Durvalumab

Durvalumab is used to treat locally advanced or metastatic urothelial carcinoma and unresectable stage III non-small cell lung cancer (NSCLC).

Durvalumab is available under the following different brand names: Imfinzi.

Dosage Forms and Strengths

Solution for Injection (single-dose vial)

• 120 mg/2.4mL (50mg/mL)
• 500 mg/10mL (50mg/mL)

Dosage Considerations – Should be Given as Follows:

Locally Advanced or Metastatic Urothelial Carcinoma

Patients who have disease progression

• During or following platinum-containing chemotherapy
• Within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
• 10 mg/kg intravenously (IV) every 2 weeks infused over 1 hour
• Continue until disease progression or unacceptable toxicity

Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC)

• Disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy
• 10 mg/kg IV every 2 weeks infused over 1 hour
• 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 orally followed by a taper
• Grade 3 or 4: Permanently discontinue; administer prednisone (or equivalent) 1-4 mg/kg/day orally followed by a taper

Hepatitis

• For each of the following parameters, administer prednisone (or equivalent) 1-2 mg/kg/day orally followed by a taper
• Withhold dose
  • Grade 2 ALT or AST (greater than 3-5 x ULN) or total bilirubin (TB) greater than 1.5-3 x ULN
  • Grade 3 ALT or AST up to 8 x ULN or TB up to 5 x ULN

• Permanently discontinue
  • Grade 3 ALT or AST greater than 8 x ULN or TB greater than 5 x ULN
  • Concurrent ALT or AST greater than 3 x ULN and TB greater than 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 orally 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 orally 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 orally followed by a taper
• Grade 2 (creatinine greater than 1.5-3 x ULN): Withhold dose
• Grade 3 (creatinine greater than 3-6 x ULN): Permanently discontinue
• Grade 4 (creatinine greater than 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 more than 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 in pediatric patients

Common side effects of Durvalumab include:

• Fatigue
• Infusion-related reactions
• Musculoskeletal pain
• Constipation
• Decreased appetite
• Nausea
• Swelling of extremities
• Urinary tract infection (UTI)
• Fever
• Abdominal pain
• Shortness of breath
• Diarrhea/colitis
• Low sodium levels (hyponatremia), grades 3-4
• Low white blood cells (lymphopenia), grades 3-4
• Rash

Less common side effects of durvalumab include:

• Cough
• Anemia, grades 3-4
• Infusion-related reactions, grades 3-4
• Increased alkaline phosphatase, grades 3-4
• Hypermagnesemia, grades 3-4
• Hypercalcemia, grades 3-4
• Hyperglycemia, grades 3-4
• Immune-mediated pneumonitis or ILD
• Increased AST, grades 3-4
• Immune-mediated hepatitis
• Increased ALT, grades 3-4
• Hyperbilirubinemia, grades 3-4
• Increased creatinine, grades 3-4
• Neutropenia, grades 3-4
• Hyperkalemia, grades 3-4
• Hypokalemia, grades 3-4
• Hypoalbuminemia, grades 3-4
• Immune-mediated pneumonitis or ILD, grades 3-4

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Diphenhydramine Topical has no listed severe interactions with other drugs.
• Diphenhydramine Topical has no listed serious interactions with other drugs.
• Diphenhydramine Topical has no listed moderate interactions with other drugs.
• Diphenhydramine Topical has no listed mild interactions with other drugs.

Warnings

This medication contains durvalumab. Do not take Imfinzi if you are allergic to durvalumab or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• None

Effects of Drug Abuse

• No information available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Durvalumab?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Durvalumab?"

Cautions

• Immune-mediated pneumonitis or interstitial lung disease reported; monitor for signs and symptoms; evaluate patients with suspected pneumonitis with radiographic imaging
• 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
• Immune-mediated colitis or diarrhea reported; monitor for signs and symptoms
• Immune-mediated endocrinopathies (e.g., 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 (e.g., 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

Pregnancy and Lactation

Based on its mechanism of action, durvalumab 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.

Females of reproductive potential are advised to use effective contraception during treatment and for 3 months following the last dose of durvalumab.

It is unknown if durvalumab is 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, breastfeeding women are advised not to breastfeed during treatment with durvalumab and for at least 3 months after the last dose.