Durvalumab

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

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

Safety and efficacy not established

>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%)

Durvalumab works by causing your immune system to attack tumor cells. Durvalumab may cause your immune system to attack healthy organs and tissues in your body. This could lead to serious or life-threatening side effects on your lungs, liver, pancreas, kidneys, intestines, thyroid, or adrenal glands.

Call your doctor at once if you have symptoms such as: fever, flu symptoms, muscle pain or weakness, vision changes, chest pain, trouble breathing, severe stomach pain or diarrhea, skin rash, increased or decreased urination, weight changes, hair loss, dark urine, or jaundice (yellowing of your skin or eyes).

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

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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

• MEDI4736

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 disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Withdraw appropriate volume from vial (solution should be clear to opalescent and colorless to slightly yellow and free of visible particles; do not use if cloudy, discolored or if visible particulates are present) and transfer to IV bag containing NS or D5W. Mix by gently inverting bag (do not shake). The final concentration of the diluted solution should be between 1 and 15 mg/mL. Discard unused portion of the vial.

10 mg/kg IV over 60 minutes every 2 weeks
Duration of therapy: Until disease progression or unacceptable toxicity

Uses: For the treatment of patients with locally advanced or metastatic urothelial carcinoma who:
1) Have disease progression during or following platinum-containing chemotherapy
2) Have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

Data not available

Data not available

Data not available