymphoblastic Leukemia

  The recommended starting dosage of JYLAMVO is 20 mg/m²orally once weekly, as part of a combination chemotherapy maintenance regimen. After initiating JYLAMVO, periodically monitor absolute neutrophil count (ANC) and platelet count and adjust the dose to maintain ANC at a desirable level and for excessive myelosuppression.

  Mycosis Fungoides

  The recommended dosage of JYLAMVO is 25 mg to 75 mg orally once weekly when administered as a single agent or 10 mg/m²orally twice weekly as part of a combination chemotherapy regimen.

  Relapsed or Refractory Non-Hodgkin Lymphomas

  The recommended dosage of JYLAMVO is 2.5 mg orally 2 to 4 times per week (maximum 10 mg per week) as part of a metronomic combination chemotherapy regimen.
  )
• Mycosis fungoides
  :
  The recommended dosage is 25 mg to 75 mg orally once weekly as monotherapy; 10 mg/m² orally twice weekly as part of combination chemotherapy. (
  2.2 Recommended Dosage for Neoplastic Diseases

  Acute Lymphoblastic Leukemia

  The recommended starting dosage of JYLAMVO is 20 mg/m²orally once weekly, as part of a combination chemotherapy maintenance regimen. After initiating JYLAMVO, periodically monitor absolute neutrophil count (ANC) and platelet count and adjust the dose to maintain ANC at a desirable level and for excessive myelosuppression.

  Mycosis Fungoides

  The recommended dosage of JYLAMVO is 25 mg to 75 mg orally once weekly when administered as a single agent or 10 mg/m²orally twice weekly as part of a combination chemotherapy regimen.

  Relapsed or Refractory Non-Hodgkin Lymphomas

  The recommended dosage of JYLAMVO is 2.5 mg orally 2 to 4 times per week (maximum 10 mg per week) as part of a metronomic combination chemotherapy regimen.
  )
• Relapsed or refractory non-Hodgkin lymphoma
  :
  The recommended dosage is 2.5 mg orally two to four times per week as part of metronomic combination chemotherapy. (
  2.2 Recommended Dosage for Neoplastic Diseases

  Acute Lymphoblastic Leukemia

  The recommended starting dosage of JYLAMVO is 20 mg/m²orally once weekly, as part of a combination chemotherapy maintenance regimen. After initiating JYLAMVO, periodically monitor absolute neutrophil count (ANC) and platelet count and adjust the dose to maintain ANC at a desirable level and for excessive myelosuppression.

  Mycosis Fungoides

  The recommended dosage of JYLAMVO is 25 mg to 75 mg orally once weekly when administered as a single agent or 10 mg/m²orally twice weekly as part of a combination chemotherapy regimen.

  Relapsed or Refractory Non-Hodgkin Lymphomas

  The recommended dosage of JYLAMVO is 2.5 mg orally 2 to 4 times per week (maximum 10 mg per week) as part of a metronomic combination chemotherapy regimen.
  )
• Rheumatoid Arthritis
  :
  The recommended starting dosage is 7.5 mg orally once weekly; adjust dose to achieve an optimal response. (
  2.3 Recommended Dosage for Rheumatoid Arthritis

  The recommended starting dosage of JYLAMVO is 7.5 mg orally once weekly with escalation to achieve optimal response. Dosages of more than 20 mg once weekly result in an increased risk of serious adverse reactions, including myelosuppression. When responses are observed, the majority occur between 3 and 6 weeks from initiation of treatment; however, responses have occurred up to 12 weeks after treatment initiation.

  Administer folic acid or folinic acid to reduce the risk of methotrexate adverse reactions

  [see Warnings and Precautions (5.10)]

  .
  )
• pJIA:
  The recommended starting dosage is 10 mg/m² orally once weekly; adjust dose to achieve an optimal response. (
  2.4 Recommended Dosage for Polyarticular Juvenile Idiopathic Arthritis

  The recommended starting dose of JYLAMVO is 10 mg/m²orally once weekly with escalation to achieve optimal response. Dosages of more than 30 mg/m²

  once weekly result in an increased risk of serious adverse reactions, including myelosuppression. When responses are observed, the majority occurred between 3 and 6 weeks from initiation of treatment; however, responses have occurred up to 12 weeks after treatment initiation.

  Administer folic acid or folinic acid to reduce the risk of methotrexate adverse reactions

  [see Warnings and Precautions (5.10)]

  .
  )
• Psoriasis
  :
  The recommended dosage is 10 mg to 25 mg orally once weekly until adequate response is achieved. (
  2.5 Recommended Dosage for Psoriasis

  The recommended dosage of JYLAMVO is 10 mg to 25 mg orally once weekly until an adequate response is achieved. Adjust the dose gradually to achieve optimal clinical response; do not exceed a dose of 30 mg per week. Once optimal clinical response has been achieved, reduce the dosage to the lowest possible dosing regimen.

  Administer folic acid or folinic acid supplementation to reduce the risk of methotrexate adverse reactions

  [see Warnings and Precautions (5.10)]

  .
  )

Oral solution: clear yellow solution containing methotrexate 2 mg/mL.