Patient information: uses, side effects, how to take - Avtozma

What is the most important information I should know about AVTOZMA?

AVTOZMA can cause serious side effects including:1.Serious Infections. AVTOZMA is a medicine that affects your immune system. AVTOZMA can lower the ability of your immune system to fight infections. Some people have serious infections while taking AVTOZMA, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections. Your healthcare provider should assess you for TB before starting AVTOZMA (except if you have COVID-19).

If you have COVID-19, your healthcare provider should monitor you for signs and symptoms of new infections during and after treatment with AVTOZMA.

Your healthcare provider should monitor you closely for signs and symptoms of TB during and after treatment with AVTOZMA.

You should not start taking AVTOZMA if you have any kind of infection unless your healthcare provider says it is okay.

Before starting AVTOZMA, tell your healthcare provider if you:

think you have an infection or have symptoms of an infection, with or without a fever, such as:

sweating or chills
shortness of breath
warm, red, or painful skin or sores on your body

feel very tired
muscle aches
blood in phlegm
diarrhea or stomach pain

cough
weight loss
burning when you urinate or urinating more often than normal

are being treated for an infection.
get a lot of infections or have infections that keep coming back.
have diabetes, HIV, or a weak immune system. People with these conditions have a higher chance for infections.
have TB, or have been in close contact with someone with TB.
live or have lived, or have traveled to certain parts of the country (such as the Ohio and Mississippi River valleys and the Southwest) where there is an increased chance for getting certain kinds of fungal infections (histoplasmosis, coccidiomycosis, or blastomycosis). These infections may happen or become more severe if you use AVTOZMA. Ask your healthcare provider if you do not know if you have lived in an area where these infections are common.
have or have had hepatitis B.

After starting AVTOZMA, call your healthcare provider right away if you have any symptoms of an infection. AVTOZMA can make you more likely to get infections or make worse any infection that you have.

2.Tears (perforation) of the stomach or intestines.

Tell your healthcare provider if you have had diverticulitis (inflammation in parts of the large intestine) or ulcers in your stomach or intestines. Some people taking AVTOZMA get tears in their stomach or intestine. This happens most often in people who also take nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or methotrexate.
Tell your healthcare provider right away if you have fever and new onset stomach-area pain that does not go away, and a change in your bowel habits.

3.Liver problems (Hepatotoxicity): Some people have experienced serious life-threatening liver problems, which required a liver transplant or led to death. Your healthcare provider may tell you to stop taking AVTOZMA if you develop new or worse liver problems during treatment with AVTOZMA. Tell your healthcare provider right away if you have any of the following symptoms:

feeling tired (fatigue)
lack of appetite for several days or longer (anorexia)
yellowing of your skin or the whites of your eyes (jaundice)
abdominal swelling and pain on the right side of your stomach-area
light colored stools

weakness
nausea and vomiting
confusion
dark "tea-colored" urine

4.Changes in certain laboratory test results. Your healthcare provider should do blood tests before you start receiving AVTOZMA. If you have rheumatoid arthritis (RA) or giant cell arteritis (GCA) your healthcare provider should do blood tests every 4 to 8 weeks after you start receiving AVTOZMA for the first 6 months and then every 3 months after that. If you have polyarticular juvenile idiopathic arthritis (PJIA) you will have blood tests done every 4 to 8 weeks during treatment. If you have systemic juvenile idiopathic arthritis (SJIA) you will have blood tests done every 2 to 4 weeks during treatment. These blood tests are to check for the following side effects of AVTOZMA:

low neutrophil count. Neutrophils are white blood cells that help the body fight off bacterial infections.
low platelet count. Platelets are blood cells that help with blood clotting and stop bleeding.
increase in certain liver function tests.
increase in blood cholesterol levels. You may also have changes in other laboratory tests, such as your blood cholesterol levels. Your healthcare provider should do blood tests to check your cholesterol levels 4 to 8 weeks after you start receiving AVTOZMA.

Your healthcare provider will determine how often you will have follow-up blood tests. Make sure you get all your follow-up blood tests done as ordered by your healthcare provider.

You should not receive AVTOZMA if your neutrophil or platelet counts are too low or your liver function tests are too high.

Your healthcare provider may stop your AVTOZMA treatment for a period of time or change your dose of medicine if needed because of changes in these blood test results.5.Cancer. AVTOZMA may increase your risk of certain cancers by changing the way your immune system works. Tell your healthcare provider if you have ever had any type of cancer.

See "What are the possible side effects with AVTOZMA?" for more information about side effects.

What is AVTOZMA?

AVTOZMA is a prescription medicine called an Interleukin-6 (IL-6) receptor antagonist. AVTOZMA is used:

To treat adults with moderately to severely active rheumatoid arthritis (RA), after at least one other medicine called a Disease-Modifying Anti-Rheumatic Drug (DMARD) has been used and did not work well.
To treat adults with giant cell arteritis (GCA).
To treat people with active PJIA ages 2 and above.
To treat people with active SJIA ages 2 and above.
To treat people age 2 years and above who experience severe or life-threatening Cytokine Release Syndrome (CRS) following chimeric antigen receptor (CAR) T cell treatment.
To treat hospitalized people ages 2 years and above with coronavirus disease 2019 (COVID-19) receiving systemic corticosteroids and requiring supplemental oxygen or mechanical ventilation.
AVTOZMA is not approved for subcutaneous use in people with CRS or COVID-19.

It is not known if AVTOZMA is safe and effective in children with PJIA, SJIA, CRS or COVID-19 under 2 years of age or in children with conditions other than PJIA, SJIA, CRS or COVID-19.

Do not take AVTOZMA: if you are allergic to tocilizumab products, or any of the ingredients in AVTOZMA. See the end of this Medication Guide for a complete list of ingredients in AVTOZMA.

Before you receive AVTOZMA, tell your healthcare provider about all of your medical conditions, including if you:

have an infection. See "What is the most important information I should know about AVTOZMA?"
have liver problems.
have any stomach-area (abdominal) pain or been diagnosed with diverticulitis or ulcers in your stomach or intestines.
have had a reaction to tocilizumab products or any of the ingredients in AVTOZMA before.
have or had a condition that affects your nervous system, such as multiple sclerosis.
have recently received or are scheduled to receive a vaccine:
- All vaccines should be brought up-to-date before starting AVTOZMA, unless urgent treatment initiation is required.
- People who take AVTOZMA should not receive live vaccines.
- People taking AVTOZMA can receive non-live vaccines.
plan to have surgery or a medical procedure.
are pregnant or plan to become pregnant. AVTOZMA may harm your unborn baby. Tell your healthcare provider if you become pregnant or think you may be pregnant during treatment with AVTOZMA.
are breastfeeding or plan to breastfeed. It is not known if AVTOZMA passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take AVTOZMA.

Tell your healthcare provider about all of the medicines you take, including prescription, over-the-counter medicines, vitamins and herbal supplements. AVTOZMA and other medicines may affect each other causing side effects.

Especially tell your healthcare provider if you take:

any other medicines to treat your RA. Taking AVTOZMA with these medicines may increase your risk of infection.
medicines that affect the way certain liver enzymes work. Ask your healthcare provider if you are not sure if your medicine is one of these.

Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.

How will I receive AVTOZMA?

Into a vein (IV or intravenous infusion) for Rheumatoid Arthritis, Giant Cell Arteritis, PJIA, SJIA, CRS or COVID- 19:

If your healthcare provider prescribes AVTOZMA as an IV infusion, you will receive AVTOZMA from a healthcare provider through a needle placed in a vein in your arm. The infusion will take about 1 hour to give you the full dose of medicine.
For rheumatoid arthritis, giant cell arteritis or PJIA you will receive a dose of AVTOZMA about every 4 weeks.
For SJIA you will receive a dose of AVTOZMA about every 2 weeks.
For CRS you will receive a single dose of AVTOZMA, and if needed, additional doses.
For COVID-19, you will receive a single dose of AVTOZMA, and if needed one additional dose.
While taking AVTOZMA, you may continue to use other medicines that help treat your rheumatoid arthritis, PJIA, SJIA or COVID-19 such as methotrexate, non-steroidal anti-inflammatory drugs (NSAIDs) and prescription steroids, as instructed by your healthcare provider.
Keep all of your follow-up appointments and get your blood tests as ordered by your healthcare provider.

Under the skin (SC or subcutaneous injection) for Rheumatoid Arthritis, Giant Cell Arteritis, PJIA or SJIA:

See the Instructions for Use at the end of this Medication Guide for instructions about the right way to prepare and give your AVTOZMA injections at home.
AVTOZMA is available as a single-dose Prefilled Syringe or single-dose Prefilled Autoinjector.
You may also receive AVTOZMA as an injection under your skin (subcutaneous). If your healthcare provider decides that you or a caregiver can give your injections of AVTOZMA at home, you or your caregiver should receive training on the right way to prepare and inject AVTOZMA. Do not try to inject AVTOZMA until you have been shown the right way to give the injections by your healthcare provider.
For PJIA or SJIA, you may self-inject with the Prefilled Syringe or Prefilled Autoinjector, or your caregiver can give you AVTOZMA, if both your healthcare provider and parent/legal guardian find it appropriate.
Your healthcare provider will tell you how much AVTOZMA to use and when to use it.

What are the possible side effects with AVTOZMA?

AVTOZMA can cause serious side effects, including:

See "What is the most important information I should know about AVTOZMA?"
Hepatitis B infection in people who carry the virus in their blood. If you are a carrier of the hepatitis B virus (a virus that affects the liver), the virus may become active while you use AVTOZMA. Your healthcare provider may do blood tests before you start treatment with AVTOZMA and while you are using AVTOZMA. Tell your healthcare provider if you have any of the following symptoms of a possible hepatitis B infection:

feel very tired
vomiting
chills
dark urine

skin or eyes look yellow
clay-colored bowel movements
stomach discomfort
skin rash

little or no appetite
fevers
muscle aches

Serious Allergic Reactions.Serious allergic reactions, including death, can happen with AVTOZMA. These reactions can happen with any infusion or injection of AVTOZMA, even if they did not occur with an earlier infusion or injection. Stop taking AVTOZMA, contact your healthcare provider, and get emergency help right away if you have any of the following signs of a serious allergic reaction:
- swelling of your face, lips, mouth, or tongue
- trouble breathing
- wheezing
- severe itching
- skin rash, hives, redness, or swelling outside of the injection site area
- dizziness or fainting
- fast heartbeat or pounding in your chest (tachycardia)
- sweating
Nervous system problems. While rare, Multiple Sclerosis has been diagnosed in people who take AVTOZMA. It is not known what effect AVTOZMA may have on some nervous system disorders.

The most common side effects of AVTOZMA include:

upper respiratory tract infections (common cold, sinus infections)
headache
increased blood pressure (hypertension)
injection site reactions

Tell your healthcare provider about any side effect that bothers you or does not go away. These are not all the possible side effects of AVTOZMA. For more information, ask your healthcare provider or pharmacist.

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

General information about the safe and effective use of AVTOZMA.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not give AVTOZMA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about AVTOZMA that is written for health professionals.

What are the ingredients in AVTOZMA?

Active ingredient: tocilizumab-anoh.

Inactive ingredients of Intravenous AVTOZMA: histidine, L-histidine hydrochloride monohydrate, methionine, polysorbate 80, threonine, and water for Injection.

Inactive ingredients of Subcutaneous AVTOZMA: histidine, L-histidine hydrochloride monohydrate, methionine, polysorbate 80, threonine, and water for Injection.

Manufactured by: CELLTRION, Inc., 23, Academy-ro, Yeonsu-gu, Incheon, 22014, Republic of Korea

US License Number 1996

Distributed by: CELLTRION USA, Inc., One Evertrust Plaza, Suite 1207, Jersey City, NJ 07302, USA

Instructions for Use

AVTOZMA^®(AV-TOZE'-MAH)

(tocilizumab-anoh)

Injection, For Subcutaneous Use

Single-dose Prefilled Syringe

Read and follow the Instructions for Use that come with your AVTOZMA Preﬁlled Syringe before you start using it and each time you get a reﬁll. There may be new information. Before you use AVTOZMA, make sure your healthcare provider shows you the right way to use it.

Important Information

Do not remove the prefilled syringe cap until you are ready to inject AVTOZMA.
Do not try to take apart the prefilled syringe at any time.
Do not reuse the same syringe.
Do not shake the prefilled syringe.
Do not use the prefilled syringe if it has been dropped or damaged.

Storing AVTOZMA

Store the unused prefilled syringe in the original carton in a refrigerator between 36°F to 46°F (2°C to 8°C). Do not freeze.
When removed from the refrigerator, AVTOZMA can be stored up to 3 weeks at or below 77°F (25°C). If necessary, the prefilled syringe may be returned to the refrigerator once within these 3 weeks and stored refrigerated until the expiry date. The prefilled syringe must be discarded if not used within the 3-week period.
Keep the prefilled syringe out of direct sunlight.
Do not remove the prefilled syringe from its original carton during storage.
Do not leave the prefilled syringe unattended.
Keep the prefilled syringe out of the reach of children.

Parts of your Prefilled Syringe (See Figure A).

Figure A

Preparing for the Injection

	1. Gather the supplies for the injection. a. Prepare a clean, flat surface, such as a table or countertop, in a well-lit area. b. Take the carton containing the preﬁlled syringe out of the refrigerator. c. Make sure you have the following supplies (see Figure B ):-Carton containing AVTOZMA preﬁlled syringe Not included in the carton: Cotton ball or gauze Adhesive bandage FDA-cleared sharps disposal container Alcohol swab
Figure B
	2. Inspect the carton (see Figure C). a. Look at the carton and make sure you have the correct medicine and dose strength. (AVTOZMA) b. Check the expiration (EXP) date on the carton to make sure the date has not passed. Do not use the prefilled syringe if the expiration (EXP) date has passed. Do not use the prefilled syringe if the carton looks like it has been opened or damaged if you are opening the carton for the first time and check to make sure that it is properly sealed.
Figure C
	3. Inspect the Prefilled Syringe. a. Open the carton and remove 1 single-dose prefilled syringe from the carton. Return any remaining AVTOZMA prefilled syringes in the carton to the refrigerator. b. Check the expiration (EXP) date on the AVTOZMA prefilled syringe (see Figure D ). Do not use the prefilled syringe if the expiration (EXP) date has passed. If the expiration (EXP) date has passed, safely throw away (dispose of) the prefilled syringe in your FDA-cleared sharps disposal container and get a new one. c. Check the prefilled syringe to make sure it is not damaged and shows no sign of leakage. Do not use the prefilled syringe if it has been dropped, damaged, or has leaked.
Figure D
	4. Wait 30 minutes. a. Leave the prefilled syringe outside of the carton at room temperature between 64.4°F to 82.4°F (18°C to 28°C) for 30 minutes to allow it to warm up (see Figure E ). Do not warm the prefilled syringe using heat sources such as hot water or a microwave. Do not leave the prefilled syringe in the direct sunlight. Do not remove the cap while allowing your prefilled syringe to reach room temperature. If the prefilled syringe does not reach room temperature, this could cause discomfort and make it hard to push the plunger.
Figure E
	5. Inspect the medicine. a. Hold your AVTOZMA with the cap pointing down. b. Look at the medicine and conﬁrm that the liquid is clear, to slightly pearly and colorless to yellow and does not contain any particles or ﬂakes (see Figure F ). Do not use the prefilled syringe if the liquid is discolored, cloudy, or has particles or ﬂakes in it. Safely dispose of the prefilled syringe in a FDA-cleared sharps disposal container and use a new one. Air bubbles are normal.
Figure F
	6. Wash your hands. a. Wash your hands with soap and water and dry them thoroughly (see Figure G ).
Figure G
	7. Choose an injection site (see Figure H). a. You may inject into The front of the thighs The stomach (abdomen), except for the 2 inches (5 cm) around the belly button. The outer area of the upper arm (only if you are a caregiver). Do not inject into the upper arm by yourself. Choose a different injection site for each new injection at least 1 inch (2.5 cm) from the last area you injected. Do not inject into moles, scars, bruises, or areas where the skin is tender, red, hard or not intact.
Figure H
	8. Clean the injection site. a. Wipe the injection site with an alcohol swab and let it air dry for about 10 seconds (see Figure I ). This will reduce the chance of getting an infection. Do not touch the injection site again before giving the injection. Do not fan or blow on the clean area.
Figure I

Giving the Injection

	9. Remove the cap. a. Hold the prefilled syringe by the syringe body using 1 hand. Gently pull the cap straight off with the other hand (see Figure J ). Note: If you cannot remove the cap, you should ask a caregiver for help or contact your healthcare provider. Do not hold the plunger while removing the cap. You may see a drop of liquid at the tip of the needle. This is normal. If the preﬁlled syringe is not used within 5 minutes of needle cap removal, the preﬁlled syringe should be thrown away (disposed of) in the puncture resistant container or sharps container and a new preﬁlled syringe should be used. b. Throw away (dispose of) the cap right away in your FDA-cleared sharps disposal container (see step 14 and Throw away (dispose of) preﬁlled syringe and Figure N ) Do not re-cap the preﬁlled syringe. Do not touch the needle shield at the tip of the preﬁlled syringe to avoid accidental needle stick injury.
Figure J
	10. Insert the preﬁlled syringe into the injection site. a. Gently pinch a fold of skin at the injection site with 1 hand. Note: Pinching the skin is important to make sure that you inject under the skin (into fatty tissue) but not any deeper (into muscle). b. With a quick and "dart-like" motion, insert the Needle completely into the fold of skin at a 45 to 90-degree angle (see Figure K ). Note: It is important to use the correct angle to make sure the medicine is delivered under the skin (into fatty tissue), or the injection could be painful, and the medicine may not work. Do not touch the plunger while inserting the needle into the skin. Do not pull back on the plunger rod at any time.
Figure K
	11. Give the injection. a. After the needle is inserted, release the pinch. b. Slowly push the plunger all the way down until the full dose of medicine gets injected, and the syringe is empty (see Figure L ). Do not change the position of the prefilled syringe after the injection has started. If the plunger is not fully pressed, the needle guard will not extend to cover the needle when it is removed. If the needle is not covered, proceed carefully to dispose of the syringe (see step 14. Throw away (dispose of) prefilled syringe .
Figure L
	12. Remove the prefilled syringe from the injection site. a. After the preﬁlled syringe is empty, remove the needle from the injection site and release the plunger until the entire needle is covered by the guard (see Figure M ). Some bleeding may occur (see step 13. Care for the injection site ). In case of skin contact with medicine, wash the area that touched the medicine with water. Do not reuse the preﬁlled syringe.
Figure M