Actemra

Name: Actemra

What is tocilizumab?

Tocilizumab reduces the effects of a substance in the body that can cause inflammation.

Tocilizumab is used to treat moderate to severe rheumatoid arthritis in adults. It is sometimes given together with other arthritis medicines.

Tocilizumab is used to treat systemic juvenile idiopathic arthritis (or "Still disease") in children who are at least 2 years old. It is sometimes given together with methotrexate (Rheumatrex, Trexall).

Tocilizumab is also used in adults to treat giant cell arteritis, or inflammation of the lining of your arteries (blood vessels that carry blood from your heart to other parts of your body).

Tocilizumab is usually given after other medications have been tried without successful treatment of symptoms.

Tocilizumab may also be used for purposes not listed in this medication guide.

What happens if I miss a dose?

Call your doctor for instructions if you miss an appointment for your tocilizumab injection.

What other drugs will affect tocilizumab?

Tell your doctor about all your current medicines and any you start or stop using, especially:

  • any other medicines to treat rheumatoid arthritis, such as abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, or rituximab.

This list is not complete and many other drugs can interact with tocilizumab. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you. Not all possible interactions are listed in this medication guide.

Uses for Actemra

Rheumatoid Arthritis in Adults

Management of moderately to severely active rheumatoid arthritis in adults who have had an inadequate response to one or more DMARDs.1

Can be used alone or in combination with methotrexate or other nonbiologic DMARDs (e.g., hydroxychloroquine, leflunomide, minocycline, sulfasalazine7 ).1 3 4 5 6 29

Do not use concomitantly with other biologic DMARDs, such as tumor necrosis factor (TNF; TNF-α) blocking agents (e.g., adalimumab, certolizumab, etanercept, golimumab, infliximab), interleukin-1 (IL-1) receptor antagonists (e.g., anakinra), anti-CD20 monoclonal antibodies (e.g., rituximab), and selective costimulation modulators (e.g., abatacept); concomitant use has not been studied and there is a possibility of increased immunosuppression and increased risk of infection.1

Juvenile Idiopathic Arthritis (JIA)

Management of active systemic or polyarticular JIA.1 20 21

Can be used alone or in combination with methotrexate.1

Do not use concomitantly with other biologic DMARDs; concomitant use has not been studied, and there is a possibility of increased immunosuppression and increased risk of infection.1

Cautions for Actemra

Contraindications

  • Known hypersensitivity to the drug.1 (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Warnings

Infectious Complications

Serious, sometimes fatal infections (including bacterial, mycobacterial, invasive fungal, viral, protozoal, or other opportunistic infections) reported in patients with rheumatoid arthritis, particularly in those receiving concomitant therapy with other immunosuppressive agents (e.g., methotrexate, corticosteroids).1 Opportunistic infections include tuberculosis, cryptococcal infection, aspergillosis, candidiasis, and pneumocystosis.1 Infections may be disseminated.1

Serious infections also reported in patients with polyarticular or systemic JIA.1 20 21

Do not initiate tocilizumab in patients with active infections, including localized infections.1 Consider potential risks and benefits of the drug prior to initiating therapy in patients with a history of chronic, recurring, serious, or opportunistic infections; patients with underlying conditions that may predispose them to infections; and patients who have been exposed to tuberculosis or who have resided or traveled in regions where tuberculosis or mycoses are endemic.1

Closely monitor patients during and after treatment with tocilizumab for the development of signs or symptoms of infection.1 If new infection occurs during therapy, perform thorough diagnostic evaluation (appropriate for immunocompromised patient), initiate appropriate anti-infective therapy, and closely monitor patient.1 If serious infection, opportunistic infection, or sepsis develops, discontinue tocilizumab until the infection is controlled.1

Evaluate all patients for latent tuberculosis and for risk factors for tuberculosis prior to and periodically during therapy.1 When indicated, initiate an appropriate antimycobacterial regimen for the treatment of latent tuberculosis infection prior to tocilizumab therapy.1 Consider initiation of antimycobacterial therapy prior to initiation of tocilizumab in individuals with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment cannot be confirmed and in individuals with a negative test for latent tuberculosis who have risk factors for tuberculosis.1 Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.1

Monitor all patients, including those with a negative test for latent tuberculosis, for active tuberculosis.1

Viral reactivation can occur in patients receiving immunosuppressive therapies.1 Herpes zoster exacerbation reported in patients receiving tocilizumab.1

Other Warnings/Precautions

GI Perforation

GI perforation reported, usually as a complication of diverticulitis in patients with rheumatoid arthritis and most commonly in patients receiving concomitant therapy with NSAIAs, corticosteroids, or methotrexate.1 The relative contribution of these agents versus IV tocilizumab to the occurrence of GI perforation remains to be determined.1

Caution is advised if tocilizumab is used in patients at risk for GI perforation.1

Promptly evaluate patients with new-onset abdominal symptoms for evidence of GI perforation.1

Hematologic Effects

Possible neutropenia or thrombocytopenia.1

Reduction in neutrophil count to <1000/mm3 reported in patients receiving tocilizumab.1 Decreases in neutrophil count to <1000/mm3 did not appear to be associated with serious infection.1

In clinical trials, decreases in platelet counts were not associated with severe bleeding.1

Monitor neutrophil and platelet counts 4–8 weeks after initiation of therapy and every 3 months thereafter in adults with rheumatoid arthritis, at the time of the second tocilizumab infusion and every 4–8 weeks thereafter in patients with polyarticular JIA, and at the time of the second infusion and every 2–4 weeks thereafter in patients with systemic JIA.1

Dosage adjustment, treatment interruption, or discontinuance may be necessary.1 (See Dosage under Dosage and Administration.)

Hepatic Effects

Elevated aminotransferase concentrations may occur.1 In clinical trials, changes were reversible following reduction of the tocilizumab or concomitant DMARD dosage or interruption of tocilizumab therapy and were not associated with clinical evidence of hepatic injury.1

Incidence and magnitude of aminotransferase elevations were increased with concomitant use of hepatotoxic drugs (e.g., methotrexate).1

Monitor serum ALT and AST 4–8 weeks after initiation of therapy and every 3 months thereafter in adults with rheumatoid arthritis, at the time of the second tocilizumab infusion and every 4–8 weeks thereafter in patients with polyarticular JIA, and at the time of the second infusion and every 2–4 weeks thereafter in patients with systemic JIA.1 Monitor other liver function tests when clinically indicated.1

Dosage adjustment, treatment interruption, or discontinuance of tocilizumab or concomitantly administered DMARDs may be necessary.1 (See Dosage under Dosage and Administration.)

Effects on Serum Lipids

Increased serum concentrations of total cholesterol, triglycerides, LDL-cholesterol, and/or HDL-cholesterol reported.1

Monitor lipoprotein concentrations 4–8 weeks after initiation of tocilizumab therapy and approximately every 24 weeks thereafter in adults with rheumatoid arthritis or patients with polyarticular or systemic JIA.1

Manage lipid disorders as clinically appropriate.1

Malignancies

Immunosuppressive therapy may increase the risk of malignancies.1 Whether treatment with tocilizumab affects development of malignancies remains to be determined.1 Malignancies were reported in clinical trials.1

Sensitivity Reactions

Serious hypersensitivity reactions, including fatal anaphylaxis in patients receiving IV infusions of the drug, reported.1 15 Tocilizumab is contraindicated in patients with known hypersensitivity to the drug.1

Hypersensitivity reactions requiring treatment discontinuance (e.g., anaphylaxis, generalized erythema, rash, urticaria) reported during clinical trials in various patient populations and with either IV or sub-Q therapy.1 Hypersensitivity reactions, including anaphylaxis and death, reported during postmarketing experience in patients receiving various IV dosages (with or without concomitant antirheumatic therapy), including in patients who received premedication.1 Hypersensitivity reactions, including anaphylaxis, have occurred both with and without prior hypersensitivity reactions and as early as the first IV infusion.1

Have appropriate agents and equipment available for immediate use in case a serious hypersensitivity reaction occurs during IV tocilizumab infusion.1 Patients receiving sub-Q therapy should seek medical attention if they experience symptoms of a hypersensitivity reaction (see Advice to Patients).1

If a hypersensitivity reaction occurs, immediately stop administration and permanently discontinue the drug.1

Nervous System Effects

Effect of tocilizumab on demyelinating disorders remains to be determined.1 Multiple sclerosis and chronic inflammatory demyelinating polyneuropathy reported rarely in patients with rheumatoid arthritis receiving tocilizumab.1

Monitor patients receiving tocilizumab for signs and symptoms suggestive of a demyelinating disorder.1 Exercise caution when considering tocilizumab therapy in patients with preexisting or recent-onset demyelinating disorders.1

Immunization

Do not administer live vaccines to patients receiving tocilizumab.1 Bring vaccinations up to date prior to initiation of tocilizumab therapy.1 (See Vaccines under Interactions.)

Immunogenicity

Antibodies to tocilizumab, including neutralizing antibodies, may develop; some patients with antibody development have experienced hypersensitivity reactions resulting in treatment discontinuance.1 Antibody detection rates appear similar with IV or sub-Q administration.1

Specific Populations

Pregnancy

Category C.1

Pregnancy registry at 877-311-8972.1

Lactation

Not known whether tocilizumab is distributed into milk or is absorbed systemically following ingestion.1 Because IgG distributes into milk, tocilizumab may distribute into milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy of IV tocilizumab for management of active polyarticular or systemic JIA established in pediatric patients ≥2 years of age.1 20 21 Safety and efficacy not established in children <2 years of age or for the management of conditions other that polyarticular or systemic JIA in children.1

Safety and efficacy of sub-Q administration not established in pediatric patients.1

Pattern of adverse effects (including liver enzyme elevations, neutropenia, thrombocytopenia, and lipid abnormalities) in patients with polyarticular or systemic JIA is similar to that observed in adults with rheumatoid arthritis.1 20

No evidence of toxicity, including no impairment of skeletal growth, immune function, and sexual maturation, observed in studies of a murine analog of tocilizumab in juvenile mice.1

Geriatric Use

Geriatric patients in general may have a higher incidence of infections than younger adults.1 In clinical trials of tocilizumab, serious infections reported more frequently in patients ≥65 years of age than in younger adults.1 Use tocilizumab with caution in this age group.1

Hepatic Impairment

Safety and efficacy not established in patients with hepatic impairment, including those with serologic evidence of HBV or HCV infection.1 Use in patients with active hepatic disease or hepatic impairment is not recommended.1

Renal Impairment

Not evaluated in patients with moderate to severe renal impairment.1

Common Adverse Effects

Upper respiratory tract infection,1 3 4 5 20 21 nasopharyngitis,1 3 4 20 21 headache,1 3 4 5 20 21 hypertension,1 3 4 5 increased ALT concentrations,1 3 4 5 reactions at the sub-Q injection site (e.g., erythema, pruritus, pain, hematoma).1 22 23 Adverse effect profiles for IV and sub-Q tocilizumab are similar except for higher frequency of injection site reactions with sub-Q administration.1 22 23 24

Advice to Patients

  • A copy of the manufacturer’s patient information (medication guide) for tocilizumab must be provided to all patients and/or caregivers.1 Importance of advising patients and/or caregivers about potential benefits and risks of tocilizumab.1 Importance of patients and/or caregivers reading the medication guide prior to initiation of therapy and each time the drug is infused or the prescription is refilled.1

  • Importance of instructing patient and/or caregiver regarding proper dosage and administration of tocilizumab, including use of aseptic technique, and proper disposal of needles and syringes if it is determined that the patient and/or caregiver is competent to safely administer the drug.1

  • Importance of consulting clinician if the sub-Q injection does not deliver the full dose.1

  • Risk of hypersensitivity reactions.1 Importance of contacting clinician prior to administering the next dose if manifestations of an allergic reaction (e.g., urticaria, rash, flushing) occur; importance of seeking immediate medical attention if manifestations of a serious allergic reaction (e.g., difficulty breathing, chest pain, feelings of faintness or dizziness, abdominal pain or vomiting, swelling of the lips, tongue, or face) occur.1

  • Risk of increased susceptibility to infection.1 Importance of informing clinicians immediately if any signs or symptoms suggestive of infection (e.g., fever; sweating; cough; dyspnea; diarrhea; burning or pain upon urination; warm, red, or painful skin) develop.1

  • Risk of GI perforation.1 Importance of informing clinician immediately if severe, persistent abdominal pain occurs.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., biologic antirheumatic drugs, immunizations) and OTC drugs, as well as any other illnesses (e.g., history of tuberculosis; concomitant, chronic, or recurring infections).1

  • Importance of periodic laboratory monitoring.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Commonly used brand name(s)

In the U.S.

  • Actemra

Available Dosage Forms:

  • Solution

Therapeutic Class: Immunological Agent

Pharmacologic Class: Monoclonal Antibody

Before Using Actemra

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of tocilizumab injection in children with PJIA and SJIA. However, safety and efficacy have not been established in children younger than 2 years of age.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of tocilizumab injection in the elderly. However, elderly patients are more likely to have serious infections, which may require caution in patients receiving tocilizumab injection.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Adenovirus Vaccine
  • Bacillus of Calmette and Guerin Vaccine, Live
  • Cholera Vaccine, Live
  • Infliximab
  • Influenza Virus Vaccine, Live
  • Measles Virus Vaccine, Live
  • Mumps Virus Vaccine, Live
  • Poliovirus Vaccine, Live
  • Rotavirus Vaccine, Live
  • Rubella Virus Vaccine, Live
  • Smallpox Vaccine
  • Typhoid Vaccine
  • Varicella Virus Vaccine
  • Yellow Fever Vaccine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Chronic inflammatory demyelinating polyneuropathy (nerve problem) or
  • Hyperlipidemia (high fats in the blood) or
  • Liver disease, history of or
  • Multiple sclerosis or
  • Neutropenia (low level of white blood cells) or
  • Stomach or bowel problems (eg, diverticulitis, perforations, ulcers) or
  • Thrombocytopenia (low number of platelets) or
  • Weak immune system (eg, HIV, cancer, or steroid use)—Use with caution. May make these conditions worse.
  • Herpes zoster, history of or
  • Tuberculosis, history of—Use with caution. May cause infections to come back (reactivate).
  • Infections (eg, hepatitis B, bacteria, virus, fungus), active or recurring or
  • Liver disease, active—Should not be used in patients with these conditions.

Precautions While Using Actemra

It is very important that your doctor check your or your child's progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

You or your child will need to have a skin test for tuberculosis before using this medicine. Tell your doctor if you or anyone in your home has ever had a positive reaction to a tuberculosis skin test.

This medicine will lower the number of some types of blood cells in your body. Because of this, you may bleed or get infections more easily. To help with these problems, avoid being near people who are sick or have infections. Wash your hands often. Stay away from rough sports or other situations where you could be bruised, cut, or injured. Brush and floss your teeth gently. Be careful when using sharp objects, including razors and fingernail clippers. Tell your doctor if you have any kind of infection before you start using this medicine. Also tell your doctor if you have ever had an infection that would not go away or an infection that kept coming back.

Call your doctor right away if you or your child start to have a cough that won't go away, weight loss, night sweats, fever, chills, or flu-like symptoms, such as a runny or stuffy nose, headache, blurred vision, or feeling generally ill. These may be signs that you have an infection.

This medicine may cause serious stomach and bowel problems, especially if you have a history of ulcers or diverticulosis. Check with your doctor right away if you or your child start having severe stomach cramps or pain, black, tarry stools, diarrhea, fever, or vomiting that is severe and sometimes bloody while being treated with this medicine.

Using this medicine may increase your risk of having certain cancers. Talk to your doctor if you have unusual bleeding, bruising, or weakness, swollen lymph nodes in the neck, underarms, or groin, or unexplained weight loss. Also, check with your doctor right away if your skin has red, scaly patches, or raised bumps that are filled with pus.

Tocilizumab may cause headaches and skin reactions, such as a rash or itching, while you are receiving the injection or within 24 hours after you receive it. Check with your doctor or nurse right away if you or your child have any of these symptoms.

This medicine may cause serious types of allergic reactions, including anaphylaxis. This can be life-threatening and requires immediate medical attention. Tell your doctor right away if you or your child have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth after using this medicine.

While you or your child are being treated with tocilizumab, and after you stop treatment with it, it is important to see your doctor about the immunizations (vaccinations) you should receive. Do not get any immunizations (vaccines) without your doctor's approval. Tocilizumab may lower your body's resistance, and there is a chance you might get the infection the vaccine is meant to prevent. In addition, you should not be around other persons living in your household who receive live virus vaccines because there is a chance they could pass the virus on to you. Some examples of live vaccines include measles, mumps, influenza (nasal flu vaccine), poliovirus (oral form), rotavirus, and rubella. Do not get close to them and do not stay in the same room with them for very long. If you have questions about this, talk to your doctor.

This medicine may increase the amounts of cholesterol and fats in your blood. If this condition occurs, your doctor may give you some medicines that can lower their amounts. Talk to your doctor if you or your child have concerns.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Overdosage

There are limited data available on overdoses with Actemra. One case of accidental overdose was reported with intravenous Actemra in which a patient with multiple myeloma received a dose of 40 mg per kg. No adverse drug reactions were observed. No serious adverse drug reactions were observed in healthy volunteers who received single doses of up to 28 mg per kg, although all 5 patients at the highest dose of 28 mg per kg developed dose-limiting neutropenia.

In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions. Patients who develop adverse reactions should receive appropriate symptomatic treatment.

PRINCIPAL DISPLAY PANEL - 0.9 mL Syringe Box

NDC 50242-138-01

Actemra®

(tocilizumab)
Injection

162 mg / 0.9 mL

For Subcutaneous
Injection Only

Single Dose Prefilled
Syringe - Discard Unused
Portion

Sterile

ATTENTION
PHARMACIST:
Each patient is required
to receive the enclosed
Medication Guide.

Refrigerate Immediately

Rx only

Each Prefilled Syringe
Contains:
162 mg/0.9 mL

Genentech

10146668

Actemra 
tocilizumab injection, solution, concentrate
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:50242-135
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
tocilizumab (tocilizumab) tocilizumab 20 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
sucrose  
polysorbate 80  
SODIUM PHOSPHATE, DIBASIC, DODECAHYDRATE  
sodium phosphate, monobasic, dihydrate  
Packaging
# Item Code Package Description
1 NDC:50242-135-01 1 VIAL, SINGLE-USE in 1 BOX
1 4 mL in 1 VIAL, SINGLE-USE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA125276 01/08/2010
Actemra 
tocilizumab injection, solution, concentrate
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:50242-136
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
tocilizumab (tocilizumab) tocilizumab 20 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
sucrose  
polysorbate 80  
SODIUM PHOSPHATE, DIBASIC, DODECAHYDRATE  
sodium phosphate, monobasic, dihydrate  
Packaging
# Item Code Package Description
1 NDC:50242-136-01 1 VIAL, SINGLE-USE in 1 BOX
1 10 mL in 1 VIAL, SINGLE-USE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA125276 01/08/2010
Actemra 
tocilizumab injection, solution, concentrate
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:50242-137
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
tocilizumab (tocilizumab) tocilizumab 20 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
sucrose  
polysorbate 80  
SODIUM PHOSPHATE, DIBASIC, DODECAHYDRATE  
sodium phosphate, monobasic, dihydrate  
Packaging
# Item Code Package Description
1 NDC:50242-137-01 1 VIAL, SINGLE-USE in 1 BOX
1 20 mL in 1 VIAL, SINGLE-USE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA125276 01/08/2010
Actemra 
tocilizumab injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:50242-138
Route of Administration SUBCUTANEOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
tocilizumab (tocilizumab) tocilizumab 180 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
polysorbate 80  
histidine  
histidine monohydrochloride monohydrate  
arginine  
arginine hydrochloride  
methionine  
water  
Packaging
# Item Code Package Description
1 NDC:50242-138-01 1 SYRINGE, GLASS in 1 BOX
1 0.9 mL in 1 SYRINGE, GLASS
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA125472 10/21/2013
Labeler - Genentech, Inc. (080129000)
Registrant - Genentech, Inc. (080129000)
Establishment
Name Address ID/FEI Operations
Chugai Pharma Manufacturing Co Ltd 716464891 MANUFACTURE(50242-135, 50242-136, 50242-137), API MANUFACTURE(50242-135, 50242-136, 50242-137), ANALYSIS(50242-135, 50242-136, 50242-137)
Establishment
Name Address ID/FEI Operations
Roche Pharma AG 315009878 ANALYSIS(50242-135, 50242-136, 50242-137, 50242-138)
Establishment
Name Address ID/FEI Operations
F. Hoffmann-La Roche Ltd 485244961 LABEL(50242-135, 50242-136, 50242-137, 50242-138), ANALYSIS(50242-138), PACK(50242-135, 50242-136, 50242-137, 50242-138)
Establishment
Name Address ID/FEI Operations
Genentech, Inc. (Oceanside) 146373191 ANALYSIS(50242-135, 50242-136, 50242-137, 50242-138), API MANUFACTURE(50242-135, 50242-136, 50242-137, 50242-138)
Establishment
Name Address ID/FEI Operations
Genentech, Inc. (SSF) 080129000 ANALYSIS(50242-135, 50242-136, 50242-137, 50242-138)
Establishment
Name Address ID/FEI Operations
Roche Diagnostics GmbH 315028860 ANALYSIS(50242-135, 50242-136, 50242-137)
Establishment
Name Address ID/FEI Operations
Genentech, Inc. (Vacaville) 004074162 ANALYSIS(50242-138)
Establishment
Name Address ID/FEI Operations
Roche Singapore Technical Operations Pte. Ltd. (RSTO) 937189173 ANALYSIS(50242-135, 50242-136, 50242-137, 50242-138)
Revised: 09/2017   Genentech, Inc.

Actemra Overview

Actemra is a prescription medication used to treat rheumatoid arthritis (RA) in adults. It is used to treat systemic juvenile idiopathic arthritis (SJIA) or polyarticular juvenile idiopathic arthritis (PJIA) in children 2 years or older. This medication is also used to treat giant cell arteritis, inflammation of the lining of the arteries.

Actemra is referred to as an interleukin-6, or IL-6, receptor inhibitor. IL-6 is a molecule produced by the body that binds to the IL-6 receptor and causes inflammation. Patients with arthritis have increased levels of IL-6 in their body. By blocking the IL-6 receptor, Actemra can decrease the symptoms of arthritis.

Actemra comes in an injectable form to be given directly into a vein (IV) or under the skin by a healthcare provider, depending on the condition being treated. 

It is usually given once every 4 weeks for RA and PJIA, every 2 weeks for SJIA and once every week for giant cell arteritis. 

Common side effects of Actemra are cold-like symptoms, increased blood pressure, and headache. 

Actemra and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category C. It is not known if Actemra will harm your unborn baby. 

Pregnancy Registry: Genentech has a registry for pregnant women who take Actemra. The purpose of this registry is to check the health of the pregnant mother and her baby. If you are pregnant or become pregnant while taking Actemra, talk to your healthcare provider about how you can join this pregnancy registry or you may contact the registry at 1 -877-311-8972 to enroll. 

Actemra Usage

You will receive Actemra from a healthcare provider through a needle placed in a vein in your arm (IV or intravenous infusion). The infusion will take about 1 hour to give you the full dose of medicine.

This medication is also injected under the skin for giant cell arteritis. 

  • For rheumatoid arthritis, you will receive a dose of Actemra about every 4 weeks.
  • For SJIA you will receive a dose of Actemra about every 2 weeks.
  • For giant cell arteritis, you will receive a dose once every week. This medication is given together with a tapering course of glucocorticoids. 
  • If you miss a scheduled dose of Actemra, ask your healthcare provider when to schedule your next infusion.
  • While taking Actemra, you may continue to use other medicines that help treat your rheumatoid arthritis or SJIA such as methotrexate, non-steroidal anti-inflammatory drugs (NSAIDs) and prescription steroids, as instructed by your healthcare provider. 
  • Keep alI of your follow-up appointments and get your blood tests as ordered by your healthcare provider.

 

Dosing & Uses

Dosage Forms & Strengths

injection, solution for IV infusion

  • 20mg/mL in 4, 10, and 20mL vials

single-use prefilled syringe for SC injection

  • 162mg/0.9mL

Rheumatoid Arthritis

Indicated for adults with moderate-to-severe active rheumatoid arthritis with inadequate response to 1 or more DMARDs as an IV infusion or SC injection

May use alone or in combination with methotrexate or other DMARDs

IV infusion

  • 4 mg/kg IV q4weeks initially; may increase to 8 mg/kg q4wk based on clinical response 
  • Not to exceed 800 mg/dose q4weeks
  • Reduction of dose from 8 mg/kg to 4 mg/kg is recommended for management of certain dose-related laboratory changes; see Dosage Modifications

SC injection

  • Weight <100 kg: 162 mg SC every other week, followed by an increase to every week based on clinical response
  • Weight ≥100 kg: 162 mg SC every week
  • Transition IV to SC: Administer first SC dose instead of the next scheduled IV dose

Giant Cell Arteritis

Indicated for treatment of giant cell arteritis (GCA) in adults

162 mg SC once weekly in combination with a tapering course of glucocorticoids

Based on clinical considerations, may consider administering 162 mg SC every other week in combination with a tapering course of glucocorticoids

May be used alone following discontinuation of glucocorticoids (eg, interruption of dosing may be needed for management of dose-related laboratory abnormalities, IV administration is not approved for GCA)

Cytokine Release Syndrome

Indicated for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (CRS) in adults and pediatric patients aged ≥2 years

SC is not approved for CRS

8 mg/kg IV; may administer up to 3 additional doses of tocilizumab if no clinical improvement in signs/symptoms of CRS after first dose; not to exceed 800 mg/dose

Interval between consecutive doses should be >8 hr

May be administered as monotherapy or with corticosteroids

Dosage Modifications

The following apply to RA and GCA

Dose reductions have not been studied in PJIA and SJIA populations

Renal impairment

  • Mild: No dosage adjustment required
  • Moderate-to-severe: Has not been studied

Hepatic impairment

  • Not recommended with active hepatic disease or hepatic impairment

Transaminase elevations

  • >1-3 x ULN
    • Modify dose of other DMARDs if possible
    • For persistent increases and receiving IV infusion, reduce dose to 4 mg/kg or discontinue therapy and restart when ALT/AST return to normal; for persistent increases and receiving SC injection, reduce injection frequency to every other week or hold dosing until ALT/AST return to normal, resume at every other week and increase frequency to every week as clinically appropriate
  • >3-5x ULN
    • Confirmed by repeat testing
    • Hold tocilizumab until <3x ULN and follow recommendations above for > 1-3x ULN
    • For persistent increases >3x ULN, discontinue tocilizumab
  • >5 x ULN
    • Discontinue therapy

Neutropenia

  • ANC >1000/mm³: Maintain dose
  • ANC <500/mm³: Discontinue therapy
  • ANC 500-1000/mm³
    • Discontinue therapy until ANC >1000 cells/mm³: For patients receiving IV, restart at 4 mg/kg and increase to 8 mg/kg as clinically appropriate; for patients receiving SC injection, restart 162 mg at every other week and increase frequency to every week as clinically appropriate

Thrombocytopenia

  • <50,000/mm³: Discontinue therapy
  • 50,000-10,0000/mm³
    • Discontinue therapy until >100,000/mm³ for patients receiving IV infusion, restart therapy at 4 mg/kg and increase to 8 mg/kg if clinically warranted; for patients receiving SC injection, restart at 162 mg every other week and increase frequency to every week as clinically appropriate

Dosing Considerations

Monitor neutrophils, platelets, and ALT/AST 4-8 weeks following of therapy and q3months thereafter

Monitor lipids 4-8 weeks following initiation of therapy and then at ~24 week intervals

Use not recommended if

  • ANC <2000/mm³
  • Platelets <100,000/mm³
  • ALT or AST >1.5x ULN
  • Note: Patients with severe or life-threatening CRS frequently have cytopenias or elevated ALT or AST due to the lymphodepleting chemotherapy or CRS; evaluate the potential benefit of treating CRS versus the risks of short-term treatment with tocilizumab

Systemic Sclerosis (Orphan)

Orphan designation for treatment of systemic sclerosis

Orphan sponsor

  • Genentech, Inc.; 1 DNA Way; South San Francisco, CA 94080-4990

Dosage Forms & Strengths

injection, solution for IV infusion

  • 20mg/mL in 4, 10, and 20mL vials

Systemic Juvenile Idiopathic Arthritis (SJIA, Still's Disease)

SC use is not approved for SJIA

<2 years: Safety and efficacy not established

≥2 years or older (<30 kg): 12 mg/kg IV q2weeks 

≥2 years or older (≥30 kg): 8 mg/kg IV q2weeks

May be administered as monotherapy or with methotrexate

Polyarticular Juvenile Idiopathic Arthritis (PJIA)

<2 years: Safety and efficacy not established

≥2 years or older (<30 kg): 10 mg/kg IV q4weeks 

≥2 years or older (≥30 kg or more): 8 mg/kg IV q4weeks

May be administered as monotherapy or with methotrexate

Cytokine Release Syndrome (CRS)

Indicated for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (CRS) in adults and pediatric patients aged ≥2 years

SC is not approved for CRS

<2 years: Safety and efficacy not established

≥2 years (<30 kg): 12 mg/kg IV

≥2 years (≥30 kg): 8 mg/kg IV

May be administered as monotherapy or with corticosteroids

May administer up to 3 additional doses of tocilizumab if no clinical improvement in signs/symptoms of CRS after first dose; not to exceed 800 mg/dose

Interval between consecutive doses should be >8 hr

Dosage Modifications

Dose reduction has not been studied in the PJIA and SJIA populations

Dose interruptions are recommended for liver enzyme abnormalities, low neutrophil counts, and low platelet counts in patients with PJIA and SJIA at levels similar to what is outlined for adults with RA

Dosing Considerations

Monitor neutrophils, platelets, ALT and AST at the time of the second infusion and thereafter every 4-8 weeks for PJIA and every 2-4 weeks for SJIA

Monitor lipids 4-8 weeks following initiation of therapy and then at ~24 week intervals

Increased risk of serious infections in patient ≥65 years of age; caution should be used when treating the elderly

What happens if i miss a dose (actemra)?

Call your doctor for instructions if you miss an appointment for your tocilizumab injection.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

For Healthcare Professionals

Applies to tocilizumab: intravenous solution, subcutaneous solution

Respiratory

Very common (10% or more): Upper respiratory tract infection
Common (1% to 10%): Cough, dyspnea, nasopharyngitis, bronchitis[Ref]

Nervous system

Common (1% to 10%): Headache, dizziness[Ref]

Cardiovascular

Common (1% to 10%): Hypertension[Ref]

Dermatologic

Common (1% to 10%): Rash, pruritus, urticaria
Frequency not reported: Angioedema
Postmarketing reports: Stevens-Johnson Syndrome[Ref]

General

The most common serious adverse reactions were serious infections.[Ref]

Hypersensitivity

Of the 2876 patients tested for anti-tocilizumab (the active ingredient contained in Actemra) antibodies in controlled clinical trials, 1.6% (46 patients) were positive; 5 patients experienced a hypersensitivity reaction that lead to treatment withdrawal. However, in 1.1% (30 patients) of those who developed antibodies there was no apparent correlation to clinical response.[Ref]

Common (1% to 10%): Hypersensitivity reaction
Postmarketing reports: Fatal anaphylaxis[Ref]

Oncologic

Frequency not reported: Malignancies[Ref]

Gastrointestinal

Common (1% to 10%): Abdominal pain, mouth ulceration, gastritis, diarrhea
Uncommon (0.1% to 1%): Stomatitis, gastric ulcer, diverticulitis
Rare (0.01% to 0.1%): Gastrointestinal perforation (most patients who developed GI perforations were taking concomitant nonsteroidal anti-inflammatory medications (NSAIDs), corticosteroids, or methotrexate)[Ref]

Hematologic

Very common (10% or more): Leukopenia, neutropenia, thrombocytopenia[Ref]

Hepatic

Common (1% to 10%): Transaminases increased, total bilirubin increased[Ref]

Immunologic

Common (1% to 10%): Cellulitis, pneumonia, oral herpes simplex, herpes zoster[Ref]

Local

Common (1% to 10%): Injection site reaction[Ref]

Metabolic

Very common (10% or more): Hypercholesterolemia
Common (1% to 10%): Weight increased, peripheral edema
Uncommon (0.1% to 1%): Hypertriglyceridemia[Ref]

Musculoskeletal

Common (1% to 10%): Back pain
Frequency not reported: Bacterial arthritis[Ref]

Ocular

Common (1% to 10%): Conjunctivitis[Ref]

Other

Common (1% to 10%): Peripheral edema[Ref]

Renal

Uncommon (0.1% to 1%): Nephrolithiasis[Ref]

Endocrine

Uncommon (0.1% to 1%): Hypothyroidism[Ref]

Some side effects of Actemra may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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