Natalizumab

Indications

Natalizumab is used for: Multiple Sclerosis, Crohn's Disease

Adult Dose

Intravenous Relapsing-remitting multiple sclerosis Adult: As monotherapy: 300 mg via infusion over 1 hour once every 4 weeks. Discontinue use if no progress is shown after 6 months of treatment. Crohn's disease Adult: Moderate to severe, refractory cases: 300 mg via infusion over 1 hour once every 4 weeks. Discontinue use if no progress is shown within 12 weeks upon initiation of treatment.

Child Dose

Renal Dose

Administration

IV Preparation Concentrate is a colorless opalescent solution Visually inspect for particulate matter or discoloration - do not use if either present Withdraw 15 mL from the vial and dilute in 100 mL 0.9% NaCl; no other diluent should be used Gently invert to mix - do not shake Make sure no particulate matter is present After dilution, use immediately or within 8 hr (keep refrigerated at 2-8°C) If refrigerated, warm before using Do not freeze IV Administration Infuse over 1 hr After infusion is complete flush with 0.9% NaCl Do not coadminister any other drugs either through Y-site or dissolved in same solution Observe patients during infusion and for 1 hr after infusion is complete Promptly discontinue infusion upon any signs or symptoms consistent with a hypersensitivity-type reaction Use of filtration devices during administration has not been evaluated Other medications should not be injected into infusion set side ports or mixed with natalizumab

Contra Indications

Patient with or with history of progressive multifocal leukoencephalopathy (PML), active malignancies (except cutaneous basal cell carcinoma), active infection. Immunocompromised patients. Concomitant use of immunosuppressants, immunomodulator, antineoplastics, and TNF-α inhibitors.

Precautions

Patient with chronic infections, history of recurring infections and/or underlying conditions that may predispose them to develop infections, presence of anti-JCV antibodies. Hepatic impairment. Pregnancy and lactation.

Pregnancy-Lactation

Pregnancy There are no adequate data on the developmental risk associated with use in pregnant women Animal data 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 Doses were not maternally toxic but produced the expected pharmacological effects in maternal animals Lactation Natalizumab has been detected in human milk No data available on the effects of this exposure on the breastfed infant or the effects of the drug on milk production

Interactions

Potentially Fatal: Increased risk of opportunistic infections with immunosuppressants (e.g. 6-mercaptopurine, azathioprine, ciclosporin, methotrexate), immunomodulators (e.g. interferon beta or glatiramer), antineoplastics, and TNF-α inhibitors.

Side Effects

Side effects of Natalizumab : >10% Fatigue (10%) Diarrhea (10%) Urinary urgency/frequency (9%) Sinusitis (8%) Vaginal infections (8%) Arthralgia (8%) Cough (3-7%) Viral infection (7%) Dermatitis (7%) Pharyngolaryngeal pain (6%) Peripheral edema (6%) Rash (6%) Dysmenorrhea (2-6%) Vertigo (6%) Dyspepsia (5%) Abnormal liver function test (5%) Irregular menstruation (5%) Urinary incontinence (4%) Toothache (4%) Pruritus (4%) Lower abdominal pain (4%) Constipation (4%) Vaginal infections (4%) Limb injury (3%) Viral infections (3%) Urinary tract infections (3%) Flatulence (3%) Skin laceration (2%) Aphthous stomatitis (2%) Amenorrhea (2%) Ovarian cyst (2%) Somnolence (2%) Acute hypersensitivity reactions (2%) Thermal burn (1%) Dry skin (1%) Tremor (1%) Night sweats (1%)

Mode of Action

Natalizumab is a recombinant humanised monoclonal antibody that selectively binds to the alpha-4 integrin molecules. It prevents the migration of leucocytes into the CNS and the gut, thus reducing frequency of relapse, inflammation, and demyelination.