ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد ایتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Durvalumab: Drug information

Durvalumab: Drug information
(For additional information see "Durvalumab: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Imfinzi
Brand Names: Canada
  • Imfinzi
Pharmacologic Category
  • Antineoplastic Agent, Anti-PD-L1 Monoclonal Antibody;
  • Antineoplastic Agent, Immune Checkpoint Inhibitor;
  • Antineoplastic Agent, Monoclonal Antibody
Dosing: Adult
Biliary tract cancer, advanced

Biliary tract cancer, advanced (off-label use): IV: 1,500 mg once every 3 weeks (in combination with gemcitabine and cisplatin) for up to 8 cycles, followed by 1,500 mg once every 4 weeks as a single agent until disease progression or unacceptable toxicity (Oh 2022).

Non-small cell lung cancer, unresectable

Non-small cell lung cancer (stage 3), unresectable:

Note: In the clinical trial, durvalumab was initiated within 6 weeks after chemoradiotherapy; treatment was continued beyond 12 months if disease control was achieved at the end of 12 months but then progressed during follow-up (Antonia 2017; Antonia 2018).

Patients ≥30 kg: IV: 10 mg/kg once every 2 weeks or 1,500 mg once every 4 weeks; continue until disease progression or unacceptable toxicity or a maximum of 12 months.

Patients <30 kg: IV: 10 mg/kg once every 2 weeks; continue until disease progression or unacceptable toxicity or a maximum of 12 months.

Small cell lung cancer, extensive stage

Small cell lung cancer, extensive stage:

Patients ≥30 kg: IV: 1,500 mg once every 3 weeks (in combination with etoposide and either carboplatin or cisplatin) for 4 cycles, followed by 1,500 mg once every 4 weeks as a single agent; continue until disease progression or unacceptable toxicity (Paz-Ares 2019).

Patients <30 kg: IV: 20 mg/kg once every 3 weeks (in combination with etoposide and either carboplatin or cisplatin) for 4 cycles, followed by 10 mg/kg once every 2 weeks as a single agent; continue until disease progression or unacceptable toxicity.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Renal impairment prior to treatment initiation:

CrCl 30 to 89 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, there is no clinically relevant effect on pharmacokinetics.

CrCl 15 to 29 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Renal toxicity during treatment:

Immune-mediated nephritis with kidney dysfunction: If durvalumab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to ≤ grade 1, then follow with a corticosteroid taper.

Grade 2 or grade 3 serum creatinine elevation: Withhold durvalumab; resume durvalumab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper. Permanently discontinue durvalumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Grade 4 serum creatinine elevation: Permanently discontinue durvalumab.

Dosing: Hepatic Impairment: Adult

Hepatic impairment prior to treatment initiation:

Mild impairment (bilirubin ≤ ULN and AST > ULN or bilirubin >1 to 1.5 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling; however, there is no clinically relevant effect on pharmacokinetics.

Moderate impairment (bilirubin >1.5 to 3 times ULN and any AST) or severe (bilirubin >3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Hepatotoxicity during treatment:

If durvalumab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to ≤ grade 1, then follow with a corticosteroid taper. Permanently discontinue durvalumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Immune-mediated hepatitis without tumor involvement of the liver:

AST or ALT >3 up to 8 × ULN or total bilirubin >1.5 up to 3 × ULN: Withhold durvalumab treatment. Resume durvalumab treatment with complete or partial resolution (to grade 0 or 1) of hepatitis after corticosteroid taper.

AST or ALT >8 × ULN or total bilirubin >3 × ULN: Discontinue durvalumab permanently.

Immune-mediated hepatitis with tumor involvement of the liver: Note: If AST and ALT are ≤ ULN at baseline, follow recommendations for hepatitis without tumor involvement of the liver.

If baseline AST or ALT >1 up to 3 × ULN and increases to >5 up to 10 × ULN or baseline AST or ALT >3 up to 5 × ULN and increases to >8 up to 10 × ULN: Withhold durvalumab treatment. Resume durvalumab treatment with complete or partial resolution (to grade 0 or 1) of hepatitis after corticosteroid taper.

If AST or ALT increases to >10 × ULN or total bilirubin increases to >3 × ULN: Discontinue durvalumab permanently.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult

Note: No dose reduction for durvalumab is recommended. Other concomitant combination therapy medications may also require treatment interruption, dosage reduction, and/or discontinuation.

Immune-mediated adverse reactions (general information): 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 inability to reduce corticosteroid dose to prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating corticosteroids. In general, if durvalumab treatment interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone [or equivalent]) until improvement to ≤ grade 1; upon improvement to ≤ grade 1, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants if immune-mediated adverse reaction is not controlled with systemic corticosteroid therapy. Systemic corticosteroids may not be necessary for certain adverse reactions. Hormone replacement therapy may be required for endocrinopathies (if clinically indicated). See table for additional dosage modification guidance.

Additional management recommendations: Consider withholding checkpoint inhibitor therapy for most grade 2 toxicities and resume when symptoms and/or lab values resolve to ≤ grade 1; systemic corticosteroids (initial dose of 0.5 to 1 mg/kg/day prednisone [or equivalent]) may be administered if indicated for grade 2 toxicities (ASCO [Schneider 2021]). Refer to guideline for further information regarding management of immune-mediated adverse reactions associated with checkpoint inhibitor therapy.

Durvalumab Recommended Dosage Modifications for Adverse Reactions

Adverse reaction

Severity

Durvalumab dosage modification

a SJS = Stevens-Johnson Syndrome; TEN = toxic epidermal necrolysis; DRESS = drug rash with eosinophilia and systemic symptoms.

b Refer to prednisone monograph for tapering recommendations when used for immune-mediated adverse reactions associated with checkpoint inhibitor therapy.

Immune-mediated adverse reactions

Cardiovascular toxicity: Myocarditis

Grade 2, 3, or 4

Permanently discontinue durvalumab.

Dermatologic toxicity

Mild or moderate nonexfoliative rash

May be managed with topical emollients and/or topical corticosteroids.

Exfoliative dermatologic conditions: Suspected SJS, TEN, or DRESSa

Withhold durvalumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper.b Permanently discontinue durvalumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Confirmed SJS, TEN, or DRESSa

Permanently discontinue durvalumab.

Endocrinopathies

Grade 3 or 4

Withhold durvalumab until clinically stable or permanently discontinue (depending on severity).

Adrenal insufficiency, ≥ grade 2

Initiate symptomatic management (including hormone replacement as clinically indicated).

Diabetes, type 1

Initiate insulin as clinically indicated.

Hypophysitis

Withhold or discontinue durvalumab (depending on severity). Initiate hormone replacement therapy as clinically indicated.

Hyperthyroidism

Initiate medical management as clinically indicated.

Hypothyroidism

Initiate thyroid hormone replacement therapy as clinically indicated.

GI toxicity: Colitis

Grade 2 or 3

Withhold durvalumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper.b Permanently discontinue durvalumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Grade 4

Permanently discontinue durvalumab.

Neurologic toxicities

Grade 2

Withhold durvalumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper.b Permanently discontinue durvalumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Grade 3 or 4

Permanently discontinue durvalumab.

Ocular disorders: Vogt-Koyanagi-Harada-like syndrome

May require systemic corticosteroids to reduce the risk of permanent vision loss.

Pulmonary toxicity: Pneumonitis

Grade 2

Withhold durvalumab; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taper.b Permanently discontinue durvalumab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.

Grade 3 or 4

Permanently discontinue durvalumab.

Other adverse reactions

Infusion reactions

Grade 1 or 2

Interrupt or slow the rate of durvalumab infusion. Consider premedication(s) with subsequent doses.

Grade 3 or 4

Permanently discontinue durvalumab.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Imfinzi: 120 mg/2.4 mL (2.4 mL); 500 mg/10 mL (10 mL) [contains polysorbate 80]

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Imfinzi: 50 mg/mL (2.4 mL, 10 mL) [contains polysorbate 80]

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Imfinzi: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761069s028lbl.pdf#page=26

Administration: Adult

IV: Infuse over 60 minutes through an IV line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter. Do not administer other medications through the same IV line. Administer durvalumab prior to chemotherapy (when used in combination) on the same day.

Monitor for infusion reactions. Interrupt or slow the infusion for grade 1 or 2 infusion-related reactions (consider premedications with subsequent infusions); discontinue permanently for grade 3 or 4 reactions.

Use: Labeled Indications

Non–small cell lung cancer, unresectable: Treatment of unresectable stage 3 non-small cell lung cancer in adults whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

Small cell lung cancer, extensive stage: First-line treatment of extensive-stage small cell lung cancer in combination with etoposide and either carboplatin or cisplatin in adults.

Use: Off-Label: Adult

Biliary tract cancer, advanced

Medication Safety Issues
Sound-alike/look-alike issues:

Durvalumab be confused with atezolizumab, avelumab, daratumumab, denosumab, dinutuximab, dostarlimab, duvelisib, emapalumab, nivolumab, pembrolizumab

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Dermatologic: Pruritus (12%), skin rash (≤23%)

Endocrine & metabolic: Hyperglycemia (52%), hyperkalemia (32%), hypocalcemia (46%), hyponatremia (33%), hypothyroidism (7% to 12%), increased gamma-glutamyl transferase (24%)

Gastrointestinal: Diarrhea (18%)

Hematologic & oncologic: Lymphocytopenia (43%; grades 3/4: 17%)

Hepatic: Increased serum alanine aminotransferase (39%), increased serum aspartate aminotransferase (36%)

Nervous system: Fatigue (34%)

Respiratory: Cough (≤40%), dyspnea (25%), pneumonia (17%), pneumonitis (≤34%), productive cough (≤40%), radiation pneumonitis (≤34%), upper respiratory tract infection (26%)

Miscellaneous: Fever (15%)

1% to 10%:

Cardiovascular: Peripheral edema (<10%)

Dermatologic: Dermatitis (≤2%), night sweats (<10%)

Endocrine & metabolic: Hyperthyroidism (7%)

Gastrointestinal: Abdominal pain (10%), colitis (2%)

Genitourinary: Dysuria (<10%)

Hepatic: Hepatitis (1%)

Immunologic: Antibody development (3%; neutralizing: <1%)

Infection: Increased susceptibility to infection (<10%)

Nervous system: Voice disorder (<10%)

Miscellaneous: Infusion related reaction (2%; including severe infusion-related reaction) (SITC [Brahmer 2021])

<1%:

Cardiovascular: Myocarditis, pericarditis, vasculitis

Endocrine & metabolic: Adrenocortical insufficiency, hypoparathyroidism, hypophysitis (grade 3), pituitary insufficiency (grade 3), thyroiditis, type 1 diabetes mellitus (grade 3)

Gastrointestinal: Duodenitis, gastritis, increased serum amylase, increased serum lipase, pancreatitis

Hematologic & oncologic: Aplastic anemia, hemolytic anemia, immune thrombocytopenia, immunological signs and symptoms (hemophagocytic lymphohistiocytosis), lymphadenitis (histiocytic necrotizing lymphadenitis [Kikuchi lymphadenitis]), sarcoidosis

Immunologic: Organ transplant rejection (solid)

Infection: Systemic inflammatory response syndrome

Nervous system: Demyelinating disease, encephalitis, Guillain-Barre syndrome, meningitis, myasthenia (myasthenic syndrome), myasthenia gravis (including exacerbation of myasthenia gravis), neuropathy (autoimmune), paresis (nerve)

Neuromuscular & skeletal: Myelitis, myositis, polymyositis, rhabdomyolysis

Ophthalmic: Iritis, uveitis

Renal: Nephritis

Postmarketing:

Dermatologic: Pemphigoid (SITC [Brahmer 2021]), Stevens-Johnson syndrome (SITC [Brahmer 2021]), toxic epidermal necrolysis (SITC [Brahmer 2021])

Gastrointestinal: Cholangitis (SITC [Brahmer 2021]), cholecystitis (SITC [Brahmer 2021]), esophagitis (SITC [Brahmer 2021]), nausea (SITC [Brahmer 2021]), xerostomia (SITC [Brahmer 2021])

Hematologic & oncologic: Neutropenia (SITC [Brahmer 2021]), pure red cell aplasia (SITC [Brahmer 2021])

Hepatic: Hepatotoxicity (Chalasani 2021)

Immunologic: Sjögren's syndrome (SITC [Brahmer 2021])

Neuromuscular & skeletal: Arthralgia (SITC [Brahmer 2021]), arthritis (SITC [Brahmer 2021]), myalgia (SITC [Brahmer 2021]), polymyalgia rheumatica (SITC [Brahmer 2021])

Ophthalmic: Dry eye syndrome (SITC [Brahmer 2021])

Renal: Acute kidney injury (SITC [Brahmer 2021])

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to durvalumab or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Adverse reactions (immune-mediated): PD-1/PD-L1 blockers (including durvalumab) remove immune response inhibition, thus potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Severe and fatal immune-mediated adverse reactions may occur in any organ system or tissue. Reactions generally occur during treatment (may occur at any time after durvalumab initiation); reactions may also occur after durvalumab discontinuation. Early identification and management of immune-mediated reactions are necessary to ensure safe use of durvalumab. If suspected immune-mediated reactions occur, initiate appropriate workup to exclude alternative causes (including infection). Medically manage immune-mediated adverse reactions promptly and refer for specialty consultation as appropriate.

• Dermatologic toxicity: Durvalumab may cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti-PD-1/PD-L1 monoclonal antibodies. Immune-mediated dermatologic adverse reactions (including grade 3 events) occurred with durvalumab. Immune-mediated dermatologic reactions were treated with systemic corticosteroids, and reactions resolved in over half of patients.

• Endocrinopathies: Durvalumab is associated with immune-mediated endocrinopathies.

- Adrenal insufficiency: Adrenal insufficiency (primary or secondary) may occur. Grade 3 events have been reported (rare). Systemic corticosteroids were administered for adrenal insufficiency; most patients remained on corticosteroid therapy. Withhold or permanently discontinue durvalumab for adrenal insufficiency, depending on the severity.

- Diabetes mellitus: Type 1 diabetes mellitus has occurred (which may present with diabetic ketoacidosis), including rare grade 3 events. Long-term insulin therapy has been required in some cases.

- Hypophysitis: Durvalumab has been associated with immune-mediated hypophysitis, which may present with acute mass effect symptoms, including headache, photophobia, or visual field defects. Hypophysitis may lead to hypopituitarism. Grade 3 hypophysitis/hypopituitarism occurred rarely; systemic corticosteroids were administered.

- Thyroid disorders: Immune-mediated thyroid disorders have occurred. Depending on severity, immune-mediated thyroid disorders may require treatment interruption or permanent discontinuation. Systemic corticosteroids were required in one-third of patients with hyperthyroidism. Resolution occurred in the majority of patients with hyperthyroidism. Hypothyroidism has occurred, including grade 3 cases. Hypothyroidism may follow hyperthyroidism. Systemic corticosteroids were necessary in some patients, and a majority of patients required long-term thyroid hormone replacement therapy. Thyroiditis may present with or without endocrinopathy. Thyroiditis occurred rarely and did not result in permanent discontinuation of durvalumab. Systemic corticosteroids or endocrine therapy were required in some patients.

• GI adverse effects: Immune-mediated colitis has occurred with durvalumab, including grade 3 and 4 cases. Diarrhea is the primary colitis symptom. Systemic corticosteroids were administered for immune-mediated colitis; the majority of patients with colitis experienced resolution. Some patients required other immunosuppressants (rarely) to manage colitis. Cytomegalovirus infection or reactivation has been observed in patients with corticosteroid-refractory, immune-mediated colitis. Pancreatitis (including increased serum amylase and lipase levels), gastritis, and duodenitis have also been reported.

• Hepatotoxicity: Immune-mediated hepatitis has occurred with durvalumab, including grade 3 and fatal cases. Systemic corticosteroids were used to manage immune-mediated hepatitis; resolution occurred in over half of patients. Mycophenolate (in combination with corticosteroids) was used to manage hepatitis rarely.

• Infusion reactions: Infusion reactions have been observed with durvalumab, including severe or life-threatening infusion-related reactions.

• Nephrotoxicity: Immune-mediated nephritis with renal dysfunction has occurred (rarely), including grade 3 cases. Nephritis was treated with systemic corticosteroids and resolved in most patients.

• Ocular toxicity: Immune-mediated uveitis, iritis, and other ocular inflammatory toxicities may occur with durvalumab. Some cases can be associated with retinal detachment. Differing grades of visual impairment (including blindness) may occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome.

• Pulmonary toxicities: Immune-mediated pneumonitis has been observed (both in patients who did or did not receive prior radiation), including grade 3 and 4 and fatal cases. Pneumonitis incidence is higher in patients who have received prior thoracic radiation. Pneumonitis was managed with systemic corticosteroids in the majority of cases and resolved in approximately half of the affected patients. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to durvalumab were similar whether durvalumab was administered as a single agent or in combination with chemotherapy.

• Other immune-mediated toxicities: Other clinically relevant immune-mediated disorders have been observed rarely with durvalumab use (or other anti-PD-1/PD-L1 monoclonal antibodies) and may affect any organ system (may be fatal), including myocarditis, pericarditis, vasculitis, meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy, myositis/polymyositis, rhabdomyolysis (and associated sequelae including renal failure), arthritis, polymyalgia rheumatic, hypoparathyroidism, hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, and solid organ transplant rejection.

Disease-related concerns:

• Hematopoietic stem cell transplant: Fatal and other serious complications may occur in patients who received allogeneic hematopoietic stem cell transplant (HSCT) before or after treatment with an anti-PD-1/PD-L1 monoclonal antibody. Transplant-related complications may include hyperacute graft-versus-host disease (GVHD), acute or chronic GVHD, hepatic veno-occlusive disease (also known as sinusoidal obstruction syndrome) after reduced-intensity conditioning, and steroid-requiring febrile syndrome (with no identified infectious etiology). These complications may occur despite intervening therapy between durvalumab and HSCT. Manage early signs/symptoms of transplant-related complications promptly. Assess the risks/benefits of treatment with an anti-PD-1/PD-L1 monoclonal antibody prior to or after an allogenic HSCT.

• Myasthenia gravis: Checkpoint inhibitors may worsen or precipitate new myasthenia gravis (MG), especially within the first 16 weeks of treatment; use with caution. Patients with well-controlled MG may be considered for checkpoint inhibitor therapy if MG treatment is maintained (or reinitiated in patients whose MG is in remission), combination therapy (eg, anti–CTLA-4 with anti–PD-a/PD-L1 monoclonal antibodies) is avoided, and respiratory and bulbar function are closely followed. In patients who develop overt MG during checkpoint inhibitor therapy, early aggressive treatment with plasma exchange or IVIG in combination with high-dose corticosteroids may be required (AAN [Narayanaswami 2021]).

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Antibiotics: May diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy

Corticosteroids (Systemic): May diminish the therapeutic effect of Immune Checkpoint Inhibitors. Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended Risk D: Consider therapy modification

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Inhibitors of the Proton Pump (PPIs and PCABs): May diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy

Ketoconazole (Systemic): Immune Checkpoint Inhibitors may enhance the hepatotoxic effect of Ketoconazole (Systemic). Risk C: Monitor therapy

Reproductive Considerations

Patients who could become pregnant should use effective contraception during therapy and for at least 3 months after the last durvalumab dose.

Pregnancy Considerations

Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to durvalumab may cause fetal harm. Durvalumab is a humanized monoclonal antibody (IgG1). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Breastfeeding Considerations

It is not known if durvalumab is present in breast milk; however, endogenous immunoglobulins are excreted in breast milk. Due to the potential for adverse events in a breastfed infant, breastfeeding is not recommended by the manufacturer during therapy or for at least 3 months after the last durvalumab dose.

Monitoring Parameters

Monitor liver function; renal (creatinine); thyroid function tests (at baseline, periodically during treatment); blood glucose (for hyperglycemia). Monitor closely for clinical signs/symptoms of immune-mediated adverse reactions, including adrenal insufficiency, colitis/diarrhea (consider initiating or repeating infectious workup in patients with corticosteroid-refractory immune-mediated colitis to exclude alternative causes), dermatologic toxicity, diabetes/hyperglycemia, hepatitis/hepatotoxicity, hypophysitis or hypopituitarism, pneumonitis, ocular toxicity, and thyroid disorders. Monitor for signs/symptoms of infusion reactions. If received/receiving hematopoietic stem cell transplant, monitor closely for early signs/symptoms of transplant-related complications.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Additional suggested monitoring (ASCO [Schneider 2021):

Prior to therapy: CBC with differential, serum chemistries, creatine kinase; comprehensive clinical assessment including performance status, weight, body mass index, heart rate, blood pressure, and oxygen saturation; consider chest x-ray, electrocardiogram, and CT scan; assess history of autoimmune conditions, organ-specific disease, endocrinopathies, neuropathy, and infectious disease; assess bowel habits, respiratory symptoms, skin (for rash), arthralgias, and neurologic symptoms.

During therapy: Assess blood pressure, weight, heart rate, and oxygen saturation; assess for infections, screen for hyperglycemia/diabetes (polyuria, polydipsia, weight loss); eye exam (including intraocular pressure after 6 weeks), CBC with differential, serum chemistries, and creatine kinase; monitor bone mineral density (with long-term therapy).

Mechanism of Action

Durvalumab is a human immunoglobulin G1 kappa monoclonal antibody which blocks programmed cell death ligand 1 (PD-L1) binding to PD-1 and CD80 (B7.1); PD-L1 blockade leads to increased T-cell activation, allowing T-cells to kill tumor cells (Massard 2016). PD-L1 is an immune check point protein expressed on tumor cells and tumor infiltrating cells and down regulates anti-tumor t-cell function by binding to PD-1 and B7.1; blocking PD-1 and B7.1 interactions restores antitumor t-cell function (Fehrenbacher 2016; Rosenberg 2016).

Pharmacokinetics

Note: The steady state AUC, Ctrough, and Cmax in patients who received 1,500 mg once every 4 weeks are 6% higher, 19% lower, and 55% higher (respectively) compared to those who received 10 mg/kg once every 2 weeks. Based on pharmacokinetic modeling data and safety exposure relationships, there are no anticipated clinically meaningful differences in efficacy and safety for 1,500 mg once-every-4-weeks doses compared to 10 mg/kg once-every-2-weeks doses in patients with non–small cell lung cancer weighing >30 kg.

Distribution: Vdss: 5.6 L

Half-life, elimination: Terminal half-life: ~18 days

Excretion: Steady-state clearance: 8.2 mL/hour

Pricing: US

Solution (Imfinzi Intravenous)

120MG/2.4ML (per mL): $453.10

500 mg/10 mL (per mL): $453.09

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Imfinzi (AR, AT, AU, BR, CZ, DE, EE, ES, FR, GB, HK, HR, HU, IL, IN, IS, JP, LB, LT, LV, MY, NL, NO, NZ, PL, PT, RO, SG, SK, TH)


For country abbreviations used in Lexicomp (show table)
  1. Alade SL, Brown RE, Paquet A Jr. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593-597. [PubMed 3960626]
  2. Antonia SJ, Villegas A, Daniel D, et al; PACIFIC Investigators. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377(20):1919-1929. [PubMed 28885881]
  3. Antonia SJ, Villegas A, Daniel D, et al; PACIFIC Investigators. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350. doi:10.1056/NEJMoa1809697 [PubMed 30280658]
  4. Brahmer JR, Abu-Sbeih H, Ascierto PA, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 2021;9(6):e002435. doi:10.1136/jitc-2021-002435 [PubMed 34172516]
  5. Centers for Disease Control and Prevention (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. [PubMed 6423951]
  6. Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR; Practice parameters committee of the American College of Gastroenterology. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116(5):878-898. doi:10.14309/ajg.0000000000001259 [PubMed 33929376]
  7. Fehrenbacher L, Spira A, Ballinger M, et al; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016;387(10030):1837-1846. doi: 10.1016/S0140-6736(16)00587-0. [PubMed 26970723]
  8. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  9. Imfinzi (durvalumab) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; May 2022.
  10. Imfinzi (durvalumab) [product monograph]. Mississauga, Ontario, Canada: AstraZeneca Canada Inc; April 2022.
  11. Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313. [PubMed 12534540]
  12. Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172. [PubMed 10985636]
  13. Massard C, Gordon MS, Sharma S, et al. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol. 2016;34(26):3119-3125. doi:10.1200/JCO.2016.67.9761 [PubMed 27269937]
  14. Narayanaswami P, Sanders DB, Wolfe G, et al. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology. 2021;96(3):114-122. doi:10.1212/WNL.0000000000011124 [PubMed 33144515]
  15. Oh DY, He AR, Qin S, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemsitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. American Society of Clinical Oncology. https://d32wbias3z7pxg.cloudfront.net/meeting/286/abstract/pdf/286-14141-204876.pdf. Accessed June 6, 2022.
  16. Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646. [PubMed 22235228]
  17. Paz-Ares L, Dvorkin M, Chen Y, et al; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939. doi:10.1016/S0140-6736(19)32222-6 [PubMed 31590988]
  18. Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344. [PubMed 19626656]
  19. Powles T, van der Heijden MS, Castellano D, et al; DANUBE study investigators. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2020;21(12):1574-1588. doi:10.1016/S1470-2045(20)30541-6 [PubMed 32971005]
  20. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016;387(10031):1909-1920. doi: 10.1016/S0140-6736(16)00561-4. [PubMed 26952546]
  21. Schneider BJ, Naidoo J, Santomasso BD, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol. 2021;39(36):4073-4126. doi:10.1200/JCO.21.01440 [PubMed 34724392]
  22. Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8960):1312-1313. [PubMed 7746084]
Topic 112994 Version 98.0