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Pharmacologic class: Recombinant humanized IgG4K monoclonal antibody
Therapeutic class: Immunologic agent
Pregnancy risk category C
FDA Box Warning
Drug increases risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability.
Monitor patient and withhold drug immediately at first sign or symptom suggestive of PML.
Drug is available only through a special restricted distribution program, TOUCH® Prescribing Program, and must be administered only to patients enrolled in this program.
Binds to the α4-subunit of α4β1 and α4β7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the α4-mediated adhesion of leukocytes to their counterreceptor(s). The receptors for the α4 family of integrins include vascular cell adhesion molecule-1 (VCAM-1), which is expressed on activated vascular endothelium, and mucosal address in cell adhesion molecule-1 (MAdCAM-1) present on vascular endothelial cells of the GI tract. Disruption of these molecular interactions prevents transmigration of leukocytes across the endothelium into inflamed parenchymal tissue. Specific mechanisms by which drug exerts its effects in multiple sclerosis (MS) and Crohn's disease haven't been fully defined.
Solution for infusion: 300 mg/15-ml vial (20 mg/ml)
Indications and dosages
➣ Relapsing forms of MS; moderately to severely active Crohn's disease in patients with evidence of inflammation who have had inadequate response to or can't tolerate conventional therapy
Adults: 300 mg by I.V. infusion over approximately 1 hour q 4 weeks. In Crohn's disease, discontinue in patient who hasn't experienced therapeutic benefit by 12 weeks of induction therapy and in patient who can't discontinue long-term concomitant steroids within 6 months of starting natalizumab.
• Hypersensitivity to drug
• History of or current PML
Use cautiously in:
• hepatic impairment
• infections, immune reconstitution inflammatory syndrome
• concurrent use of TNFa inhibitors, antineoplastics, prolonged immunosuppressant or immunomodulatory therapy; systemic medical condition resulting in significantly compromised immune system (avoid use)
• pregnant or breastfeeding patients
• children younger than age 18 (safety and efficacy not established).
Don't give as I.V. push or bolus.
• To prepare solution, withdraw 15 ml of drug concentrate from vial. Inject concentrate into 100 ml 0.9% sodium chloride injection, leading to concentration of 2.6 mg/ml. Don't use other I.V. diluents or mix with other drugs. Gently invert vial to mix completely; don't shake. Following dilution, infuse solution immediately or refrigerate at 2° to 8° C (36° to 46° F), and use within 8 hours.
• Infuse 300 mg in 100 ml 0.9% sodium chloride injection over approximately 1 hour (infusion rate approximately 5 mg/minute). After infusion is complete, flush with 0.9% sodium chloride injection.
Observe patient during infusion and for 1 hour after infusion is complete. Promptly discontinue infusion at first sign or symptom consistent with a hypersensitivity reaction.
Obtain MRI scan in MS patients before starting therapy to help differentiate subsequent MS signs and symptoms from those of PML. Withhold drug immediately at first sign or symptom suggestive of PML.
• Be aware that a baseline brain MRI in patients with Crohn's disease may help distinguish preexisting lesions from newly developed lesions.
For patients with Crohn's disease who start drug while taking long-term corticosteroids, start steroid withdrawal as soon as therapeutic benefit has occurred. If patient can't discontinue systemic corticosteroids within 6 months, discontinue natalizumab.
Discontinue drug in patients with jaundice or other evidence of significant liver injury.
CNS: headache, fatigue, depression, somnolence, vertigo, tremor, PML
EENT: tonsillitis, pharyngolaryngeal pain, sinusitis
GI: nausea, diarrhea, constipation, dyspepsia, gastroenteritis, abdominal discomfort, flatulence, aphthous stomatitis, exacerbation of Crohn's disease, intestinal obstruction or stenosis
GU: vaginitis; irregular menstruation; dysmenorrhea; amenorrhea; ovarian cyst; urinary tract infection; urinary incontinence, urgency, frequency
Hepatic: abnormal liver function test values
Musculoskeletal: arthralgia, extremity pain, back pain, muscle cramps, joint swelling, limb injury
Respiratory: upper and lower respiratory tract infections, cough
Skin: rash, dermatitis, pruritus, urticaria, dry skin, skin laceration, thermal burn
Other: infections, chest discomfort, seasonal allergy, weight changes, tooth infections, toothache, herpes infection, night sweats, rigors, peripheral edema, influenza-like illness, immunosuppression, infusion reactions, hypersensitivity reactions including anaphylaxis
Drug-drug. Corticosteroids, immunosuppressants (such as azathioprine, cyclosporine, 6-mercaptopurine, methotrexate), TNFα inhibitors: increased risk of PML and other infections
Drug-diagnostic tests. Circulating basophils, eosinophils, lymphocytes, monocytes, nucleated RBCs: increased levles
Hemoglobin: decreased level
• Monitor CBC with differential and hepatic function tests.
Continue to monitor patient for hypersensitivity reactions; infection; hepatotoxicity; signs and symptoms of immune reconstitution inflammatory syndrome (including unanticipated clinical decline in patient's condition after return of immune function and in some cases after apparent clinical improvement; and PML signs and symptoms (such as progressive weakness on one side of the body, limb clumsiness, vision disturbances, and changes in thinking, memory, and orientation leading to confusion and personality changes).
• Explain the TOUCH Prescribing Program to patient.
Instruct patient to immediately report hypersensitivity reactions (such as flushing, nausea, headache, dizziness, fatigue, hives, or itching); signs and symptoms of infections; signs and symptoms of hepatotoxicity (such as yellowing of skin or eyes, dark urine, or right upper abdominal pain or discomfort); unanticipated clinical decline in condition or new signs and symptoms; or signs and symptoms of PML (such as progressive weakness on one side of the body, limb clumsiness, vision disturbances, and changes in thinking, memory, and orientation leading to confusion and personality changes).
• Instruct patient to tell prescriber about all drugs he's taking, because some drugs have potential for serious drug interactions and shouldn't be taken with natalizumab.
• Advise female patient of childbearing age that drug should be used during pregnancy only if potential benefit justifies potential risk to fetus.
• Advise breastfeeding patient that she should decide whether to discontinue breastfeeding or discontinue drug, taking into account importance of drug for her treatment.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.
ClassificationTherapeutic: anti multiple sclerosis agents
Pharmacologic: monoclonal antibodies
Adverse Reactions/Side Effects
Central nervous system
- hepatotoxicity (life-threatening)
- allergic reactions including anaphylaxis
- PML (life-threatening)
- infusion-related reactions
Drug-Drug interaction↑ risk of infection with immunosupressants (avoid concurrent use).
Route/DosageNOTE: Because of the risk of PML, natalizumab is available only under a special restricted distribution program, the TOUCH Prescribing Program. Prescribers, pharmacies, and patients must be enrolled in the program to obtain the drug.
- Observe patient during infusion and for 1 hr after infusion is completed. Assess for signs of hypersensitivity reactions (urticaria, dizziness, fever, rash, rigors, pruritus, nausea, flushing, hypotension, dyspnea, chest pain, anaphylaxis), especially during first 2 hrs of infusion. If symptoms occur, discontinue natalizumab and treat symptoms.
- Assess for new signs or symptoms suggestive of PML, an opportunistic infection of the brain caused by the JC virus, leading to death or severe disability; withhold dose and notify health care professional promptly. Monitor during therapy and for at least 6 months following discontinuation. PML symptoms may begin gradually but usually worsen rapidly. Symptoms vary depending on which part of the brain is infected (mental function declines rapidly and progressively, causing dementia; speaking becomes increasingly difficult; partial blindness; difficulty walking; rarely, headaches and seizures occur). Diagnosis is usually made via gadolinium-enhanced MRI and CSF analysis. Risk of PML increases with the number of infusions. Withhold natalizumab at first sign of PML.
- Obtain an MRI of the brain prior to initiating therapy to help in differentiating symptoms of MS with those of PML.
- MS: Assess frequency of exacerbations of symptoms of multiple sclerosis periodically during therapy.
- Crohn's disease: Assess abdominal pain and frequency, quantity, and consistency of stools at beginning and during therapy.
- Lab Test Considerations: May cause ↑ lymphocytes, monocytes, eosinophils, basophils, and nucleated RBCs. These ↑ persist during therapy but usually return to baseline within 16 weeks after last dose. Neutrophil ↑ do not usually occur.
- May cause hepatotoxicity. Monitor for ↑ serum hepatic enzymes and total bilirubin may occur within 6 days after the first dose or for the first time after multiple doses. Discontinue if jaundice or other evidence of hepatotoxicity occurs.
- Monitor serum JCV antibodies periodically during therapy. Patients with a negative antibody should be retested periodically during therapy due potential for false-positive results or a new infection.
Potential Nursing DiagnosesDeficient knowledge, related to medication regimen (Patient/Family Teaching)
- Intermittent Infusion: Diluent: Dilute 300 mg in 100 mL of 0.9% NaCl. Invert to mix solution; do not shake. Do not mix with other diluents. Solution is colorless and clear to slightly opalescent. Do not administer solutions that are discolored or contain particulate matter. Administer immediately after dilution or refrigerate and use within 8 hrs. Concentration: 2.6 mg/mL.
- Rate: Infuse over 1 hr. Do not use filtration devices. Do not administer as IV push or bolus injection.
- Inform patient of purpose of medication. Patients must visit their health care professional/prescriber 3 and 6 months after first infusion and every 6 months thereafter for follow-up exam.
- Instruct patient to read the Medication Guide before starting the infusion. Natalizumab is available only through a special restricted distribution program called the TOUCH™ Prescribing Program, MS-TOUCH for multiple sclerosis and CD-TOUCH for Crohn's Disease, and must be administered only to patients enrolled in this program.
- Instruct patient to report symptoms of PML (progressive weakness on one side of the body or clumsiness of limbs; disturbance of vision; changes in thinking, memory, and orientation leading to confusion and personality changes), hypersensitivity reactions, hepatotoxicity (yellowing of the skin and eyes, unusual darkening of the urine, nausea, feeling tired or weak, vomiting), or worsening of symptoms (new or sudden change in your thinking, eyesight, balance, or strength or other problems) that persist over several days to health care professional immediately.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Instruct patient to inform all health care professionals about treatment with natalizumab.
- Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
- Decrease in frequency of clinical exacerbations in patients with multiple sclerosis.
- Decrease in signs and symptoms of Crohn's disease.
- Patients must be evaluated at 3 mo and 6 mo after first infusion and every 6 mo thereafter to determine effectiveness.