Indication:
DRUG INNOVATION - NOVEL DRUG APPROVALS FOR 2016
No Drug Name Active Ingredient Approval Date FDA-Approved use
on Approval date
9. Atezolizumab Tecentriq 5/18/2016 To treat urothelial carcinoma, the most common type of bladder
cancer
Approved by FDA on 5/18/2016 (Ref- FDA approved List- 2016)
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
TECENTRIQ safely and effectively. See full prescribing information
for TECENTRIQ.
TECENTRIQ (atezolizumab) injection, for intravenous use
Initial U.S. Approval: 2016
INDICATIONS AND USAGE
TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody
indicated for the treatment of patients with locally advanced or metastatic
urothelial carcinoma who:
1.Have disease progression during or following platinum-containing chemotherapy
2.Have disease progression within 12 months of neoadjuvant or adjuvant
treatment with platinum-containing chemotherapy
This indication is approved under accelerated approval based on tumor
response rate and duration of response.
Continued approval for this indication may be contingent upon verification
and description of clinical benefit in confirmatory trials.
Adverse Reaction:
ADVERSE REACTIONS
Most common adverse reactions (= 20% of patients) included: fatigue,
decreased appetite, nausea, urinary tract infection, pyrexia, and constipation,
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
1.Immune-Related Pneumonitis:
Withhold for moderate and permanently discontinue for severe or
life-threatening pneumonitis.
2. Immune-Related Hepatitis:
Monitor for changes in liver function.Withhold for moderate and
permanently discontinue for severe or life-threatening transaminase
or total bilirubin elevation.
3. Immune-Related Colitis:
Withhold for moderate or severe, and permanently discontinue
for life-threatening colitis.
4. Immune-Related Endocrinopathies :
i.Hypophysitis: Withhold for moderate or severe and permanently
discontinue for life-threatening hypophysitis.
ii. Thyroid Disorders: Monitor for changes in thyroid function.
Withhold for symptomatic thyroid disease.
iii. Adrenal Insufficiency: Withhold for symptomatic adrenal
insufficiency.
iv. Type 1 Diabetes Mellitus: Withhold for = Grade 3 hyperglycemia.
5. Immune-Related Myasthenic Syndrome/Myasthenia Gravis, GuillainBarré
or Meningoencephalitis:
Permanently discontinue for any grade.
i. Ocular Inflammatory Toxicity:
Withhold for moderate and permanently discontinue for severe
ocular inflammatory toxicity
ii. Immune-Related Pancreatitis:
Withhold for moderate or severe, and permanently discontinue
for life-threatening pancreatitis, or any grade of recurring
pancreatitis.
6. Infection:
Withhold for severe or life-threatening infection.
7. Infusion Reaction:
Interrupt or slow the rate of infusion for mild or moderate infusion
reactions and discontinue for severe or lifethreatening
infusion reactions.
8.Embryo-Fetal Toxicity:
TECENTRIQ can cause fetal harm. Advise females of reproductive
potential of the potential risk to a fetus and use of effective
contraception.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody
indicated for the treatment of patients with locally advanced or metastatic
urothelial carcinoma who:
1.Have disease progression during or following platinum-containing chemotherapy
2.Have disease progression within 12 months of neoadjuvant or adjuvant
treatment with platinum-containing chemotherapy
This indication is approved under accelerated approval based on tumor
response rate and duration of response.
Continued approval for this indication may be contingent upon verification
and description of clinical benefit in confirmatory trials.
DOSAGE AND ADMINISTRATION
Administer 1200 mg as an intravenous infusion over 60 minutes
every 3 weeks.
Dilute prior to intravenous infusion.
DOSAGE FORMS AND STRENGTHS
Injection: 1200 mg/20 mL (60 mg/mL) solution in a single-dose vial
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling
(Medication Guide).
Inform patients of the risk of immune-related adverse reactions that
may require corticosteroid treatment and interruption or discontinuation
of TECENTRIQ.
Pneumonitis:
Advise patients to contact their healthcare provider immediately
for any new or worsening cough, chest pain, or shortness of breath
Hepatitis:
Advise patients to contact their healthcare provider immediately
for jaundice, severe nausea or vomiting, pain on the right side of abdomen,
lethargy, or easy bruising or bleeding.
Colitis:
Advise patients to contact their healthcare provider immediately for
diarrhea or severe abdominal pain..
Endocrinopathies:
Advise patients to contact their healthcare provider immediately for signs
or symptoms of hypophysitis, hyperthyroidism, hypothyroidism, adrenal
insufficiency, or type 1 diabetes mellitus, including diabetic ketoacidosis.
Meningoencephalitis, myasthenic syndrome/myasthenia gravis,
and Guillain-Barré :
Advise patients to contact their healthcare provider immediately for signs or
symptoms of meningitis, myasthenic syndrome/myasthenia gravis,
or Guillain-Barré syndrome .
Genentech, Inc.
14/Regional (Urothelial Carcinoma): 06May16 Clean and Final Tecentriq USPI.docx
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1 Mechanism of Action
PD-L1 may be expressed on tumor cells and/or tumor-infiltrating immune cells
and can contribute to the inhibition of the anti-tumor immune response in
the tumor microenvironment.
Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen
presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation and
cytokine production.
Atezolizumab is a monoclonal antibody that binds to PD-L1 and blocks its
interactions with both PD-1 and B7.1 receptors. This releases the PD-L1/PD-1
mediated inhibition of the immune 368 response, including activation of the
anti-tumor immune response without inducing antibody dependent cellular
cytotoxicity. In syngeneic mouse tumor models, blocking PD-L1 activity
resulted in decreased tumor growth.
2. Pharmacokinetics
Patients’ exposures to atezolizumab increased dose proportionally over
the dose range of 373 1 mg/kg to 20 mg/kg, including the fixed dose 1200 mg
administered every 3 weeks.
Based on a population analysis that included 472 patients in the dose range,
the typical population clearance was 0.20 L/day, volume of distribution
at steady state was 6.9 L, and the terminal half-life was 27 days.
The population PK analysis suggests steady state is obtained after
6 to 9 weeks (2 to 3 cycles) of repeated dosing. The systemic accumulation
in area under the curve (AUC), maximum concentration (Cmax) and trough
concentration (Cmin) was 1.91, 1.46 and 2.75-fold, respectively.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
Based on its mechanism of action, TECENTRIQ can cause fetal harm when
administered to a pregnant woman. There are no available data on the use of
TECENTRIQ in pregnant women.
Animal studies have demonstrated that inhibition of the PD L1/PD-1 pathway
can lead to increased risk of immune-related rejection of the developing fetus
resulting in fetal death [see Data].
If this drug is used during pregnancy, or if the patient becomes pregnant while
taking this drug, advise the patient of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth
defects and miscarriage in clinically recognized pregnancies is 2% to 4%
and 15% to 20%, respectively.
2. Lactation
Risk Summary
There is no information regarding the presence of atezolizumab in human milk,
the effects on the breastfed infant, or the effects on milk production.
As human IgG is excreted in human milk, the potential for absorption and harm
to the infant is unknown.
Because of the potential for serious adverse reactions in breastfed infants
from TECENTRIQ, advise a lactating woman not to breastfeed during treatment
and for at least 5 months after the last dose.
3. Pediatric Use
The safety and effectiveness of TECENTRIQ have not been established
in pediatric patients.
4.Geriatric Use
Of the 310 patients with urothelial carcinoma treated with TECENTRIQ
in Study 1, 59% were 65 years or older. No overall differences in safety
or efficacy were observed between patients = 65 years of age and
younger patients.
5. Renal Impairment
Based on a population pharmacokinetic analysis, no dose adjustment
of TECENTRIQ is recommended for patients with renal impairment .
6. Hepatic Impairment
Based on a population pharmacokinetic analysis, no dose adjustment
of TECENTRIQ is recommended for patients with mild hepatic impairment.
TECENTRIQ has not been studied in patients with moderate or severe
hepatic impairment.
7.OVERDOSAGE
There is no information on overdose with TECENTRIQ.
