Natalizumab
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From MedlinePlus, U.S. National Library of Medicine
Boxed 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 restricted distribution program called the TYRUKO REMS Program ( 5.1 , 5.2 ).
Integrin Receptor Antagonist
Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Preparation and administration
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Dilution Instructions 1. Use aseptic technique when preparing TYRUKO solution for intravenous infusion. Each vial is intended for single use only. Discard any unused portion. 2. TYRUKO is a colorless and clear to slightly opalescent solution. Inspect the TYRUKO vial for particulate material and discoloration prior to dilution and administration.
If visible particulates are observed and/or the liquid in the vial is discolored, the vial must not be used. 3. To prepare the diluted solution, withdraw 15 mL of TYRUKO from the vial using a sterile needle and syringe. Inject TYRUKO into 100 mL of 0.9% Sodium Chloride Injection, USP. No other intravenous diluents may be used to prepare the TYRUKO diluted solution. 4.
Gently invert the TYRUKO diluted solution to mix completely. Do not shake. Inspect the solution visually for particulate material prior to administration. 5. The final dosage diluted solution has a concentration of 2.6 mg/mL. 6. Following dilution, infuse TYRUKO solution immediately, or refrigerate the diluted solution at 2°C to 8°C, and use within 4 hours.
If stored at 2°C to 8°C, allow the diluted solution to warm to room temperature prior to infusion. DO NOT FREEZE.
Administration Instructions
Infuse TYRUKO 300 mg in 100 mL 0.9% Sodium Chloride Injection, USP, over approximately one hour (infusion rate approximately 5 mg per minute). Do not administer TYRUKO as an intravenous push or bolus injection. After the infusion is complete, flush with 0.9% Sodium Chloride Injection, USP.
Observe patients during all infusions. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity-type reaction [see Warnings and Precautions] .
Post-infusion, for the first 12 infusions, observe patients for one hour after the infusion is complete. For patients who have received 12 infusions without evidence of a hypersensitivity reaction, observe patients post-infusion for the 13th and subsequent infusions according to clinical judgment.
Use of filtration devices during administration has not been evaluated. Other medications should not be injected into infusion set side ports or mixed with TYRUKO.
Drug interactions
Check natalizumab against a medication listLabel text (2 paragraphs)
Because of the potential for increased risk of PML and other infections, Crohn’s disease patients receiving natalizumab products should not be treated with concomitant immunosuppressants (e.g., 6‑ mercaptopurine, azathioprine, cyclosporine, or methotrexate) or inhibitors of TNF-α, and corticosteroids should be tapered in those patients with Crohn’s disease who are on chronic corticosteroids when they start TYRUKO therapy [see Indications and Usage ( 1.2 ) and Warnings and Precautions ( 5.1 , 5.6 )] .
Ordinarily, MS patients receiving chronic immunosuppressant or immunomodulatory therapy should not be treated with TYRUKO [see Indications and Usage ( 1.1 ) and Warnings and Precautions ( 5.1 , 5.6 )] .
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 and lactation
Pregnancy
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), serum levels in fetuses at delivery were approximately 35% of maternal serum natalizumab levels. There were no effects on embryofetal development; however, natalizumab-related immunological and hematologic changes were observed in the fetuses at the two highest doses.
These changes included decreases in lymphocytes (CD3+ and CD20+), changes in lymphocyte subpopulation percentages, mild anemia, reduced platelet count, increased spleen weights, and reduced liver and thymus weights associated with increased splenic extramedullary hematopoiesis, thymic atrophy, and decreased hepatic hematopoiesis.…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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