NATALIZUMAB

NATALIZUMAB (na-tal'-i-zu-mab) Tysabri Classifications: biologic response modifier; monoclonal antibody; integrin inhibitor; Therapeutic: immunomodulator; monoclonal antibody Prototype: Basiliximab Pregnancy Category: C

Availability

300 mg/15 mL injection

Action

Natalizumab is a recombinant immunoglobulin-G4 (IgG4) monoclonal antibody thought to interfere with the migration of lymphocytes and monocytes into the CNS endothelium of patients with multiple sclerosis, thereby reducing inflammation and demyelination of CNS white matter.

Therapeutic Effect

Inhibition of T-cell infiltration into the brain is thought to impede the demyelinating process of multiple sclerosis. It reduces relapses and occurrence of brain lesions. Natalizumab is also thought to attenuate T-lymphocyte–mediated intestinal inflammation in Crohn's disease and possibly ulcerative colitis.

Uses

Treatment of relapsing forms of multiple sclerosis.

Unlabeled Uses

Treatment of Crohn's disease.

Contraindications

Safety and efficacy of the drug have not been established for chronic progressive multiple sclerosis. Prior hypersensitivity to natalizumab; murine protein hypersensitivity; progressive multifocal leukoencephalopathy; active infection; females of childbearing age; pregnancy (category C); lactation; children <18 y.

Cautious Use

Coadministration with other immunosuppressive medication; diabetes mellitus, immunocompromised patients; exposure to infection or tuberculosis.

Route & Dosage

Multiple Sclerosis Adult: IV 300 mg infused over 1 h every 4 wk

Administration

Intravenous PREPARE: IV Infusion: Before and after dilution, solution should be colorless and clear to slightly opaque. Do not use if the solution has visible particles, flakes, color, or is cloudy. Withdraw 15 mL from the vial and add to an IV bag with 100 mL of NS. Do not use with any other diluent. Gently invert the bag to mix; do not shake. The IV solution must be used within 8 h.   ADMINISTER: IV Infusion: Flush IV line before/after with NS. Infuse over 1 h. Do not give a bolus dose. Stop infusion immediately if S&S of hypersensitivity appear.   INCOMPATIBILITIES Solution/additive/Y-site: Do not mix or infuse with other drugs.

• Store IV solution for up to 8 h at 2°–8° C (36°–46° F). Allow solution to warm to room temperature before administration

Adverse Effects (≥1%)

Body as a Whole: Anaphylaxis (rare, usually within 2 h of infusion), infections, fatigue, rigors. CNS: Depression, headache, syncope, tremor. CV: Chest discomfort. GI: Abdominal discomfort, abnormal liver function tests. Hematologic: Local bleeding from infusion site. Musculoskeletal: Arthralgia. Respiratory: Pneumonia. Skin: Acute urticaria. Urogenital: Urinary frequency, irregular menstruation, amenorrhea, dysmenorrhea. Other: Infusion-related reactions (headache, dizziness, fatigue, hypersensitivity reactions, urticaria, pruritus, and rigors).

Interactions

Drug : May reduce the effectiveness of vaccines and toxoids; may increase risk of infection with immunosuppressants.

Pharmacokinetics

Half-Life: 11 d.

Nursing Implications

Assessment & Drug Effects

• During IV infusion and for 1–2 h after, monitor closely for S&S of hypersensitivity (e.g., urticaria, dizziness, fever, rash, chills, pruritus, nausea, flushing, hypotension, dyspnea, and chest pain).
• Monitor neurological status frequently. Report promptly any emerging S&S of dysfunction.
• Lab tests: Baseline and periodic CBC with differential.

Patient & Family Education

• Report immediately any of the following during/after IV infusion: difficulty breathing, wheezing or shortness of breath, swelling or tightness about the neck and throat, chest pain, skin rash or hives.
• Report promptly S&S of infection (e.g., cough, fever, chills, or sore throat).

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug