Durvalumab (Monograph)

Brand name: Imfinzi
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Jun 10, 2025. Written by ASHP.

Introduction

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

Uses for Durvalumab

Non-small Cell Lung Cancer (NSCLC)

Used in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by continued use as a single agent as adjuvant treatment after surgery, for treatment of resectable (tumors ≥4 cm and/or node positive) NSCLC with no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements in adults.

Used for the treatment of unresectable stage III NSCLC that has not progressed following platinum-based chemotherapy combined with radiation therapy in adults.

Used in combination with tremelimumab-actl and platinum-based chemotherapy for treatment of metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations in adults.

Guidelines for NSCLC have been published by the American Society of Clinical Oncology (ASCO), including for stage III and stage IV NSCLC. For patients with stage III NSCLC receiving concurrent chemoradiation without disease progression during initial therapy, consolidation with durvalumab for up to 12 months should be offered. The living guideline by ASCO for the treatment of patients with stage IV NSCLC without driver mutations states that clinicians may offer durvalumab and tremelimumab plus platinum-based chemotherapy as a first-line treatment option for stage IV patients with good performance status.

Small Cell Lung Cancer (SCLC)

Used as a single agent for treatment of limited-stage SCLC that has not progressed following concurrent platinum-based chemotherapy and radiation therapy in adults (designated an orphan drug by FDA for this use in SCLC).

Used in combination with etoposide and either carboplatin or cisplatin as first-line treatment of extensive-stage SCLC in adults (designated an orphan drug by FDA for this use in SCLC).

Guidelines for SCLC have been published by ASCO and Ontario Health (Cancer Care Ontario). For patients with extensive-stage SCLC, first-line systemic therapy with cisplatin or carboplatin plus etoposide plus immunotherapy (e.g., atezolizumab or durvalumab) followed by maintenance immunotherapy should be offered if there are no contraindications. An ASCO guideline rapid recommendation update states that patients with limited-stage SCLC who have completed concurrent chemoradiotherapy and do not have disease progression should be offered consolidation immunotherapy (i.e., durvalumab) for up to 2 years if there are no contraindications to immunotherapy.

Biliary Tract Cancer

Used in combination with gemcitabine and cisplatin for treatment of locally advanced or metastatic biliary tract cancer in adults (designated an orphan drug by FDA for this use).

Recommendations for the treatment of advanced and metastatic disease are available from international experts. For advanced or metastatic biliary tract cancer, cisplatin-gemcitabine combined with either durvalumab or pembrolizumab is a viable first-line treatment option.

Hepatocellular Carcinoma

Used in combination with tremelimumab-actl for treatment of unresectable hepatocellular carcinoma in adults (designated an orphan drug by FDA for this use).

ASCO recommends atezolizumab plus bevacizumab or durvalumab plus tremelimumab for first-line treatment of patients with advanced hepatocellular carcinoma, Child-Pugh class A liver disease, and ECOG performance status of 0 or 1. May offer sorafenib, lenvatinib, or durvalumab as first-line treatment for such patients when contraindications to atezolizumab plus bevacizumab or durvalumab plus tremelimumab exist. The American Association for the Study of Liver Diseases (AASLD) makes similar recommendations.

Endometrial Cancer

Used in combination with carboplatin and paclitaxel, followed by use as a single agent, for treatment of primary advanced or recurrent endometrial cancer that is mismatch repair deficient, as determined by an FDA-approved test, in adults.

The American College of Obstetricians and Gynecologists (ACOG) has published a practice bulletin on the management of endometrial cancer. This was published before durvalumab, in combination with carboplatin and paclitaxel, was approved for use in endometrial cancer and therefore does not discuss the use of durvalumab in treatment.

Durvalumab Dosage and Administration

General

Pretreatment Screening

• Screen endometrial tumor specimen for presence of mismatch repair deficiency (dMMR) as determined by an FDA-approved test.

• Screen non-small cell lung cancer for epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

• Determine exposure to prior thoracic radiation.

• Obtain baseline weight.

• Obtain baseline creatinine, liver enzymes, and thyroid function.

• Verify pregnancy status in women of reproductive potential.

Patient Monitoring

• Monitor weight prior to each infusion.

• Monitor for pregnancy in female patients.

• Monitor patients closely for clinical manifestations of underlying immune-mediated adverse reactions including but not limited to pneumonitis, colitis, adrenal insufficiency, hypophysitis, dermatitis or rash, myocarditis, neurological toxicity, and pancreatitis.

• Monitor creatinine, liver enzymes, and thyroid function periodically.

• Monitor patients for hyperglycemia or other signs and symptoms of diabetes.

• Monitor for signs and symptoms of infusion-related reactions.

Administration

IV Administration

Administer by IV infusion.

Commercially available as injection concentrate; must be diluted prior to IV administration.

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

Administer using a sterile, low-protein-binding 0.2- to 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.

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.

Combination Regimens: Order of Administration

With tremelimumab-actl, infuse tremelimumab-actl first, followed by durvalumab.

With tremelimumab-actl and platinum-based chemotherapy, infuse tremelimumab-actl first, followed by durvalumab, and then platinum-based chemotherapy.

With tremelimumab-actl and pemetrexed therapy, infuse tremelimumab-actl first, followed by durvalumab, and then pemetrexed.

With carboplatin and paclitaxel, infuse durvalumab first and then carboplatin and paclitaxel.

Combination Regimens: Infusion Instructions

With tremelimumab-actl, administer tremelimumab-actl over 60 minutes. Observe for 60 minutes. Administer durvalumab as a separate IV infusion over 60 minutes.

With tremelimumab-actl and platinum-based chemotherapy/pemetrexed therapy, for cycle 1, administer tremelimumab-actl over 1 hour. Wait 1 to 2 hours and then administer durvalumab over 1 hour. Wait 1-2 hours and then administer platinum-based chemotherapy. If no infusion reactions occur during cycle 1, give subsequent infusions of durvalumab immediately after tremelimumab-actl. Reduce time between the completion of durvalumab infusion and the start of chemotherapy to 30 minutes.

Dosage

Adults

Resectable Non-Small Cell Lung Cancer (NSCLC)

IV

Weight ≥30 kg

Neoadjuvant: 1500 mg in combination with chemotherapy every 3 week for up to 4 cycles. Continue therapy until disease progression that precludes definitive surgery, recurrence, unacceptable toxicity occurs, or a maximum of 12 cycles after surgery.

Adjuvant: 1500 mg as a single agent every 4 weeks for up to 12 cycles after surgery. Continue therapy until disease progression that precludes definitive surgery, recurrence, unacceptable toxicity occurs, or a maximum of 12 cycles after surgery.

Weight <30 kg

Neoadjuvant: 20 mg/kg in combination with chemotherapy every 3 week for up to 4 cycles. Continue therapy until disease progression that precludes definitive surgery, recurrence, unacceptable toxicity occurs, or a maximum of 12 cycles after surgery.

Adjuvant: 20 mg/kg as a single agent every 4 weeks for up to 12 cycles after surgery. Continue therapy until disease progression that precludes definitive surgery, recurrence, unacceptable toxicity occurs, or a maximum of 12 cycles after surgery.

Unresectable Stage III NSCLC

IV

Weight ≥30 kg: 10 mg/kg every 2 weeks or 1500 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs, or for a maximum of 12 months.

Weight <30 kg: 10 mg/kg every 2 weeks. Continue therapy until disease progression or unacceptable toxicity occurs, or for a maximum of 12 months.

Metastatic NSCLC

IV

Weight ≥30 kg

Non-squamous: 1500 mg every 3 weeks for cycles 1—5 and then every 4 weeks for cycles 6—8; given in combination with appropriately dosed tremelimumb and platinum-based chemotherapy. Continue therapy until disease progression or unacceptable toxicity occurs.

Squamous: 1500 mg every 3 weeks for cycles 1—5 and then every 4 weeks for cycles 6—8; given in combination with appropriately dosed tremelimumb and platinum-based chemotherapy. Continue therapy until disease progression or unacceptable toxicity occurs.

Weight <30 kg

Non-squamous: 20 mg/kg every 3 weeks for cycles 1—5 and then every 4 weeks for cycles 6—8; given in combination with appropriately dosed tremelimumb and platinum-based chemotherapy. Continue therapy until disease progression or unacceptable toxicity occurs.

Squamous: 20 mg/kg every 3 weeks for cycles 1—5 and then every 4 weeks for cycles 6—8; given in combination with appropriately dosed tremelimumb and platinum-based chemotherapy. Continue therapy until disease progression or unacceptable toxicity occurs.

Limited-Stage Small Cell Lung Cancer (SCLC)

IV

Weight ≥30 kg: 1500 mg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs or for a maximum of 24 months.

Weight <30 kg: 20 mg/kg every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs or for a maximum of 24 months.

Extensive-Stage SCLC

IV

Weight ≥30 kg: 1500 mg in combination with chemotherapy every 3 weeks for 4 cycles followed by 1500 mg every 4 weeks as a single agent. Continue therapy until disease progression or unacceptable toxicity occurs.

Weight <30 kg: 20 mg/kg in combination with chemotherapy every 3 weeks for 4 cycles followed by 10 mg/kg every 2 weeks as a single agent. Continue therapy until disease progression or unacceptable toxicity occurs.

Biliary Tract Cancer

IV

Weight ≥30 kg: 1500 mg in combination with chemotherapy every 3 weeks for up to 8 cycles followed by 1500 mg every 4 weeks as a single agent. Continue therapy until disease progression or unacceptable toxicity occurs.

Weight <30 kg: 20 mg/kg in combination with chemotherapy every 3 weeks for up to 8 cycles followed by 20 mg/kg every 4 weeks as a single agent. Continue therapy until disease progression or unacceptable toxicity occurs.

Unresectable Hepatocellular Carcinoma

IV

Weight ≥30 kg: 1500 mg following a single dose of tremelimumab-actl 300 mg at day 1 of cycle 1 and then continue durvalumab 1500 mg as a single agent every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Weight <30 kg: 20 mg/kg following a single dose of tremelimumab-actl 4 mg/kg at day 1 of cycle 1 and then continue durvalumab 20 mg/kg as a single agent every 4 weeks. Continue therapy until disease progression or unacceptable toxicity occurs.

Endometrial Cancer (Mismatch Repair Deficient)

IV

Weight ≥30 kg: 1120 mg in combination with carboplatin and paclitaxel every 3 weeks for 6 cycles, followed by durvalumab 1500 every 4 weeks as a single agent. Continue therapy until disease progression or unacceptable toxicity occurs.

Weight <30 kg: 15 mg/kg in combination with carboplatin and paclitaxel every 3 weeks for 6 cycles, followed by durvalumab 20 mg/kg every 4 weeks as a single agent. Continue therapy until disease progression or unacceptable toxicity occurs.

Dosage Modifications for Toxicity

Withhold durvalumab for severe (grade 3) immune mediated adverse reactions. Permanently discontinue durvalumab for life-threatening (grade 4) immune-mediated adverse reactions, recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dosage to ≤10 mg of prednisone or equivalent per day within 12 weeks of initiating corticosteroids. Specific recommendations that differ from these general guidelines are summarized in Table 1.

Resume in patients with complete or partial resolution (grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or an inability to reduce corticosteroid dose to 10 mg of prednisone or less per day (or equivalent) within 12 weeks of initiating corticosteroids.

Permanently discontinue for grade 3 colitis when administered as part of a tremelimumab-actl containing regimen.

If AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue treatment based on recommendations for hepatitis with no liver involvement.

Special Populations

Hepatic Impairment

No dosage recommendations in patients with mild or moderate hepatic impairment. Not studied in patients with severe hepatic impairment.

Renal Impairment

No dosage recommendations in patients with mild or moderate renal impairment. Not studied in patients with severe renal impairment.

Geriatric Patients

No specific dosage recommendations at this time.

Cautions for Durvalumab

Contraindications

• None.

Warnings/Precautions

Immune-mediated Adverse Reactions

Severe or fatal immune-mediated adverse reactions can occur in any organ system or tissue; generally occur during therapy but can manifest after discontinuation.

Monitor patients closely for clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue durvalumab depending on severity. In general, if durvalumab requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg per day prednisone or equivalent) until improvement to grade 1 or less. Upon improvement to grade 1 or less, initiate corticosteroid taper and continue to taper over ≥1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Certain reactions, such as endocrinopathies and dermatologic reactions, do not necessarily require systemic steroids.

Immune-mediated Pneumonitis

Immune-mediated pneumonitis can occur with higher incidence in patients with prior thoracic radiation. Monitor patients for manifestations of pneumonitis.

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). Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or an inability to reduce corticosteroid dose to ≤10 mg of prednisone per day (or equivalent) within 12 weeks of initiating corticosteroids.

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

Immune-mediated Colitis

Diarrhea or colitis, including immune-mediated colitis (requiring corticosteroid therapy), reported. Intestinal perforation has been observed in other studies of durvalumab in combination with tremelimumab-actl. Monitor patients for manifestations of colitis or diarrhea.

If grade 2 or 3 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. Permanently discontinue for grade 3 colitis when administered as part of a tremelimumab-actl containing regimen.

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). Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or an inability to reduce corticosteroid dose to ≤10 mg of prednisone per day (or equivalent) within 12 weeks of initiating corticosteroids.

If grade 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.

If any grade of intestinal perforation occurs, permanently discontinue durvalumab.

Immune-mediated Hepatitis

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.

In patients without hepatic tumor involvement, if ALT or AST concentrations >3–8 times ULN or total bilirubin concentrations >1.5–3 times 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 ULN or total bilirubin concentrations >3 times ULN occur, permanently discontinue durvalumab and initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of corticosteroid dosage.

In patients with hepatic tumor involvement, if ALT or AST increases to more than 1 and up to 3 times ULN at baseline and increases to no more than 5 and up to 10 times the ULN, or if ALT or AST is more than 3 and up to 5 times ULN at baseline and increases no more than 8 and up to 10 times ULN, 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 increases to more than 10 times ULN or total bilirubin increases to more than 3 times 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.

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). Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or an inability to reduce corticosteroid dose to ≤10 mg of prednisone per day (or equivalent) within 12 weeks of initiating corticosteroids.

Immune-mediated Endocrinopathies

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

Adrenal Insufficiency: Monitor for signs and symptoms of adrenal insufficiency.

If grade 3 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 or permanently discontinue depending on severity.

Hypophysitis: Monitor for signs and symptoms of hypophysitis. Hypophysitis can cause hypopituitarism.

If grade 3 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 or permanently discontinue depending on severity.

Thyroid Disorders: Evaluate thyroid function prior to initiation and periodically during therapy. If immune-mediated thyroiditis, hypothyroidism, or hyperthyroidism occur, if appropriate, initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of the corticosteroid dosage, if possible. Withhold or discontinue durvalumab based on severity.

If immune-mediated hypothyroidism occurs, initiate thyroid hormone replacement therapy as clinically indicated. If immune-mediated hyperthyroidism occurs, initiate appropriate medical therapy.

Type 1 Diabetes, which can Present with Diabetic Ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue durvalumab based on the severity.

Immune-mediated Nephritis with Renal Dysfunction

Evaluate renal function prior to initiation and periodically thereafter.

If grade 2 or 3 elevations in blood creatinine 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.

For toxicity not resulting in permanent drug discontinuance, resume durvalumab therapy when toxicity resolves to grade 0 or 1 and corticosteroid dosage is reduced to ≤10 mg of prednisone daily (or equivalent). Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or an inability to reduce corticosteroid dosage to ≤10 mg of prednisone per day (or equivalent) within 12 weeks of initiating corticosteroids.

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

Immune-mediated Dermatologic Reactions

Immune-mediated rash or dermatitis (e.g., drug rash with eosinophilia and systemic symptoms [DRESS], Stevens-Johnson syndrome [SJS]/toxic epidermal necrolysis [TEN]) reported.

Monitor patients for signs and symptoms of rash or dermatitis. If DRESS, SJS, or TEN suspected, interrupt durvalumab therapy and initiate systemic corticosteroid therapy (1–2 mg/kg of prednisone daily [or equivalent]) followed by tapering of 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). Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or an inability to reduce corticosteroid dosage to ≤10 mg of prednisone per day (or equivalent) within 12 weeks of initiating corticosteroids. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or an inability to reduce corticosteroid dosage to ≤10 mg of prednisone per day (or equivalent) within 12 weeks of initiating corticosteroids.

If DRESS, SJS, or TEN confirmed, permanently discontinue durvalumab and initiate appropriate treatment.

Immune-mediated Pancreatitis

Monitor patients for signs and symptoms of pancreatitis.

If grade 3 pancreatitis occurs, interrupt durvalumab therapy and initiate appropriate treatment.

If grade 4 pancreatitis occurs, permanently discontinue durvalumab and initiate appropriate treatment.

Other Immune-mediated Adverse Reactions

Have involved the following general systems: cardiac/vascular, nervous system, ocular, gastrointestinal, musculoskeletal, connective tissue, endocrine, hematologic, and immune systems.

If grade 2 immune-mediated toxicity 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.

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). Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or an inability to reduce corticosteroid dose to ≤10 mg of prednisone per day (or equivalent) within 12 weeks of initiating corticosteroids.

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 corticosteroid dosage.

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.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) After Durvalumab

Transplant-related complications can occur and include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider benefits versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.

Fetal/Neonatal Morbidity and Mortality

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

Avoid pregnancy during therapy. Verify pregnancy status in women of reproductive potential prior to initiation. 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.

Immmunogenicity

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 based on findings from animal studies and mechanism of action. No available data on use in pregnant women. Increase in premature delivery, fetal loss, and premature neonatal death observed in animals.

Apprise pregnant women of potential fetal hazard.

Lactation

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

Females and Males of Reproductive Potential

Verify pregnancy status prior to initiation.

Advise women to use effective contraception during treatment and for 3 months following the last dose.

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 or moderate hepatic impairment. Data lacking in patients with severe hepatic impairment.

Renal Impairment

Clearance not affected by mild or moderate renal impairment. Data lacking in patients with severe renal impairment.

Common Adverse Effects

Durvalumab with Chemotherapy: The most common adverse reactions (≥20% of patients with resectable, Stage II/III NSCLC [neoadjuvant /adjuvant]) are anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash.

Durvalumab as a Single Agent: The most common adverse reactions (≥20% of patients with unresectable, Stage III NSCLC) are cough, fatigue, pneumonitis/radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash. The most common adverse reactions (≥20% of patients with LS-SCLC) are pneumonitis or radiation pneumonitis, and fatigue.

Durvalumab with Tremelimumab-actl and Platinum-Based Chemotherapy: The most common adverse reactions (≥20% of patients with metastatic NSCLC) were nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea.

Durvalumab with Platinum-Based Chemotherapy: The most common adverse reactions (≥20% of patients with ES-SCLC) are nausea, fatigue/asthenia, and alopecia.

Durvalumab with Gemcitabine and Cisplatin: The most common adverse reactions (≥20% of patients with BTC) are fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia.

Durvalumab with Tremelimumab-actl: The most common adverse reactions (≥20% of patients with uHCC) are rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain.

Durvalumab with Carboplatin and Paclitaxel, followed by Durvalumab as a Single Agent: The most common adverse reactions (≥20% of patients with endometrial cancer) were peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, decreased magnesium, increased ALT, increased AST, diarrhea, vomiting, cough, decreased potassium, dyspnea, headache, and increased alkaline phosphatase.

Drug Interactions

No formal drug interaction studies to date. CYP-based drug interactions not anticipated.

Durvalumab Pharmacokinetics

Absorption

Bioavailability

Steady-state concentrations achieved within approximately 16 weeks.

Systemic exposure is dose proportional at doses ≥3 mg/kg every 2 weeks.

Distribution

Extent

Not known whether durvalumab is distributed into human milk. Maternal IgG excreted into human milk.

Elimination

Half-life

Approximately 21 days.

Special Populations

Mild to moderate hepatic impairment (total bilirubin concentration ≤3 times ULN with any AST concentration) does not affect pharmacokinetics. Lack of data for severe hepatic impairment (total bilirubin concentration >3 times ULN with any AST concentration).

Mild to moderate renal impairment (Cl_Cr ≥30—89 mL/minute) does not affect clearance.

Age, gender, race, albumin levels, lactate dehydrogenase levels, soluble PD-L1, and tumor burden 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 (up to 25ºC) for up to 8 hours or at 2–8°C for up to 28 days (total storage time from initial vial entry until start of IV infusion). Do not freeze.

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

• Advise patients to read the manufacturer's medication guide.

• Risk of immune-mediated pneumonitis. Advise patients to inform their clinician immediately if new or worsening cough, chest pain, or shortness of breath occurs.

• Risk of immune-mediated hepatitis. Advise patients to inform their clinician immediately if signs and symptoms of liver damage (e.g., jaundice, severe nausea or vomiting, abdominal pain [particularly in the right upper quadrant], lethargy, easy bruising or bleeding) occur.

• Risk of immune-mediated colitis. Advise patients to inform their clinician immediately if diarrhea, blood or mucus in stools, or severe abdominal pain, occur.

• Risk of immune-mediated endocrine effects. Advise patients to inform their clinician immediately if manifestations of hypophysitis, hyperthyroidism, hypothyroidism, adrenal insufficiency, or type 1 diabetes mellitus occur.

• Risk of immune-mediated nephritis. Advise patients to inform their clinician immediately if signs or symptoms of nephritis occur.

• Risk of immune-mediated dermatologic effects. Advise patients to inform their 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 pancreatitis, aseptic meningitis, encephalitis, immune thrombocytopenia , myocarditis, hemolytic anemia, myositis, uveitis, keratitis, or myasthenia gravis 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. Advise patients to inform their 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, and angioedema, occur.

• Advise patients of potential risk of post-transplant complications.

• Risk of fetal harm. Advise women of childbearing potential that they should use an effective method of contraception while receiving the drug and for at least 3 months after discontinuance of therapy. Advise women of the importance of informing clinicians if they are or plan to become pregnant. If pregnancy occurs, advise pregnant women of potential risk to the fetus.

• Advise patients to avoid breast-feeding while receiving the drug and for at least 3 months after discontinuance of therapy.

• Advise patients to inform their 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).

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

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