(a te zoe LIZ ue mab)
Urothelial carcinoma, locally advanced or metastatic: Treatment of locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
There are no contraindications listed in the manufacturers labeling.
Urothelial carcinoma, locally advanced or metastatic: IV: 1,200 mg every 3 weeks (Rosenberg 2016); continue until disease progression or unacceptable toxicity
Refer to adult dosing.
No dosage adjustment is necessary.
Hepatic impairment prior to treatment:
Mild impairment (bilirubin ≤ upper limit of normal (ULN) and AST > ULN or bilirubin <1 times ULN and any AST): No dosage adjustment is necessary.
Moderate to severe impairment (bilirubin > ULN and AST > ULN or bilirubin ≥1 to 1.5 times ULN and any AST): There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied).
Hepatotoxicity during treatment:
AST or ALT >3 to 5 times ULN or total bilirubin >1.5 to 3 times ULN: Withhold treatment.
AST or ALT >5 times ULN or total bilirubin >3 times ULN: Discontinue permanently.
Immune-mediated hepatitis:
Grade 2 or greater transaminase elevations (with or without total bilirubin elevations): Withhold treatment and initiate high-dose systemic corticosteroids (prednisone 1 to 2 mg/kg daily or equivalent, followed by a taper)
Severe (grade 3) or life-threatening (grade 4): Permanently discontinue treatment and initiate high-dose systemic corticosteroids (prednisone 1 to 2 mg/kg daily or equivalent, followed by a taper)
Withdraw 1,200 mg (20 mL) from vial and dilute into 250 mL of sodium chloride 0.9% (NS) in a polyvinyl chloride (PVC), polyethylene (PE), or polyolefin (PO) infusion bag. Dilute only with NS. Mix by gently inverting; do not shake.
IV: Infuse the initial dose over 60 minutes, if tolerated, may infuse subsequent doses over 30 minutes. May be infused with or without a 0.2- to 0.22-micron sterile, non-pyrogenic, low-protein binding in-line filter. Do not administer as an IV push or bolus. Do not administer other medications at the same time through the same IV line. Monitor for infusion reactions.
Store intact vials at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F). Do not freeze. Do not shake. Store in original carton to protect from light. Solutions diluted in NS for infusion should be used immediately after preparation; if not used immediately, may be stored for up to 6 hours (including administration time) at room temperature or 24 hours refrigerated at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F). Do not freeze.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Tecentriq: 1200 mg/20 mL (20 mL)
Compatible in NS.
Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid combination
Monitor liver function tests (at baseline and periodically during treatment), thyroid function (prior to and periodically during treatment), serum glucose. Monitor for signs/symptoms of colitis, diarrhea, endocrinopathies, hepatitis, hypophysitis, infection, infusion reactions, meningitis and encephalitis, neuropathy (motor and sensory), pancreatitis (acute), rash, and pneumonitis.
>10%:
Cardiovascular: Peripheral edema (18%)
Central nervous system: Fatigue (52%)
Dermatologic: Skin rash (15%; grades 3/4: <1%), pruritus (13%)
Endocrine & metabolic: Hyponatremia
Gastrointestinal: Decreased appetite (26%), nausea (25%), constipation (21%), colitis (19% to 20%), diarrhea (18% to 20%; grades 3/4: 2%), abdominal pain (17%), vomiting (17%)
Genitourinary: Urinary tract infection (22%; grades 3/4: 9%), hematuria (14%)
Hematologic & oncologic: Lymphocytopenia
Infection: Infection (38%; grades 3/4: 12%)
Neuromuscular & skeletal: Back pain ( ≤15%), neck pain ( ≤15%), arthralgia (14%)
Respiratory: Dyspnea (16%), cough (14%)
Miscellaneous: Fever (21%)
1% to 10%:
Cardiovascular: Venous thromboembolism
Central nervous system: Guillain-Barre syndrome ( ≤1%), meningoencephalitis ( ≤1%), myasthenia ( ≤1%), myasthenia gravis ( ≤1%), confusion
Endocrine & metabolic: Hyperglycemia (grades 3/4: 5%), hypothyroidism (3% to 4%; grade 1/2: 2%; grade 3: <1%), hypoalbuminemia, hyperthyroidism ( ≤1%)
Gastrointestinal: Increased serum amylase ( ≤1%), increased serum lipase ( ≤1%), pancreatitis ( ≤1%), intestinal obstruction
Genitourinary: Urinary tract obstruction
Hematologic & oncologic: Anemia
Hepatic: Increased serum ALT (grades 3/4: 2% to 3%), increased serum AST (grades 3/4: 2% to 3%), hepatitis (1%), increased serum alkaline phosphatase, serum bilirubin
Infection: Sepsis
Ophthalmic: Intraocular inflammation ( ≤1%)
Renal: Increased serum creatinine (grades 3/4: 3%), acute renal failure
Respiratory: Pneumonitis (1% to 3%), pneumonia
Miscellaneous: Infusion related reaction (severe: 1% to 2%)
<1% (Limited to important or life-threatening): Adrenocortical insufficiency, diabetes mellitus (with ketoacidosis), hypophysitis
Concerns related to adverse effects:
- Adrenal insufficiency: Grades 1 to 3 adrenal insufficiency have been reported. For symptomatic adrenal insufficiency, withhold atezolizumab treatment and administer IV methylprednisolone 1 to 2 mg/kg/day and convert to oral prednisone 1 to 2 mg/kg/day or equivalent upon improvement in symptoms. When symptoms improve to grade 1 or lower, begin to taper steroids over at least 1 month. Resume atezolizumab treatment if symptoms improves to grade 0 or 1 within 12 weeks and corticosteroids have been reduced to oral prednisone ≤10 mg/day and patient is stable on adrenal replacement therapy (if needed).
- Diabetes mellitus: New-onset diabetes with ketoacidosis has been observed with atezolizumab. For type 1 diabetes, initiate insulin treatment. For grade 3 or higher hyperglycemia (fasting blood glucose >250 to 500 mg/dL), withhold atezolizumab; resume when metabolic control is achieved on insulin therapy.
- Gastrointestinal toxicity: Immune-mediated colitis or diarrhea (defined as requiring corticosteroids and with no clear alternative etiology) has occurred in nearly one-fifth of patients receiving atezolizumab, some events included grade 3 and 4 diarrhea. The median onset for some patients was 1.7 months (range: ~1 to 3 months). Monitor for signs/symptoms of colitis and diarrhea. Withhold treatment for grade 2 or 3 diarrhea or colitis. For grade 2 diarrhea or colitis, if symptoms persist for >5 days or recur, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone equivalent). For grade 3 diarrhea or colitis, administer IV methylprednisolone 1 to 2 mg/kg/day and convert to oral corticosteroids upon improvement in symptoms. If grade 2 and 3 symptoms improve to grade 0 or 1, taper corticosteroids over at least 1 month. Resume atezolizumab treatment if improves to grade 0 or 1 within 12 weeks and corticosteroids have been reduced to oral prednisone ≤10 mg/day. Discontinue permanently for grade 4 diarrhea or colitis. Pancreatitis, increases in amylase and lipase levels, and symptomatic pancreatitis (without other etiology) have occurred with atezolizumab. Monitor for signs/symptoms of acute pancreatitis. Discontinue permanently for grade 4 or any grade recurrent pancreatitis. Withhold treatment for grade 3 or higher serum amylase or lipase increases, or for grade 2 or 3 pancreatitis. Administer IV methylprednisolone 1 to 2 mg/kg/day and convert to oral corticosteroids (prednisone 1 to 2 mg/kg/day or equivalent) upon improvement in symptoms. Resume atezolizumab if amylase and lipase levels improve to grade 1 or lower within 12 weeks, pancreatitis symptoms have resolved, and corticosteroids have been reduced to oral prednisone ≤10 mg/day.
- Hepatotoxicity: Immune-mediated hepatitis (defined as requiring corticosteroids and with no clear alternative etiology), including fatal cases, has occurred with atezolizumab. Liver test abnormalities have been reported, including grade 3 and 4 events. The median time to onset was 1.1 months (range: 0.4 to 7.7 months). Monitor for signs/symptoms of hepatitis; monitor liver function tests. Administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) followed by a taper for grade 2 or higher transaminase elevations (with or without elevated bilirubin). Withhold treatment until resolution for grade 2 and permanently discontinue for grade 3 or 4 immune-mediated hepatitis. Some patients with treatment interruption for immune-mediated hepatitis did not have recurrence upon resuming treatment.
- Hypophysitis: Hypophysitis has occurred in patients receiving atezolizumab (rare). Monitor for signs/symptoms of hypophysitis. Administer corticosteroids and hormone replacement as indicated. Withhold treatment for grade 2 or 3 hypophysitis; discontinue permanently for grade 4 hypophysitis.
- Infection: Infections occurred in over 1/3 of patients receiving atezolizumab. Grade 3 and 4 infections have occurred, with urinary tract infection being the most common cause of grade 3 or higher infection. There have been case reports of fatal infections. Serious infections, including sepsis, herpes encephalitis, and mycobacterial infection leading to retroperitoneal hemorrhage have been reported. Monitor for signs/symptoms of infection. Manage suspected and confirmed infections with antibiotics. Withhold treatment for grade 3 or higher infections.
- Infusion-related reactions: Severe infusion reactions have been reported in clinical trials. Interrupt or slow the infusion rate in patients with mild to moderate infusion reactions. Permanently discontinue for grade 3 or 4 infusion reactions.
- Pulmonary toxicity: Immune-mediated pneumonitis and interstitial lung disease (defined as requiring corticosteroids and with no clear alternative etiology), including fatal cases, have been reported in patients receiving atezolizumab. The median time to onset was 2.6 months (range: 0.5 to 4.2 months) and the median duration was 15 days (range: 6 days to >3 months). Monitor for signs (with radiographic imaging) and symptoms of pneumonitis. Administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) followed by a taper for grade 2 or higher pneumonitis. Withhold treatment until resolution for grade 2 pneumonitis; permanently discontinue for grade 3 or 4 pneumonitis.
- Thyroid disorders: Hypothyroidism occurred in patients who received atezolizumab (including grades 1, 2, and 3 events), with a median time to first onset of 5.4 months (range: 21 days to 11.3 months). Hyperthyroidism was also reported, including grades 1 and 2 events, with a median onset of 3.2 months (range: 1.4 to 5.8 months). Monitor thyroid function prior to and periodically during treatment. Patients with abnormal thyroid function tests who are asymptomatic can receive atezolizumab treatment. For symptomatic hypothyroidism, withhold atezolizumab treatment and initiate thyroid replacement therapy as needed. Isolated hypothyroidism should be managed with replacement therapy and without corticosteroids. For symptomatic hyperthyroidism, withhold atezolizumab and initiate antithyroid medications as needed. Resume atezolizumab treatment when symptoms of hypo- or hyperthyroidism are controlled and thyroid function is improving.
- Other immune-mediated toxicities: Other immune-mediated adverse events have occurred, including meningoencephalitis, myasthenic syndrome/myasthenia gravis, Guillain-Barre syndrome, and ocular inflammatory toxicity. Monitor for clinical signs/symptoms of meningitis and encephalitis; discontinue permanently for any grade meningitis or encephalitis; administer IV corticosteroids (methylprednisolone 1 to 2 mg/kg/day) and convert to oral therapy (prednisone 60 mg/day or equivalent) upon improvement; when symptoms improve to grade 1 or lower, taper corticosteroids over at least 1 month. Monitor for neuropathy (motor and sensory); permanently discontinue for any grade myasthenic syndrome/myasthenia gravis or Guillain-Barre syndrome and begin appropriate medical management; consider systemic corticosteroids (prednisone 1 to 2 mg/kg/day).
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Adverse events were observed in animal reproduction studies. Based on the mechanism of action, atezolizumab is expected to cause fetal harm if used during pregnancy. Women of reproductive potential should use effective contraception during therapy and for at least 5 months after the last dose.
Atezolizumab is a humanized monoclonal antibody immune checkpoint inhibitor that binds to programmed death ligand 1 (PD-L1) to selectively prevent the interaction between the programmed cell death-1 (PD-1) and B7.1 (also known as CD80) receptors, while still allowing interaction between PD-L2 and PD-1. PD-L1 is an immune check point protein expressed on tumor cells and tumor infiltrating cells and down regulates anti-tumor t-cell function by binding to PD-1 and B7.1; blocking PD-1 and B7.1 interactions restores antitumor t-cell function (Fehrenbacher 2016, Rosenberg 2016).
Vdss: 6.9 L
27 days
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience lack of appetite, nausea, vomiting, constipation, abdominal pain, back pain, neck pain, or joint pain. Have patient report immediately to prescriber signs of infusion reaction, signs of bowel problems (black, tarry, or sticky stools; bloody stools; severe abdominal pain; or diarrhea), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), signs of a severe pulmonary disorder (lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse), signs of thyroid, pituitary, or adrenal gland problems (mood changes, behavorial changes, weight changes, constipation, deeper voice, dizziness, passing out, cold sensation, severe fatigue, hair loss, persistent headache, or decreased libido), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of infection, signs of low sodium (headache, trouble focusing, memory problems, illogical thinking, weakness, seizures, or change in balance), swelling of arms or legs, hematuria, severe loss of strength and energy, angina, bruising, bleeding, vison changes, eye pain, or severe eye irritation (HCAHPS)
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.