Durvalumab
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From MedlinePlus, U.S. National Library of Medicine
Programmed Death Ligand-1 Blocker
Dosing in kidney impairment
Immune-Mediated Adverse Reactions ∘ Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, solid organ transplant rejection, and immune-mediated pancreatitis. o Monitor for early identification and management.
Systemic corticosteroids were required in all patients with immune-mediated hepatitis, while 2 patients (2/23) required use of other immunosuppressants. Immune-Mediated Endocrinopathies Adrenal Insufficiency IMFINZI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated.
Withhold or permanently discontinue IMFINZI based on the severity [see Dosage and Administration ] . IMFINZI as a Single Agent Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (< 0.1%) adverse reactions. Events resolved in 1 of the 9 patients and did not lead to permanent discontinuation of IMFINZI in any patients.
Systemic corticosteroids were required in all patients with adrenal insufficiency; of these, the majority remained on systemic corticosteroids. IMFINZI with Tremelimumab-actl Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (0.3%) adverse reactions.
Events resolved in 2 of the 6 patients. Systemic corticosteroids were required in all 6 patients, and of these, 1 patient required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving IMFINZI in combination with tremelimumab-actl, including Grade 3 (0.8%) adverse reactions.
Events resolved in 2 of the 13 patients and resulted in permanent discontinuation in 1 patient. Systemic corticosteroids were required in all patients with adrenal insufficiency. One patient also required endocrine therapy. Hypophysitis IMFINZI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts.
| Adverse Reaction | SeverityBased on National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. | Dosage Modification |
| Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1)] | ||
| Grade 2 | WithholdResume 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. | |
| Grade 3 or 4 | Permanently discontinue | |
| Grade 2 | Withhold | |
| Grade 3 | Withhold or permanently discontinuePermanently discontinue IMFINZI for Grade 3 colitis when administered as part of a tremelimumab-actl containing regimen. | |
| Grade 4 | Permanently discontinue | |
| Any grade | Permanently discontinue | |
| ALT or AST increases to more than 3 and up to 8 times the ULNortotal bilirubin increases to more than 1.5 and up to 3 times ULN | Withhold | |
| ALT or AST increases to more than 8 times ULNortotal bilirubin increases to more than 3 times the ULN | Permanently discontinue | |
| AST or ALT is more than 1 and up to 3 times ULN at baseline and increases to more than 5 and up to 10 times ULN orAST or ALT is more than 3 and up to 5 times ULN at baseline and increases to more than 8 and up to 10 times ULN | Withhold | |
| AST or ALT increases to more than 10 times ULNortotal bilirubin increases to more than 3 times ULN | Permanently discontinue | |
| Grade 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity | |
| Grade 2 or 3 increased blood creatinine | Withhold | |
| Grade 4 increased blood creatinine | Permanently discontinue | |
| Suspected SJS, TEN, or DRESS | Withhold | |
| Confirmed SJS, TEN, or DRESS | Permanently discontinue | |
| Grade 2, 3, or 4 | Permanently discontinue | |
| Grade 2 | Withhold | |
| Grade 3 or 4 | Permanently discontinue | |
| Other Adverse Reactions | ||
| Grade 1 or 2 | Interrupt or slow the rate of infusion | |
| Grade 3 or 4 | Permanently discontinue | |
| ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal. | ||
Preparation and administration
Prepare this dose
Your numbers for durvalumab. Take vial strength, diluent, and limits from the label below.
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Preparation and Administration Preparation
Visually inspect drug product for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard the vial if the solution is cloudy, discolored, or visible particles are observed.
Do not shake the vial.
Withdraw the required volume from the vial(s) of IMFINZI and transfer into an intravenous bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Mix diluted solution by gentle inversion. Do not shake the solution. The final concentration of the diluted solution should be between 1 mg/mL and 15 mg/mL.
Discard partially used or empty vials of IMFINZI. Storage of Infusion Solution
IMFINZI does not contain a preservative.
Administer infusion solution immediately once prepared. If the infusion solution is not administered immediately and needs to be stored, the time from preparation until the completion of the infusion should not exceed: ∘ 28 days in a refrigerator at 2°C to 8°C (36°F to 46°F) ∘ 8 hours at room temperature up to 25°C (77°F)
Do not freeze.
Do not shake. Administration
Administer infusion solution intravenously over 60 minutes through an intravenous line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter.
Use separate infusion bags and filters for each drug product. IMFINZI in Combination with Other Products
Administer all intravenous drug products as separate infusions.
Do not co-administer other intravenous drugs through the same infusion line.
For platinum-based chemotherapy, refer to Prescribing Information for administration information.
For pemetrexed therapy, refer to Prescribing Information for administration information.
For BCG therapy, refer to BCG Prescribing Information for administration information. Combination Regimens: Order of Administration IMFINZI in Combination with Tremelimumab-actl
Infuse tremelimumab-actl first, followed by IMFINZI on the same day of dosing. IMFINZI in Combination with Tremelimumab-actl and Platinum-Based Chemotherapy
Infuse tremelimumab-actl first, followed by IMFINZI and then platinum-based chemotherapy on the day of dosing. IMFINZI in Combination with Tremelimumab-actl and Pemetrexed Therapy
Infuse tremelimumab-actl first, followed by IMFINZI and then pemetrexed therapy on the day of dosing. IMFINZI in Combination with Carboplatin and Paclitaxel
Infuse IMFINZI first and then carboplatin and paclitaxel on the same day of dosing. IMFINZI in Combination with Chemotherapy
Infuse IMFINZI first and then chemotherapy on the same day of dosing. IMFINZI in combination with BCG
If IMFINZI is given on the same day as BCG, infuse IMFINZI first, then administer BCG as an intravesical instillation. Combination Regimens: Infusion Instructions IMFINZI in Combination with Tremelimumab-actl
Administer tremelimumab-actl over 60 minutes followed by a 60 minute observation period. Then administer IMFINZI as a separate intravenous infusion over 60 minutes. IMFINZI in Combination with Tremelimumab-actl and Platinum-Based Chemotherapy/ Pemetrexed Therapy Cycle 1
Infuse tremelimumab-actl over 60 minutes. One to two hours after completion of tremelimumab-actl infusion, infuse IMFINZI over 60 minutes. One to two hours after completion of IMFINZI infusion, administer platinum-based chemotherapy. Subsequent Cycles
If there are no infusion reactions during cycle 1, subsequent cycles of IMFINZI can be given immediately after tremelimumab-actl. The time between the end of the IMFINZI infusion and the start of chemotherapy can be reduced to 30 minutes.
| Weekcontinue IMFINZI until disease progression or intolerable toxicity.note the dosing interval change from every 3 weeks to every 4 weeks starting at cycle 5. | |||||||||||||||||||||||||
| 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | 24 | |
| Cycle: | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | |||||||||||||||||
| IMFINZIintravenous infusion over 60 minutes [see Dosage and Administration (2.4)]. | X | X | X | X | X | X | X | X | |||||||||||||||||
| Tremelimumab-actlif patients receive fewer than 4 cycles of platinum-based chemotherapy, the remaining cycles of tremelimumab-actl (up to a total of 5) should be given after the platinum-based chemotherapy phase, in combination with IMFINZI, every 4 weeks. | X | X | X | X | X | ||||||||||||||||||||
| Chemotherapy | X | X | X | X | Xoptional pemetrexed therapy from week 12 until disease progression or intolerable toxicity for patients with non-squamous disease who received treatment with pemetrexed and carboplatin/cisplatin. | X | X | X | |||||||||||||||||
| Adverse Reaction | SeverityBased on National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. | Dosage Modification |
| Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1)] | ||
| Grade 2 | WithholdResume 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. | |
| Grade 3 or 4 | Permanently discontinue | |
| Grade 2 | Withhold | |
| Grade 3 | Withhold or permanently discontinuePermanently discontinue IMFINZI for Grade 3 colitis when administered as part of a tremelimumab-actl containing regimen. | |
| Grade 4 | Permanently discontinue | |
| Any grade | Permanently discontinue | |
| ALT or AST increases to more than 3 and up to 8 times the ULNortotal bilirubin increases to more than 1.5 and up to 3 times ULN | Withhold | |
| ALT or AST increases to more than 8 times ULNortotal bilirubin increases to more than 3 times the ULN | Permanently discontinue | |
| AST or ALT is more than 1 and up to 3 times ULN at baseline and increases to more than 5 and up to 10 times ULN orAST or ALT is more than 3 and up to 5 times ULN at baseline and increases to more than 8 and up to 10 times ULN | Withhold | |
| AST or ALT increases to more than 10 times ULNortotal bilirubin increases to more than 3 times ULN | Permanently discontinue | |
| Grade 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity | |
| Grade 2 or 3 increased blood creatinine | Withhold | |
| Grade 4 increased blood creatinine | Permanently discontinue | |
| Suspected SJS, TEN, or DRESS | Withhold | |
| Confirmed SJS, TEN, or DRESS | Permanently discontinue | |
| Grade 2, 3, or 4 | Permanently discontinue | |
| Grade 2 | Withhold | |
| Grade 3 or 4 | Permanently discontinue | |
| Other Adverse Reactions | ||
| Grade 1 or 2 | Interrupt or slow the rate of infusion | |
| Grade 3 or 4 | Permanently discontinue | |
| ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal. | ||
Contraindications
None. None. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, IMFINZI can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of IMFINZI in pregnant women. In animal reproduction studies, administration of durvalumab to pregnant cynomolgus monkeys from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed at the clinical dose of 10 mg/kg based on area under the curve (AUC), resulted in an increase in premature delivery, fetal loss, and premature neonatal death ( see Data ).
Human immunoglobulin G1 (IgG1) is known to cross the placental barrier; therefore, durvalumab has the potential to be transmitted from the mother to the developing fetus. Apprise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data As reported in the literature, the PD-1/PD-L1 pathway plays a central role in preserving pregnancy by maintaining maternal immune tolerance to the fetus. In mouse allogeneic pregnancy models, disruption of PD-L1 signaling was shown to result in an increase in fetal loss.
The effects of durvalumab on prenatal and postnatal development were evaluated in reproduction studies in cynomolgus monkeys. Durvalumab was administered from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed at a clinical dose of 10 mg/kg (based on AUC). Administration of durvalumab resulted in premature delivery, fetal loss (abortion and stillbirth), and increase in neonatal deaths. Durvalumab was detected in infant serum on postpartum Day 1, indicating the presence of placental transfer of durvalumab.
Based on its mechanism of action, fetal exposure to durvalumab may increase the risk of developing immune-mediated disorders or altering the normal immune response and immune-mediated disorders have been reported in PD-1 knockout mice.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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