tocilizumab(redirected from Actemra)
Pharmacologic class: Interleukin-6 (IL-6) receptor inhibitor
Therapeutic class: Immunomodulator
Pregnancy risk category C
FDA Box Warning
Serious infections leading to hospitalization or death, including tuberculosis (TB) and bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving tocilizumab.
If a serious infection develops, interrupt therapy until infection is controlled.
Perform test for latent TB; if positive, start treatment for TB before starting tocilizumab.
Monitor all patients for active TB during treatment, even if initial latent TB test is negative.
Binds specifically to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors; decreases levels of C-reactive protein to within normal range; decreases rheumatoid factor, erythrocyte sedimentation rate, serum amyloid A; increases hemoglobin
Solution for injection, concentrate: 80 mg/4 ml, 200 mg/10 ml, 400 mg/20 ml (20 mg/ml) in single-use vials
⊘Indications and dosages
➣ Moderate to severe active rheumatoid arthritis in patients who have had inadequate response to one or more tumor necrosis factor (TNF) antagonists
Adults: Initially (when used in combination with disease-modifying antirheumatic drugs [DMARDs] or as monotherapy), 4 mg/kg by I.V. infusion over 60 minutes q 4 weeks; may increase to 8 mg/kg by I.V. infusion over 60 minutes q 4 weeks based on clinical response. Maximum dosage, 800 mg/infusion.
➣ Active systemic juvenile idiopathic arthritis (SJIA)
Children age 2 and older weighing 30 kg (66 lb) or more: 8 mg/kg (alone or with methotrexate) by I.V. infusion over 60 minutes q 2 weeks
Children age 2 and older weighing less than 30 kg: 12 mg/kg (alone or with methotrexate) by I.V. infusion over 60 minutes q 2 weeks
• Elevated liver enzyme levels
• Neutropenia, thrombocytopenia
• Hypersensitivity to drug
Use cautiously in:
• active hepatic disease or hepatic impairment (use not recommended)
• absolute neutrophil count less than 2,000/mm3, platelet count less than 100,000/mm3, ALT or AST more than 1.5 times the upper limit of normal (use not recommended)
• patients who may be at increased risk for GI perforation (such as patients with diverticulitis)
• patients at risk for infection
• demyelinating disorders (such as multiple sclerosis and chronic inflammatory demyelinating polyneuropathy)
• active infection (don't use)
• concurrent use of biological DMARDs such as TNF antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies, selective co-stimulation modulators, and live vaccines (avoid use)
• concurrent use of CYP3A4 substrates when decrease in effectiveness is undesirable (such as oral contraceptives, lovastatin, atorvastatin)
• concurrent use of immunosuppressants and corticosteroids
• elderly patients
• pregnant or breastfeeding patients
• children younger than age 2 and for conditions other than SJIA (safety and efficacy not established).
Be aware that drug should only be administered by healthcare professional with appropriate medical support to manage anaphylaxis. If anaphylaxis or other clinically significant hypersensitivity reaction occurs, stop drug immediately and permanently.
• Evaluate patient for TB risk factors; test for latent infection before starting therapy.
• Consider risks and benefits of treatment before starting therapy in patients with chronic or recurrent infection, in those who have been exposed to TB, in those with history of serious or opportunistic infection, in those who have resided or traveled in areas of endemic TB or endemic mycoses, and in those with underlying conditions that may predispose to infection.
• For adults and SJIA patients who weigh 30 kg or more, dilute concentrated solution to 100 ml in 0.9% sodium chloride for I.V. infusion using 100-ml infusion bag.
• For SJIA patients weighing less than 30 kg, dilute to 50 ml in 0.9% sodium chloride for I.V. infusion using 50-ml infusion bag.
• Withdraw a volume of 0.9% sodium chloride injection from infusion bag or bottle equal to volume of drug required for dose.
• Slowly add drug for I.V. infusion from each vial into infusion bag. Gently invert bag to avoid foaming to mix solution. Allow fully diluted solution to reach room temperature before infusing. Don't mix or infuse with other drugs. Discard unused product.
Administer as single I.V. drip infusion over 1 hour; don't administer as bolus or push.
• Interrupt therapy if patient develops serious infection, opportunistic infection, or sepsis until infection has been controlled.
Be aware that interruption or discontinuation of drug may be needed for management of dose-related laboratory abnormalities, including elevated liver enzyme levels, neutropenia, and thrombocytopenia. If appropriate, concomitant methotrexate or other drugs should be dose-modified or stopped.
• On initiation or discontinuation of tocilizumab in patients being treated with CYP450 substrates with narrow therapeutic indices, monitor therapeutic effect of drugs such as warfarin or drug concentration of drugs such as cyclosporine or theophylline.
CNS: headache, dizziness
GI: gastroenteritis, diverticulitis, mouth ulcerations, upper abdominal pain, gastritis, GI perforation
GU: urinary tract infection
Hematologic: neutropenia, decreased platelets
Hepatic: abnormal liver function test results, increased lipids
Musculoskeletal: bacterial arthritis
Respiratory: upper respiratory tract infection, pneumonia, bronchitis
Skin: cellulitis, rash
Other: herpes zoster exacerbation, other serious and opportunistic infections, sepsis, malignancies, infusion reactions, hypersensitivity reactions including anaphylaxis
Drug-drug. CYP450 substrates with narrow therapeutic indices (such as cyclosporine, theophylline, warfarin): increased metabolism of these drugs
Omeprazole, simvastatin: decreased exposure of these drugs
Drug-diagnostic tests. ALT, AST, HDL, LDL, total cholesterol, triglycerides: increased levels
Neutrophils, platelets: decreased counts
• Monitor CBC with differential, particularly neutrophils and platelets, and hepatic function tests, particularly ALT and AST, every 4 to 8 weeks. Monitor ALT, AST, neutrophils, and platelets every 2 to 4 weeks in children with SJIA. Monitor lipid levels approximately 4 to 8 weeks after initiation of therapy, then at approximately 24-week intervals in adults and children.
Continue to closely watch for signs and symptoms of hypersensitivity, demyelinating disorders, serious infection, and sepsis.
• Be aware that patients who develop new infection during treatment should undergo prompt and complete diagnostic workup appropriate for immunocompromised patients, receive appropriate antimicrobial therapy, and undergo close monitoring.
• Continue to closely monitor patients for signs and symptoms of TB, including patients who tested negative for latent TB before start of therapy.
Monitor patients who may be at increased risk for GI perforation. Promptly evaluate for early identification of GI perforation in patients who present with new-onset abdominal signs and symptoms.
Be aware that treatment with immunosuppressants may increase risk of malignancies.
• Instruct patient or caregiver about importance of telling prescriber about known infections before starting drug.
• Tell patient or caregiver that TB test will be done before start of therapy and tests for blood counts and liver function will be done frequently.
Instruct patient to immediately seek medical attention if hives, rash, throat swelling, or difficulty breathing occurs.
Instruct patient or caregiver of importance of immediately contacting prescriber if severe, persistent abdominal pain; change in bowel habits; infection (fever, chills, cough, or burning on urination); or other new signs and symptoms occur.
• Instruct patient or caregiver that patient shouldn't receive live vaccines during therapy.
• Advise female patient of childbearing age to inform prescriber if she becomes pregnant during therapy.
• Advise breastfeeding patient that she should decide whether to discontinue breastfeeding or discontinue drug, taking into account importance of drug for her treatment.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.
Pharmacologic: interleukin antagonists
Time/action profile (improvement)
|IV||within 1 mo||4 mo||unknown|
Adverse Reactions/Side Effects
Central nervous system
- headache (most frequent)
Ear, Eye, Nose, Throat
- nasopharyngitis (most frequent)
- upper respiratory tract infections (most frequent)
- hypertension (most frequent)
- gastrointestinal perforation (life-threatening)
- ↑ liver enzymes (most frequent)
- neutropenia (life-threatening)
- thrombocytopenia (life-threatening)
- ↑ lipids
- anaphylaxis (life-threatening)
- serious infections including tuberculosis, disseminated fungal infections and infections with opportunistic pathogens
- hypersensitivity reactions including anaphylaxis (life-threatening)
- infusion reactions
Drug-Drug interactionMay alter the activity of CYP450 enzymes ; the effects of the following drugs should be monitored: cyclosporine, theophylline, warfarin, hormonal contraceptives, atorvastatin and lovastatin. Other drugs which are substrates for this system should also be monitored; effect may persist for several weeks after discontinuation.May ↓ antibody response to and ↑ risk of adverse reactions to live virus vaccines ; do not administer concurrently.
Systemic Juvenile Idiopathic Arthritis
Polyarticular Juvenile Idiopathic Arthritis
- Assess pain and range of motion before and periodically during therapy.
- Assess for signs of infection (fever, dyspnea, flu-like symptoms, frequent or painful urination, redness or swelling at the site of a wound), including tuberculosis, prior to injection. Tocilizumab is contraindicated in patients with active infection. Monitor new infections closely; most common are upper respiratory tract infections, bronchitis, and urinary tract infections. Signs and symptoms of inflammation may be lessened due to suppression from tocilizumab. Infections may be fatal, especially in patients taking immunosuppressive therapy. If patient develops a serious infection, discontinue tocilizumab until infection is controlled.
- Monitor for injection site reactions (redness and/or itching, rash, hemorrhage, bruising, pain, or swelling). Rash will usually disappear within a few days. Application of a towel soaked in cold water may relieve pain or swelling.
- Monitor patient for signs of anaphylaxis (urticaria, dyspnea, facial edema) following injection. Medications (antihistamines, corticosteroids, epinephrine) and equipment should be readily available in the event of a severe reaction. Discontinue tocilizumab immediately if anaphylaxis or other severe allergic reaction occurs.
- Assess patient for latent tuberculosis with a tuberculin skin test prior to initiation of therapy. Treatment of latent tuberculosis should be started before therapy with tocilizumab.
- Assess for signs and symptoms of systemic fungal infections (fever, malaise, weight loss, sweats, cough, dypsnea, pulmonary infiltrates, serious systemic illness with or without concomitant shock). Ascertain if patient lives in or has traveled to areas of endemic mycoses. Consider empiric antifungal treatment for patients at risk of histoplasmosis and other invasive fungal infections until the pathogens are identified. Consult with an infectious diseases specialist. Consider stopping tocilizumab until the infection has been diagnosed and adequately treated.
- Lab Test Considerations: Assess CBC with platelet count and liver function prior to initiating therapy and every 4–8 wks during therapy. Do not administer tocilizumab to patients with an absolute neutrophil count (ANC) <2000/mm3, platelet count <100,000/mm3, or ALT or AST above 1.5 times the upper limit of normal (ULN).
- If ANC > 1000/mm3, maintain dose. If ANC 500–1000/mm3, interrupt IV tocilizumab until ANC >1000/mm3, then resume at 4 mg/kg and ↑ to 8 mg/kg as clinically appropriate or reduce subcut tocilizumab to every other week and increase frequency to every week as clinically appropriate. If ANC <500/mm3, discontinue tocilizumab.
- If platelet count 50,000–100,000/mm3, interrupt dosing until platelet count is >100,000/mm3 then resume IV dosing at 4 mg/kg and ↑ to 8 mg/kg as clinically appropriate or reduce subcut tocilizumab to every other week and increase frequency to every week as clinically appropriate. If platelet count is <50,000/mm3, discontinue tocilizumab.
- If liver enzymes persistently ↑ >1–3x ULN, reduce IV tocilizumab dose to 4 mg/kg and reduce subcut injection to every other week or interrupt until AST/ALT have normalized. If >3–5x ULN (confirmed by repeat testing), interrupt tocilizumab until <3x ULN and follow recommendations for ↑ >1–3x ULN. If persistent ↑ >1–3x ULN or >5x ULN, discontinue tocilizumab.
- Monitor lipid levels every 4–8 wks following initiation of therapy, then at 6 month intervals. May cause ↑ total cholesterol, triglycerides, LDL cholesterol, and/or HDL cholesterol.
Potential Nursing DiagnosesChronic pain (Indications)
Risk for infection (Adverse Reactions)
- Administer a tuberculin skin test prior to administration of tocilizumab. Patients with latent TB should be treated for TB prior to therapy.
- Immunizations should be current prior to initiating therapy. Patients on tocilizumab may receive concurrent vaccinations, except for live vaccines.
- Do not administer solutions that are discolored or contain particulate matter. Discard unused solution.
- Other DMARDs should be continued during tocilizumab therapy.
- Children: Do not change dose based on single visit weight; weight fluctuates.
- To switch from IV to Subcut, administer next dose Subcut instead of IV.
- Subcutaneous: Only for adult patients with RA. Solution is clear and colorless to pale yellow; do not administer solutions that are discolored or contain particulate matter. Rotate injection sites; avoid sites with moles, scars, areas where skin is tender, bruised, red, hard, or not intact.
- Intermittent Infusion: Diluent: Withdraw volume of 0.9% NaCl from a 100 mL bag (50 mL bag for children <30 kg) equal to volume of solution required for patient's dose. Slowly add tocilizumab from each vial to infusion bag. Invert slowly to mix; avoid foaming. Do not infuse solutions that are discolored or contain particulate matter. Diluted solution is stable for 24 hr if refrigerated or at room temperature; protect from light. Allow solution to reach room temperature before infusing.
- Rate: Infuse over 60 min. Do not administer via IV push or bolus.
- Y-Site Incompatibility: Do not infuse concomitantly in the same line with other drugs.
- Instruct patient on the purpose for tocilizumab. If a dose is missed, contact health care professional to schedule next infusion. Instruct patient and caregiver in correct technique for subcut injections and care and disposal of equipment.
- Caution patient to notify health care professional immediately if signs of infection (fever, sweating, chills, muscle aches, cough, shortness of breath, blood in phlegm, weight loss, warm, red or painful skin or sores, diarrhea or stomach pain, burning on urination, urinary frequency, feeling tired), fever and stomach-area pain that does not go away, change bowel habits, severe rash, swollen face, or difficulty breathing occurs while taking. If signs and symptoms of anaphylaxis occur, discontinue injections and notify health care professional immediately.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
- Instruct patient to notify health care professional of medication regimen prior to treatment or surgery.
- Advise female patients to notify health care professional if pregnancy is planned or suspected or if breast feeding, Pregnant women should be encouraged to participate in the pregnancy registry by calling 1-877-311-8972.
- Decreased pain and swelling with decreased rate of joint destruction in patients with rheumatoid arthritis, systemic idiopathic juvenile arthritis, or polyarticular juvenile idiopathic arthritis.