durvalumab (Rx)

>10%

Adverse effects are for all grades unless otherwise specified Fatigue (39%) Infusion-related reactions (29.7%) Musculoskeletal pain (24%) Constipation (21%) Decreased appetite/hypophagia Nausea (16%) Peripheral edema (15%) Urinary tract infection (15%) Pyrexia/tumor associated fever (14%) Abdominal pain (14%) Dyspnea/exertional dyspnea (13%) Diarrhea/colitis (13%) Hyponatremia, grades 3-4 (12%) Lymphopenia, grades 3-4 (11%) Rash (11%)

1-10%

Adverse effects are for all grades unless otherwise specified

Cough (10%)

Anemia, grades 3-4 (8%)

Infusion-related reactions, grades 3-4 (6%)

Increased alkaline phosphatase, grades 3-4 (4%)

Hypermagnesemia, grades 3-4 (4%)

Hypercalcemia, grades 3-4 (3%)

Hyperglycemia, grades 3-4 (3%)

Immune-mediated pneumonitis or ILD (2.3%)

Increased AST, grades 3-4 (2%)

Immune-mediated hepatitis (1.1%)

Increased ALT, grades 3-4 (1%)

Hyperbilirubinemia, grades 3-4 (1%)

Increased creatinine, grades 3-4 (1%)

Neutropenia, grades 3-4 (1%)

Hyperkalemia, grades 3-4 (1%)

Hypokalemia, grades 3-4 (1%)

Hypoalbuminemia, grades 3-4 (1%)

<1%

Immune-mediated pneumonitis or ILD, grades 3-4 (0.4%)

Contraindications

None

Cautions

Immune-mediated pneumonitis or interstitial lung disease reported; monitor for signs and symptoms; evaluate patients with suspected pneumonitis with radiographic imaging (see Dosage Modifications)

Administer corticosteroids, prednisone 1 to 2 mg per kg per day or equivalent for moderate (Grade 2) pneumonitis or prednisone 1 to 4 mg per kg per day or equivalent for more severe (Grade 3-4) pneumonitis, followed by taper; interrupt or permanently discontinue therapy based on the severity

Immune-mediated hepatitis reported; monitor for abnormal liver tests each cycle during treatment (see Dosage Modifications)

Immune-mediated colitis or diarrhea reported; monitor for signs and symptoms (see Dosage Modifications)

Immune-mediated endocrinopathies (eg, hypothyroidism, hyperthyroidism, adrenal insufficiency, type 1 diabetes mellitus, hypophysitis, hypopituitarism) have occurred; monitor for symptoms of these conditions (see Dosage Modifications)

Rare reports of other immune-mediated adverse effects (eg, aseptic meningitis, hemolytic anemia, rash, ITP, myocarditis, myositis, nephritis, uveitis, keratitis) have occurred (see Dosage Modifications)

Severe infusion-related reactions reported; monitor for signs and symptoms and slow infusion rate or interrupt infusion if needed; if severe, withhold or permanently discontinue (see Dosage Modifications)

Can cause fetal harm (see Pregnancy)

Pregnancy

Based on its mechanism of action, can cause fetal harm if administered to a pregnant woman

Human immunoglobulin G1 (IgG1) is known to cross the placental barrier; therefore, durvalumab has the potential to be transmitted from the mother to the developing fetus

In animal reproduction studies, administration of durvalumab to pregnant cynomolgus monkeys from the confirmation of pregnancy through delivery resulted in increased in premature delivery, fetal loss, and premature neonatal death

Contraception: Advise females of reproductive potential to use effective contraception during treatment and for 3 months following the last dose

Lactation

Unknown if distributed in human breast milk; human IgG1 is excreted in human milk

Durvalumab was present in the milk of lactating cynomolgus monkeys and was associated with premature neonatal death

Because of the potential for adverse reactions in breastfed infants, advise breastfeeding women not to breastfeed during treatment and for at least 3 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.

Mechanism of Action

Human IgG1 kappa monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, and therefore overcoming/preventing PD-L1-mediated inhibition/suppression of T-cell activation

Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, without inducing antibody dependent cell-mediated cytotoxicity

Distribution

Vd: 5.6 L

Elimination

Half-life: 17 days

Clearance: 8.24 mL/h

IV Compatibilities

0.9% NaCl

D5W

IV Preparation

Visually inspect drug product for particulate matter and discoloration; should appear clear to opalescent, colorless to slightly yellow solution, and free from visible particles

Discard the vial if the solution is cloudy, discolored, or visible particles are observed

Do not shake the vial

Withdraw the required volume for the dose from the vial(s) and transfer into an IV bag containing 0.9% NaCl or D5W

Mix diluted solution by gentle inversion; do not shake the solution

The final concentration of the diluted solution should be between 1-15 mg/mL

Discard partially used or empty vials

Administer infusion solution immediately once prepared (also see Storage)

IV Administration

Administer diluted solution via IV infusion over 1 hr through an IV line containing a sterile, low-protein binding 0.2 or 0.22 micron inline filter

Do not coadminister other drugs through the same infusion line

Storage

Does not contain a preservative

Do not freeze

Do not shake

Unopened vial

• Refrigerate at 2-8°C (36-46°F)
• Store in original carton to protect from light

Diluted solution

• Administer infusion solution immediately once prepared
• If infusion solution is not administered immediately and needs to be stored, the total time from vial puncture to the start of the administration should not exceed the following:
• 24 hr in a refrigerator at 2-8°C (36-46°F), or
• 4 hr at room temperature up to 25°C (77°F)