Natalizumab Side Effects

It is possible that some side effects of natalizumab may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to natalizumab: intravenous solution

As well as its needed effects, natalizumab may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking natalizumab, check with your doctor or nurse immediately:

More common
  • Body produces substance that can bind to drug making it less effective or cause side effects
  • cough
  • difficulty with swallowing
  • dizziness
  • fast heartbeat
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • shortness of breath
  • skin rash, hives, or itching
  • tightness in the chest
  • unusual tiredness or weakness
Rare
  • Abdominal or stomach fullness
  • blurred vision
  • changes in behavior
  • chest pain
  • confusion
  • difficult or labored breathing
  • faintness or lightheadedness when getting up suddenly from a lying or sitting position
  • feeling of warmth
  • feeling unusually cold
  • fever
  • gaseous abdominal or stomach pain
  • nausea
  • redness of the face, neck, arms, and occasionally, upper chest
  • shivering
  • sneezing
  • sore throat
  • sweating
  • thoughts of killing oneself
  • yellow eyes or skin
Incidence not known
  • Back pain
  • convulsions
  • drowsiness
  • headache

Some natalizumab side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common
  • Bladder pain
  • blistering, crusting, irritation, itching, or reddening of the skin
  • bloody or cloudy urine
  • cracked, dry, scaly skin
  • diarrhea
  • difficult, burning, or painful urination
  • difficulty with moving
  • discouragement
  • feeling sad or empty
  • frequent, strong, or increased urge to urinate
  • irregular menstruation
  • irritability
  • itching of the vagina or genital area
  • loss of appetite
  • loss of interest or pleasure
  • lower back or side pain
  • muscle pain or stiffness
  • pain during sexual intercourse
  • pain in the joints
  • pain, cramps, or heavy bleeding
  • passing urine more often
  • stomach pain
  • stomach soreness or discomfort
  • swelling
  • swollen glands
  • thick, white vaginal discharge with no odor or with a mild odor
  • trouble concentrating
  • trouble sleeping
Less common
  • Absent, missed, or irregular menstrual periods
  • chest discomfort
  • fainting
  • local bleeding
  • shakiness in the legs, arms, hands, or feet
  • stopping of menstrual bleeding
  • trembling or shaking of the hands or feet

For Healthcare Professionals

Applies to natalizumab: intravenous concentrate

Nervous system

Nervous system side effects have included headache (up to 38%), dizziness (10% or greater), vertigo (6%), tremors (up to 3%), somnolence (2%), and syncope (2%). At least three cases of progressive multifocal leukoencephalopathy (PML) have been reported. Herpes infections of the central nervous system have been reported during postmarketing experience and have included herpes simplex virus (HSV) encephalitis, HSV meningitis, and herpes zoster virus meningitis. PML has also been reported during postmarketing experience.[Ref]

One patient, a 46-year-old female, developed PML after she received 37 doses of natalizumab over 33 months. The other patient received 28 doses of natalizumab before developing PML and remains severely disabled.

In postmarketing experience, one MS patient who received natalizumab developed herpes encephalitis and died; a second MS patient developed herpes meningitis and recovered with appropriate treatment.[Ref]

Respiratory

Respiratory side effects have included opportunistic infections. These have included pneumocystis carinii pneumonia, pulmonary mycobacterium avium intracellulare, bronchopulmonary aspergillosis, and Burkholderia cepacia. Upper respiratory tract infection (22%), lower respiratory tract infection (up to 17%), influenza (12%), influenza-like illness (up to 11%), nasopharyngitis (10% or greater), sinusitis (7%), cough (up to 7%), and pharyngolaryngeal pain (6%) have been reported. At least one patient who had been administered natalizumab (3 mg per kg) experienced bronchospasm that rapidly responded to antihistamines and corticosteroids.[Ref]

Psychiatric

Psychiatric side effects have included depression (19%), including suicidal ideation or attempt.[Ref]

Gastrointestinal

Gastrointestinal side effects have included nausea (17%), gastroenteritis (11%), abdominal discomfort (11%), diarrhea (10%), tooth infections (9%), dyspepsia (5%), constipation (4%), toothache (4%), lower abdominal pain (4%), flatulence (3%), aphthous stomatitis (2%), intestinal obstruction or stenosis (2%), cholelithiasis (1%), and abdominal adhesions (0.3%). At least one case of cryptosporidial gastroenteritis has been reported with prolonged use.[Ref]

Immunologic

Development of antibodies to natalizumab occurred by week 12 in most of the patients (82%) who became persistently antibody-positive. The presence of anti-natalizumab antibodies was correlated with a reduction in serum natalizumab levels. Persistent antibody-positivity to natalizumab was associated with a substantial decrease in the effectiveness of the drug.[Ref]

Immunologic side effects have included immunosuppression/infections, including pneumonias and urinary tract infections (including serious cases), gastroenteritis, vaginal infections, tooth infections, tonsillitis, and herpes infections. Herpes (8%), tonsillitis (7%), and viral infection (up to 7%) have been reported. Antibodies to natalizumab were detected in approximately 9% of patients at least once during treatment with persistent antibody-positivity in 6% of patients. Immune reconstitution inflammatory syndrome (IRIS) has been reported in the majority of patients who discontinued natalizumab as a result of developing PML, but not in patients who discontinued natalizumab for other reasons; in most cases, IRIS occurred within days to several weeks after plasma exchange was used to remove circulating natalizumab.[Ref]

Hepatic

Hepatic side effects have included abnormal liver function tests (5%). Clinically significant liver injury (including markedly elevated serum hepatic enzymes and elevated total bilirubin) has been reported during postmarketing experience.[Ref]

Other

Other side effects have included fatigue (up to 27%), peripheral edema (up to 6%), chest discomfort (up to 5%), rigors (3%), limb injury (3%), skin laceration (2%), and thermal burn (1%). At least one case of shakiness has also been reported.[Ref]

Local

Local side effects have included infusion related reactions including headache, nausea, dizziness, fatigue, hypersensitivity reactions, urticaria, pruritus, flushing, and rigors in up to 24% of patients. Infusion related anaphylactic reactions have been reported in less than 1% of patients.[Ref]

Genitourinary

Genitourinary side effects have included urinary tract infection (up to 21%), vaginitis (up to 10%), urinary urgency/frequency (9%), vaginal infections (up to 8%), dysmenorrhea (up to 6%), irregular menstruation (5%), urinary incontinence (4%), amenorrhea (2%), and ovarian cyst (2%).[Ref]

Musculoskeletal

Musculoskeletal side effects have included arthralgia (up to 19%), pain in extremity (16%), back pain (12%), muscle cramp (5%), and joint swelling (2%).[Ref]

Dermatologic

Dermatologic side effects have included rash (up to 12%), dermatitis (up to 7%), pruritus (4%), perianal abscess (2% or greater), urticaria (1%), dry skin (1%), and night sweats (1%). Serum sickness-like illness and severe cutaneous Candida infection have been reported in at least one patient each.[Ref]

Hypersensitivity

Patients experiencing hypersensitivity reactions recovered with treatment and/or discontinuation of the infusion. Patients who developed antibodies to natalizumab were more likely to have an infusion-related reaction.[Ref]

Hypersensitivity side effects have included allergic reaction (7%), acute hypersensitivity (up to 4%), seasonal allergy (3%), and anaphylaxis/anaphylactoid reactions. An infusion-related reaction has been reported to occur within 2 hours of the start of an infusion. At least 2 cases of allergic dermatitis have also been reported.[Ref]

Hematologic

Hematologic side effects have included increases in circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. Hypereosinophilia (greater than 2,000 eosinophils/mm3) and at least one case of immune thrombocytopenic purpura have been reported.[Ref]

Metabolic

Metabolic side effects have included weight decreased and increased in 2% of patients.[Ref]

Cardiovascular

Cardiovascular side effects have included pericarditis.[Ref]

Ocular

Ocular side effects have included at least one case of ocular toxoplasmosis reactivation.[Ref]

References

1. "Product Information. Tysabri (natalizumab)." Elan Pharmaceutical/Athena Neurosciences Inc, South San Francisco, CA.

2. Sweet BV "Natalizumab update." Am J Health Syst Pharm 64 (2007): 705-16

3. Wenning W, Haghikia A, Laubenberger J, et al. "Treatment of progressive multifocal leukoencephalopathy associated with natalizumab." N Engl J Med 361 (2009): 1075-80

4. Goodin DS, Cohen BA, O'Connor P, Kappos L, Stevens JC "Assessment: the use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology." Neurology 71 (2008): 766-73

5. Carson KR, Focosi D, Major EO, et al. "Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a Review from the Research on Adverse Drug Events and Reports (RADAR) Project." Lancet Oncol 10 (2009): 816-24

6. Vennegoor A, Wattjes MP, van Munster ET, et al. "Indolent course of progressive multifocal leukoencephalopathy during natalizumab treatment in MS." Neurology 76 (2011): 574-6

7. "Natalizumab (Tysabri) for Crohn's Disease." Obstet Gynecol 112 (2008): 693-694

8. Vermersch P, Kappos L, Gold R, et al. "Clinical outcomes of natalizumab-associated progressive multifocal leukoencephalopathy." Neurology 76 (2011): 1697-704

9. Hartung HP "New cases of progressive multifocal leukoencephalopathy after treatment with natalizumab." Lancet Neurol 8 (2009): 28-31

10. Clifford DB, Deluca A, Simpson DM, Arendt G, Giovannoni G, Nath A "Natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: lessons from 28 cases." Lancet Neurol 9 (2010): 438-446

11. Ko MY, Stefoski D, Balabanov R, et al. "Indolent course of progressive multifocal leukoencephalopathy during natalizumab treatment in MS." Neurology 77 (2011): 1020

12. Keegan BM "Natalizumab for multiple sclerosis: a complicated treatment." Lancet Neurol 10 (2011): 677-8

13. Hellwig K, Kleiter I, Gold R, Clifford DB, Major EO "Immune reconstitution inflammatory syndrome in natalizumab-associated PML." Neurology 78 (2012): 371

14. Blair NF, Brew BJ, Halpern JP "Natalizumab-associated PML identified in the presymptomatic phase using MRI surveillance." Neurology 78 (2012): 507-8

15. Lenhard T, Biller A, Mueller W, Metz I, Schonberger J, Wildemann B "Immune reconstitution inflammatory syndrome after withdrawal of natalizumab?" Neurology 75 (2010): 831-3

16. Targan SR, Feagan BG, Fedorak RN, et al. "Natalizumab for the Treatment of Active Crohn's Disease: Results of the ENCORE Trial." Gastroenterology 132 (2007): 1672-1683

17. Hellwig K, Gold R, Marousi S, et al. "Immune reconstitution inflammatory syndrome after withdrawal of natalizumab?" Neurology 76 (2011): 1362-3

18. Linda H, von Heijne A, Major EO, et al. "Progressive multifocal leukoencephalopathy after natalizumab monotherapy." N Engl J Med 361 (2009): 1081-7

19. Tan IL, McArthur JC, Clifford DB, Major EO, Nath A "Immune reconstitution inflammatory syndrome in natalizumab-associated PML." Neurology 77 (2011): 1061-7

20. Zecca C, Nessi F, Bernasconi E, Gobbi C "Ocular toxoplasmosis during natalizumab treatment." Neurology 73 (2009): 1418-9

21. Major EO "Reemergence of PML in natalizumab-treated patients--new cases, same concerns." N Engl J Med 361 (2009): 1041-3

22. Rice GP, Hartung HP, Calabresi PA "Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale." Neurology 64 (2005): 1336-42

23. Gutwinski S, Erbe S, Munch C, Janke O, Muller U, Haas J "Severe cutaneous Candida infection during natalizumab therapy in multiple sclerosis." Neurology 74 (2010): 521-3

24. Cohen M, Rocher F, Brunschwig C, Lebrun C "Recurrent pericarditis due to natalizumab treatment." Neurology 72 (2009): 1616-7

25. Sheremata WA, Vollmer TL, Stone LA, Willmer-Hulme AJ, Koller M "A safety and pharmacokinetic study of intravenous natalizumab in patients with MS." Neurology 52 (1999): 1072-4

26. Phillips JT, O'Connor PW, Havrdova E, et al. "Infusion-related hypersensitivity reactions during natalizumab treatment." Neurology 67 (2006): 1717-8

27. Abbas M, Lalive PH, Chofflon M, Simon HU, Chizzolini C, Ribi C "Hypereosinophilia in patients with multiple sclerosis treated with natalizumab." Neurology 77 (2011): 1561-4

28. Stosic M, De Jesus P, McCarthy J, Hutton G, Rivera V "Immune thrombocytopenic purpura in a patient with multiple sclerosis treated with natalizumab." Neurology 77 (2011): 505-7

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