Natalizumab

Natalizumab is a prescription medication used to treat relapsing forms of multiple sclerosis. It is also used to treat moderate to severe Crohn's disease in adults. 

• Natalizumab is available under the following different brand names: Tysabri 

Common side effects of Natalizumab include:

• Headache,
• Tired feeling,
• Joint or muscle pain,
• Redness or irritation at the injection site,
• Swelling hands/feet/ankles,
• Changes in the menstrual cycle,
• Stomach pain,
• Diarrhea,
• Skin rash,
• Depression,
• Painful menstrual cramps, or
• Cold symptoms such as stuffy nose, sneezing, or sore throat.

Serious side effects of Natalizumab include:

• Hives
• Itching
• Trouble breathing
• Chest pain and dizziness
• Wheezing
• Chills
• Rash
• Nausea
• Flushing of skin
• Low blood pressure
• Infections.
• Low platelet counts.
• Easy bruising
• Heavier menstrual periods than are normal
• Bleeding from the gums or nose that is new or takes longer than usual to stop
• Small scattered red spots on your skin that are red, pink, or purple
• Bleeding from a cut that is hard to stop.

Rare side effects of Natalizumab include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injectable solution

• 300 mg/15 mL

Multiple Sclerosis

Adult dosage

• 300 mg Intravenous infusion every 4 weeks

Crohn Disease

Adult dosage

• 300 mg Intravenous infusion every 4 weeks

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Natalizumab has severe interactions with no other drugs.
• Natalizumab has serious interactions with the following drugs:
  • axicabtagene ciloleucel
  • baricitinib
  • beclomethasone, inhaled
  • brexucabtagene autoleucel
  • certolizumab pegol
  • ciltacabtagene autoleucel
  • idecabtagene vicleucel
  • ifosfamide
  • influenza virus vaccine quadrivalent, adjuvanted
  • influenza virus vaccine trivalent, adjuvanted
  • lisocabtagene maraleucel
  • lomustine
  • mechlorethamine
  • melphalan
  • ocrelizumab
  • procarbazine
  • tisagenlecleucel
  • upadacitinib
  • vedolizumab
• Natalizumab has moderate interactions with the following drugs:
  • belatacept
  • cabazitaxel
  • denosumab
  • fingolimod
  • hydroxyurea
  • meningococcal group B vaccine
  • ofatumumab SC
  • olaparib
  • ponesimod
  • sipuleucel-T
  • trastuzumab
  • trastuzumab deruxtecan
• Natalizumab has minor interactions with the following drug:
  • interferon beta 1a

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity
• Active/history of progressive multifocal leukoencephalopathy 

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Natalizumab?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Natalizumab?”

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 the development of infections
• Possibility of anaphylactic reaction; observe patients during and for 1 hour after infusion to see if symptoms of hypersensitivity-type reactions develop
• Herpes infections
  • Therapy increases the s risk of developing encephalitis and meningitis caused by herpes simplex and varicella-zoster viruses; serious, life-threatening, and sometimes fatal cases reported in the post-marketing setting in multiple sclerosis patients receiving therapy; laboratory confirmation in those cases was based on positive PCR for viral DNA in cerebrospinal fluid
  • The duration of treatment of the drug before onset ranged from a few months to several years; monitor patients receiving the drug for signs and symptoms of meningitis and encephalitis
  • If herpes encephalitis or meningitis occurs, discontinue therapy, and administer appropriate treatment for herpes encephalitis/meningitis
• Acute renal necrosis
  • Acute retinal necrosis (ARN) is a fulminant viral infection of other retina caused by the family of herpesviruses (. g, varicella zoster, herpes simplex virus); a higher risk of ARN is observed in patients being administered treatment
  • Patients presenting with eye symptoms, including decreased visual acuity, redness, or eye pain, should be referred for retinal screening for ARN; some ARN cases occurred in patients with central nervous system (CNS) herpes infections (. g, herpes meningitis or encephalitis)
  • Serious cases of ARN leading to the blindness of one or both eyes reported in some patients; following a clinical diagnosis of ARN, consider discontinuation of therapy; the treatment reported in ARN cases included anti-viral therapy and, in some cases, surgery
• Hepatotoxicity
  • Clinically significant liver injury, including acute liver failure requiring transplant, reported in patients treated in the post-marketing setting
  • Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, were reported as early as six days after the first dose; signs of liver injury have also been reported for the first time after multiple doses
  • In some patients, liver injury recurred upon rechallenge, providing evidence that treatment caused the injury; the combination of transaminase elevations and elevated bilirubin without evidence of obstruction is generally recognized as an important predictor of severe liver injury that may lead to death or the need for a liver transplant in some patients
  • Therapy should be discontinued in patients with jaundice or other evidence of significant liver injury (. g, laboratory evidence)
• Progressive multifocal leukoencephalopathy
  • Infection by the JC virus is required for the development of PML; do not use anti-JCV antibody testing to diagnose PML; anti-JCV antibody negative status indicates that antibodies to the JC virus have not been detected; patients who are anti-JCV antibody negative have a lower risk of PML than those who are positive; patients who are anti-JCV antibody negative are still at risk of developing PML due to potential for a new JCV infection or a false negative test result
  • Some patients’ serostatus may change intermittently; patients with a negative anti-JCV antibody test result should be retested periodically
  • For purposes of risk assessment, a patient with a positive anti-JCV antibody test at any time is considered anti-JCV antibody positive regardless of results of any prior or subsequent anti-JCV antibody testing; when assessed, anti-JCV antibody status should be determined using an analytically and clinically validated immunoassay
  • After plasma exchange (PLEX), 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 to avoid false positive anti-JCV antibody test results
  • Healthcare professionals should monitor patients on treatment for any new sign or symptom suggestive of PML; symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes
  • The progression of deficits usually leads to death or severe disability over weeks or months; withhold dosing immediately and perform an appropriate diagnostic evaluation at the first sign or symptom suggestive of PML
  • MRI findings may be apparent before clinical signs or symptoms; cases of PML diagnosed based on MRI findings and the detection of JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms specific to PML, have been reported
  • Many patients subsequently became symptomatic with PML; monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML if present
  • Consider monitoring patients at high risk for PML more frequently; lower PML-related mortality and morbidity have been reported following discontinuation in patients with PML who were initially asymptomatic compared to patients with PML who had characteristic clinical signs and symptoms at diagnosis
  • It is not known whether these differences are due to early detection and discontinuation of therapy or due to differences in disease in these patients
  • There are no known interventions that can reliably prevent PML or that can adequately treat PML if it occurs; PML has been reported following discontinuation of the drug in patients who did not have findings suggestive of PML at the time of discontinuation; patients should continue to be monitored for any new signs or symptoms that may be suggestive of PML for at least six months following discontinuation of treatment
  • There are no known interventions that can reliably prevent PML; PML has been reported following discontinuation of treatment in patients who did not have findings suggestive of PML at the time of discontinuation; patients should continue to be monitored for any new signs or symptoms that may be suggestive of PML for at least six months following discontinuation of treatment
  • In multiple sclerosis patients, an MRI scan should be obtained before initiating therapy; this MRI may help differentiate subsequent multiple sclerosis symptoms from PM; in Crohn’s disease patients, a baseline brain MRI may also be helpful to distinguish pre-existent lesions from newly developed lesions, but brain lesions at baseline that could cause diagnostic difficulty while on therapy are uncommon
  • For diagnosis of PML, an evaluation including a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA is recommended; if the initial evaluations for PML are negative but clinical suspicion for PML remains, continue to withhold dosing, and repeat the evaluations
  • There are no known interventions that can adequately treat PML if it occurs; three sessions of PLEX over 5 to 8 days have been shown to accelerate drug clearance in a study of 12 patients with MS who did not have PML, although, in most patients, alpha-4 integrin receptor binding remained high
  • Adverse events which may occur during PLEX include clearance of other medications and volume shifts, which have the potential to lead to hypotension or pulmonary edema; although PLEX has not been prospectively studied in treated patients with PML, it has been used in such patients in the post-marketing setting to remove drug more quickly from the circulation
  • There is no evidence that PLEX has any benefit in the treatment of opportunistic infections such as PML
  • JC virus infection of granule cell neurons in the cerebellum (. e., JC virus granule cell neuronopathy [JCV GCN]) reported in patients treated with drug; JCV GCN can occur with or without concomitant PML; JCV GCN can cause cerebellar dysfunction (. g., ataxia, incoordination, apraxia, visual disorders), and neuroimaging can show cerebellar atrophy
  • For diagnosis of JCV GCN, an evaluation that includes a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA, is recommended; JCV GCN should be managed similarly to PML
  • Immune reconstitution inflammatory syndrome (IRIS) has been reported in most treated patients who developed PML and subsequently discontinued therapy; in almost all cases, IRIS occurred after PLEX was used to eliminate circulating drug
  • Immune reconstitution presents as a clinical decline in a patient’s condition after drug removal (and in some cases after apparent clinical improvement) that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes in the MRI
  • Therapy has not been associated with IRIS in patients discontinuing treatment for reasons unrelated to PML; in treated patients with PML, IRIS has been reported within days to several weeks after PLEX; monitoring for the development of IRIS and appropriate treatment of associated inflammation should be undertaken.

Pregnancy and Lactation

• There are no adequate data on the developmental risk associated with use in pregnant women
• 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