Actemra

Name: Actemra

What are the side effects of tocilizumab?

The most common adverse effects of tocilizumab in clinical studies were:

  • respiratory tract infections,
  • headaches,
  • hypertension (high blood pressure), and
  • elevations in liver tests suggesting liver injury.

Injection site reactions (rash, redness, swelling, itching) may also occur. Use of tocilizumab has been associated with serious infections such as: 

  • tuberculosis,
  • sepsis (bacteria in the blood) and
  • fungal infections.

Individuals with active infections should not be treated with tocilizumab. Tocilizumab may worsen or cause new diseases of the nervous system. In studies, some patients who used tocilizumab developed cancer. Other side effects include:

  • reduced levels of white blood cells or platelets,
  • reactivation of herpes zoster infection (shingles), and
  • hypersensitivity (allergic) reactions.

In studies, gastrointestinal perforation was observed in patients with diverticulitis.

What is the dosage for tocilizumab?

The recommended dose of tocilizumab is 4-8 mg/kg administered as a single 60 minute intravenous infusion every 4 weeks.

How is tocilizumab given?

Before you start treatment with tocilizumab, your doctor may perform tests to make sure you do not have tuberculosis or other infections.

Tocilizumab is injected into a vein through an IV. A healthcare provider will give you this type of injection.

Tocilizumab is sometimes injected under the skin. You may be shown how to use this type of injection at home using a prefilled syringe. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of used needles and syringes.

Tocilizumab is usually given every 1 to 4 weeks. Follow your doctor's instructions.

Use a disposable needle only once, then throw away in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

Do not use tocilizumab if it has changed colors or has particles in it. Call your pharmacist for new medication.

Each tocilizumab prefilled syringe is for one use only. Throw away after one use, even if there is still some medicine left in it after injecting your dose.

Store the prefilled syringes in their original container in a refrigerator. Protect from moisture and light. Do not freeze. Throw away any prefilled syringes not used before the expiration date on the medicine label.

Tocilizumab can lower blood cells that help your body fight infections and help your blood to clot. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often. Your injections may be delayed based on the results of these tests.

Some infections are more likely to occur in certain areas of the world. Tell your doctor where you live and where you have recently traveled or plan to travel to during treatment.

If you have ever had hepatitis B, tocilizumab can cause this condition to come back or get worse. You will need frequent blood tests to check your liver function during treatment and for several months after you stop using this medicine.

If you need surgery, tell the surgeon ahead of time that you are using tocilizumab. You may need to stop using the medicine for a short time.

Tocilizumab can have long-lasting effects on your body. You may need certain medical tests every 6 months after you stop using this medication.

You may be treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice.

Tocilizumab side effects

Get emergency medical help if you have signs of an allergic reaction: hives; chest pain, difficulty breathing, feeling like you might pass out; swelling of your face, lips, tongue, or throat.

Serious and sometimes fatal infections may occur during treatment with tocilizumab. Call your doctor right away if you have signs of infection such as:

  • fever, chills, muscle pain, night sweats, mouth sores, white patches in your throat, weight loss, feeling very tired;

  • fast heart rate, rapid breathing, chest pain, wheezing, cough, shortness of breath;

  • redness or swelling under your skin, painful skin sores, blistering skin rash with burning or tingly feeling;

  • watery diarrhea, pain or burning when you urinate;

  • blurred vision, bone pain, confusion, headache, nausea, swollen glands.; or

  • severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Also call your doctor at once if you have:

  • severe stomach cramps, bloating, diarrhea or constipation;

  • black, bloody, or tarry stools;

  • coughing up blood or vomit that looks like coffee grounds; or

  • signs of perforation (a hole or tear) in your stomach or intestines--fever, ongoing stomach pain, change in bowel habits.

Common side effects may include:

  • runny or stuffy nose, sinus pain, sore throat;

  • headache;

  • high blood pressure (blurred vision, buzzing in your ears, anxiety, confusion, shortness of breath, uneven heartbeats); or

  • pain, swelling, burning, or irritation around the IV needle or where an injection was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Stability

Storage

Parenteral

Injection (for Sub-Q Use)

2–8°C; do not freeze.1 Store prefilled syringes in original carton to protect from light.1 Keep prefilled syringes dry.1

Injection Concentrate (for IV Use)

2–8°C; do not freeze.1 Store vials in original carton to protect from light.1

Following dilution, 2–8°C or room temperature for up to 24 hours.1 Protect from light.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible

Sodium chloride 0.9%

Actions

  • Binds specifically to both soluble and membrane-bound IL-6 receptors and inhibits IL-6-mediated signaling through these receptors, thereby resulting in a reduction in inflammatory mediator production.1 3 4 5 9 10

  • IL-6, a pleiotropic proinflammatory cytokine, is produced by various cell types (e.g., T-cells, B-lymphocytes, monocytes, fibroblasts, synoviocytes, endothelial cells) and has a broad spectrum of biologic activities,1 3 4 5 9 10 12 including involvement in T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, stimulation of hematopoietic precursor cell proliferation and differentiation, and induction of osteoclast differentiation and activation.1 4 5 9 10 12

  • IL-6 is overexpressed in synovial tissue in patients with rheumatoid arthritis and is thought to contribute to synovial proliferation and joint destruction in patients with the disease.4 9 10 12 Elevated levels of IL-6 in serum and synovial fluid correlate with clinical and laboratory measures of disease activity in patients with rheumatoid arthritis.3 5 9 10 12

  • IL-6 is elevated in serum and synovial fluid in patients with polyarticular or systemic JIA; elevated IL-6 levels correlate with disease activity.20 21 26 27 28

Warnings and Precautions

Serious Infections

Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, protozoal, or other opportunistic pathogens have been reported in patients receiving immunosuppressive agents including Actemra. The most common serious infections included pneumonia, urinary tract infection, cellulitis, herpes zoster, gastroenteritis, diverticulitis, sepsis and bacterial arthritis [see Adverse Reactions (6.1)]. Among opportunistic infections, tuberculosis, cryptococcus, aspergillosis, candidiasis, and pneumocystosis were reported with Actemra. Other serious infections, not reported in clinical studies, may also occur (e.g., histoplasmosis, coccidioidomycosis, listeriosis). Patients have presented with disseminated rather than localized disease, and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids which in addition to rheumatoid arthritis may predispose them to infections.

Do not administer Actemra in patients with an active infection, including localized infections. The risks and benefits of treatment should be considered prior to initiating Actemra in patients:

  • with chronic or recurrent infection;
  • who have been exposed to tuberculosis;
  • with a history of serious or an opportunistic infection;
  • who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or
  • with underlying conditions that may predispose them to infection.

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with Actemra, as signs and symptoms of acute inflammation may be lessened due to suppression of the acute phase reactants [see Dosage and Administration (2.6), Adverse Reactions (6.1), and Patient Counseling Information (17)].

Hold Actemra if a patient develops a serious infection, an opportunistic infection, or sepsis. A patient who develops a new infection during treatment with Actemra should undergo a prompt and complete diagnostic workup appropriate for an immunocompromised patient, initiate appropriate antimicrobial therapy, and closely monitor the patient.

Tuberculosis

Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating Actemra.

Consider anti-tuberculosis therapy prior to initiation of Actemra in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient.

Closely monitor patients for the development of signs and symptoms of tuberculosis including patients who tested negative for latent tuberculosis infection prior to initiating therapy.

It is recommended that patients be screened for latent tuberculosis infection prior to starting Actemra. The incidence of tuberculosis in worldwide clinical development programs is 0.1%. Patients with latent tuberculosis should be treated with standard antimycobacterial therapy before initiating Actemra.

Viral Reactivation

Viral reactivation has been reported with immunosuppressive biologic therapies and cases of herpes zoster exacerbation were observed in clinical studies with Actemra. No cases of Hepatitis B reactivation were observed in the trials; however patients who screened positive for hepatitis were excluded.

Gastrointestinal Perforations

Events of gastrointestinal perforation have been reported in clinical trials, primarily as complications of diverticulitis in patients treated with Actemra. Use Actemra with caution in patients who may be at increased risk for gastrointestinal perforation. Promptly evaluate patients presenting with new onset abdominal symptoms for early identification of gastrointestinal perforation [see Adverse Reactions (6.1)].

Laboratory Parameters

Rheumatoid Arthritis and Giant Cell Arteritis

Neutropenia

Treatment with Actemra was associated with a higher incidence of neutropenia. Infections have been uncommonly reported in association with treatment-related neutropenia in long-term extension studies and postmarketing clinical experience.

– It is not recommended to initiate Actemra treatment in patients with a low neutrophil count, i.e., absolute neutrophil count (ANC) less than 2000 per mm3. In patients who develop an absolute neutrophil count less than 500 per mm3 treatment is not recommended. – Monitor neutrophils 4 to 8 weeks after start of therapy and every 3 months thereafter [see Clinical Pharmacology (12.2)]. For recommended modifications based on ANC results see Dosage and Administration (2.9).

Thrombocytopenia

Treatment with Actemra was associated with a reduction in platelet counts. Treatment-related reduction in platelets was not associated with serious bleeding events in clinical trials [see Adverse Reactions (6.1, 6.2)].

– It is not recommended to initiate Actemra treatment in patients with a platelet count below 100,000 per mm3. In patients who develop a platelet count less than 50,000 per mm3 treatment is not recommended. – Monitor platelets 4 to 8 weeks after start of therapy and every 3 months thereafter. For recommended modifications based on platelet counts see Dosage and Administration (2.9).

Elevated Liver Enzymes

Treatment with Actemra was associated with a higher incidence of transaminase elevations. These elevations did not result in apparent permanent or clinically evident hepatic injury in clinical trials [see Adverse Reactions (6.1, 6.2)]. Increased frequency and magnitude of these elevations was observed when potentially hepatotoxic drugs (e.g., MTX) were used in combination with Actemra.

In one case, a patient who had received Actemra 8 mg per kg monotherapy without elevations in transaminases experienced elevation in AST to above 10× ULN and elevation in ALT to above 16× ULN when MTX was initiated in combination with Actemra. Transaminases normalized when both treatments were held, but elevations recurred when MTX and Actemra were restarted at lower doses. Elevations resolved when MTX and Actemra were discontinued.

– It is not recommended to initiate Actemra treatment in patients with elevated transaminases ALT or AST greater than 1.5× ULN. In patients who develop elevated ALT or AST greater than 5× ULN treatment is not recommended. – Monitor ALT and AST levels 4 to 8 weeks after start of therapy and every 3 months thereafter. When clinically indicated, other liver function tests such as bilirubin should be considered. For recommended modifications based on transaminases [see Dosage and Administration (2.9)].

Lipid Abnormalities

Treatment with Actemra was associated with increases in lipid parameters such as total cholesterol, triglycerides, LDL cholesterol, and/or HDL cholesterol [see Adverse Reactions (6.1, 6.2)].

– Assess lipid parameters approximately 4 to 8 weeks following initiation of Actemra therapy, then at approximately 24 week intervals. – Manage patients according to clinical guidelines [e.g., National Cholesterol Educational Program (NCEP)] for the management of hyperlipidemia.

Polyarticular and Systemic Juvenile Idiopathic Arthritis

A similar pattern of liver enzyme elevation, low neutrophil count, low platelet count and lipid elevations is noted with Actemra treatment in the PJIA and SJIA populations. Monitor neutrophils, platelets, ALT and AST at the time of the second infusion and thereafter every 4 to 8 weeks for PJIA and every 2 to 4 weeks for SJIA. Monitor lipids as above for approved adult indications [see Dosage and Administration (2.9)].

Immunosuppression

The impact of treatment with Actemra on the development of malignancies is not known but malignancies were observed in clinical studies [see Adverse Reactions (6.1)]. Actemra is an immunosuppressant, and treatment with immunosuppressants may result in an increased risk of malignancies.

Hypersensitivity Reactions, Including Anaphylaxis

Hypersensitivity reactions, including anaphylaxis, have been reported in association with Actemra [see Adverse Reactions (6)] and anaphylactic events with a fatal outcome have been reported with intravenous infusion of Actemra. Anaphylaxis and other hypersensitivity reactions that required treatment discontinuation were reported in 0.1% (3 out of 2644) of patients in the 6-month controlled trials of intravenous Actemra, 0.2% (8 out of 4009) of patients in the intravenous all-exposure RA population, 0.7% (8 out of 1068) in the subcutaneous 6-month controlled RA trials, and in 0.7% (10 out of 1465) of patients in the subcutaneous all-exposure population. In the SJIA controlled trial with intravenous Actemra, 1 out of 112 patients (0.9%) experienced hypersensitivity reactions that required treatment discontinuation. In the PJIA controlled trial with intravenous Actemra, 0 out of 188 patients (0%) in the Actemra all-exposure population experienced hypersensitivity reactions that required treatment discontinuation. Reactions that required treatment discontinuation included generalized erythema, rash, and urticaria. Injection site reactions were categorized separately [see Adverse Reactions (6)].

In the postmarketing setting, events of hypersensitivity reactions, including anaphylaxis and death have occurred in patients treated with a range of doses of intravenous Actemra, with or without concomitant therapies. Events have occurred in patients who received premedication. Hypersensitivity, including anaphylaxis events, have occurred both with and without previous hypersensitivity reactions and as early as the first infusion of Actemra [see Adverse Reactions (6.5)]. Actemra for intravenous use should only be infused by a healthcare professional with appropriate medical support to manage anaphylaxis. For Actemra subcutaneous injection, advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop administration of Actemra immediately and discontinue Actemra permanently. Do not administer Actemra to patients with known hypersensitivity to Actemra [see Contraindications (4) and Adverse Reactions (6)].

Demyelinating Disorders

The impact of treatment with Actemra on demyelinating disorders is not known, but multiple sclerosis and chronic inflammatory demyelinating polyneuropathy were reported rarely in RA clinical studies. Monitor patients for signs and symptoms potentially indicative of demyelinating disorders. Prescribers should exercise caution in considering the use of Actemra in patients with preexisting or recent onset demyelinating disorders.

Active Hepatic Disease and Hepatic Impairment

Treatment with Actemra is not recommended in patients with active hepatic disease or hepatic impairment [see Adverse Reactions (6.1), Use in Specific Populations (8.6)].

Vaccinations

Avoid use of live vaccines concurrently with Actemra as clinical safety has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving Actemra.

No data are available on the effectiveness of vaccination in patients receiving Actemra. Because IL-6 inhibition may interfere with the normal immune response to new antigens, it is recommended that all patients, particularly pediatric or elderly patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating Actemra therapy. The interval between live vaccinations and initiation of Actemra therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.

PRINCIPAL DISPLAY PANEL - 20 mL Vial Box

NDC 50242-137-01

Actemra®
(tocilizumab)
Injection

400 mg/20 mL

(20 mg/mL)

For Intravenous Infusion only after
dilution.
Single-Use Vial; Discard unused portion

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

No Preservative

Rx only

Genentech

10175060

Actemra Drug Class

Actemra is part of the drug class:

  • Interleukin inhibitors

Actemra and Lactation

Tell your doctor if you plan to breastfeed or are breastfeeding.

It is not known if Actemra is excreted in human breast milk. You and your doctor should decide if you will take Actemra or breastfeed. You should not do both.

Actemra Dosage

Your doctor will determine your Actemra dose based on your weight. The recommended dose of Actemra is 4-8 mg/kg administered as a single 60 minute intravenous (into a vein) infusion every 4 weeks for treating RA or PJIA.

For SJIA, you will receive a dose of Actemra about every 2 weeks.

For giant cell arteritis, you will receive a dose of Actemra (162mg) once every week. In some cases, some will receive Actemra once every other week.

Other Requirements

It is important you keep all of your medical and laboratory appointments while receiving Actemra. Call your doctor for instructions if you miss an appointment for your Actemra injection.

Important information

Serious and sometimes fatal infections may occur during treatment with Actemra. Stop using this medicine and call your doctor right away if you have signs of infection such as: fever, chills, body aches, flu symptoms, cough, sweating, feeling short of breath, diarrhea, weight loss, sores on your skin, painful urination, or feeling very tired.

Before you start treatment with Actemra, your doctor may perform tests to make sure you do not have tuberculosis or other infections. While using Actemra, you may need frequent medical tests.

What happens if I miss a dose?

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

What should I avoid while receiving Actemra?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while using Actemra. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Actemra side effects

Get emergency medical help if you have signs of an allergic reaction to Actemra: hives; chest pain, difficulty breathing, feeling like you might pass out; swelling of your face, lips, tongue, or throat.

Serious and sometimes fatal infections may occur during treatment with Actemra. Call your doctor right away if you have signs of infection such as:

  • fever, chills, muscle pain, night sweats, mouth sores, white patches in your throat, weight loss, feeling very tired;

  • fast heart rate, rapid breathing, chest pain, wheezing, cough, shortness of breath;

  • redness or swelling under your skin, painful skin sores, blistering skin rash with burning or tingly feeling;

  • watery diarrhea, pain or burning when you urinate;

  • blurred vision, bone pain, confusion, headache, nausea, swollen glands.; or

  • severe skin reaction - fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Also call your doctor at once if you have:

  • severe stomach cramps, bloating, diarrhea or constipation;

  • black, bloody, or tarry stools;

  • coughing up blood or vomit that looks like coffee grounds; or

  • signs of perforation (a hole or tear) in your stomach or intestines - fever, ongoing stomach pain, change in bowel habits.

Common Actemra side effects may include:

  • runny or stuffy nose, sinus pain, sore throat;

  • headache;

  • high blood pressure (blurred vision, buzzing in your ears, anxiety, confusion, shortness of breath, uneven heartbeats); or

  • pain, swelling, burning, or irritation around the IV needle or where an injection was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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