Atezolizumab

Pregnancy

Based on its mechanism of action, can cause fetal harm when administered during pregnancy; advise females of reproductive potential to use effective contraception during treatment and for at least 5 months following the last dose

Based on animal studies, atezolizumab may impair fertility in females of reproductive potential while receiving treatment

Lactation

Unknown if distributed in human breast milk

Advise lactating woman not to breastfeed during treatment and for at least 5 months after the last dose

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

You should not use atezolizumab if you are allergic to it.

To make sure atezolizumab is safe for you, tell your doctor if you have:

• an active infection;

• an immune system disorder such as lupus, ulcerative colitis, or Crohn's disease;

• a history of organ transplant;

• a breathing disorder;

• liver disease; or

• a nervous system disorder such as myasthenia gravis or Guillain Barré syndrome.

Do not use atezolizumab if you are pregnant. It could harm the unborn baby. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 5 months after your last dose.

It is not known whether atezolizumab passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine or within 5 months after your last dose. If you use a breast pump during this time, throw out any milk you collect. Do not feed it to your baby.

General

Restricted Distribution

• Obtain atezolizumab through a limited network of specialty distributors.3 5

• Contact manufacturer at 800-551-22313 or consult the Tecentriq website () for specific availability information.5

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.1 Do not administer by rapid IV injection (e.g., IV push or bolus).1

Atezolizumab injection concentrate must be diluted prior to administration.1 Immediate administration recommended.1 (See Storage under Stability.)

Do not infuse simultaneously through the same IV line with other drugs.1

Use of low-protein-binding 0.2- to 0.22-mcm inline filter is optional.1

Undiluted solution should be colorless to slightly yellow.1 Do not use if it is cloudy or discolored or if particulate matter is present.1

Do not shake vial.1

Withdraw 20 mL of atezolizumab injection concentrate (containing 60 mg/mL) and dilute in a PVC, polyethylene, or polyolefin infusion bag containing 250 mL of 0.9% sodium chloride.1 Do not use any other diluent.1 Mix the diluted solution by gentle inversion; do not shake.1 Discard any partially used vial.1

Initial dose: Administer over 60 minutes.1

Subsequent doses: Administer over 30 minutes (if first infusion well tolerated).1

Dosage

Adults

1.2 g every 3 weeks.1 Continue therapy until disease progression or unacceptable toxicity occurs.1

1.2 g every 3 weeks.1 Continue therapy until disease progression or unacceptable toxicity occurs.1

If grade 2 immune-mediated pneumonitis occurs, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Immune-mediated Pneumonitis under Cautions.)

If grade 3 or 4 immune-mediated pneumonitis occurs, discontinue drug.1

For grade 2 immune-mediated hepatitis, serum ALT or AST elevations >3 times but ≤5 times the ULN, or total bilirubin concentrations >1.5 times but ≤3 times the ULN, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Immune-mediated Hepatic Effects under Cautions.)

For grade 3 or 4 immune-mediated hepatitis, ALT or AST elevations >5 times the ULN, or total bilirubin concentrations >3 times the ULN, discontinue drug.1

If grade 2 or 3 immune-mediated colitis or diarrhea occurs, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Immune-mediated GI Effects under Cautions.)

If grade 4 immune-mediated colitis or diarrhea occurs, discontinue drug.1

If symptomatic immune-mediated hypophysitis, adrenal insufficiency, hypothyroidism, or hyperthyroidism occurs or if grade 3 or 4 immune-mediated hyperglycemia occurs, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Immune-mediated Endocrine Effects under Cautions.)

If grade 4 immune-mediated hypophysitis occurs, discontinue drug.1

If grade 2 immune-mediated ocular inflammatory toxicity, grade 2 or 3 immune-mediated pancreatitis, or grade 3 or 4 elevations in amylase or lipase concentrations (>2 times the ULN) occur, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Other Immune-mediated Effects under Cautions.)

If myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, meningoencephalitis, grade 3 or 4 immune-mediated ocular inflammatory toxicity, grade 4 immune-mediated pancreatitis, or recurrent immune-mediated pancreatitis of any severity occurs, discontinue drug.1

If grade 2 infusion-related reactions occur, interrupt infusion until reaction resolves to grade 0 or 1.1 (See Infusion-related Effects under Cautions.)

If grade 3 or 4 infusion-related reactions occur, discontinue drug.1

If grade 3 or 4 infection occurs, interrupt therapy.1 (See Infectious Complications under Cautions.)

If grade 3 rash occurs, interrupt therapy until toxicity resolves to grade 0 or 1.1

If grade 4 rash occurs, discontinue drug.1

Special Populations

Hepatic Impairment

Mild hepatic impairment: No dosage adjustment required.1 (See Special Populations under Pharmacokinetics.)

Moderate or severe hepatic impairment: No dosage recommendations at this time.1

Renal Impairment

Mild, moderate, or severe renal impairment: No dosage adjustment required.1 (See Special Populations under Pharmacokinetics.)

Geriatric Patients

No special dosage recommendations at this time.1 (See Geriatric Use under Cautions.)

No formal drug interaction studies to date.1

Storage

Parenteral

2–8°C.1 Do not freeze; protect from light.1

Diluted solution: Room temperature for ≤6 hours from time of preparation (including infusion time) or 2–8°C for ≤24 hours.1 Do not freeze.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

• If you have an allergy to atezolizumab or any part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are breast-feeding. Do not breast-feed while you take atezolizumab and for 5 months after you stop taking it.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• If you need to store atezolizumab at home, talk with your doctor, nurse, or pharmacist about how to store it.

There are no contraindications listed in the manufacturer's labeling.

Refer to adult dosing.

No dosage adjustment is necessary (the effect on atezolizumab pharmacokinetics in patients with estimated glomerular filtration rate 15 to 29 mL/minute has not been studied and is unknown).

Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid combination

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Atezolizumab is injected into a vein through an IV. A healthcare provider will give you this injection.

This medicine is given slowly and the IV infusion can take up to 60 minutes to complete.

Atezolizumab is usually given once every 3 weeks until your body no longer responds to the medication.

Atezolizumab can increase your risk of infection by changing the way your immune system works. You will need frequent medical tests.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Call your doctor for instructions if you miss an appointment for your atezolizumab injection.

Data not available

This drug should be used during pregnancy only if the benefit outweighs the risk. AU TGA pregnancy category: D US FDA pregnancy category: Not assigned. Risk Summary: -Based on animal studies, this drug impairs fertility in females of reproductive potential. -Based on its mechanism of action, this drug can cause harm to a developing fetus.

Animal reproduction studies have not been conducted to evaluate the 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 to disrupt tolerance to a fetus and to result in an increase in fetal loss. There are no controlled data in human pregnancy. It is not known whether this drug can cause fetal harm or adversely affect reproductive capacity in humans. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D and X are being phased out.