Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 300mg/15mL
Multiple Sclerosis
Indicated as monotherapy for patients with relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease
300 mg IV infusion q4wk
When initiating and continuing treatment, consider whether expected benefit is sufficient to offset risk of PML
Crohn Disease
Indicated for moderate-to-severe Crohn disease in adults who had inadequate/intolerant response to conventional treatment and TNF-alpha inhibitors
300 mg IV q4wk
Dosing Considerations
Because natalizumab increases risk of progressive multifocal leukoencephalopathy (PML), it is recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate multiple sclerosis therapy
Additional or previous immunosuppressive therapy increases risk for PML; therefore, do not administer concomitantly with immunosuppressants (eg, 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate) or TNF-alpha inhibitors
<18 years: Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>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%)
Postmarketing Reports
Hemolytic anemia
Warnings
Black Box Warnings
Increased risk of progressive multifocal leukoencephalopathy, an opportunistic viral infection of the brain caused by the JC virus in immunocompromised patients that usually leads to death or severe disability
Immune reconstitution inflammatory syndrome may occur in patients who have developed PML; IRIS is a rare condition characterized by severe inflammatory response
Because of the risk of PML, natalizumab is available only through a special restricted distribution program; prescribers, infusion centers, and pharmacies associated with infusion centers registered with the program, are able to prescribe, distribute, or infuse the product to patients who are enrolled in and meet all the conditions of the TOUCH Prescribing Program
Healthcare professionals should monitor patients on natalizumab for any new sign or symptom that may be suggestive of PML
Withhold dose immediately at the first sign or symptom suggestive of PML
For diagnosis, an evaluation that includes a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended
Consider assessing anti-JCV antibody status prior to treatment or during treatment if antibody status is unknown; the Stratify JCV Antibody ELISA test (Focus Diagnostics) was cleared by FDA on January 20, 2012
Factors known to increase risk of PML in natalizumab-treated patients
- Longer treatment duration, especially beyond 2 years
- Prior treatment with an immunosuppressant (eg, mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate)
- Presence of anti-JCV antibodies
- Patients with all 3 known risk factors have an estimated risk of PML of 11/1,000
- The risks and benefits of continuing treatment with natalizumab should be carefully considered in patients who are found to be anti-JCV antibody positive and have 1 or more additional risk factors
- PML has been reported following discontinuation in patients who did not have findings suggestive of PML at the time of discontinuation; continue to monitor for any new signs or symptoms that may be suggestive of PML for ~6 months following discontinuation
Contraindications
Hypersensitivity
Active/history of progressive multifocal leukoencephalopathy
Cautions
Increased risk of PML with prolonged duration of therapy, prior treatment with immunosuppressants, or positive anti-JCV antibody status (see Black Box Warnings)
Do not use with other immunosuppressives; may increase the risk for certain infections; monitor patients for development of infections
Possibility of anaphylactic reaction; observe patients during and for 1 hr after infusion to see if symptoms of hypersensitivity-type reactions develop
Increased risk of developing encephalitis and meningitis caused by HSV and VZV; serious, life-threatening, and sometimes fatal cases reported; discontinue therapy if this occurs and treat appropriately
Severe hepatic injury reported as early as 6 days following therapy initiation, including markedly elevated LFTs and bilirubin; discontinue in patients with jaundice or with significant liver injury
After plasma exchange, wait at least two weeks to test for anti-JCV antibodies to avoid false negative test results caused by the removal of serum antibodies; after infusion of intravenous immunoglobulin (IVIg), wait at least 6 months (5 half-lives) for the IVIg to clear in order to avoid false positive anti-JCV antibody test results
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
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Recombinant humanized monoclonal antibody that binds to the α4-subunit of α4β1 and α4β7 integrins, prevents leukocyte-endothelial adhesion and leukocyte extravasation
Absorption
Peak plasma concentration: 64-132 mcg/mL
Distribution
Vd: 5.7 L (multiple sclerosis); 5.2L (Crohn disease)
Elimination
Half-Life: 7-15 days (multiple sclerosis); 3-17 days (Crohn disease)
Administration
IV Compatibility
0.9% NaCl
IV Incompatibility H3
No other IV diluents may be used to prepare diluted solution
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
Storage
Unopened vials: Refrigerate at 2-8°C (36-46°F); do not use beyond expiration date on the carton and vial label; do not freeze or shake; protect from light
Diluted solution: Refrigerate at 2-8°C; use within 8 hr
Images
Patient Handout
Formulary
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