Natalizumab

Hepatotoxicity, including acute liver failure requiring transplant, has been reported with use. Signs of hepatotoxicity, including transaminase and bilirubin elevation occurred as early as 6 days after the first dose; may recur with treatment rechallenge; discontinue use with jaundice or signs/symptoms of hepatic injury.

Serious, life-threatening herpes infections, including fatalities (herpes encephalitis or herpes meningitis infections caused by herpes simplex and varicella zoster viruses) have occurred within a few months to several years of natalizumab treatment. Monitor patients for signs/symptoms of meningitis and encephalitis. In the presence of herpes encephalitis or meningitis, discontinue therapy. Acute retinal necrosis (ARN), a fulminant viral infection of the retina caused by the family of herpes viruses (eg, varicella zoster, herpes simplex virus) has also been observed during natalizumab treatment. Some cases occurred in patients with CNS herpes infections (eg, herpes meningitis, encephalitis); serious cases may result in blindness. Following diagnosis of ARN, consider discontinuation of natalizumab.

Hypersensitivity reactions including serious systemic reactions (eg, anaphylaxis) have occurred in • Immune reconstitution inflammatory syndrome (IRIS): IRIS has been reported in patients after discontinuing natalizumab due to PML. In most cases, this occurred within days to weeks after plasma exchange was used in an attempt to remove natalizumab. IRIS is a rare condition which is characterized by severe inflammation during or following immune system recovery, which can result in a decline in patient condition, including neurological symptoms and death.

Use may be associated with an increased risk of infections, including opportunistic infections and serious herpes infections (rare, postmarketing reports; concurrent use of antineoplastic, immunosuppressant [including short-course corticosteroids], or immunomodulating agents may increase this risk); discontinue therapy until successful resolution of the infection.

Reversible increases in circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells may occur; changes persist during natalizumab exposure but usually return to baseline within 16 weeks after the last dose. Mild transient decreases in hemoglobin levels may also occur.

Natalizumab increases the risk of developing fatal or disabling progressive multifocal leukoencephalopathy (PML, an opportunistic viral infection of the brain caused by the JC virus). Risk factors for development of PML include duration of therapy (especially >2 years), prior use of immunosuppressants (eg, azathioprine, cyclophosphamide, methotrexate, mitoxantrone, mycophenolate), and the presence of anti JC virus antibodies. Monitor for any new signs/symptoms suggestive of PML; immediately withhold treatment at the first sign or symptom suggesting PML. For diagnosis of PML, an evaluation should include a gadolinium-enhanced MRI scan of the brain and (if indicated) analysis of CSF for JCV DNA. Cases of PML have been diagnosed based on MRI findings and the detection of JCV DNA in the CSF without specific PML signs/symptoms (including progressive weakness on one side of the body, limb clumsiness, visual disturbance, changes in thinking, memory, personality or orientation) reported. Use should ordinarily be avoided in patients who are significantly immunocompromised or receiving chronic immunosuppressant or immunomodulatory therapy. For an early diagnosis of PML, consider periodic monitoring for radiographic signs of PML. Anti-JCV antibody testing prior to or during treatment may be considered; testing should not be used to diagnose PML and should not be performed for at least 2 weeks after plasma exchange. Patients who are anti-JCV antibody negative are still at risk for develo

Natalizumab should not be used in combination with immunosuppressants or tumor necrosis factor (TNF) inhibitors in patients with Crohn disease; aminosalicylates may be used concurrently with natalizumab. For patients who begin treatment while on chronic oral corticosteroids, begin tapering oral steroids when the onset of natalizumab therapeutic benefit is observed; discontinue use if patient cannot be tapered off of oral corticosteroids within 6 months of therapy initiation. If additional concomitant corticosteroids are required and exceed 3 months/year (in addition to initial corticosteroid taper), consider discontinuing therapy. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

There are no data available concerning the effect of vaccination or secondary transmission of infection by live vaccines in patients receiving natalizumab. Other warnings/precautions:

Use should be restricted to patients with inadequate response to or intolerant of other therapies for Crohn disease or multiple sclerosis. Carefully evaluate the overall benefit to risk in patients that develop persistent antibodies to natalizumab.

Access is restricted through a REMS program called the TOUCH Prescribing Program; prescribers and pharmacies must be certified with the Tysabri Outreach Unified Commitment to Health (TOUCH) Prescribing Program. Patients must also be enrolled in the TOUCH Prescribing Program (800-456-2255) to receive natalizumab (MS-TOUCH for multiple sclerosis or CD-TOUCH for Crohn disease).