Natalizumab (Intravenous)

Designed to reduce the severity and frequency of MS flareups and Crohn's disease episodes, natalizumab is a monoclonal antibody which works on the immune system.

Overview

Natalizumab is an intravenous treatment for people with relapsing-remitting forms of multiple sclerosis (MS). It does not completely cure the condition, but it can help to reduce the frequency and severity of flareups. MS flareups occur when the nerves stop functioning correctly, which causes a range of symptoms including lack of muscle control, muscle weakness and numbness, vision and speech problems, and issues with bladder control. Natalizumab tends to be reserved for patients who have not had successful results from other MS medicines, or who are unable to take other MS medicines for various reasons.

Natalizumab is also sometimes used to prevent episodes in people with Crohn's disease. This condition causes the body to attack the digestive tract lining, which leads to diarrhea, abdominal pain, fever, and weight loss. Again, natalizumab is reserved for Crohn's disease patients who haven't had successful treatment with other medicines.

The way natalizumab works is by stopping certain actions in the immune system so that the body does not have an inflammatory response, which is what causes flareups of both Crohn's disease and MS. The medicine is only available with a doctor's prescription and is designed to be injected intravenously (into a vein). For this reason, it must be administered in a hospital or clinical setting and given by a doctor or nurse. In the US, the drug is known by the brand name Tysabri.

Conditions Treated?

  • Multiple sclerosis (MS)
  • Crohn's disease

Type Of Medicine?

  • Monoclonal antibody

Side Effects

Sometimes natalizumab can cause a variety of unwanted side effects as well as its needed effects. Although it is unlikely that all of these side effects will occur, some of them can be very dangerous and require urgent medical attention. Patients should be aware of all potential side effects so that they can recognize the severe ones.

The following side effects should be reported to your doctor or nurse immediately:

  • Sneezing
  • Sore throat
  • Cough
  • Difficulty swallowing
  • Tightness in the chest
  • Chest pain
  • Shortness of breath
  • Labored or difficult breathing
  • Fast heartbeat
  • Back pain
  • Convulsions
  • Abdominal or stomach fullness
  • Gaseous abdominal or stomach pain
  • Nausea
  • Blurred vision
  • Dizziness
  • Drowsiness
  • Faintness or lightheadedness when arising
  • Puffiness or swelling of eyelids or face, lips or tongue
  • Redness of face, neck, arms, and sometimes upper chest
  • Skin rash, hives, or itching
  • Yellow skin or eyes
  • Headache
  • Feeling of warmth
  • Fever
  • Feeling unusually cold
  • Shivering
  • Confusion
  • Changes in behavior
  • Suicidal thoughts

The following side effects are less serious and only require medical attention if they become very severe or persistent. If you have questions about them, consult your doctor or nurse.

  • Bladder pain
  • Frequent, strong, or increased urge to urinate
  • Passing urine more often
  • Difficult, painful, or burning urination
  • Bloody or cloudy urine
  • Diarrhea
  • Loss of appetite
  • Local bleeding
  • Irregular, missed, or absent menstruation
  • Stopping of menstrual bleeding
  • Thick, white vaginal discharge with mild or no odor
  • Pain, cramps, or heavy bleeding
  • Itching of vagina or genital area
  • Pain during sexual intercourse
  • Stomach pain, soreness, or discomfort
  • Pain in lower back or side
  • Chest discomfort
  • Muscle pain or stiffness
  • Pain in joints
  • Shakiness in arms or lags
  • Trembling or shaking of hands or feet
  • Swelling
  • Blistering, crusting, itching, irritation or reddening of skin
  • Dry, cracked, scaly skin
  • Swollen glands
  • Fainting
  • Difficulty moving
  • Feeling empty or sad
  • Discouragement
  • Irritability
  • Loss of interest or pleasure
  • Difficulty concentrating
  • Difficulty sleeping

This may not be an exhaustive list of all side effects that could occur with use of natalizumab. If you notice any others not listed here, consult your doctor or nurse immediately. Your doctor may report new side effects to the FDA on your behalf.

Dosage

Natalizumab can only be administered by a doctor or nurse in a hospital, infusion center, or other clinical environment. Before receiving the drug, you must enroll on the TOUCH program, which has been established to manage the risks of treatment with this drug. Your doctor must also be registered with the TOUCH program, and you can only receive the medicine at a TOUCH registered infusion center.

Nurses usually administer natalizumab injections, but the TOUCH program requires that your doctor sees you every three months at the beginning of your treatment, and every six months thereafter to assess your progress and check whether natalizumab is working for you as efficiently as it should. You will be given a patient medication guide at the start of your treatment, and you should read this before each injection.

Natalizumab is administered via an injection into the vein. It is injected very slowly over the course of one hour. The risk of serious allergic reaction to the drug is highest within two hours of the start of the injection, so you will be required to stay in the hospital for around an hour after the injection has finished. If you notice any unusual side effects or symptoms during this time, tell your nurse or doctor immediately. Generally, natalizumab is administered once every four weeks, but this may vary depending on your medical history and other factors personal to you.

Patients who are receiving natalizumab for Crohn's disease can expect to see an improvement in their symptoms within a few months. If after 12 weeks of treatment symptoms do not get better, your doctor may stop the treatment because the risk of harmful side effects is too high to warrant administering a treatment which is not effective.

Interactions

Natalizumab can interact with other medicines and cause harmful side effects or other complications. It is very important to tell your doctor about all the medicines your take, including those prescribed to you, those purchased over the counter, and any herbal supplements or multivitamins that you consume. Once you begin treatment with natalizumab, you should tell each doctor or pharmacist that you are being given the medicine. Never start, stop, or change a medicine without first checking with a doctor.

It is particularly important to mention the following medicines:

  • Cyclosporine
  • Azathioprine
  • 6-mercaptopurine
  • Infliximab
  • Adalimumab
  • Golimumab
  • Certolizumab
  • Methotrexate
  • Etanercept

Warnings

Risk of serious brain infection

Natalizumab may increase the risk of patients contracting progressive multifocal leukoencephalopathy (PML). This is a rare infection of the brain which cannot be cured, treated, or prevented, and which usually causes severe disability or death.

The following risk factors can increase the chance of a patient developing PML during treatment with natalizumab:

  • Past treatments or medicines which weaken the immune system
  • Receiving many doses of natalizumab, particularly if treatment has continued for two years or more
  • Previous exposure to John Cunningham virus (JCV), something which many are exposed to in childhood and usually causes no symptoms, unless the immune system is weakened

Doctors usually administer blood tests before administering natalizumab for the first time to check whether patients have been exposed to natalizumab. They may also want to test your brain with a magnetic resonance imaging (MRI) scan. These tests may be repeated periodically during treatment. However, if you have had a plasma exchange in the past two weeks, you should not have your blood tested because the results will not be accurate.

Risk of other infections

Since natalizumab weakens the immune system, it may increase the risk of you developing encephalitis and meningitis, which are caused by the herpes or varicella virus. Symptoms of these conditions include fever, headache, and confusion, which should be reported to a doctor.

Risk of IRIS

Immune reconstitution inflammatory syndrome (IRIS) may occur in patients who develop PML while taking natalizumab and are forced to suddenly stop taking the medicine. This inflammatory reaction can cause burning, stinging, tingling, heat, redness, and swelling of the skin.

Allergy

Natalizumab may cause very severe allergic reaction. Tell your doctor if you have had a reaction to the drug in the past, or to any of the ingredients in the drug. It is safest to mention all allergies that you suffer from to your doctor so that they can check the ingredients list for potential harmful allergies. If you notice rash, hives, itching, swelling of the eyelids, face, tongue, or throat, chest pain, or breathing problems after receiving natalizumab injections, seek emergency medical care.

Interactions with other medical conditions

Natalizumab may make liver disease worse, and doctors are cautious in prescribing it to patients with this condition. Depending on the severity of the liver disease, it may still be prescribed only in smaller dosages and with closer monitoring of liver function.

This drug is not suitable for people with progressive multifocal leukoencephalopathy (PML).

Natalizumab is not suitable for people with weakened immune systems, such as those with HIV or AIDS, leukemia, or lymphoma, or those who have had an organ transplant. This is because the drug will make them even more susceptible to serious infections, including PML.

Pregnancy and breastfeeding

Animal studies have demonstrated that natalizumab could harm the fetus, and there is limited data available on the effects of the drug during human pregnancy. The drug is therefore not recommended for use during pregnancy unless potential benefits or treatment far outweigh potential risks to the fetus.

Natalizumab is excreted in human breast milk, but its effects on nursing infants are unknown. Breastfeeding patients should choose to either discontinue nursing in order to receive natalizumab, or avoid use of the drug so that they can continue to breastfeed.

Pediatric use

The safety and efficacy of natalizumab in children has not been established. The drug is therefore not recommended for the pediatric population.

Storage

Since natalizumab is administered by a doctor or nurse at an infusion center or hospital, patients are not expected to store the medicine at home. However, patients will be given a medication guide, and they should retain this for future reference and read it before each injection.

Summary

Natalizumab is a monoclonal antibody which can help to control flareups and symptoms of multiple sclerosis (MS) and Crohn's disease. The drug should only be used if patients have already received other treatments for their condition which have been unsuccessful.

Natalizumab weakens the immune system and it can cause a very serious brain infection called progressive multifocal leukoencephalopathy (PML) which may cause sever disability or death. The risk of developing the infection is highest in those who have been receiving natalizumab for more than two years, and those who have been exposed to John Cunningham virus (JCV).

Due to the high risks associated with natalizumab, the drug is only available via the TOUCH program. Patients must be enrolled in the TOUCH program and can only receive treatment from TOUCH-registered doctors and at TOUCH-registered infusion centers.

Natalizumab is administered via intravenous injection. The medicine is diluted and injected very slowly into a vein over the course of an hour. IVs must be administered via a nurse at an infusion center, and patients must remain under supervision for an hour after the injection. Usually, the drug is administered once every four weeks, with blood tests and sometimes MRI scans being performed intermittently to assess how the drug is working and check for severe side effects or complications.