Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 50mg/mL (2.4-mL, 10-mL single-dose vials)
Urothelial Carcinoma
Indicated for locally advanced or metastatic urothelial carcinoma in patients who have disease progression during/following platinum-containing chemotherapy OR within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
10 mg/kg IV q2Weeks
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 q2Weeks
Continue until disease progression or unacceptable toxicity, or a maximum of 12 months
Small Cell Lung Cancer
Indicated, in combination with carboplatin or cisplatin, for first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC)
Cycle 1-4
- Each cycle is 21 days
-
Day 1
- Durvalumab 1500 mg IV (if patient’s body weight ≤30 kg, dose at 20 mg/kg IV) PLUS
- Etoposide 80-100 mg/m2 IV PLUS
- Carboplatin AUC 5 or 6 OR
- Cisplatin 75-80 mg/m2 IV
-
Day 2-3
- Etoposide 80-100 mg/m2 IV qDay
Subsequent cycles
- Note: Cycle is 28 days
- Durvalumab 1500 mg IV (if patient’s body weight ≤30kg, dose at 20 mg/kg until weight >30 kg) q4Weeks
- Continue until disease progression or unacceptable toxicity
Dosage Modifications
No dose reductions are recommended; withhold and/or discontinue to manage adverse effects described below
Withhold dose until Grade ≤1 or resolved and taper corticosteroid dose to prednisone ≤10 mg/day (or equivalent)
- Grade 2 pneumonitis
- Hepatitis (ALT/AST >3 to ≤8x ULN or total bilirubin >1.5 to ≤5x ULN)
- Grade 2 colitis or diarrhea
- Nephritis (creatinine 1.5-3x ULN)
- Grade 2 for longer than 1 week or Grade 3 rash or dermatitis
Withhold dose until clinical stable
- Hyperthyroidism
- Thyroiditis
- Adrenal insufficiency
- Hypophysitis/hypopituitarism
- Type 1 diabetes mellitus
- Grade 3 or 4 infection
Interrupt or slow rate of infusion
- Grade 1 or 2 infusion-related reactions
Permanently discontinue
- Grade 3 or 4 pneumonitis
- Hepatitis ([ALT/AST >8x ULN or total bilirubin > 5x ULN] or [concurrent ALT/AST >3x ULN and total bilirubin >2x ULN with no other cause])
- Grade 3 or 4 colitis or diarrhea
- Nephritis (creatinine >3x ULN)
- Grade 4 rash or dermatitis
- Grade 3 or 4 infusion-related reactions
- Grade 4 other immune-mediated adverse reactions
- Grade 2 or 3 adverse reaction that does not recover to Grade ≤1 within 12 weeks after last durvalumab dose
- Inability to reduce to prednisone ≤10 mg/day (or equivalent) within 12 weeks after last durvalumab dose
- Recurrent Grade 3 or 4 (severe or life-threatening) adverse reaction
Renal impairment
- Mild-to-moderate (CrCl ≥30 mL/min): No dosage adjustment necessary
- Severe (CrCl <30 mL/min): Pharmacokinetics unknown
Hepatic impairment
- Mild (bilirubin ≤ULN and AST >ULN OR bilirubin >1-1.5x ULN and any AST): No dosage adjustment necessary
- Moderate-to-severe (bilirubin >1.5x ULN and any AST): Pharmacokinetics unknown
Orphan Designations
Hepatocellular carcinoma
Orphan sponsor
- AstraZeneca Pharmaceuticals LP; 1800 Concord Pike; Wilmington, Delaware 19803
Safety and efficacy not established
Adverse Effects
>10%
Urothelial carcinoma
-
All grades
- Fatigue (39%)
- Musculoskeletal pain (24%)
- Constipation (21%)
- Decreased appetite (19%)
- Nausea (16%)
- Peripheral edema (15%)
- Urinary tract infection (15%)
- Pyrexia or tumor-associated fever (14%)
- Abdominal pain (14%)
- Dyspnea/exertional dyspnea (13%)
- Diarrhea/colitis (13%)
- Rash (11%)
-
Grade 3-4
- Hyponatremia (12%)
- Lymphopenia (11%)
NSLC
-
All grades
- Hyperglycemia (52%)
- Hypocalcemia (46%)
- Lymphopenia (43%)
- Cough/productive cough (40%)
- Increased ALT (39%)
- Increased AST (36%)
- Fatigue (34%)
- Pneumonitis/radiation pneumonitis (34%)
- Hyponatremia (33%)
- Hyperkalemia (32%)
- Upper respiratory tract infections (26%)
- Dyspnea (25%)
- Increased GGT (24%)
- Rash (23%)
- Diarrhea (18%)
- Pneumonia (17%)
- Pyrexia (15%)
- Pruritus (12%)
- Hypothyroidism (12%)
-
Grade 3-4
- Lymphopenia (17%)
SCLC (Combination with etoposide + carboplatin OR cisplatin)
-
All grades
- Neutropenia (41%)
- Nausea (34%)
- Fatigue/asthenia (32%)
- Alopecia (31%)
- Decreased appetite (18%)
- Constipation (17%)
- Vomiting (15%)
- Cough/productive cough (15%)
- Lymphopenia (14%)
- Anemia (13%)
- Thrombocytopenia (12%)
- Rash (11%)
-
Grade 3-4
- Hyponatremia (11%)
- Hypomagnesemia (11%)
1-10%
Urothelial carcinoma
-
All grades
- Cough/productive cough (10%)
-
Grade 3-4
- Fatigue (6%)
- Urinary tract infection (4.4%)
- Hypermagnesemia (4.2%)
- Increased alkaline phosphatase (4.1%)
- Musculoskeletal pain (3.8%)
- Hypercalcemia (3%)
- Hyperglycemia (3%)
- Abdominal pain (2.7%)
- Increased AST (2.4%)
- Dyspnea/exertional dyspnea (2.2%)
- Nausea (1.6%)
- Peripheral edema (1.6%)
- Hyperbilirubinemia (1.2%)
- Increased creatinine (1.2%)
- Neutropenia (1.2%)
- Hyperkalemia (1.2%)
- Hypokalemia (1.2%)
- Hypoalbuminemia (1.2%)
- Constipation (1.1%)
- Diarrhea/colitis (1.1%)
NSLC
-
All grades
- Abdominal pain (10%)
- Pneumonitis/radiation pneumonitis (3.4%)
- Dyspnea (1.5%)
-
Grade 3-4
- Hyperglycemia (8%)
- Pneumonia (7%)
- Hyponatremia (3.6%)
- Increased GGT (3.4%)
- Increased AST (2.8%)
- Increased ALT (2.3%)
- Hyperkalemia (1.1%)
SCLC (Combination with etoposide + carboplatin OR cisplatin)
-
All grades
- Diarrhea (10%)
- Hyperthyroidism (10%)
-
Grade 3-4
- Hyperglycemia (5%)
- Increased alkaline phosphate (4.9%)
- Increased ALT (4.9%)
- Increased AST (4.6%)
- Hypocalcemia (3.5%)
- Increased blood creatine (3.4%)
- Fatigue/asthenia (3.4%)
- Hyperkalemia (1.5%)
- Diarrhea (1.1%)
- Alopecia (1.1%)
<1%
Urothelial carcinoma
-
Grade 3-4
- Increased ALT (0.6%)
- Pyrexia or tumor-associated fever (0.5%)
- Decreased appetite (0.5%)
- Rash (0.5%)
NSCLC
-
Grade 3-4
- Fatigue (0.8%)
- Cough/productive cough (0.6%)
- Diarrhea (0.6%)
- Rash (0.6%)
- Abdominal pain (0.4%)
- Upper respiratory tract infections (0.4%)
- Hypothyroidism (0.2%)
- Pyrexia (0.2%)
- Hypocalcemia (0.2%)
SCLC (Combination with etoposide + carboplatin OR cisplatin)
-
Grade 3-4
- Cough/productive cough (0.8%)
- Vomiting (0.8%)
- Constipation (0.8%)
- Decreased appetite (0.8%)
- Nausea (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
Immune-mediated hepatitis reported; monitor for abnormal liver tests each cycle during treatment
Immune-mediated colitis or diarrhea reported; monitor for signs and symptoms
Immune-mediated endocrinopathies (eg, hypothyroidism, hyperthyroidism, adrenal insufficiency, type 1 diabetes mellitus, hypophysitis, hypopituitarism) have occurred; monitor for symptoms of these conditions
Rare reports of other immune-mediated adverse effects (eg, aseptic meningitis, hemolytic anemia, rash, ITP, myocarditis, myositis, nephritis, uveitis, keratitis) have occurred
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
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
Animal data
- 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
- Females of reproductive potential: 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
Absorption
Steady-state was reached at ~16 weeks
Distribution
Vd (steady-state); 5.6 L
Elimination
Clearance (steady-state): 8.2 L/hr
Half-life: ~18 days
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
Infuse 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
SCLC: Administer durvalumab first prior to all other chemo on Day 1 of each cycle
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.
