⛔ FDA Black Box Warning
WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY Natalizumab products increase the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Risk factors for the development of PML include the presence of anti-JCV antibodies, duration of therapy, and prior use of immunosuppressants. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYRUKO [see Warnings and Precautions ( 5.1 )] . - Healthcare professionals should monitor patients on TYRUKO for any new sign or symptom that may be suggestive of PML. TYRUKO dosing should be withheld immediately at the first sign or symptom suggestive of PML. For diagnosis, an evaluation that includes a gadolinium-enhanced magnetic resonance imaging (MRI) scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )] . - Because of the risk of PML, TYRUKO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TYRUKO REMS Program [see Warnings and Precautions ( 5.2 )] . WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY See full prescribing information for complete boxed warning • Natalizumab products increase the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability ( 5.1 ). • Risk factors for the development of PML include the presence of anti-JCV antibodies, duration of therapy, and prior use of immunosuppressants. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYRUKO ( 5.1 ). • Monitor patients, and withhold TYRUKO immediately at the first sign or symptom suggestive of PML ( 4 , 5.1 ). • Because of the risk of PML, TYRUKO is available only through a
Contraindications
4 CONTRAINDICATIONS • TYRUKO is contraindicated in patients who have or have had progressive multifocal leukoencephalopathy (PML) [see Warnings and Precautions ( 5.1 )] . • TYRUKO is contraindicated in patients who have had a hypersensitivity reaction to natalizumab products or any of the ingredients in TYRUKO. Observed reactions range from urticaria to anaphylaxis [see Warnings and Precautions ( 5.5 )] . • Patients who have or have had PML ( 4 ) • Patients who have had a hypersensitivity reaction to natalizumab products ( 4 , 5.3 )
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary There are no adequate data on the risk of major birth defects, miscarriage, or other adverse maternal outcomes associated with the use of natalizumab products in pregnant women. Adverse fetal outcomes of neonatal thrombocytopenia and anemia have been reported (see Clinical Considerations ) . In animal studies, administration of natalizumab during pregnancy produced fetal immunologic and hematologic effects in monkeys at doses similar to the human dose and reduced offspring survival in guinea pigs at doses greater than the human dose. These doses were not maternally toxic but produced the expected pharmacological effects in maternal animals ( see Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations Fetal/Neonatal Adverse Reactions Cases of neonatal thrombocytopenia and anemia in infants born to women exposed to natalizumab products during pregnancy were reported in the post-marketing setting [see Warnings and Precautions ( 5.8 )] . Therefore, a CBC should be obtained in neonates who were exposed to TYRUKO in utero. Data Animal Data In developmental toxicity studies conducted in guinea pigs and monkeys, at natalizumab doses up to 30 mg/kg (7 times the recommended human dose based on body weight [mg/kg]), transplacental transfer and in utero exposure of the embryo/fetus was demonstrated in both species. In a study in which pregnant guinea pigs were administered natalizumab (0, 3, 10, or 30 mg/kg) by intravenous (IV) infusion on alternate days throughout organogenesis (gestation days [GD] 4‑30), no effects on embryofetal development were observed. When pregnant monkeys were administered natalizumab (0, 3, 10, or 30 mg/kg) by IV infusion on alternative days throughout organogenesis (GDs 20-70), ser