Atezolizumab and hyaluronidase (human recombinant)
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Specialty pharmacy: therapy management checklist, storage and cold chain, dosing calendar, Medicare Part D coverage.
Endoglycosidase, Programmed Death Receptor-1 Blocking Antibody
Dosing in kidney impairment
4 CONTRAINDICATIONS TECENTRIQ HYBREZA is contraindicated in patients with known hypersensitivity to hyaluronidase or to any of its excipients. TECENTRIQ HYBREZA is contraindicated in patients with known hypersensitivity to hyaluronidase or any of its excipients. 5 WARNINGS AND PRECAUTIONS Immune-Mediated Adverse Reactions Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, and solid organ transplant rejection.
Immune-Mediated Endocrinopathies Adrenal Insufficiency: TECENTRIQ HYBREZA can cause primary or secondary adrenal insufficiency, including Grade 3 adverse reactions. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold or permanently discontinue TECENTRIQ HYBREZA depending on severity [see Dosage and Administration ] .
Immune-mediated adrenal insufficiency occurred in 0.8% (2/247) of patients with locally advanced or metastatic NSCLC receiving TECENTRIQ HYBREZA as monotherapy in the IMscin001 trial [see Adverse Reactions ] , including Grade 2 (0.4%) adverse reactions. Adrenal insufficiency led to the withholding of TECENTRIQ HYBREZA in both patients.
Systemic corticosteroids were required in 50% (1/2) of patients with adrenal insufficiency who received TECENTRIQ HYBREZA as monotherapy; this single patient remained on systemic corticosteroids. Hypophysitis: TECENTRIQ HYBREZA can cause immune-mediated hypophysitis, including Grade 2 adverse reactions. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts.
Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue TECENTRIQ HYBREZA depending on severity [see Dosage and Administration ] . Immune-Mediated Nephritis with Renal Dysfunction TECENTRIQ HYBREZA can cause immune-mediated nephritis, including Grade 3 adverse reactions. Intravenous Atezolizumab in Combination with Cobimetinib and Vemurafenib: Immune-mediated nephritis with renal dysfunction occurred in 1.3% (3/230) of patients receiving intravenous atezolizumab in combination with cobimetinib and vemurafenib in the IMspire150 trial [see Adverse Reactions ], including Grade 2 (1.3%) adverse reactions.
Gastrointestinal : Pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis. Musculoskeletal and Connective Tissue : Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic. Endocrine : Hypoparathyroidism. Hematologic/Immune : Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection.
| Adverse Reaction | SeverityBased on Common Terminology Criteria for Adverse Events (CTCAE), version 5 | Dosage Modification |
|---|---|---|
| ALT = alanine aminotransferase, AST = aspartate aminotransferase, ULN = upper limit normal, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson syndrome, TEN = toxic epidermal necrolysis | ||
| Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1)] | ||
| Pneumonitis | Grade 2 | WithholdResume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating steroids |
| Grades 3 or 4 | Permanently discontinue | |
| Colitis | Grades 2 or 3 | Withhold |
| Grade 4 | Permanently discontinue | |
| Hepatitis with no tumor involvement of the liver | AST or ALT increases to more than 3 and up to 8 times ULN or Total bilirubin increases to more than 1.5 and up to 3 times ULN | Withhold |
| AST or ALT increases to more than 8 times ULN or Total bilirubin increases to more than 3 times ULN | Permanently discontinue | |
| Hepatitis with tumor involvement of the liverIf AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue TECENTRIQ HYBREZA based on recommendations for hepatitis with no liver involvement | Baseline AST or ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULN or Baseline AST or ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN | Withhold |
| AST or ALT increases to more than 10 times ULN or Total bilirubin increases to more than 3 times ULN | Permanently discontinue | |
| Endocrinopathies | Grades 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity |
| Nephritis with Renal Dysfunction | Grades 2 or 3 increased blood creatinine | Withhold |
| Grade 4 increased blood creatinine | Permanently discontinue | |
| Exfoliative Dermatologic Conditions | Suspected SJS, TEN, or DRESS | Withhold |
| Confirmed SJS, TEN, or DRESS | Permanently discontinue | |
| Myocarditis or pericarditis | Grades 2, 3, or 4 | Permanently discontinue |
| Neurological Toxicities | Grade 2 | Withhold |
| Grades 3 or 4 | Permanently discontinue | |
| Other Adverse Reactions | ||
| Infusion-Related Reactions [see Warnings and Precautions (5.2)] | Grades 1 or 2 | Pause or slow the rate of injection Premedication with antipyretic and antihistamines may be considered for subsequent doses. |
| Grades 3 or 4 | Permanently discontinue | |
Preparation and administration
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Important Dosage and Administration Information TECENTRIQ HYBREZA has different recommended dosage and administration than intravenous atezolizumab products. To reduce the risk of medication errors, prior to administration, check the vial labels to ensure that the drug being prepared is subcutaneously administered TECENTRIQ HYBREZA and not intravenously administered atezolizumab.
Do not substitute TECENTRIQ HYBREZA for or with intravenous atezolizumab products because they have different recommended dosages. Adult patients who are treated with intravenous atezolizumab can switch to subcutaneous TECENTRIQ HYBREZA at their next scheduled dose. Adult patients who are treated with TECENTRIQ HYBREZA can switch to intravenous atezolizumab at their next scheduled dose.
Pediatric patients 12 years of age and older who weigh 40 kg or greater and are treated with intravenous atezolizumab can switch to subcutaneous TECENTRIQ HYBREZA at their next scheduled dose [see Indications and Usage ]. Pediatric patients who are treated with TECENTRIQ HYBREZA can switch to intravenous atezolizumab at their next scheduled dose.
TECENTRIQ HYBREZA is for subcutaneous use in the thigh only. Administer over approximately 7 minutes. Inject in healthy skin and never into areas where the skin is red, bruised, tender, or hard. When possible, alternate injections between the left and right thigh. Ensure the injection site is at least 2.5 cm from the previous site.
Do not administer TECENTRIQ HYBREZA intravenously. TECENTRIQ HYBREZA must be administered by a healthcare professional. Do not administer the remaining volume in the tubing to the patient. If using concomitant subcutaneous drugs, administer at sites other than the thighs.
Recommended Dosage and Administration Instructions The recommended dosage of TECENTRIQ HYBREZA in adult patients and pediatric patients (12 years of age and older who weigh 40 kg or greater) is one 15 mL injection (containing 1,875 mg of atezolizumab and 30,000 units of hyaluronidase, referred to as TECENTRIQ HYBREZA) administered subcutaneously in the thigh over approximately 7 minutes every 3 weeks.
The recommended dosage for pediatric patients 12 years of age and older who weigh less than 40 kg has not been established [see Use in Specific Populations , Clinical Pharmacology ]. Administration instructions for TECENTRIQ HYBREZA as monotherapy and in combination with other therapeutic agents are presented in Table 1 .
For the recommended dosage of each therapeutic agent administered in combination with TECENTRIQ HYBREZA refer to the product's respective Prescribing Information. [See table below.] Metastatic Non-Small Cell Lung Cancer Until disease progression or unacceptable toxicity Non-Small Cell Lung Cancer Administer TECENTRIQ HYBREZA prior to chemotherapy and bevacizumab when given on the same day.
Until disease progression or unacceptable toxicity Small Cell Lung Cancer Administer TECENTRIQ HYBREZA prior to chemotherapy when given on the same day. Hepatocellular Carcinoma Administer TECENTRIQ HYBREZA prior to bevacizumab when given on the same day. Bevacizumab is administered intravenously at 15 mg/kg every 3 weeks.
Melanoma Prior to initiating TECENTRIQ HYBREZA, patients should receive the following 28-day treatment cycle of cobimetinib and vemurafenib: Days 1 to 21: cobimetinib 60 mg orally once daily in combination with 960 mg of oral vemurafenib twice daily Days 22 to 28: withhold cobimetinib and administer vemurafenib 720 mg orally twice daily Alveolar Soft Part Sarcoma Administer TECENTRIQ HYBREZA as monotherapy Until disease progression or unacceptable toxicity Muscle Invasive Bladder Cancer Administer TECENTRIQ HYBREZA as monotherapy Up to one year, unless there is disease recurrence or unacceptable toxicity
Preparation Instructions TECENTRIQ HYBREZA does not contain any antimicrobial preservative. If the TECENTRIQ HYBREZA dose is not administered immediately, refer to "Storage Instructions" [see Dosage and Administration ]. Remove the vial from the refrigerator and allow the solution to acclimate to room temperature. Visually inspect for particulate matter and discoloration prior to administration.
Discard the vial if the solution is cloudy, discolored, or visible particles are observed. Do not shake, freeze, or dilute. The unpunctured vial may be stored at room temperature in ambient light for a maximum of 4 hours prior to the preparation for administration. Use an 18-gauge transfer needle and syringe to withdraw the entire contents of the TECENTRIQ HYBREZA solution from the vial.
Discard the vial and any residual drug remaining. TECENTRIQ HYBREZA is compatible with stainless steel transfer and injection needles, and polypropylene, polycarbonate, polyvinyl chloride, and polyurethane syringe material and subcutaneous administration sets. Remove the transfer needle from the syringe and replace it with a subcutaneous administration set (e.g. winged/butterfly) containing 23-gauge, 24-gauge, or 25-gauge hypodermic needle and with a priming volume that does not exceed 0.5 mL for administration.
Prime the subcutaneous administration line with TECENTRIQ HYBREZA to eliminate the air in the line and stop when the fluid reaches the needle. Ensure the syringe contains exactly 15 mL of TECENTRIQ HYBREZA after priming the administration line by expelling any excess volume from the syringe. Administer immediately to avoid needle clogging.
Discard any unused portion remaining.
Storage Instructions Do not store the prepared syringe that has been attached to the already-primed subcutaneous administration set. If the prepared syringe containing TECENTRIQ HYBREZA is not for immediate use, do not attach a subcutaneous administration set. The capped syringe may be stored at room temperature [at up to 25°C (77°F)] in ambient room lighting for up to 8 hours and in the refrigerator [2°C to 8°C (36°F to 46°F)] for up to 72 hours.
Do not shake or freeze. If the prepared syringe is stored at 2°C to 8°C (36°F to 46°F), allow the syringe to acclimate to room temperature prior to administration.
| Adverse Reaction | SeverityBased on Common Terminology Criteria for Adverse Events (CTCAE), version 5 | Dosage Modification |
|---|---|---|
| ALT = alanine aminotransferase, AST = aspartate aminotransferase, ULN = upper limit normal, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson syndrome, TEN = toxic epidermal necrolysis | ||
| Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1)] | ||
| Pneumonitis | Grade 2 | WithholdResume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating steroids |
| Grades 3 or 4 | Permanently discontinue | |
| Colitis | Grades 2 or 3 | Withhold |
| Grade 4 | Permanently discontinue | |
| Hepatitis with no tumor involvement of the liver | AST or ALT increases to more than 3 and up to 8 times ULN or Total bilirubin increases to more than 1.5 and up to 3 times ULN | Withhold |
| AST or ALT increases to more than 8 times ULN or Total bilirubin increases to more than 3 times ULN | Permanently discontinue | |
| Hepatitis with tumor involvement of the liverIf AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue TECENTRIQ HYBREZA based on recommendations for hepatitis with no liver involvement | Baseline AST or ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULN or Baseline AST or ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN | Withhold |
| AST or ALT increases to more than 10 times ULN or Total bilirubin increases to more than 3 times ULN | Permanently discontinue | |
| Endocrinopathies | Grades 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity |
| Nephritis with Renal Dysfunction | Grades 2 or 3 increased blood creatinine | Withhold |
| Grade 4 increased blood creatinine | Permanently discontinue | |
| Exfoliative Dermatologic Conditions | Suspected SJS, TEN, or DRESS | Withhold |
| Confirmed SJS, TEN, or DRESS | Permanently discontinue | |
| Myocarditis or pericarditis | Grades 2, 3, or 4 | Permanently discontinue |
| Neurological Toxicities | Grade 2 | Withhold |
| Grades 3 or 4 | Permanently discontinue | |
| Other Adverse Reactions | ||
| Infusion-Related Reactions [see Warnings and Precautions (5.2)] | Grades 1 or 2 | Pause or slow the rate of injection Premedication with antipyretic and antihistamines may be considered for subsequent doses. |
| Grades 3 or 4 | Permanently discontinue | |
Drug interactions
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- Atezolizumab and hyaluronidase (human recombinant)
Contraindications
4 CONTRAINDICATIONS TECENTRIQ HYBREZA is contraindicated in patients with known hypersensitivity to hyaluronidase or to any of its excipients. TECENTRIQ HYBREZA is contraindicated in patients with known hypersensitivity to hyaluronidase or any of its excipients. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for atezolizumab and hyaluronidase (human recombinant). Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on its mechanism of action [see Clinical Pharmacology (12.1) ] , TECENTRIQ HYBREZA can cause fetal harm when administered to a pregnant woman . There are no available data on the use of TECENTRIQ HYBREZA 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 ) . Advise females of reproductive potential of the potential risk to a fetus [see Warnings and Precautions (5.4) ] . 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. Data Animal Data: TECENTRIQ HYBREZA for subcutaneous injection contains atezolizumab and hyaluronidase [see Description (11) ] . Atezolizumab : Animal reproduction studies have not been conducted with atezolizumab to evaluate its effect on reproduction and fetal development. A literature-based assessment of the effects on reproduction demonstrated that a central function of the PD-L1/PD-1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to a fetus.
Blockage of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to a fetus and to result in an increase in fetal loss; therefore, potential risks of administering atezolizumab during pregnancy include increased rates of abortion or stillbirth. As reported in the literature, there were no malformations related to the blockade of PD-L1/PD-1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 and PD-L1 knockout mice. Based on its mechanism of action, fetal exposure to atezolizumab may increase the risk of developing immune-mediated disorders or altering the normal immune response.
Hyaluronidase : In an embryo-fetal study, mice were dosed daily by subcutaneous injection during the period of organogenesis with hyaluronidase (recombinant human) at dose levels up to 2,200,000 U/kg, which is > 2,400 times higher than the human dose. The study found no evidence of teratogenicity. Reduced fetal weight and increased numbers of fetal resorptions were observed, with no effects found at a daily dose of 360,000 U/kg, which is > 400 times higher than the human dose.
In a peri-and post-natal reproduction study, mice have been dosed daily by subcutaneous injection, with hyaluronidase (recombinant human) from implantation through lactation and weaning at dose levels up to 1,100,000 U/kg, which is >…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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