Trade Names:Tysabri- Injection 20 mg/mL
Exact mechanism of action is unknown; however, animal data demonstrate a reduction of leukocyte migration into brain parenchyma and a reduction of plaque formation.
Mean C max is approximately 110 mcg/mL. Steady-state trough concentrations range from 23 to 29 mcg/mL. After 4 wk of dosing, the time to steady state is approximately 24 wk.
Vd is 5.7 L.
The mean t ½ is about 11 days; Cl is 16 mL/h.
A less than proportional increase in Cl occurs as body weight increases, such that a 43% increase in body weight produces a 32% increase in Cl.
Treatment of relapsing forms of multiple sclerosis to delay the accumulation of physical disability and reduce the frequency of clinical exacerbations; inducing and maintaining clinical response and remission in adults with moderately to severely active Crohn disease with evidence of inflammation who have had an inadequate response to or are unable to tolerate conventional Crohn disease therapies and tumor necrosis factor (TNF)–alpha inhibitors.
Patients who have progressive multifocal leukoencephalopathy (PML); hypersensitivity to any component of the product.
IV 300 mg infused over 1 h every 4 wk.
Refrigerate between 36° and 46°F. Do not shake or freeze. Protect from light. Store diluted solution at 36° to 46°F; administer within 8 h of preparation.
May increase the risk of infection.
None well documented.
Headache (38%); fatigue (27%); depression (19%); vertigo (6%); somnolence (2%); tremor (1%); herpes encephalitis, herpes meningitis (postmarketing); PML.
Rash (12%); dermatitis (7%); pruritus (4%); acute urticaria, skin laceration (2%); dry skin, night sweats (1%).
Tonsillitis (7%); pharyngolaryngeal pain (6%).
Dyspepsia, nausea (17%); abdominal discomfort, gastroenteritis (11%); diarrhea (10%); tooth infections (9%); constipation, lower abdominal pain, toothache (4%); flatulence (3%); aphthous stomatitis (2%).
UTI (21%); vaginitis (10%); urinary urgency/frequency (9%); dysmenorrhea (6%); irregular menstruation (5%); urinary incontinence (4%); dysmenorrhea (3%); amenorrhea, ovarian cyst (2%).
Abnormal LFTs (5%); hepatic injury, including elevated LFT and bilirubin (postmarketing).
Weight increase or decrease (2%).
Arthralgia (19%); pain in extremity (16%); back pain (12%); muscle cramp (5%); rigors (3%); joint swelling (2%).
Upper respiratory tract infection (22%); lower respiratory tract infection (17%); sinusitis (8%); cough (7%).
Infusion-related reactions (24%); influenza (12%); influenza-like illness (11%); detectable natalizumab antibodies (9%); herpes (8%); viral infection (7%); peripheral edema (6%); chest discomfort, other hypersensitivity reactions (5%); acute hypersensitivity reactions (4%); limb injury, seasonal allergy (3%); thermal burn (1%).
Natalizumab therapy increases the risk of PML, an opportunistic viral infection of the brain that usually leads to death or severe disability. Natalizumab is available only through a special restricted distribution program, and only prescribers, infusion centers, and pharmacies associated with registered infusion centers are able to prescribe, distribute, or infuse the product. The product must only be administered to patients who are enrolled in and meet the conditions of the prescribing program.
Monitor patients for any new signs or symptoms suggestive of PML. Withhold natalizumab immediately at the first sign or symptom suggestive of PML.
Evaluate the patient 3 and 6 mo after the first infusion and every 6 mo thereafter.
Category C .
Safety and efficacy not established.
Studies did not include sufficient numbers of patients 65 yr of age and older to determine whether they respond differently than younger patients.
Has been associated with hypersensitivity reactions, including serious systemic reactions (eg, anaphylaxis).
Circulating basophils, eosinophils, lymphocytes, monocytes, and nucleated RBCs may be increased; transient, mild decreases in hemoglobin concentrations may occur.
The immune system effects of natalizumab may increase the risk of infection.
Clinically significant liver injury has been reported during postmarketing. Signs of liver injury have occurred as early as 6 days after the first dose.
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