Rebif Rebidose Titration Pack (Intramuscular, Subcutaneous)

Interferon beta-1a injection is used to treat the relapsing types of multiple sclerosis (MS), which include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. This medicine will not cure MS, but it may slow down some of the disabling effects and reduce the number of relapses. Interferons are natural substances made by the body to help fight infections. Interferon beta-1a is a synthetic (man-made) version of these substances.

This medicine is available only with your doctor's prescription.

It is very important for your doctor to check your progress at regular visits to ensure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

This medicine may make some people feel anxious, irritable, or show other unusual behaviors. It may also cause some people to have suicidal thoughts and tendencies or to feel more depressed. If you or your caregiver notice any of these side effects, tell your doctor right away.

Contact your doctor immediately if you have dark urine, a constant loss of appetite, flu-like symptoms, headaches, ongoing vomiting, a general feeling of tiredness or weakness, light-colored stools, pain or tenderness in the upper right part of your stomach, or yellowing of your eyes or skin. These could be signs of a serious liver problem.

This medicine may cause serious allergic reactions, including anaphylaxis, which can be life-threatening and needs immediate medical help. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or swelling of your hands, face, or mouth while using this medicine.

This medicine may lower the number of white blood cells in your blood, increasing your chance of getting an infection. It can also reduce the number of platelets in your blood, which are necessary for proper blood clotting. If this happens, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If possible, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you develop a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in your urine or stools, or tiny red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may suggest other ways to clean your teeth and gums. Consult your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be cautious when using sharp objects, such as a safety razor or fingernail or toenail clippers, to avoid cuts.
• Avoid contact sports or other activities that could lead to bruising or injury.

This medicine may cause redness, pain, or swelling at the injection site. Some patients have developed serious skin infections or damage (necrosis), including a permanent depression under the skin at the injection site. Contact your doctor immediately if you notice indented skin, blue-green to black skin discoloration, or pain, redness, or peeling skin.

This medicine commonly causes flu-like reactions, including aching muscles, chills, fever, headaches, joint pain, and nausea. Taking your shot at bedtime may help you sleep through these symptoms. Your doctor may suggest a medicine to help manage the pain or fever (e.g., acetaminophen or ibuprofen). Follow your doctor's instructions carefully on how to prevent or treat these symptoms.

Thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, may occur while you are using this medicine. Tell your doctor right away if you have black, tarry stools, blood in your urine, difficulty speaking, fever, tiny red spots on your skin, seizures, stomach pain, unusual bleeding or bruising, or yellowing of your eyes or skin.

This medicine may cause pulmonary arterial hypertension (high blood pressure in the lungs). Contact your doctor immediately if you have trouble breathing or feel unusually tired or weak.

This medicine contains albumin, which comes from human blood. Some human blood products have transmitted certain viruses to people who have received them, although the risk is low. Both human donors and donated blood are tested for viruses to keep the risk of transmission low. Discuss this risk with your doctor if you are concerned. The Avonex® prefilled autoinjector pen and prefilled syringe do not contain albumin from donated human blood.

The tip cap of the Avonex® prefilled syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions in people who are sensitive to latex. Inform your doctor if you have a latex allergy before starting this medicine.

In deciding to use a medicine, you and your doctor need to consider the risks and benefits. Here are some important points to think about:

Allergies

Inform your doctor if you have ever had any unusual or allergic reactions to this medicine or any other medicines. Also, let your healthcare professional know if you have any other allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

There have not been appropriate studies on how interferon beta-1a injection affects children. Safety and effectiveness have not been established.

Geriatric

Although appropriate studies on how interferon beta-1a injection affects older adults have not been done, there are no expected age-related issues that would limit its usefulness. However, older patients are more likely to have kidney, liver, or heart problems related to aging, which may require caution when using interferon beta-1a injection.

Breast Feeding

There are no adequate studies on the effects of this medication on infants while breastfeeding. Consider the potential benefits and risks before using this medication while breastfeeding.

Interactions with Medicines

Some medicines should not be taken together, while others may be used together even if there is a chance of interaction. In these cases, your doctor may adjust the dose or take other precautions. It is important for your healthcare professional to know if you are taking any of the medicines listed below. The following interactions are significant but may not include all possible interactions.

Using this medicine with any of the following medicines is usually not recommended, but may be necessary in some cases. If both are prescribed, your doctor may adjust the dose or frequency of one or both medicines.

• Levoketoconazole
• Methotrexate

Using this medicine with any of the following medicines may increase the risk of certain side effects, but using both may be the best option for you. If both medicines are prescribed together, your doctor may change the dose or how often you take one or both of the medicines.

• Zidovudine

Interactions with Food/Tobacco/Alcohol

Some medicines should not be used around the time of eating food or specific types of food due to potential interactions. Using alcohol or tobacco with certain medicines may also cause interactions. Talk to your healthcare professional about using your medicine with food, alcohol, or tobacco.

Other Medical Problems

Having other medical conditions may affect how you use this medicine. Be sure to tell your doctor if you have any other medical problems, especially:

• History of alcohol abuse
• Severe chest pain (angina)
• Autoimmune disorders (e.g., autoimmune hepatitis, idiopathic thrombocytopenia)
• History of bone marrow problems (decreased red or white blood cells)
• Congestive heart failure
• History of depression or mental issues
• Heart disease (e.g., cardiomyopathy)
• Heart rhythm problems (e.g., arrhythmia)
• Liver disease
• History of seizures or epilepsy
• Thyroid problems—Use with caution. May worsen these conditions.

• History of allergy to human albumin—Should not be used in these patients.

• Infection—May reduce your body's ability to fight infections.

Along with its needed effects, a medicine may cause some unwanted effects. Not all of these side effects may happen, but if they do, they might need medical attention.

Check with your doctor right away if any of the following side effects happen:

More common

• Black, tarry stools
• chest pain
• chills
• cough
• diarrhea
• fever
• flu-like symptoms
• headache
• joint pain
• muscle aches
• nausea
• pain
• painful or difficult urination
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• trouble breathing
• unusual bleeding or bruising
• unusual tiredness or weakness

Less common

• Clumsiness or unsteadiness
• decreased hearing
• difficulty swallowing
• dizziness
• fainting
• feeling of warmth
• hives or itching
• mood changes, especially with thoughts of suicide
• muscle spasms
• pain or discharge from the vagina
• pelvic discomfort, aching, or heaviness
• redness of the face, neck, arms, and sometimes, upper chest
• redness, swelling, or tenderness at the injection site
• runny or stuffy nose
• seizures
• skin lesions
• sneezing
• sore throat
• speech problems
• stomach pain
• swelling of the face, lips, or eyelids

Rare

• Earache
• general feeling of discomfort or illness
• loss of appetite
• painful blisters on the trunk of the body
• painful cold sores or blisters on the lips, nose, eyes, or genitals

Incidence not known

• Bleeding gums
• blue-green to black skin discoloration
• blood in the urine or stools
• bloody nose
• chest discomfort or tightness
• confusion
• constipation
• dark urine
• decreased urine output
• depressed mood
• dilated neck veins
• dry skin and hair
• fast, irregular, or pounding heartbeat
• feeling cold
• general tiredness and weakness
• hair loss
• heavier menstrual periods
• high fever
• irregular breathing
• light-colored stools
• loss of bladder control
• mental depression
• mood or other mental changes
• muscle cramps and stiffness
• nausea or vomiting
• nervousness
• pain, redness, or sloughing of skin at the injection site
• pale skin
• persistent loss of appetite
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids, or around the eyes, face, lips, or tongue
• redness, blistering, peeling, or loosening of the skin
• sensitivity to heat
• skin rash
• slowed heartbeat
• sudden loss of consciousness
• sweating
• swelling of the face, fingers, feet, or lower legs
• swelling of the mouth or throat
• throat tightness
• upper right stomach pain or tenderness
• weight gain or loss
• yellow eyes and skin

Some side effects may happen that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Your health care professional may also be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Heartburn
• indigestion
• sour stomach

Less common

• Hair loss
• trouble sleeping

Other side effects not listed may also happen in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You can report side effects to the FDA at 1-800-FDA-1088.

In the U.S.

• Avonex
• Avonex Pen
• Rebif
• Rebif Rebidose
• Rebif Rebidose Titration Pack

Available Dosage Forms:

• Solution
• Kit

Therapeutic Class: Immunological Agent

Pharmacologic Class: Interferon, Beta (class)

Find detailed information on biosimilars for this medication.

A nurse or other trained health professional will give you this medicine. You may also be taught how to give your medicine at home. This medicine is given as a shot under your skin (usually in the stomach, back of the upper arm, buttocks, or thighs) or into a muscle (usually in the thigh). A nurse or other trained health professional should watch the first Avonex® injection you give yourself.

If you are injecting interferon beta-1a yourself, use it exactly as directed by your doctor. Do not change your dose or dosing schedule without checking first with your doctor. The exact amount of medicine you need has been carefully worked out. Using too much will increase the risk for side effects, while using too little may not improve your condition.

You will be shown the body areas where this shot can be given. Use a different body area each time you give yourself a shot. Keep track of where you give each shot to make sure you rotate body areas. Do not inject into skin areas that are irritated, reddened, bruised, infected, or scarred in any way.

Check the injection site after 2 hours for redness, swelling, and tenderness.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

Rebif® comes as an autoinjector or a prefilled syringe. It works best if you use it at the same time (usually in the late afternoon or evening) on the same 3 days (eg, Monday, Wednesday, and Friday) at least 48 hours apart each week.

Avonex® comes as a prefilled autoinjector pen or a prefilled syringe.

Use a new needle or syringe each time you inject your medicine. Do not use any other needle for the prefilled autoinjector pen.

Each package of medicine contains a Medication Guide and a sheet called Instructions for Use. Read this information carefully and make sure you understand:

• How to prepare the injection.
• How to use disposable syringes or autoinjectors.
• How to store the syringes or autoinjectors.

Allow Avonex® prefilled autoinjector pens and prefilled syringes and Rebif® autoinjector to warm to room temperature before injection by removing from the refrigerator for about 30 minutes. Do not heat them in a microwave oven or in hot water.

You may also receive other medicines (fever medicine, pain medicine) to help prevent or lessen flu-like symptoms (eg, fever, cough, chills, body aches) that may occur during treatment with this medicine.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form: For multiple sclerosis: Adults— Avonex®: At first, 7.5 micrograms (mcg) injected into a muscle once a week on the same day (eg, every Monday at bedtime). Your doctor will increase your dose by 7.5 mcg each week for the next 3 weeks until you reach 30 mcg weekly. Rebif®: At first, 4.4 or 8.8 mcg injected under the skin 3 times a week. Your doctor will adjust your dose as needed. Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Avonex®: If you miss a dose, give it as soon as you can. Go back to your regular schedule the following week. Do not use this medicine 2 days in a row.

Rebif®: If you miss a dose, give it as soon as you can. Skip the next day and give your regular dose 48 hours later. Go back to your regular schedule the following week. Do not use this medicine 2 days in a row.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store in the refrigerator. Do not freeze.

Store prefilled autoinjector pens or prefilled syringes in the refrigerator. Do not freeze. If refrigeration is not available, Rebif® prefilled syringes may be kept for up to 30 days at room temperature, away from heat (temperatures above 77 degrees F) and direct light. Avonex® prefilled autoinjector pens and prefilled syringes may be stored for up to 7 days at room temperature, away from heat (temperatures above 77 degrees F) and direct light.

Put the used needles into a hard, closed container that the needles cannot poke through. Keep this container away from children and pets.