Tecentriq

Tecentriq

atezolizumab

Manufacturer:

Roche

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Atezolizumab.
Description
Active ingredient: atezolizumab.
Tecentriq is supplied as single-use vials containing preservative-free, colorless to slightly yellow solution, at an active ingredient concentration of 60 mg/mL, as follows: 20 mL vial containing a total of 1200 mg atezolizumab.
Excipients/Inactive Ingredients: L-Histidine, Glacial Acetic Acid, Sucrose, Polysorbate 20, Water for Injection.
Action
Pharmacotherapeutic Group: Anti-neoplastic agent, humanized immunoglobulin G1 (IgG1) monoclonal antibody. ATC code: L01XC32.
Pharmacology: Pharmacodynamics: Mechanism of Action: Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells suppresses cytotoxic T-cell activity through the inhibition of T-cell proliferation and cytokine production. PD-L1 may be expressed on tumor cells and tumor-infiltrating immune cells, and can contribute to the inhibition of the antitumor immune response in the microenvironment.
Atezolizumab is an Fc-engineered humanized immunoglobulin G1 (IgG1) monoclonal antibody that directly binds to PD-L1 and blocks interactions with the PD-1 and B7.1 receptors, releasing PD-L1 / PD-1 pathway-mediated inhibition of the immune response, including reactivating the antitumor immune response. Atezolizumab leaves the PD-L2/PD-1 interaction intact. In syngeneic mouse tumor models, blocking PD-L1 activity resulted in decreased tumor growth.
Clinical / Efficacy Studies: Second Line Non-Small Cell Lung Cancer (2L NSCLC): OAK: A phase III, open-label, multi-center, international, randomized study, GO28915 (OAK), was conducted to evaluate the efficacy and safety of Tecentriq compared with docetaxel in patients with locally advanced or metastatic NSCLC who have progressed during or following a platinum-containing regimen. A total of 1225 patients were enrolled, with the primary analysis population consisting of the first 850 randomized patients. Eligible patients were stratified by PD-L1 expression status in tumor-infiltrating immune cells (IC), by the number of prior chemotherapy regimens, and by histology.
Patients were randomized (1:1) to receive either Tecentriq or docetaxel. This study excluded patients who had a history of autoimmune disease, active or corticosteroid-dependent brain metastases, administration of a live, attenuated vaccine within 28 days prior to enrollment, administration of systemic immunostimulatory agents within 4 weeks or systemic immunosuppressive medications within 2 weeks prior to enrollment. Tumor assessments were conducted every 6 weeks for the first 36 weeks, and every 9 weeks thereafter. Tumor specimens were evaluated prospectively for PD-L1 expression on tumor cells (TC) and IC and the results were used to define the PD-L1 expression subgroups for the analyses described as follows.
The demographic and baseline disease characteristics of the primary analysis population were well balanced between the treatment arms. The median age was 64 years (range: 33 to 85), and 61% of patients were male. The majority of patients were white (70%). Approximately three-fourths of patients had non-squamous disease (74%), 10% had known EGFR mutation, 0.2% had known ALK rearrangements, 10% had CNS metastases at baseline, and most patients were current or previous smokers (82%). Baseline ECOG performance status was 0 (37%) or 1 (63%). Seventy five percent of patients received only one prior platinum-based therapeutic regimen.
Tecentriq was administered as a fixed dose of 1200 mg by IV infusion every 3 weeks. No dose reduction was allowed. Patients were treated until loss of clinical benefit as assessed by the investigator. Docetaxel was administered 75 mg/m2 by IV infusion on day 1 of each 21 day cycle until disease progression. For all treated patients, the median duration of treatment was 2.1 months for the docetaxel arm and 3.4 months for the Tecentriq arm.
The primary efficacy endpoint was OS. The key results of this study with a median survival follow-up of 21 months are summarized in Table 1. Kaplan-Meier curves for OS in the ITT population are presented in Figure 1. Figure 2 summarizes the results of OS in the ITT and PD-L1 subgroups, demonstrating OS benefit with Tecentriq in all subgroups, including those with PD-L1 expression <1% in TC and IC. (See Table 1 and Figure 1 and Figure 2.)

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An improvement in OS was observed with Tecentriq compared to docetaxel in both non-squamous NSCLC patients (hazard ratio [HR] of 0.73, 95% CI: 0.60, 0.89; median OS of 15.6 vs. 11.2 months for Tecentriq and docetaxel, respectively) and squamous NSCLC patients (HR of 0.73, 95% CI: 0.54, 0.98; median OS of 8.9 vs. 7.7 months for Tecentriq and docetaxel, respectively). The observed OS improvement was consistently demonstrated across subgroups of patients including those with brain metastases at baseline (HR of 0.54, 95% CI: 0.31, 0.94; median OS of 20.1 vs. 11.9 months for Tecentriq and docetaxel respectively) and patients who were never smokers (HR of 0.71, 95% CI: 0.47, 1.08; median OS of 16.3 vs. 12.6 months for Tecentriq and docetaxel, respectively). However, patients with EGFR mutations did not show improved OS with Tecentriq compared to docetaxel (HR of 1.24, 95% CI: 0.71, 2.18; median OS of 10.5 vs. 16.2 months for Tecentriq and docetaxel respectively).
Prolonged time to deterioration of patient-reported pain in chest as measured by the EORTC QLQ-LC13 was observed with Tecentriq compared with docetaxel (HR 0.71, 95% CI: 0.49, 1.05; median not reached in either arm). The time to deterioration in other lung cancer symptoms (i.e. cough, dyspnea, and arm/shoulder pain) as measured by the EORTC QLQ-LC13 was similar between Tecentriq and docetaxel. The average global health status and functioning scores (i.e. physical, role, social, emotional, and cognitive) as measured by the EORTC QLQ-C30 did not show clinically meaningful deterioration over time for both treatment groups, suggesting maintained health-related quality of life and patient-reported functioning for patients remaining on treatment.
POPLAR: A phase II, multi-center, international, randomized, open-label, controlled study GO28753 (POPLAR), was conducted in patients with locally advanced or metastatic NSCLC. The primary efficacy outcome was overall survival. A total of 287 patients were randomized 1:1 to receive either Tecentriq or docetaxel. Randomization was stratified by PD-L1 expression status in IC, by the number of prior chemotherapy regimens and by histology. An updated analysis with a total of 200 deaths observed and a median survival follow-up of 22 months showed a median OS of 12.6 months in patients treated with Tecentriq, vs. 9.7 months in patients treated with docetaxel (HR of 0.69, 95% CI: 0.52, 0.92). ORR was 15.3% vs. 14.7% and median DOR was 18.6 months vs. 7.2 months for Tecentriq vs. docetaxel, respectively.
Immunogenicity: As with all therapeutic proteins, there is the potential for immune response to atezolizumab. Across multiple phase III studies, 13.1% to 38.5% of patients developed treatment-emergent anti-drug antibodies (ADAs). ADA positivity appeared to have no clinically relevant impact on pharmacokinetics or safety. Although some variability was observed across the studies, overall, ADA positivity appeared to have no clinically relevant impact on efficacy.
Immunogenicity assay results are highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of incidence of antibodies to Tecentriq with the incidence of antibodies to other products may be misleading.
Pharmacokinetics: The pharmacokinetics of atezolizumab have been characterized in patients in multiple clinical trials at doses 0.01 mg/kg to 20 mg/kg and 1200 mg every 3 weeks, as well as 840 mg every 2 weeks. Exposure to atezolizumab increased dose proportionally over the dose range of 1 mg/kg to 20 mg/kg. A population analysis that included 472 patients described atezolizumab pharmacokinetics for the dose range: 1 - 20 mg/kg with a linear two-compartment disposition model with first-order elimination. Based on pharmacokinetic modeling, the overall exposure of atezolizumab administered at doses of 840 mg administered every 2 weeks, 1200 mg every 3 weeks and 1680 mg every 4 weeks are comparable. A population pharmacokinetic analysis suggests that steady-state is obtained after 6 to 9 weeks after multiple doses. The maximum systemic accumulation ratio across dosing regimen is 3.3.
Based on an analysis of exposure, safety and efficacy data, the following factors have no clinically relevant effect: age (21-89 years), body weight, gender, positive ADA status, albumin levels, tumor burden, region or ethnicity, renal impairment, mild hepatic impairment, level of PD-L1 expression, or ECOG status.
Absorption: Tecentriq is administered as an IV infusion. There have been no studies performed with other routes of administration.
Distribution: A population pharmacokinetic analysis indicates that central compartment volume of distribution (V1) is 3.28 L and volume at steady state (Vss) is 6.91 L in the typical patient.
Metabolism: The metabolism of Tecentriq has not been directly studied. Antibodies are cleared principally by catabolism.
Elimination: A population pharmacokinetic analysis indicates that the clearance of atezolizumab is 0.200 L/day and the typical terminal elimination half-life (t½) is 27 days.
Pharmacokinetics in Special Populations: Pediatric population: No studies have been conducted to investigate the pharmacokinetics of Tecentriq in children.
Geriatric population: No dedicated studies of Tecentriq have been conducted in geriatric patients. The effect of age on the pharmacokinetics of atezolizumab was assessed in a population pharmacokinetic analysis. Age was not identified as a significant covariate influencing atezolizumab pharmacokinetics based on patients of age range of 21-89 years (n=472), and median of 62 years of age. No clinically important difference was observed in the pharmacokinetics of atezolizumab among patients <65 years (n=274), patients between 65-75 years (n=152) and patients >75 years (n=46) (see Special Dosage Instructions under Dosage & Administration).
Renal impairment: No dedicated studies of Tecentriq have been conducted in patients with renal impairment. In the population pharmacokinetic analysis, no clinically important differences in the clearance of atezolizumab were found in patients with mild (eGFR 60 to 89 mL/min/1.73 m2; n=208) or moderate (eGFR 30 to 59 mL/min/1.73 m2; n=116) renal impairment compared to patients with normal (eGFR greater than or equal to 90 mL/min/1.73 m2; n=140) renal function. Only a few patients had severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2; n=8) (see Special Dosage Instructions under Dosage & Administration).
Hepatic impairment: No dedicated studies of Tecentriq have been conducted in patients with hepatic impairment. In the population pharmacokinetic analysis, there were no clinically important differences in the clearance of atezolizumab between patients with mild hepatic impairment (bilirubin ≤ ULN and AST > ULN or bilirubin >1.0 to 1.5 x ULN and any AST, n = 71) and normal hepatic function (bilirubin and AST ≤ ULN, n=401). No data are available in patients with either moderate (bilirubin > 1.5 to 3.0 x ULN and any AST) or severe (bilirubin > 3.0 x ULN and any AST) hepatic impairment. Hepatic impairment was defined by the National Cancer Institute (NCI) criteria of hepatic dysfunction (see Special Dosage Instructions under Dosage & Administration).
Toxicology: Nonclinical Safety: Carcinogenicity: No carcinogenicity studies have been conducted with Tecentriq.
Genotoxicity No mutagenicity studies have been conducted with Tecentriq.
Impairment of Fertility: No fertility studies have been conducted with Tecentriq; however, assessment of the cynomolgus monkey male and female reproductive organs was included in the chronic toxicity study. Tecentriq had an effect on menstrual cycles in all female monkeys in the 50 mg/kg dose group characterized by an irregular cycle pattern during the dosing phase and correlated with the lack of fresh corpora lutea in the ovaries at the terminal necropsy; this effect was reversible during the dose-free recovery period. There was no effect on the male reproductive organs.
Reproductive Toxicity: No reproductive or teratogenicity studies in animals have been conducted with Tecentriq. The PD-L1/PD-1 signaling pathway is well established as essential in maternal / fetal tolerance and embryo-fetal survival during gestation. Administration of Tecentriq is expected to have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo lethality.
Other: Not applicable.
Indications/Uses
Non-small cell lung cancer: Tecentriq is indicate for the treatment of patients with metastatic non-small cell lung cancer who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumour aberrations should have disease progression on approved therapy for theses aberrations prior to receiving Tecentriq.
Dosage/Direction for Use
General: Tecentriq must be administered as an intravenous (IV) infusion under the supervision of a qualified healthcare professional. Do not administer as an IV push or bolus.
Do not co-administer other medicinal products through the same infusion line.
Substitution by any other biological medicinal product requires the consent of the prescribing physician.
The initial dose of Tecentriq must be administered over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes.
Tecentriq monotherapy: Second Line Non-Small Cell Lung Cancer: The recommended dose of Tecentriq is either: 840 mg administered by IV infusion every 2 weeks, or 1200 mg administered by IV infusion every 3 weeks, or 1680 mg administered by IV infusion every 4 weeks.
Duration of treatment: Patients are treated with Tecentriq until loss of clinical benefit (see Pharmacology: Pharmacodynamics: Clinical / Efficacy Studies under Actions) or unacceptable toxicity.
Delayed or missed doses:
If a planned dose of Tecentriq is missed, it should be administered as soon as possible.
The schedule of administration should be adjusted to maintain the appropriate interval between doses.
Dose modifications: No dose reductions of Tecentriq are recommended.
Dose modifications for immune-related adverse reactions: Recommendations for specific adverse drug reactions (see General under Precautions and Clinical Trials under Adverse Reactions) are presented in Table 2. (See Table 2.)

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For other immune-related reactions, based on the type and severity of the reaction, treatment with Tecentriq should be withheld for Grades 2 or 3 immune-related adverse reactions and corticosteroid therapy (1-2 mg/kg/day prednisone or equivalent) should be initiated. If symptoms improve to ≤ Grade 1, taper corticosteroids as clinically indicated. Treatment with Tecentriq may be resumed if the event improves to ≤ Grade 1 within 12 weeks, and corticosteroids have been reduced to ≤10 mg oral prednisone or equivalent per day.
Treatment with Tecentriq should be permanently discontinued for Grade 4 immune-related adverse reactions, or when unable to reduce corticosteroid dose to the equivalent for ≤10 mg prednisone per day within 12 weeks after onset.
Special Dosage Instructions: Pediatric use: The safety and efficacy of Tecentriq in children and adolescents below 18 years of age have not been established.
Geriatric use: Based on a population pharmacokinetic analysis, no dose adjustment of Tecentriq is required in patients ≥ 65 years of age (see Geriatric Use under Precautions, and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Renal impairment: Based on a population pharmacokinetic analysis, no dose adjustment is required in patients with renal impairment (see Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Hepatic impairment: Based on a population pharmacokinetic analysis, no dose adjustment is required for patients with mild hepatic impairment. There are no data in patients with moderate or severe hepatic impairment (see Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Overdosage
There is no information on overdose with Tecentriq.
Contraindications
Tecentriq is contraindicated in patients with a known hypersensitivity to atezolizumab or any of the excipients.
Special Precautions
General: In order to improve the traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded (or stated) in the patient file.
Immune-related pneumonitis: Cases of pneumonitis, including fatal cases, have been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for signs and symptoms of pneumonitis. Refer to Dosage & Administration for recommended dose modifications.
Immune-related hepatitis: Cases of hepatitis, some leading to fatal outcomes, have been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for signs and symptoms of hepatitis. Monitor aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin prior to and periodically during treatment with Tecentriq. Consider appropriate management of patients with abnormal liver function tests (LFTs) at baseline. Refer to Dosage & Administration for recommended dose modifications.
Immune-related colitis: Cases of diarrhea or colitis have been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for signs and symptoms of colitis. Refer to Dosage & Administration for recommended dose modifications.
Immune-related endocrinopathies: Hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, and type 1 diabetes mellitus, including diabetic ketoacidosis, have been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for clinical signs and symptoms of endocrinopathies. Monitor thyroid function prior to and periodically during treatment with Tecentriq. Consider appropriate management of patients with abnormal thyroid function tests at baseline. Patients with abnormal thyroid function tests who are asymptomatic may receive Tecentiq. Refer to Dosage & Administration for recommended dose modifications.
Immune-related meningoencephalitis: Meningoencephalitis has been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for clinical signs and symptoms of meningitis or encephalitis. Refer to section 2.2 Dosage and Administration for recommended dose modifications.
Immune-related neuropathies: Myasthenic syndrome/myasthenia gravis or Guillain-Barre syndrome, which may be life threatening, were observed in patients receiving Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for symptoms of motor and sensory neuropathy. Refer to Dosage & Administration for recommended dose modifications.
Immune-related pancreatitis: Pancreatitis, including increases in serum amylase and lipase levels, has been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be closely monitored for signs and symptoms that are suggestive of acute pancreatitis. Refer to Dosage & Administration for recommended dose modifications.
Immune-related myocarditis: Myocarditis has been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for signs and symptoms of myocarditis. Refer to Dosage & Administration for recommended dose modifications.
Immune-related myositis: Cases of myositis, including fatal cases, have been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for signs and symptoms of myositis. Refer to Dosage & Administration for recommended dose modifications.
Immune-related nephritis: Nephritis has been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for changes in renal function. Refer to Dosage & Administration for recommended dose modifications.
Infusion related reactions: Infusion related reactions (IRRs) have been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Refer to Dosage & Administration for recommended dose modifications.
Special populations: Patients with autoimmune disease were excluded from clinical trials with Tecentriq. In the absence of data, Tecentriq should be used with caution in patients with autoimmune disease, after assessment of the potential risk-benefit.
Embryofetal toxicity: Based on the mechanism of action, the use of Tecentriq may cause fetal harm. 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.
Pregnant women should be advised of the potential risk to the fetus. Women of childbearing potential should be advised to use highly effective contraception during treatment with Tecentriq and for 5 months after the last dose (see Females and Males of Reproductive Potential under Use in Pregnancy & Lactation and Pharmacology: Toxicology: Reproductive Toxicity under Actions).
Drug Abuse and Dependence: No data to report.
Ability to Drive and Use Machines: No studies on the effects on the ability to drive and to use machines have been performed.
Renal Impairment: See Special Dosage Instructions under Dosage & Administration, and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.
Hepatic Impairment: See Special Dosage Instructions under Dosage & Administration, and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.
Use in Children: The safety and efficacy of Tecentriq in children and adolescents below 18 years of age has not been established.
Use in Elderly: No overall differences in safety or efficacy were observed between patients ≥ 65 years of age and younger patients (see Special Dosage Instructions under Dosage & Administration, and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Use In Pregnancy & Lactation
Females and Males of Reproductive Potential: Fertility: Based on animal studies, Tecentriq may impair fertility in females of reproductive potential while receiving treatment (see Pharmacology: Toxicology: Impairment of Fertility under Actions).
Contraception: Female patients of childbearing potential should use highly effective contraception and take active measures to avoid pregnancy while undergoing Tecentriq treatment and for at least 5 months after the last dose (see General under Precautions, and Pharmacology: Toxicology: Reproductive Toxicity under Actions).
Pregnancy: There are no clinical studies of Tecentriq in pregnant women. Tecentriq is not recommended during pregnancy unless the potential benefit for the mother outweighs the potential risk to the fetus (see Pharmacology: Toxicology: Reproductive Toxicity under Actions).
Labor and Delivery: The use of Tecentriq during labor and delivery has not been established.
Lactation: It is not known whether Tecentriq is excreted in human breast milk. No studies have been conducted to assess the impact of Tecentriq on milk production or its presence in breast milk. As the potential for harm to the nursing infant is unknown, a decision must be made to either discontinue breast-feeding or discontinue Tecentriq therapy.
Adverse Reactions
Clinical Trials: The corresponding frequency category for each adverse drug reaction is based on the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). The safety of Tecentriq is based on pooled data in 3178 patients with multiple tumor type, with supporting data from the estimated cumulative exposure in >13000 patients across all clinical trials. Table 3 summarizes the adverse drug reactions (ADRs) that have been reported in association with the use of Tecentriq. (See Table 3.)

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Additional information for selected adverse reactions: The data below reflect information for significant adverse reactions for Tecentriq. See General under Precautions, for management of the following: Immune-related pneumonitis Pneumonitis occurred in 2.7% (87/3178) of patients who received Tecentriq. Of the 87 patients, one event was fatal. The median time to onset was 3.4 months (range: 0.1 to 24.8 months). The median duration was 1.4 months (range 0 to 21.2+ months; + denotes a censored value). Pneumonitis led to discontinuation of Tecentriq in 12 (0.4%) patients. Pneumonitis requiring the use of corticosteroids occurred in 1.6% (51/3178) of patients receiving Tecentriq.
Immune-related hepatitis: Hepatitis occurred in 2.0% (62/3178) of patients who received Tecentriq. Of the 62 patients, two events were fatal. The median time to onset was 1.5 months (range 0.2 to 18.8 months). The median duration was 2.1 months (range 0 to 22.0+ months; + denotes a censored value). Hepatitis led to discontinuation of Tecentriq in 6 (0.2%) patients. Hepatitis requiring the use of corticosteroids occurred in 0.6% (18/3178) of patients receiving Tecentriq.
Immune-related colitis: Colitis occurred in 1.1% (34/3178) of patients who received Tecentriq. The median time to onset was 4.7 months (range 0.5 to 17.2 months). The median duration was 1.2 months (range: 0.1 to 17.8+ months; + denotes a censored value). Colitis led to discontinuation of Tecentriq in 8 (0.3%) patients. Colitis requiring the use of corticosteroids occurred in 0.6% (19/3178) of patients receiving Tecentriq.
Immune-related endocrinopathies: Thyroid Disorders: Hypothyroidism occurred in 5.2% (164/3178) of patients who received Tecentriq. The median time to onset was 4.9 months (range 0 to 31.3 months).
Hyperthyroidism occurred in 0.9% (30/3178) of patients who received Tecentriq. The median time to onset was 2.1 months (range 0.7 to 15.7 months). The median duration was 2.6 months (range: 0+ to 17.1+ months: + denotes a censored value).
Adrenal Insufficiency: Adrenal insufficiency occurred in 0.4% (11/3178) of patients who received Tecentriq. The median time to onset was 5.5 months (range: 0.1 to 19.0 months). The median duration was 16.8 months (range: 0 to 16.8 months). Adrenal insufficiency led to discontinuation of Tecentriq in 1 (<0.1%) patient. Adrenal insufficiency requiring the use of corticosteroids occurred in 0.3% (9/3178) of patients receiving Tecentriq.
Hypophysitis: Hypophysitis occurred in <0.1% (2/3178) of patients who received Tecentriq. The median time to onset was 7.2 months (range: 0.8 to 13.7 months). One patient required the use of corticosteroids and treatment with Tecentriq was discontinued.
Diabetes Mellitus: Diabetes mellitus occurred in 0.3% (10/3178) of patients who received Tecentriq. The median time to onset was 4.2 months (range 0.1 to 9.9 months). The median duration was 1.6 months (range: 0.1 to 15.2+ months; + denotes a censored value). Diabetes mellitus led to the discontinuation of Tecentriq in 3 (<0.1%) patients.
Immune-related meningoencephalitis: Meningoencephalitis occurred in 0.4% (14/3178) of patients who received Tecentriq. The median time to onset was 0.5 months (range 0 to 12.5 months). The median duration was 0.7 months (range 0.2 to 14.5+ months; + denotes a censored value). Meningoencephalitis requiring the use of corticosteroids occurred in 0.2% (6/3178) of patients receiving Tecentriq and led to discontinuation of Tecentriq in 4 (0.1%) patients.
Immune-related neuropathies: Neuropathies, including Guillain-Barré syndrome and demyelinating polyneuropathy, occurred in 0.2% (5/3178) of patients who received Tecentriq. The median time to onset was 7.0 months (range: 0.6 to 8.1 months). The median duration was 8.0 months (0.6 to 8.3+ months; + denotes a censored value). Guillain-Barre syndrome led to the discontinuation of Tecentriq in 1 (<0.1%) patient. Guillain-Barre syndrome requiring the use of corticosteroids occurred in <0.1% (2/3178) of patients receiving Tecentriq.
Immune-related pancreatitis: Pancreatitis, including amylase increased and lipase increased, occurred in 0.6% (18/3178) of patients who received Tecentriq. The median time to onset was 5.0 months (range: 0.3 to 16.9 months). The median duration was 0.8 months (range 0.1 to 12.0+ months; + denotes a censored value). Pancreatitis led to the discontinuation of Tecentriq in 3 (<0.1%) patients. Pancreatitis requiring the use of corticosteroids occurred in 0.1% (4/3178) of patients receiving Tecentriq.
Immune-related myositis: Myositis occurred in 0.4% (13/3178) of patients who received Tecentriq monotherapy. The median time to onset was 5.1 months (range: 0.7 to 11.0 months). The median duration was 5.0 months (range 0.7 to 22.6+ months, + denotes a censored value). Myositis led to discontinuation of Tecentriq in 1 (<0.1%) patient. Myositis requiring the use of corticosteroids occurred in 0.2% (7/3178) of patients receiving Tecentriq.
Immune-related nephritis: Nephritis, occurred in <0.1% (3/3178) of patients who received Tecentriq. The median time to onset was 13.1 months (range: 9.0 to 17.5 months). The median duration was 2.8 days (range 0.5 to 9.5+ months; + denotes a censored value). Nephritis led to discontinuation of Tecentriq in 2 (<0.1%) patients. One patient required the use of corticosteroids.
Postmarketing Experience: No new adverse drug reactions have been identified from postmarketing experience.
Drug Interactions
No formal pharmacokinetic drug-drug interaction studies have been conducted with atezolizumab. Since atezolizumab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected.
Caution For Usage
Special Instructions for Use, Handling and Disposal: Instructions for dilution: Tecentriq should be prepared by a healthcare professional using aseptic technique. Withdraw the required volume of Tecentriq liquid concentrate from the vial and dilute to the required administration volume with 0.9% sodium chloride solution. Dilute with 0.9% Sodium Chloride Injection only.
This medicinal product must not be mixed with other medicinal products.
No preservative is used in Tecentriq therefore each vial is for single use only. Discard any unused portion.
Incompatibilities: No incompatibilities have been observed between Tecentriq and IV bags with product-contacting surfaces of polyvinyl chloride (PVC), polyethylene (PE) or polyolefin bags. In addition, no incompatibilities have been observed with in-line filter membranes composed of polyethersulfone or polysulfone, and infusion sets and other infusion aids composed of PVC, PE, polybutadiene, or polyetherurethane.
Disposal of unused/expired medicines: The release of pharmaceuticals in the environment should be minimized. Medicines should not be disposed of via wastewater and disposal through household waste should be avoided. Use established "collection systems", if available in the location.
Storage
Vials: Store at 2°C to 8°C.
Tecentriq should be protected from light.
Do not freeze. Do not shake.
Shelf-Life: 3 years.
The diluted solution for infusion should be used immediately. If the solution is not used immediately, it can be stored for up to 24 hours at 2°C to 8°C, or 8 hours at ambient temperature (≤30°C).
ATC Classification
L01XC32 - atezolizumab ; Belongs to the class of monoclonal antibodies, other antineoplastic agents. Used in the treatment of cancer.
Presentation/Packing
Soln for infusion (single-use vial; preservative-free, colorless to slightly yellow solution) 1,200 mg/20 mL x 1's.
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