Tecentriq

Antineoplastic Monoclonal Antibodies Targeting Programmed Death-1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) Pathways

Emetic Risk
Minimal

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Dilution
Withdraw the required volume of atezolizumab from the vial(s).
Dilute to a final concentration between 3.2 mg/mL and 16.8 mg/mL in a polyvinyl chloride (PVC), polyethylene (PE), or polyolefin (PO) infusion bag containing 0.9% Sodium Chloride Injection.
Mix by gentle inversion; do not shake.
Storage after dilution: Store diluted solution at room temperature for no more than 6 hours (including infusion time), or under refrigeration (2 to 8 degrees C; 36 to 46 degrees F) for no more than 24 hours from the time of preparation.[60793]
 
Infusion
Administer atezolizumab prior to chemotherapy or other antineoplastic agents when given on the same day.
Do not infuse through the same IV line with other drugs.
Administer the first dose intravenously, with or without a sterile, non-pyrogenic, low protein-binding in-line filter (0.2 to 0.22 micron), over 60 minutes; do not administer atezolizumab as an IV push or bolus. If tolerated, all subsequent infusions may be infused over 30 minutes.
Interrupt or slow administration for grade 2 infusion-related reactions; the infusion may resume when symptoms have resolved to grade 0 or 1.
Permanently discontinue atezolizumab for grade 3 or 4 infusion-related reactions.[60793]

rash / Early / 0-27.0
hypermagnesemia / Delayed / 0-26.0
hypophosphatemia / Delayed / 0-22.0
hyperamylasemia / Delayed / 0-20.0
hyponatremia / Delayed / 0-15.0
hypertension / Early / 0-15.0
hypercalcemia / Delayed / 0-14.0
hyperglycemia / Delayed / 0-10.0
lymphopenia / Delayed / 0-9.0
hyperbilirubinemia / Delayed / 0-8.0
weight gain / Delayed / 0-6.0
fatigue / Early / 0-5.0
dyspnea / Early / 0-4.9
nausea / Early / 0-4.0
headache / Early / 0-4.0
dizziness / Early / 0-4.0
asthenia / Delayed / 0-4.0
hyperkalemia / Delayed / 0-3.9
hypomagnesemia / Delayed / 0-3.4
anemia / Delayed / 0-3.0
hypocalcemia / Delayed / 0-3.0
pulmonary embolism / Delayed / 0-3.0
vomiting / Early / 0-2.7
infusion-related reactions / Rapid / 0.2-2.4
anorexia / Delayed / 0-2.0
fever / Early / 0-2.0
bleeding / Early / 0-2.0
constipation / Delayed / 0-1.1
cough / Delayed / 0-1.0
aplastic anemia / Delayed / 0-1.0
hemolytic anemia / Delayed / 0-1.0
myelitis / Delayed / 0-1.0
uveitis / Delayed / 0-1.0
pruritus / Rapid / 0-1.0
edema / Delayed / 0-1.0
pericarditis / Delayed / 0-1.0
vasculitis / Delayed / 0-1.0
myocarditis / Delayed / 0-1.0
organ transplant rejection / Delayed / 0-1.0
hyperthyroidism / Delayed / 0-0.4
hypothyroidism / Delayed / 0-0.3
diabetes mellitus / Delayed / 0.2-0.2
interstitial nephritis / Delayed / 0-0.1
pleural effusion / Delayed / 1.0
GI obstruction / Delayed / Incidence not known
bowel ischemia / Delayed / Incidence not known
visual impairment / Early / Incidence not known
retinal detachment / Delayed / Incidence not known
Vogt-Koyanagi-Harada syndrome / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
pericardial effusion / Delayed / Incidence not known
cardiac tamponade / Delayed / Incidence not known
hypertensive crisis / Early / Incidence not known
atrial fibrillation / Early / Incidence not known
ventricular tachycardia / Early / Incidence not known
bradycardia / Rapid / Incidence not known
stroke / Early / Incidence not known
intracranial bleeding / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
veno-occlusive disease (VOD) / Delayed / Incidence not known
sinusoidal obstruction syndrome (SOS) / Delayed / Incidence not known
graft-versus-host disease (GVHD) / Delayed / Incidence not known
ocular hemorrhage / Delayed / Incidence not known

antibody formation / Delayed / 13.0-36.0
hypoglycemia / Early / 0-33.0
thrombocytosis / Delayed / 0-29.0
hepatotoxicity / Delayed / 0-29.0
iritis / Delayed / 0-1.0
sarcoidosis / Delayed / 0-1.0
gastritis / Delayed / 0-1.0
hypoparathyroidism / Delayed / 0-1.0
peripheral neuropathy / Delayed / 0-0.4
confusion / Early / 2.0
glossitis / Early / Incidence not known
oral ulceration / Delayed / Incidence not known
dehydration / Delayed / Incidence not known
psoriaform rash / Delayed / Incidence not known
palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known
proteinuria / Delayed / Incidence not known
hyperphosphatemia / Delayed / Incidence not known
hypernatremia / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
hemoptysis / Delayed / Incidence not known
hematuria / Delayed / Incidence not known

insomnia / Early / 0-27.0
anxiety / Delayed / 0-25.0
influenza / Delayed / 0-18.0
weight loss / Delayed / 0-18.0
rhinitis / Early / 0-16.0
purpura / Delayed / 0-1.0
cheilitis / Delayed / Incidence not known
dysesthesia / Delayed / Incidence not known
paresthesias / Delayed / Incidence not known
hypoesthesia / Delayed / Incidence not known
acneiform rash / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
lichen planus-like eruption / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
syncope / Early / Incidence not known
vertigo / Early / Incidence not known
epistaxis / Delayed / Incidence not known
dysgeusia / Early / Incidence not known

Tecentriq

Rx

Programmed death ligand-1 (PD-L1) blocking monoclonal antibody
Used in adults for certain types of melanoma, hepatocellular cancer, and lung cancer; also used in adult and pediatric patients aged 2 years and older for alveolar soft part sarcoma
Immune-mediated reactions have been reported; treatment may need to be withheld or permanently discontinued

Treatment-Related Immune-Mediated HepatitisNo Tumor Involvement of the LiverAST or ALT level of more than 3 to 8 times the ULN or a total bilirubin level of more than 1.5 to 3 times the ULN: Hold atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper). Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper. Permanently discontinue atezolizumab in patients who do not have a complete or partial resolution of toxicity or who cannot reduce their daily prednisone dose to less than 10 mg (or equivalent) within 12 weeks of initiating steroids. AST or ALT level more than 8 times the ULN or a total bilirubin level more than 3-times the ULN: Permanently discontinue atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper starting when the toxicity resolves to grade 1 or less).Tumor Involvement of the LiverBaseline AST or ALT level at the ULN or less: Hold or permanently discontinue atezolizumab based on recommendations for hepatitis with no tumor involvement of the liver.Baseline AST or ALT level of more than 1 to 3 times the ULNAST or ALT level of more than 5 to 10 times the ULN: Hold atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper). Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper. Permanently discontinue atezolizumab in patients who do not have a complete or partial resolution of toxicity or who cannot reduce their daily prednisone dose to less than 10 mg (or equivalent) within 12 weeks of initiating steroids. Baseline AST or ALT level of more than 3 to 5 times the ULNAST or ALT level of more than 8 to 10 times the ULN: Hold atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper). Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper. Permanently discontinue atezolizumab in patients who do not have a complete or partial resolution of toxicity or who cannot reduce their daily prednisone dose to less than 10 mg (or equivalent) within 12 weeks of initiating steroids. Any Baseline AST or ALT levelAST or ALT level more than 10 times the ULN or a total bilirubin level to more than 3 times the ULN: Permanently discontinue atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper starting when the toxicity resolves to grade 1 or less).

Treatment-Related Immune-Mediated Nephritis with Renal Dysfunction Grade 2 or 3 increased serum creatinine (SCr) level: Hold atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper). Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper. Permanently discontinue atezolizumab in patients who do not have a complete or partial resolution of toxicity or who cannot reduce their daily prednisone dose to less than 10 mg (or equivalent) within 12 weeks of initiating steroids. Grade 4 increased SCr level: Permanently discontinue atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper starting when the toxicity resolves to grade 1 or less).

Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.

840 mg IV every 2 weeks; 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks.

840 mg IV every 2 weeks; 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks.

15 mg/kg (maximum of 1,200 mg) IV every 3 weeks.

2 years and older: 15 mg/kg (maximum of 1,200 mg) IV every 3 weeks.1 year: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Atezolizumab is an Fc-engineered, humanized, non-glycosylated IgG1 kappa monoclonal antibody that inhibits programmed death ligand 1 (PD-L1) interactions with the PD-1 and B7.1 receptors. PD-L1 may be expressed on tumor cells and/or tumor-infiltrating immune cells, and can contribute to inhibition of the anti-tumor immune response in the tumor microenvironment; PD-1 and B7.1 receptors are found on T-cells and antigen-presenting cells. The PD-1 pathway regulates the balance between T-cell activation and protection of healthy tissues from immune-mediated damage. In cancer, the PD-1 pathway is thought to play an important role in the interaction of tumor cells with the host immune response. Binding of PD-L1 to the PD-1 and B7.1 receptors suppresses cytotoxic T-cell activity, T-cell proliferation, and cytokine production; PD-L1 expression in a tumor cell may provide adaptive immune resistance and lead to poor outcomes. Atezolizumab binds to PD-L1 and prevents its interaction with both PD-1 and B7.1 receptors, releasing the PD-L1/PD-1 mediated inhibition of an anti-tumor immune response without inducing antibody-dependent cellular cytotoxicity. In syngeneic mouse tumor models, blocking PD-L1 activity resulted in decreased tumor growth.

Atezolizumab is administered intravenously. Exposure to atezolizumab increases in a dose-proportional manner over a range of 1 mg/kg to 20 mg/kg, including the recommended fixed dose of 1,200 mg. Clearance was 0.2 L/day (CV, 29%) and volume of distribution (Vd) at steady-state was 6.9 L. Atezolizumab clearance was found to decrease over time, with a mean maximal reduction (% coefficient of variation; CV%) from baseline value of 17% (CV%, 41%); however, this was not considered statistically relevant. The terminal half-life was 27 days, with steady-state reached after 6 to 9 weeks following multiple doses.[60793]

The systemic accumulation ratio for atezolizumab was 3.3-fold when administered every 2 weeks and 1.9-fold when administered every 3 weeks.

Based on its mechanism of action, atezolizumab may cause fetal harm if used during pregnancy. Atezolizumab is an immunoglobulin G1 antibody and may cross the placental barrier. Fetal exposure to atezolizumab may increase the risk of developing immune-mediated disorders or altering the normal immune response. Advise women of reproductive potential of the risk to a fetus. The PD-1 pathway is associated with decidual CD8-positive T-cell function and the PD1/PD-L1 interaction may be important in maintaining fetal tolerance during pregnancy. PD1/PDL1 Inhibitors, such as atezolizumab, may impair maternal immune tolerance resulting in spontaneous abortion, intrauterine growth restriction, or early-onset preeclampsia.    

Due to the potential for serious adverse reactions in breastfed children, the manufacturer recommends that patients avoid breast-feeding during atezolizumab therapy and for 5 months after the final dose. It is not known if atezolizumab is present in human milk or if it has effects on the breastfed child or on milk production. Use atezolizumab with caution during breastfeeding, especially while nursing a newborn or preterm infant. Because atezolizumab is a large protein molecule (molecular weight of 145,000 Daltons), the amount of drug in milk is likely to be very low. It may also be partially destroyed in the gastrointestinal tract resulting in minimal absorption.