Durvalumab (Monograph)

Brand name: Imfinzi
Drug class: Antineoplastic Agents
- Programmed Death Ligand-1 Antagonist
- PD-L1 Inhibitor
CAS number: 1428935-60-7

Medically reviewed by Drugs.com on Sep 20, 2024. Written by ASHP.

Introduction

Antineoplastic agent; recombinant fully human anti-programmed-death ligand-1 (anti-PD-L1) monoclonal antibody.

Uses for Durvalumab

Urothelial Carcinoma

Treatment of locally advanced or metastatic urothelial carcinoma that has progressed during or following platinum-containing therapy for advanced disease or within 12 months of platinum-containing therapy in the neoadjuvant or adjuvant setting.

Accelerated approval based on tumor response rate and duration of response; improvement in disease-related symptoms or increased survival not demonstrated. Continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.

Non-small Cell Lung Cancer (NSCLC)

Treatment of unresectable stage III NSCLC that has not progressed following platinum-based chemotherapy combined with radiation therapy.

Durvalumab Dosage and Administration

General

Restricted Distribution

Obtain durvalumab through a limited network of specialty distributors.
Contact manufacturer at 844-275-2360 or consult the Imfinzi website ([Web]) for specific availability information.

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.

Durvalumab injection concentrate must be diluted prior to administration. (See Dilution under Dosage and Administration.) Immediate administration recommended. (See Storage under Stability.)

Do not infuse simultaneously through the same IV line with other drugs.

Administer through a sterile, low-protein-binding 0.2- or 0.22-μm inline filter.

Dilution

Undiluted solution should be clear to opalescent and colorless to slightly yellow. Do not use if cloudy or discolored or if particulate matter is present.

Do not shake vial.

Withdraw appropriate dose of durvalumab injection concentrate (containing 50 mg/mL) and dilute with appropriate volume of 0.9% sodium chloride or 5% dextrose injection to a final concentration of 1–15 mg/mL. Do not use any other diluent. Mix the diluted solution by gentle inversion; do not shake. Discard any partially used vials.

Rate of Administration

Administer over 60 minutes.

Dosage

Adults

Urothelial Carcinoma

IV

10 mg/kg once every 2 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

NSCLC

IV

10 mg/kg once every 2 weeks. Continue therapy until disease progression or unacceptable toxicity occurs, or for up to 12 months.

Therapy Interruption for Toxicity

Immune-mediated Pneumonitis

If grade 2 immune-mediated pneumonitis occurs, interrupt therapy until toxicity resolves to grade 0 or 1 and the patient is receiving ≤10 mg of prednisone daily (or equivalent). (See Immune-mediated Pneumonitis under Cautions.)

If grade 3 or 4 immune-mediated pneumonitis occurs, discontinue drug.

Immune-mediated Hepatic Effects

For serum ALT or AST elevations >3 times but ≤8 times the ULN or total bilirubin concentrations >1.5 times but ≤5 times the ULN, interrupt therapy until toxicity resolves to grade 0 or 1 and the patient is receiving ≤10 mg of prednisone daily (or equivalent). (See Immune-mediated Hepatic Effects under Cautions.)

For ALT or AST elevations >8 times the ULN or total bilirubin concentrations >5 times the ULN, discontinue drug.

For ALT or AST elevations >3 times the ULN and total bilirubin concentrations >2 times the ULN with no other cause, discontinue drug.

Immune-mediated GI Effects

If grade 2 immune-mediated colitis or diarrhea occurs, interrupt therapy until toxicity resolves to grade 0 or 1 and the patient is receiving ≤10 mg of prednisone daily (or equivalent). (See Immune-mediated GI Effects under Cautions.)

If grade 3 or 4 immune-mediated colitis or diarrhea occurs, discontinue drug.

Immune-mediated Endocrine Effects

If grade 2–4 immune-mediated adrenal insufficiency, hyperthyroidism, hypophysitis, hypopituitarism, or type 1 diabetes mellitus occurs, interrupt therapy until patient is clinically stable. (See Immune-mediated Endocrine Effects under Cautions.)

Immune-mediated Renal Effects

For S_cr concentrations >1.5 times but ≤3 times the ULN (i.e., grade 2), interrupt therapy until toxicity resolves to grade 0 or 1 and the patient is receiving ≤10 mg of prednisone daily (or equivalent). (See Immune-mediated Renal Effects under Cautions.)

For S_cr concentrations >3 times the ULN (i.e., grade 3 or 4), discontinue drug.

Immune-mediated Dermatologic Effects

If grade 2 immune-mediated rash or dermatitis occurs for >1 week or if grade 3 immune-mediated rash or dermatitis occurs, interrupt therapy until toxicity resolves to grade 0 or 1 and the patient is receiving ≤10 mg of prednisone daily (or equivalent). (See Immune-mediated Dermatologic Effects under Cautions.)

If grade 4 immune-mediated rash or dermatitis occurs, discontinue drug.

Other Immune-mediated Adverse Effects

If any other grade 3 immune-mediated adverse effects occur, interrupt therapy until toxicity resolves to grade 0 or 1 and the patient is receiving ≤10 mg of prednisone daily (or equivalent). (See Other Immune-mediated Effects under Cautions.)

If any other grade 4 immune-mediated adverse effects occur, discontinue drug.

Infectious Complications

If grade 3 or 4 infection occurs, interrupt therapy until patient is clinically stable. (See Infectious Complications under Cautions.)

Infusion-related Reactions

If grade 1 or 2 infusion-related reactions occur, decrease infusion rate or interrupt therapy. (See Infusion-related Reactions under Cautions.)

If grade 3 or 4 infusion-related reactions occur, discontinue drug.

Special Populations

Hepatic Impairment

Mild hepatic impairment: No dosage adjustment required. (See Special Populations under Pharmacokinetics.)

Moderate or severe hepatic impairment: No dosage recommendations at this time.

Renal Impairment

Mild or moderate renal impairment: No dosage adjustment required. (See Special Populations under Pharmacokinetics.)

Severe renal impairment: No dosage recommendations at this time.

Geriatric Patients

No dosage adjustment required. (See Geriatric Use under Cautions.)

Cautions for Durvalumab

Contraindications

No known contraindications.

Warnings/Precautions

Immune-mediated Pneumonitis

Pneumonitis, including interstitial lung disease and immune-mediated pneumonitis (requiring corticosteroid therapy), sometimes fatal, reported.

Monitor patients for manifestations of pneumonitis; evaluate those with suspected pneumonitis with radiographic imaging.

If grade 2 immune-mediated pneumonitis occurs, interrupt durvalumab therapy and initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.

For toxicity not resulting in permanent drug discontinuance, resume durvalumab therapy when toxicity resolves to grade 0 or 1 and the corticosteroid dosage is reduced to <10 mg of prednisone daily (or equivalent).

If grade 3 or 4 immune-mediated pneumonitis occurs, permanently discontinue durvalumab and initiate systemic corticosteroid (1–4 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.

Immune-mediated Hepatic Effects

Immune-mediated hepatitis (requiring corticosteroid therapy), sometimes fatal, and liver function test abnormalities reported.

Monitor liver function tests during and following discontinuation of durvalumab therapy.

If ALT or AST concentrations >3 to 8 times the ULN or total bilirubin concentrations >1.5 to 5 times the ULN occur, interrupt durvalumab therapy and initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.

If ALT or AST elevations >8 times the ULN or total bilirubin concentrations >5 times the ULN occur or if ALT or AST concentrations >3 times the ULN occur with total bilirubin concentrations >2 times the ULN, permanently discontinue durvalumab and initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.

Immune-mediated GI Effects

Diarrhea or colitis, including immune-mediated colitis (requiring corticosteroid therapy), reported.

Monitor patients for manifestations of colitis or diarrhea.

If grade 2 immune-mediated colitis or diarrhea occurs, interrupt durvalumab therapy and initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.

If grade 3 or 4 immune-mediated diarrhea or colitis occurs, permanently discontinue durvalumab and initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.

Immune-mediated Endocrine Effects

Immune-mediated endocrinopathies, such as thyroid dysfunction (i.e., hypothyroidism, hyperthyroidism), adrenal insufficiency, hypophysitis, hypopituitarism, and type 1 diabetes mellitus, reported.

Thyroid Dysfunction

Evaluate thyroid function prior to initiation and periodically during therapy.

If immune-mediated hypothyroidism occurs, initiate thyroid hormone replacement therapy as clinically indicated; may continue durvalumab therapy.

If immune-mediated hyperthyroidism occurs, initiate appropriate medical therapy and interrupt durvalumab therapy until patient is clinically stable.

Adrenal Insufficiency

Monitor for signs and symptoms of adrenal insufficiency.

If grade 2 or greater adrenal insufficiency occurs, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage; initiate hormone replacement therapy as indicated. Interrupt durvalumab therapy until patient is clinically stable.

Hypophysitis

Monitor for signs and symptoms of hypophysitis.

If grade 2 or greater hypophysitis occurs, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage; initiate hormone replacement therapy as indicated. Interrupt durvalumab therapy until patient is clinically stable.

Hypopituitarism

Monitor for signs and symptoms of hypopituitarism.

If grade 2 or greater hypopituitarism occurs, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage; initiate hormone replacement therapy as indicated. Interrupt durvalumab therapy until patient is clinically stable.

Diabetes Mellitus

Monitor for hyperglycemia or other manifestations of diabetes.

If grade 2 or greater type 1 diabetes mellitus occurs, initiate insulin treatment as clinically indicated; interrupt durvalumab therapy until patient is clinically stable.

Immune-mediated Renal Effects

Immune-mediated nephritis (evidence of renal dysfunction and requiring corticosteroid therapy), including elevations in S_cr or urea concentrations, decreased Cl_cr, acute kidney injury, renal failure, decreased glomerular filtration rate, tubulointerstitial nephritis, glomerulonephritis, sometimes fatal, reported.

Evaluate renal function prior to initiation and periodically thereafter.

If grade 2 elevations in S_cr concentrations occur, interrupt durvalumab therapy and initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.

If grade 3 or 4 elevations in S_cr concentrations occur, permanently discontinue durvalumab and initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.

Immune-mediated Dermatologic Effects

Immune-mediated rash or dermatitis (e.g., bullous dermatitis, Stevens-Johnson syndrome/toxic epidermal necrolysis) reported.

Monitor patients for signs and symptoms of rash or dermatitis.

If grade 2 rash or dermatitis occurs and persists >1 week or any grade 3 rash or dermatitis occurs, interrupt durvalumab therapy and initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.

If grade 4 rash or dermatitis occurs, permanently discontinue durvalumab and initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.

Other Immune-mediated Effects

Other immune-mediated adverse effects (sometimes fatal), including aseptic meningitis, hemolytic anemia, thrombocytopenic purpura, myocarditis, myositis, ocular inflammatory toxicity (e.g., uveitis, keratitis), reported. Immune-mediated adverse effects may occur in any organ system and following discontinuance of therapy.

If grade 2 immune-mediated toxicity is suspected, exclude other causes and initiate corticosteroid therapy as clinically indicated.

If grade 3 immune-mediated toxicity occurs, interrupt durvalumab therapy and initiate systemic corticosteroid therapy (1–4 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.

If grade 4 immune-mediated adverse effects occur, permanently discontinue durvalumab and initiate systemic corticosteroid therapy (1–4 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage.

Infectious Complications

Severe infections (e.g., sepsis, pneumonia) reported.

Monitor for signs and symptoms of infection.

If grade 3 or greater infection occurs, interrupt therapy until patient is clinically stable.

Infusion-related Reactions

Severe or life-threatening infusion-related reactions reported.

Monitor for signs and symptoms of infusion-related reactions.

If grade 1 or 2 infusion-related reactions occur, interrupt therapy or decrease infusion rate. Consider use of appropriate premedications (e.g., corticosteroids) with subsequent infusions.

If grade 3 or 4 infusion-related reactions occur, discontinue drug.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm. May disrupt maternal immune tolerance to the fetus and increase risk of fetal loss (abortion, stillbirth); also may increase risk of immune-mediated disorders.

Avoid pregnancy during therapy. Advise women of childbearing potential to use an effective contraceptive method while receiving durvalumab and for ≥3 months after drug is discontinued. If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.

Immunogenicity

Potential for immunogenicity. Development of anti-drug antibodies to durvalumab does not appear to have clinically important effects on pharmacokinetics of the drug. Number of patients with anti-durvalumab antibodies insufficient to determine whether such antibodies affect efficacy or safety of the drug.

Specific Populations

Pregnancy

May cause fetal harm. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether durvalumab is distributed into milk. Discontinue nursing during therapy and for ≥3 months after drug discontinuance.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No overall differences in safety or efficacy observed in patients ≥65 years of age compared with younger adults. Number of patients with NSCLC ≥75 years of age insufficient to determine whether they respond differently than younger adults.

Hepatic Impairment

Systemic exposure and clearance not affected by mild hepatic impairment. Data lacking in patients with moderate or severe hepatic impairment. (See Special Populations under Pharmacokinetics.)

Renal Impairment

Clearance not affected by mild or moderate renal impairment. Limited data available in patients with severe renal impairment. (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Patients with urothelial carcinoma: Fatigue, musculoskeletal pain, constipation, decreased appetite/hypophagia, nausea, peripheral edema, urinary tract infection, abdominal pain, pyrexia/tumor-associated fever, diarrhea/colitis, dyspnea/exertional dyspnea, rash, cough/productive cough, hyponatremia, lymphopenia.

Patients with NSCLC: Cough/productive cough, pneumonitis/radiation pneumonitis, fatigue, upper respiratory infections, dyspnea, rash, diarrhea, pneumonia, pyrexia, hypothyroidism, pruritus, abdominal pain, hyperglycemia, hypocalcemia, lymphopenia, elevated ALT and AST concentrations, hyponatremia, hyperkalemia, elevated concentrations of γ-glutamyltransferase (GGT).

Drug Interactions

No formal drug interaction studies to date.

Durvalumab Pharmacokinetics

Absorption

Bioavailability

Steady-state concentrations achieved within approximately 16 weeks.

Systemic exposure is dose proportional over dosage range of 3–20 mg/kg.

Distribution

Extent

Not known whether durvalumab is distributed into milk.

Elimination

Half-life

Approximately 18 days.

Special Populations

Mild hepatic impairment (total bilirubin concentrations not exceeding the ULN with AST concentrations exceeding the ULN, or total bilirubin concentrations >1 to 1.5 times the ULN with any AST concentrations): Clearance similar to that in patients with normal hepatic function.

Moderate or severe hepatic impairment (total bilirubin concentrations >1.5 times the ULN with any AST concentrations): Data not available.

Mild or moderate renal impairment (Cl_cr 30–89 mL/minute per 1.73 m²): Clearance similar to that in patients with normal renal function.

Severe renal impairment (Cl_cr 15–29 mL/minute per 1.73 m²): Data not available.

Age (range: 19–96 years), body weight (34–149 kg), gender, race, albumin concentrations, LDH concentrations, S_cr, PD-L1 expression, and ECOG performance status do not have meaningful effects on pharmacokinetics of durvalumab.

Stability

Storage

Parenteral

Injection

2–8°C in original carton. Do not freeze; protect from light.

Diluted solution may be stored at room temperature for up to 4 hours or at 2–8°C for up to 24 hours (total storage time from initial vial entry until start of IV infusion). Do not freeze.

Compatibility

Parenteral

Solution Compatibility

Compatible
Dextrose 5% in water
Sodium chloride 0.9%

Actions

IgG₁ kappa immunoglobulin that binds to PD-L1.
Overexpression of programmed-death receptor-1 (PD-1) ligands on surface of tumor cells results in activation of PD-1 and CD80 (i.e., B7.1) and suppression of cytotoxic T-cell activity, T-cell proliferation, and cytokine production.
Blocks interaction between PD-L1 and the receptors PD-1 and CD80, resulting in activation of antitumor immune response without inducing antibody-dependent cell-mediated cytotoxicity (ADCC).

Advice to Patients

Importance of advising patients to read the manufacturer's medication guide.
Risk of immune-mediated pneumonitis. Importance of informing clinician immediately if new or worsening cough, chest pain, or shortness of breath occurs.
Risk of immune-mediated hepatitis. Importance of informing clinician immediately if signs and symptoms of liver damage (e.g., jaundice, severe nausea or vomiting, abdominal pain [particularly in right upper quadrant], lethargy, easy bruising or bleeding) occur.
Risk of immune-mediated colitis. Importance of informing clinician immediately if diarrhea, severe abdominal pain, or changes in stool occur.
Risk of immune-mediated endocrine effects. Importance of informing clinician immediately if manifestations of hypophysitis, hyperthyroidism, hypothyroidism, adrenal insufficiency, or type 1 diabetes mellitus occur.
Risk of immune-mediated nephritis. Importance of informing clinician immediately if signs or symptoms of nephritis occur.
Risk of immune-mediated dermatologic effects. Importance of informing clinician immediately if signs or symptoms of severe dermatologic reactions occur.
Risk of other immune-mediated adverse effects. Importance of informing clinician immediately if manifestations of aseptic meningitis, thrombocytopenic purpura, myocarditis, hemolytic anemia, myositis, uveitis, or keratitis occur.
Risk of infections. Importance of informing clinician if fever, flu-like symptoms, cough, or painful or frequent urination occurs.
Risk of infusion-related reactions. Importance of informing clinician if signs and symptoms of such reactions, including dizziness, chills, fever, breathing difficulty (e.g., shortness of breath, wheezing), pruritus, flushing, feeling of faintness, back or neck pain, or angioedema, occur.
Risk of fetal harm. Necessity of advising women of childbearing potential to use an effective method of contraception while receiving the drug and for at least 3 months after discontinuance of therapy. Importance of women informing clinicians if they are or plan to become pregnant. If pregnancy occurs, advise pregnant women of potential risk to the fetus.
Importance of advising women to avoid breast-feeding while receiving the drug and for at least 3 months after discontinuance of therapy.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., autoimmune disorders, history of organ transplantation, liver damage, pulmonary disorders).
Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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.

Distribution of durvalumab is restricted. (See Restricted Distribution under Dosage and Administration.)