Medically reviewed by Drugs.com. Last updated on Jul 21, 2020.
(dur VAL ue mab)
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]
Brand Names: U.S.
- Antineoplastic Agent, Anti-PD-L1 Monoclonal Antibody
- Antineoplastic Agent, Monoclonal Antibody
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).
Vdss: 5.6 L
Steady-state clearance: 8.2 mL/hour
Terminal half-life: ~18 days
Use: Labeled Indications
Non-small cell lung cancer, unresectable: Treatment of unresectable stage III 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.
Urothelial carcinoma, locally advanced or metastatic: Treatment of locally advanced or metastatic urothelial carcinoma in adults who have disease progression during or following platinum-containing chemotherapy, or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to durvalumab or any component of the formulation.
Non-small cell lung cancer (stage III), unresectable: IV: 10 mg/kg once every 2 weeks; continue until disease progression or unacceptable toxicity or a maximum of 12 months. 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).
Small cell lung cancer, extensive stage: IV:
Patients >30 kg: 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: 20 mg/kg once every 3 weeks (in combination with etoposide and either carboplatin or cisplatin) for 4 cycles, followed by 20 mg/kg once every 4 weeks as a single agent; continue until disease progression or unacceptable toxicity.
Urothelial carcinoma, locally advanced or metastatic: IV: 10 mg/kg once every 2 weeks 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.
Refer to adult dosing.
Dosing: Adjustment for Toxicity
Withhold and/or discontinue durvalumab to manage adverse reactions (no dosage reductions are recommended). Note: Based on the severity of the adverse reaction, withhold or discontinue durvalumab and administer systemic corticosteroids. For adverse reactions where the dose is withheld but do not result in permanent discontinuation, resume durvalumab when the toxicity has improved to grade 1 or lower and the corticosteroid dose is reduced to ≤10 mg/day prednisone (or equivalent).
Permanently discontinue durvalumab for persistent grade 2 or 3 adverse reactions (excluding endocrinopathies) which do not recover to grade 1 or lower within 12 weeks after the last dose or for recurrent grade 3 or 4 reactions. If unable to reduce prednisone dose to ≤10 mg/day (or equivalent) within 12 weeks after the last durvalumab dose, discontinue durvalumab permanently.
Rash or dermatitis, grade 2 for >1 week or grade 3: Withhold dose. Administer systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent) followed by a taper.
Rash or dermatitis, grade 4: Discontinue permanently. Administer systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent) followed by a taper.
Adrenal insufficiency, hypophysitis/hypopituitarism, grades 2, 3, or 4: Withhold dose until clinically stable. Administer systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent) followed by a taper. Administer hormone replacement therapy as clinically indicated.
Diabetes mellitus type 1, grades 2, 3, or 4: Withhold dose until clinically stable. Initiate insulin treatment as clinically indicated.
Hyperthyroidism or thyroiditis, grades 2, 3, or 4: Withhold dose until clinically stable. Initiate appropriate medical management as clinically indicated.
Hypothyroidism: Initiate thyroid replacement therapy as clinically indicated.
Colitis or diarrhea, grade 2: Withhold dose. Administer systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent) followed by a taper.
Colitis or diarrhea, grade 3 or 4: Discontinue permanently. Administer systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent) followed by a taper.
Infection: Grade 3 or 4: Withhold dose until clinically stable. Initiate appropriate management with anti-infectives.
Grade 1 or 2: Interrupt or slow infusion. Consider premedications with subsequent doses.
Grade 3 or 4: Discontinue permanently.
Grade 3: Withhold dose. Administer systemic corticosteroids (prednisone initial dose of 1 to 4 mg/kg daily or equivalent) followed by a taper. Discontinue permanently if does not resolve to ≤ grade 1 within 30 days or if signs of respiratory and/or autonomic insufficiency are present.
Grade 4: Discontinue permanently. Administer systemic corticosteroids (prednisone initial dose of 1 to 4 mg/kg daily or equivalent) followed by a taper.
Pneumonitis, grade 2: Withhold dose. Administer systemic corticosteroids (prednisone initial dose of 1 to 2 mg/kg daily or equivalent) followed by a taper.
Pneumonitis, grade 3 or 4: Discontinue permanently. Administer systemic corticosteroids (prednisone initial dose of 1 to 4 mg/kg daily or equivalent) followed by a taper.
Grade 2: Exclude other causes and initiate corticosteroids as clinically indicated.
Grade 3: Withhold dose. Administer systemic corticosteroids (prednisone initial dose of 1 to 4 mg/kg daily or equivalent) followed by a taper.
Grade 4: Discontinue permanently. Administer systemic corticosteroids (prednisone initial dose of 1 to 4 mg/kg daily or equivalent) followed by a taper.
Withdraw appropriate volume from vial (do not use if cloudy, discolored or if visible particulates are present) and transfer to IV bag containing NS or D5W. Mix by gently inverting bag (do not shake). The final concentration of the diluted solution should be between 1 and 15 mg/mL. Discard unused portion of the vial.
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.
Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Protect vials from light (store in original packaging). Do not shake. Solutions diluted for infusion should be used immediately after preparation. If not administered immediately, may be stored (from the time of vial puncture to the start of administration) for up to 24 hours refrigerated at 2°C to 8°C (36°F to 46°F) or for up to 8 hours at room temperature (≤25°C [77°F]) (Note: Prior to August 2019, the manufacturer's labeling stated the storage time at room temperature was 4 hours). Do not freeze or shake diluted solution.
There are no known significant interactions.
Cardiovascular: Peripheral edema (≤15%)
Dermatologic: Dermatitis (≤26%), pruritus (12%), skin rash (≤26%; including immune mediated rashes)
Endocrine & metabolic: Hyperglycemia (52%), hyperkalemia (32%), hypocalcemia (46%), hyponatremia (33%), hypothyroidism (11% to 12%, including immune mediated), increased gamma-glutamyl transferase (24%)
Gastrointestinal: Abdominal pain (10% to 14%; severe abdominal pain: 3%), colitis (≤18%, including immune mediated), constipation (21%), decreased appetite (19%), diarrhea (≤18%, including immune mediated), nausea (16%)
Genitourinary: Urinary tract infection (15%)
Hematologic & oncologic: Lymphocytopenia (43%; grades 3/4: 11% to 17%)
Hepatic: Hepatitis (12%, including immune mediated), increased serum alanine aminotransferase (39%), increased serum aspartate aminotransferase (36%)
Infection: Infection (38% to 56%)
Nervous system: Fatigue (34% to 39%)
Neuromuscular & skeletal: Musculoskeletal pain (24%)
Respiratory: Cough (≤40%), dyspnea (≤25%), dyspnea on exertion (≤25%), pneumonia (17%), pneumonitis (≤34%, including immune mediated), productive cough (≤40%), radiation pneumonitis (≤34%), upper respiratory tract infection (26%)
Miscellaneous: Fever (≤15%; including tumor-associated fever)
1% to 10%:
Dermatologic: Night sweats (<10%)
Endocrine & metabolic: Dehydration (grades 3/4: ≤3%), hypercalcemia (grades 3/4: 3%), hypermagnesemia (grades 3/4: 4%), hyperthyroidism (7%, including immune mediated), hypoalbuminemia (grades 3/4: 1%), hypokalemia (grades 3/4: 1%)
Genitourinary: Dysuria (<10%)
Hematologic & oncologic: Anemia (grades 3/4: 8%), neutropenia (grades 3/4: 1%)
Hepatic: Hyperbilirubinemia (grades 3/4: 1%), increased serum alkaline phosphatase (grades 3/4: 4%), severe hepatic insufficiency (3%)
Immunologic: Antibody development (3%; neutralizing: <1%)
Infection: Increased susceptibility to infection (<10%), sepsis (>2%)
Nervous system: Voice disorder (<10%)
Renal: Acute renal failure (5%), increased serum creatinine (grades 3/4: 1%), nephritis (6%; immune mediated)
Miscellaneous: Infusion related reaction (2%)
Cardiovascular: Myocarditis (immune mediated)
Endocrine & metabolic: Adrenocortical insufficiency (immune mediated), pituitary insufficiency (immune mediated), thyroiditis (immune mediated), type 1 diabetes mellitus (immune mediated)
Hematologic & oncologic: Hemolytic anemia (immune mediated), immune thrombocytopenia
Nervous system: Aseptic meningitis (immune mediated), myasthenia gravis (immune mediated)
Neuromuscular & skeletal: Myositis (immune mediated)
Ophthalmic: Ophthalmic inflammation (immune mediated; including uveitis and keratitis)
Frequency not defined:
Endocrine & metabolic: Hypophysitis (immune mediated)
Hepatic: Hepatic injury
Concerns related to adverse effects:
• Adrenal insufficiency: Immune-related adrenal insufficiency has been reported with durvalumab. Monitor for clinical signs/symptoms of adrenal insufficiency. If grade 2 or higher adrenal insufficiency occurs, administer systemic corticosteroids and hormone replacement as clinically indicated; interrupt durvalumab treatment (based on the severity).
• Dermatologic toxicity: Durvalumab has caused immune-mediated rash. Bullous dermatitis, Stevens Johnson syndrome, and toxic epidermal necrolysis have been reported with other anti-PD-L1 monoclonal antibodies. Monitor for signs/symptoms of dermatologic toxicity. Initiate systemic corticosteroids for grade 2 rash or dermatitis lasting for more than 1 week or severe grade 3 or 4 rash/dermatitis, followed by a taper. May require treatment interruption or discontinuation (based on the severity).
• Diabetes mellitus: Immune-related type 1 diabetes mellitus has occurred in patients receiving durvalumab. The median time to onset was 1.4 months. Monitor glucose and monitor for clinical signs/symptoms of diabetes. Initiate insulin for type 1 diabetes mellitus and interrupt durvalumab treatment (based on the severity) until clinically stable.
• Gastrointestinal toxicities: Immune-mediated colitis or diarrhea occurred in patients receiving durvalumab. Grades 3 and 4 diarrhea or colitis have been reported. The median time to onset was 1.4 months (range: 1 day to 14 months). Monitor for signs/symptoms of colitis or diarrhea and manage with treatment interruption or discontinuation, and systemic corticosteroids. In clinical studies, management with systemic corticosteroids, including high-dose corticosteroids was utilized in some patients; other immunosuppressants (eg, infliximab, mycophenolate) were required (rarely). Resolution occurred in approximately three-quarters of patients who experienced immune-mediated diarrhea/colitis.
• Hepatotoxicity: Immune-mediated hepatitis has occurred in patients receiving durvalumab (some fatal). The median time to onset was ~1 month (range: 1 day to ~14 months). Monitor for signs/symptoms (including abnormal liver function tests) of hepatitis during durvalumab treatment and after discontinuation. Manage grade 2 or higher immune-mediated hepatitis with systemic corticosteroids and treatment interruption or discontinuation. In clinical studies, some patients experiencing immune-mediated hepatitis received high-dose corticosteroids; mycophenolate was required (rarely) to manage immune-mediated hepatitis. Recovery occurred in approximately half of patients experiencing immune-mediated hepatitis. Grade 3 or 4 ALT, AST, and/or total bilirubin elevations have been reported.
• Hypophysitis/hypopituitarism: Immune-related hypophysitis/hypopituitarism has occurred in patients receiving durvalumab. Monitor for clinical signs/symptoms of hypophysitis or hypopituitarism. If grade 2 or higher hypophysitis occurs, administer corticosteroids and hormone replacement therapy as indicated; interrupt durvalumab (based on the severity). Hypopituitarism leading to adrenal insufficiency and diabetes insipidus has occurred (rarely).
• Infection: Infections occurred in almost half of patients receiving durvalumab (some fatal). The most common grade 3 or 4 infections were urinary tract infections (urothelial carcinoma study) and pneumonia (non-small cell lung cancer [NSCLC] study). The overall incidence of infections was higher in a NSCLC study, compared to patients in other studies in whom radiation therapy was typically not administered immediately prior to durvalumab. Monitor for signs/symptoms of infection; if infection is suspected or confirmed, manage with anti-infectives. Withhold treatment for grade 3 or 4 infection.
• Infusion reactions: Infusion reactions have been observed with durvalumab, including severe or life-threatening infusion-related reactions. Monitor for signs/symptoms of infusion reactions. Interrupt or slow the infusion rate for mild or moderate infusion reactions (consider premedications with subsequent infusions). Discontinue durvalumab permanently for grade 3 or 4 infusion reactions.
• Nephrotoxicity: Durvalumab has caused immune-mediated nephritis (including fatal cases). Monitor renal function prior to initiating treatment and periodically during durvalumab treatment. Nephritis may require systemic corticosteroids and treatment interruption or discontinuation. Nephritis resolved in ~50% of patients. The median time to onset was 2 months (range: 1 day to ~14 months).
• Ocular toxicity: Ocular inflammatory toxicity including uveitis and keratitis have been reported. If uveitis occurs in combination with other immune-mediated reactions, evaluate for Vogt-Koyanagi-Harada syndrome; may require treatment with systemic steroids to reduce the risk of permanent vision loss.
• Pulmonary toxicities: Immune-mediated pneumonitis or interstitial lung disease has occurred in patients receiving durvalumab (including fatal cases); the incidence and severity of pneumonitis was similar when durvalumab was administered either as monotherapy or in combination with chemotherapy. The median time to onset was ~2 months (range: 1 day to ~19 months), and the median time to resolution was ~2 to 5 months (range up to ~19 months). In a non-small cell lung cancer study, the incidence of pneumonitis (including radiation pneumonitis) was higher in patients who completed definitive chemoradiation within 42 days prior to initiating durvalumab, compared to patients in other studies in whom radiation therapy was typically not administered immediately prior to durvalumab. Monitor for signs/symptoms of pneumonitis; evaluate suspected pneumonitis with radiographic imaging and manage with systemic corticosteroids and durvalumab treatment interruption or discontinuation; some patients received infliximab therapy. In clinical studies, resolution occurred in approximately half of patients experiencing immune-mediated pneumonitis.
• Thyroid disorders: Immune-related thyroid disorders have occurred in patients receiving durvalumab. Monitor thyroid function at baseline and periodically during treatment; monitor for clinical signs/symptoms of thyroid disorders. Hypothyroidism, hyperthyroidism, and thyroiditis (including grade 3 thyroiditis) have occurred in clinical trials. Hypothyroidism was preceded by thyroiditis or hyperthyroidism is some patients. Manage hypothyroidism with hormone replacement (if indicated) while continuing durvalumab. Initiate appropriate medical management for hyperthyroidism; withhold durvalumab (based on severity). Treatment with a beta-blocker and/or thioamide was administered for hyperthyroidism in some patients.
• Other immune-mediated toxicities: Other immune-related adverse reactions associated with durvalumab (rarely) include aseptic meningitis, hemolytic anemia, immune thrombocytopenia (formerly known as immune thrombocytopenic purpura), myasthenia gravis, myocarditis, and myositis. These immune-mediated toxicities usually occurred during treatment, although may occur after discontinuation. For suspected grade 2 immune-mediated reactions, exclude other causes and initiate systemic corticosteroids as clinically indicated. Administer systemic corticosteroids for grade 3 or 4 immune-mediated reactions. May require treatment interruption or discontinuation. Other immune-mediated reactions have also been reported with other anti-PD-L1 monoclonal antibodies, including pancreatitis, systemic inflammatory response syndrome, rhabdomyolysis, histiocytic necrotizing lymphadenitis, demyelination, vasculitis, hemolytic anemia, iritis, encephalitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barre syndrome and Vogt-Koyanagi-Harada syndrome.
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.
Monitor liver function (during each cycle); renal function tests (prior to treatment and each cycle); thyroid function tests (at baseline, periodically during treatment); blood glucose. Monitor for clinical signs/symptoms of adrenal insufficiency, colitis/diarrhea, dermatologic toxicity, diabetes/hyperglycemia, hepatitis/hepatotoxicity, hypophysitis or hypopituitarism, immune thrombocytopenia purpura, infection, pneumonitis (evaluate suspected pneumonitis with radiographic imaging), ocular toxicity, thyroid disorders; monitor for infusion reactions.
Females of reproductive potential should use effective contraception during therapy and for at least 3 months after the last durvalumab dose.
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).
What is this drug used for?
• It is used to treat cancer in the bladder or urinary tract.
• It is used to treat lung cancer.
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
• Bone pain
• Lack of appetite
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit.
• Infusion reaction
• Thyroid, pituitary, or adrenal gland problems like mood changes, behavioral changes, weight changes, constipation, deeper voice, dizziness, passing out, cold sensation, severe fatigue, hair loss, persistent headache, or decreased sex drive.
• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting.
• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Lung problems like shortness of breath or other trouble breathing, cough that is new or worse
• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting.
• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.
• Aseptic meningitis like headache, fever, chills, severe nausea or vomiting, stiff neck, rash, sensitivity to lights, fatigue, or confusion.
• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain.
• Black, red, tarry, or bloody stools
• Severe diarrhea
• Severe abdominal pain
• Muscle pain
• Muscle weakness
• Vision changes
• Eye pain
• Severe eye irritation
• Chest pain
• Abnormal heartbeat
• Severe loss of strength and energy
• Shortness of breath
• Excessive weight gain
• Swelling of arms or legs
• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
More about durvalumab
- Side Effects
- During Pregnancy or Breastfeeding
- Dosage Information
- Drug Interactions
- En Español
- Drug class: anti-PD-1 monoclonal antibodies
Other brands: Imfinzi