Dosing and uses of Actemra (tocilizumab)
Adult dosage forms and strengths
injection 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 q4wk initially; may increase to 8 mg/kg q4wk based on clinical response
- Not to exceed 800 mg/dose q4wk
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
Systemic Sclerosis (Orphan)
Orphan designation for treatment of systemic sclerosis
Orphan sponsor
- Genentech, Inc.; 1 DNA Way; South San Francisco, CA 94080-4990
Dosage modifications
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
Do not initiate if
- ANC <2000/mm³
- Platelets <100,000/mm³
- ALT/AST >1.5 times ULN
Transaminase elevations
- >1 to 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 to 5x ULN: Discontinue therapy and restart when <3 x ULN and follow above recommendations
- >5 x ULN: Discontinue therapy
Neutropenia
- ANC >1000/mm³: Maintain dose
- ANC 500-1000/mm³: Discontinue therapy until >1000/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
- ANC <500/mm³: Discontinue therapy
Thrombocytopenia
- 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
- <50,000/mm³: Discontinue therapy
Dosing Considerations
Monitor neutrophils, platelets, ALT, and AST every 4-8 weeks
Monitor lipids 4-8 weeks following initiation of therapy and then at ~24 week intervals
Use not recommended if
- ANC <500/mm³
- Platelets <50,000/mm³
- ALT or AST >5x ULN
Administration
Administer IV infusion over 1 hr
Rotate SC injection sites (ie, thighs, abdomen, outer area of upper arm [caregiver only]) and inject full amount of the syringe (0.9 mL)
Remove prefilled SC syringe from refrigerator 30 minutes before administration
Transition from IV to SC: Administer first SC dose instead of next scheduled
Pediatric dosage forms and strengths
injection for IV infusion
- 20mg/mL in 4, 10, and 20mL vials
Systemic Juvenile Idiopathic Arthritis (SJIA, Still's Disease)
<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
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
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
Administration
Infuse IV over 1 hr
May be administered as monotherapy or with methotrexate
Geriatric dosage forms and strengths
Increased risk of serious infections in patient ≥65 years of age; caution should be used when treating the elderly
Actemra (tocilizumab) adverse (side) effects
>10%
SC injection site reactions (7.1-10.1%)
1-10%
Upper respiratory tract infections
Nasopharyngitis
Headache
Hypertension
Increased ALt
Infusion related skin reactions (eg, rash, pruritus, urticaria)
Dose related adverse reactions including decreased neutrophil count <1000/cu.mm, decreased platelets <100,000/cu.mm
Lipid elevations
Mouth ulcerations
Gastritis
Upper abdominal pain
Postmarketing reports
Stevens-Johnson Syndrome
Warnings
Black box warnings
Serious infections leading to hospitalization or death (ie, tuberculosis; bacterial, invasive fungal, viral, or other opportunistic infections) have occurred with use
Stop therapy if serious infection occurs; can restart if infection is controlled
Test for latent tuberculosis before initiating; if positive, initiate tuberculosis therapy before starting tocilizumaB
Continue to monitor all patients for active tuberculosis during therapy
Contraindications
Hypersensitivity
Cautions
Risk for serious infections (see Black box warnings)
If a serious infection develops, interrupt therapy until infection controlled
Tocilizumab has not been studied in combination with biological DMARDs (eg, TNF antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies, selective costimulation modulators) and its use should be avoided in combination with these agents because of increased immunosuppression and risk of infection
Nonmelanoma skin cancers reported; periodic skin examination recommended
Caution if increased risk for GI perforation
May cause neutropenia, decreased platelets, elevated liver transaminases, and increased lipid parameters; monitor neutrophils, platelets, lipids, and liver function tests every 4-8 weeks
Anaphylaxis or serious hypersensitivity reactions have occurred, including fatalities, with or without concomitant arthritis therapies
Do not coadminister with live vaccines (eg, MMR, intranasal influenza); IL-6 inhibition may interfere with the normal immune response to new antigens, all patients, particularly those with PJIA and SJIA, should be current with their immunizations before initiating therapy
Pregnancy and lactation
Pregnancy category: C
Lactation: unknown whether distributed in breast milk, do not breast feed
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Actemra (tocilizumab)
Mechanism of action
Interleukin-6 receptor antagonist; changes in clinical trials observed include decreased C-reactive protein level to within normal range, decreased values in other pharmacodynamic parameters (eg, rheumatoid factor, erythrocyte sedimentation rate, amyloid A), and increased hemoglobin value
Absorption
Peak plasma time: 1 hr
Distribution
Vd: 6.4L
Elimination
Half-life: up to 11 days (4 mg/kg); up to 13 days (8 mg/kg)
Cmax: 88.3 mcg/mL (4 mg/kg); 183 mcg/mL (8 mg/kg)
Clearance: 0.0125 L/hr
Administration
Do not infuse with any other drugs as no compatibility studies have been conducted
IV Preparation
IV infusion
- Withdraw a volume of 0.9% NaCl from bag/bottle equal to volume of the solution required for the patient's dose
- Adults and children 30 kg or more: Dilute to 100 mL in 0.9% NaCl
- Children <30 kg: Dilute to 50 mL in 0.9% NaCl
- Slowly add dose to infusion bag or bottle and gently invert to mix (prevent foaming)
IV Administration
Administer as single IV infusion over 1 hr
Do NOT administer as bolus or push
Storage
Undiluted vials and prefilled SC syringes: Store refrigerated between 2-8°C (36-46°F) in original container and protect from light
After dilution: Store refrigerated between 2-8°C (36-46°F) or room temperature for up to 24 hr; protect from light
Do not freeze
Do not save unused, reconstituted drug in vials because product contains no preservatives
