Tremelimumab
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From MedlinePlus, U.S. National Library of Medicine
CTLA-4-directed Blocking Antibody
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 nephritis with renal dysfunction, immune-mediated dermatologic adverse reactions 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 : IMJUDO in combination with durvalumab 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 IMJUDO in combination with durvalumab based on the severity [see Dosage and Administration ]. IMJUDO with Durvalumab Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMJUDO in combination with durvalumab, 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). IMJUDO with Durvalumab and Platinum-Based Chemotherapy Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving IMJUDO in combination with durvalumab and platinum-based chemotherapy, 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: IMJUDO in combination with durvalumab can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts.
All patients required endocrine therapy. Immune-Mediated Nephritis with Renal Dysfunction IMJUDO in combination with durvalumab can cause immune-mediated nephritis. IMJUDO with Durvalumab Immune-mediated nephritis occurred in 1% (4/388) of patients receiving IMJUDO in combination with durvalumab, including Grade 3 (0.5%) adverse reactions.
| 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)] | ||
| Pneumonitis | 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 steroids 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 | |
| Colitis | Grade 2 | Withhold |
| Grade 3 or 4 | Permanently discontinue | |
| Intestinal perforation | Any grade | Permanently discontinue |
| Hepatitis with no tumor involvement of the liver | 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 ULN or total bilirubin increases to more than 3 times the ULN | Permanently discontinue | |
| Hepatitis with tumor involvement of the liverIf AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue durvalumab based on recommendations for hepatitis with no liver involvement. | 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 ULN orTotal bilirubin increases to more than 3 times ULN | Permanently discontinue | |
| Endocrinopathies | Grade 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity |
| Nephritis with Renal Dysfunction | Grade 2 or 3 increased blood creatinine | Withhold |
| Grade 4 increased blood creatinine | Permanently discontinue | |
| Exfoliative Dermatologic Conditions | Suspected SJS, TEN, or DRESS | Withhold |
| Confirmed SJS, TEN, or DRESS | Permanently discontinue | |
| Myocarditis | Grade 2, 3, or 4 | Permanently discontinue |
| Neurological Toxicities | Grade 2 | Withhold |
| Grade 3 or 4 | Permanently discontinue | |
| Other Adverse Reactions | ||
| Infusion-related reactions [see Warnings and Precautions (5.2)] | 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 tremelimumab. 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. Discard 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 IMJUDO and discard the vial with any unused portion.
Transfer into an intravenous bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP and dilute to a concentration between 0.1 mg/mL and 10 mg/mL. Mix diluted solution by gentle inversion. Do not shake the solution. Storage of Diluted IMJUDO Infusion Solution
IMJUDO does not contain a preservative. Administer infusion solution immediately once prepared. If infusion solution is not administered immediately and needs to be stored, the total time from preparation to the start of administration should not exceed: 24 hours in a refrigerator at 2°C to 8°C (36°F to 46°F) 24 hours at room temperature up to 30°C (86°F)
Do not freeze.
Do not shake. Administration
Administer IMJUDO infusion solution intravenously over 60 minutes through an intravenous line containing a sterile, low-protein binding 0.2 or 0.22 micron filter.
Use separate infusion bags and filters for each drug product. IMJUDO In Combination with Other Products
Administer all drug products as separate intravenous infusions.
Do not co-administer other drugs through the same infusion line.
For platinum-based chemotherapy, refer to Prescribing Information for administration information.
For pemetrexed treatment, refer to Prescribing Information for administration information. Combination Regimens: Order of Infusions IMJUDO in Combination with Durvalumab
Infuse IMJUDO, followed by durvalumab on the same day of dosing. IMJUDO in Combination with Durvalumab and Platinum-based Chemotherapy
Infuse IMJUDO first, followed by durvalumab and then platinum-based chemotherapy on the day of dosing. IMJUDO in Combination with Durvalumab and Pemetrexed Therapy
Infuse IMJUDO first, followed by durvalumab and then pemetrexed treatment on the day of dosing. Combination Regimens: Infusion Instructions IMJUDO in Combination with Durvalumab
Observe patient for 60 minutes following completion of IMJUDO infusion [see Warnings and Precautions ] . Then administer durvalumab as a separate intravenous infusion over 60 minutes IMJUDO in Combination with Durvalumab and Platinum-based Chemotherapy/ Pemetrexed Therapy Cycle 1:
Infuse IMJUDO over one hour. One to two hours after completion of IMJUDO infusion, infuse durvalumab over one hour. One to two hours after completion of durvalumab infusion, administer platinum-based chemotherapy. Subsequent Cycles: If there are no infusion reactions during cycle 1, subsequent cycles of durvalumab can be given immediately after IMJUDO.
The time between the end of the durvalumab infusion and the start of chemotherapy can be reduced to 30 minutes.
| Weekcontinue durvalumab until disease progression or intolerable toxicity.,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 | |||||||||||||||||
| IMJUDOintravenous infusion over 60 minutes [see Dosage and Administration (2.3)].,if patients receive fewer than 4 cycles of platinum-based chemotherapy, the remaining cycles of IMJUDO (up to a total of 5) should be given after the platinum-based chemotherapy phase, in combination with durvalumab, every 4 weeks. | X | X | X | X | X | ||||||||||||||||||||
| Durvalumab, | X | X | X | 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)] | ||
| Pneumonitis | 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 steroids 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 | |
| Colitis | Grade 2 | Withhold |
| Grade 3 or 4 | Permanently discontinue | |
| Intestinal perforation | Any grade | Permanently discontinue |
| Hepatitis with no tumor involvement of the liver | 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 ULN or total bilirubin increases to more than 3 times the ULN | Permanently discontinue | |
| Hepatitis with tumor involvement of the liverIf AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue durvalumab based on recommendations for hepatitis with no liver involvement. | 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 ULN orTotal bilirubin increases to more than 3 times ULN | Permanently discontinue | |
| Endocrinopathies | Grade 3 or 4 | Withhold until clinically stable or permanently discontinue depending on severity |
| Nephritis with Renal Dysfunction | Grade 2 or 3 increased blood creatinine | Withhold |
| Grade 4 increased blood creatinine | Permanently discontinue | |
| Exfoliative Dermatologic Conditions | Suspected SJS, TEN, or DRESS | Withhold |
| Confirmed SJS, TEN, or DRESS | Permanently discontinue | |
| Myocarditis | Grade 2, 3, or 4 | Permanently discontinue |
| Neurological Toxicities | Grade 2 | Withhold |
| Grade 3 or 4 | Permanently discontinue | |
| Other Adverse Reactions | ||
| Infusion-related reactions [see Warnings and Precautions (5.2)] | 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, IMJUDO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of IMJUDO in pregnant women. In animal studies, CTLA-4 blockade is associated with increased risk of immune-mediated rejection of the developing fetus and fetal death ( see Data ). Human immunoglobulin G2 (IgG2) is known to cross the placental barrier; therefore, IMJUDO has the potential to be transmitted from the mother to the developing fetus. Advise pregnant women and females of reproductive potential 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 In a reproduction study, administration of tremelimumab-actl to pregnant cynomolgus monkeys during the period of organogenesis was not associated with maternal toxicity or effects on embryo-fetal development at exposure levels approximately 4 to 31-times higher than those observed at a recommended dose range of 75 mg to 300 mg based on area under the curve (AUC). CTLA-4 plays a role in maintaining maternal immune tolerance to the fetus to preserve pregnancy and in immune regulation of the newborn.
In a murine model of pregnancy, CTLA-4 blockade resulted in increased resorptions and reduced live fetuses. Mated genetically engineered mice heterozygous for CTLA-4 (CTLA-4+/-) gave birth to CTLA-4+/- offspring and offspring deficient in CTLA-4 (homozygous negative, CTLA-4-/-) that appeared healthy at birth. The CTLA-4-/- homozygous negative offspring developed signs of a lymphoproliferative disorder and died by 3 to 4 weeks of age with multiorgan tissue destruction. Based on its mechanism of action, fetal exposure to tremelimumab-actl may increase the risk of developing immune-mediated disorders or altering the normal immune response.
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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