Dosing & Uses
Dosage Forms & Strengths
solution for injection
- 120mg/2.4mL (50mg/mL) single-dose vial
- 500mg/10mL (50mg/mL) single-dose vial
Urothelial Carcinoma
Indicated for locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy, or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
10 mg/kg IV q2wk infused over 1 hr
Continue until disease progression or unacceptable toxicity
Non-small Cell Lung Cancer
Indicated for unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy
10 mg/kg IV q2wk infused over 1 hr
Continue until disease progression or unacceptable toxicity, or a maximum of 12 months
Dosage Modifications
No dose reductions are recommended; withhold and/or discontinue to manage adverse effects described below
Pneumonitis
- Grade 2: Withhold dose; administer prednisone (or equivalent) 1-2 mg/kg/day PO followed by a taper
- Grade 3 or 4: Permanently discontinue; administer prednisone (or equivalent) 1-4 mg/kg/day PO followed by a taper
Hepatitis
- For each of the following parameters, administer prednisone (or equivalent) 1-2 mg/kg/day PO followed by a taper
- Withhold dose
- Grade 2 ALT or AST (>3-5 x ULN) or total bilirubin (TB) >1.5-3 x ULN
- Grade 3 ALT or AST ≤8 x ULN or TB ≤5 x ULN
- Permanently discontinue
- Grade 3 ALT or AST >8 x ULN or TB >5 x ULN
- Concurrent ALT or AST >3 x ULN and TB >2 x ULN with no other cause
Colitis or diarrhea
- For each of the following parameters, administer prednisone (or equivalent) 1-2 mg/kg/day PO followed by a taper
- Grade 2: Withhold dose
- Grade 3 or 4: Permanently discontinue
Thyroid disorders
- Hypothyroidism, grades 2-4: Initiate thyroid hormone replacement as clinically indicated
- Hyperthyroidism, grades 2-4: Withhold dose until clinically stable and initiate symptomatic management
Adrenal insufficiency, hypophysitis/hypopituitarism
- Grades 2-4: Withhold dose until clinically stable
- Administer prednisone (or equivalent) 1-2 mg/kg/day PO followed by a taper
- Administer hormone replacement as clinically indicated
Type 1 diabetes mellitus
- Grades 2-4: Withhold dose until clinically stable
- Initiate treatment with insulin as clinically indicated
Nephritis
- For each of the following parameters, administer prednisone (or equivalent) 1-2 mg/kg/day PO followed by a taper
- Grade 2 (creatinine >1.5-3 x ULN): Withhold dose
- Grade 3 (creatinine >3-6 x ULN): Permanently discontinue
- Grade 4 (creatinine >6 x ULN): Permanently discontinue
Rash or dermatitis
- Consider initial dose of 1-2 mg/kg/day to 2 mg/kg/day prednisone or equivalent followed by a taper
- Grade 2 for >1 week: Withhold dose
- Grade 3: Withhold dose
- Grade 4: Permanently discontinue
Infection
- Grades 3 or 4: Withhold dose
- Initiate symptomatic management; treat with anti-infectives for suspected or confirmed infections
Infusion-related reactions
- Grades 1 or 2: Interrupt or slow infusion rate; consider premedication with subsequent doses
- Grade 3 or 4: Permanently discontinue
Other
- Grade 3
- Withhold dose
- Initiate symptomatic management
- Grade 4
- Permanently discontinue
- Consider initial dose of 1-2 mg/kg/day to 2 mg/kg/day prednisone or equivalent followed by a taper
Dosing Considerations
Indication for urothelial carcinoma is approved under accelerated approval based on tumor response rate and duration of response; continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials
Small Cell Lung Cancer (Orphan)
Orphan designation for small cell lung cancer
Orphan sponsor
- AstraZeneca Pharmaceuticals LP; 1800 Concord Pike; Wilmington, Delaware 19803
Safety and efficacy not established
Adverse Effects
Adverse effects are for all grades unless otherwise specified
>10%
Fatigue (39%)
Infusion-related reactions (29.7%)
Musculoskeletal pain (24%)
Constipation (21%)
Decreased appetite/hypophagia (19%)
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%)
Warnings
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
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.
Pharmacology
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
Administration
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)
Images
Patient Handout
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
