Dosage & Administration
By using PrescriberAI, you agree to the AI Terms of Use.
Imdelltra Prescribing Information
Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRA. Initiate treatment with IMDELLTRA using the step-up dosing schedule to reduce the incidence and severity of CRS. Withhold IMDELLTRA until CRS resolves or permanently discontinue based on severity [see Dosage and Administration (2.5) and Warnings and Precautions (5.1)].
Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRA. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment and treat promptly. Withhold IMDELLTRA until ICANS resolves or permanently discontinue based on severity [see Dosage and Administration (2.5) and Warnings and Precautions (5.2)].
IMDELLTRA is indicated for the treatment of adult patients with extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.
This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Important Dosing Information
- Administer IMDELLTRA according to the step-up dosing schedule in Table 1 to reduce the incidence and severity of cytokine release syndrome (CRS) [see Dosage and Administration (2.2)].
- For Cycle 1, administer recommended concomitant medications in Table 3 before and after Cycle 1 IMDELLTRA infusions to reduce the risk of CRS reactions [see Dosage and Administration (2.3)].
- IMDELLTRA should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity including immune effector cell-associated neurotoxicity syndrome (ICANS) [see Warnings and Precautions (5.1, 5.2)].
- Due to the risk of CRS and neurologic toxicity, including ICANS, monitor patients from the start of the IMDELLTRA infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting [see Dosage and Administration (2.5) and Warnings and Precautions (5.1, 5.2)].
- Recommend that patients remain within 1-hour of an appropriate healthcare setting for a total of 48 hours from start of the infusion with IMDELLTRA following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver.
- Prior to administration of IMDELLTRA evaluate complete blood count, liver enzymes and bilirubin before each dose, and as clinically indicated [see Warnings and Precautions (5.3, 5.5)].
- Ensure patients are well hydrated prior to administration of IMDELLTRA [see Warnings and Precautions (5.1)].
Recommended Dosage and Administration
- Administer IMDELLTRA as an intravenous infusion over one hour.
- The recommended step-up dosage schedule for IMDELLTRA is provided in Table 1. Administer following step-up dosing to reduce the incidence and severity of CRS.
- After step-up dosing schedule, administer IMDELLTRA biweekly (every 2 weeks) until disease progression or unacceptable toxicity.
| Dosing Schedule | Day | Dose of IMDELLTRA | Administration Instructions | Recommended Monitoring |
|---|---|---|---|---|
| Note: see Table 4 for recommendation on restarting IMDELLTRA after dose delays. | ||||
| ||||
| Step-up Dosing Schedule Cycle 1 | Day 1 * | Step-up dose * 1 mg | Administer IMDELLTRA as a 1-hour intravenous infusion in an appropriate healthcare setting. | Monitor patients from the start of the IMDELLTRA infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting. Recommend that patients remain within 1-hour of an appropriate healthcare setting for a total of 48 hours from start of the infusion with IMDELLTRA, accompanied by a caregiver. |
| Day 8 * | 10 mg * | |||
| Day 15 | 10 mg | Observe patients for 6-8 hours post IMDELLTRA infusion †. | ||
| Cycle 2 | Day 1 and 15 | 10 mg | Observe patients for 6-8 hours post IMDELLTRA infusion †. | |
| Cycles 3 and 4 | Day 1 and 15 | 10 mg | Observe patients for 3-4 hours post IMDELLTRA infusion †. | |
| Cycle 5 and subsequent infusions | Day 1 and 15 | 10 mg | Observe patients for 2 hours post IMDELLTRA infusion †. | |
Administration
- The intravenous (IV) catheter for concomitant medications administration can be used to administer the IMDELLTRA infusion.
- To ensure patency, flush the IV catheter over 3-5 mins using 0.9% Sodium Chloride for Injection.
- Administer the reconstituted and diluted IMDELLTRA as an intravenous infusion at a constant flow rate using an infusion pump. The pump should be programmable, lockable, non-elastomeric, and have an alarm.
- Table 2 provides the infusion duration and rate.
| Infusion Duration for 250 mL IV Preparation | Infusion Rate |
|---|---|
| 1-hour | 250 mL/hour |
Recommended Concomitant Medications for IMDELLTRA Administration for Cycle 1
Administer recommended concomitant medications for IMDELLTRA administration during Cycle 1 as presented in Table 3 to reduce the risk of cytokine release syndrome [see Warnings and Precautions (5.1)].
| Treatment Day | Medication | Administration |
|---|---|---|
| Day 1 and Day 8 | Administer 8 mg of dexamethasone intravenously (or equivalent) | Within 1-hour prior to IMDELLTRA administration |
| Day 1, Day 8 and Day 15 | Administer 1 liter of normal saline intravenously over 4-5 hours | Immediately after completion of IMDELLTRA infusion |
Restarting IMDELLTRA After Dosage Delay
If a dose of IMDELLTRA is delayed, restart therapy based on the recommendation as listed in Table 4 and resume the dosing schedule accordingly [see Dosage and Administration (2.2)]. Administer recommended concomitant medications as indicated in section 2.3.
| Last Dose Administered | Time Since the Last Dose Administered | Action * |
|---|---|---|
| ||
| 1 mg on Cycle 1 Day 1 | 2 weeks or less (≤14 days) | Administer IMDELLTRA 10 mg, then resume with the planned dosage schedule. |
| Greater than 2 weeks (>14 days) | Administer IMDELLTRA step-up dose 1 mg. If tolerated, increase to 10 mg 1 week later. Then resume with the planned dosage schedule. | |
| 10 mg on Cycle 1 Day 8 | 3 weeks or less (≤21 days) | Administer IMDELLTRA 10 mg, then resume with the planned dosage schedule. |
| Greater than 3 weeks (>21 days) | Administer IMDELLTRA step-up dose 1 mg. If tolerated, increase to 10 mg 1 week later. Then resume with the planned dosage schedule. | |
| 10 mg on Cycle 1 Day 15 and subsequent Cycles every 2 weeks thereafter | 4 weeks or less (≤28 days) | Administer IMDELLTRA 10 mg, then resume with the planned dosage schedule. |
| Greater than 4 weeks (>28 days) | Administer IMDELLTRA step-up dose 1 mg. If tolerated, increase to 10 mg 1 week later. Then resume with the planned dosage schedule. | |
IMDELLTRA Dosage Modifications and Adverse Reaction Management
No dose reduction for IMDELLTRA is recommended. See Table 5 and Table 6 for recommended actions for the management of CRS, neurologic toxicity including ICANS respectively and Table 7 for cytopenias, infections and other adverse reactions.
Cytokine Release Syndrome (CRS)
Diagnose CRS based on clinical presentation [see Warnings and Precautions (5.1)]. Evaluate for and treat other causes of fever, hypoxia, and hypotension.
If CRS is suspected, manage according to the recommendations in Table 5. Monitor patients who experience Grade 2 or higher CRS (e.g., hypotension not responsive to fluids, or hypoxia requiring supplemental oxygen) with continuous cardiac telemetry and pulse oximetry.
For severe or life-threatening CRS, recommend administering tocilizumab or equivalent therapy and intensive monitoring (e.g., ICU) for supportive therapy. Perform laboratory testing to monitor for disseminated intravascular coagulation (DIC), hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function.
Table 5 provides the guidelines for grading and dosage modification and management of cytokine release syndrome.
| CRS Grade | Defining Symptoms | IMDELLTRA Dosage Modification | Management |
|---|---|---|---|
| |||
| Grade 1 | Symptoms require symptomatic treatment only (e.g., fever ≥ 100.4°F without hypotension or hypoxia). | Withhold IMDELLTRA until event resolves, then resume IMDELLTRA at the next scheduled dose †. |
|
| Grade 2 | Symptoms require and respond to moderate intervention.
| Withhold IMDELLTRA until event resolves, then resume IMDELLTRA at the next scheduled dose †. |
|
| Grade 3 | Severe symptoms defined as temperature ≥ 38°C with:
| Withhold IMDELLTRA until the event resolves, then resume IMDELLTRA at the next scheduled dose †. For recurrent Grade 3 events, permanently discontinue IMDELLTRA. | In addition to Grade 2 treatment:
|
| Grade 4 | Life-threatening symptoms defined as temperature ≥100.4°F with:
| Permanently discontinue IMDELLTRA. |
|
Neurologic Toxicity including ICANS
At the first sign of neurologic toxicity, including ICANS, withhold IMDELLTRA and consider neurology evaluation. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care, for severe or life-threatening neurologic toxicities, including ICANS [see Warnings and Precautions (5.2)]. Manage ICANS and neurologic toxicity according to the recommendations in Table 6 and consider further management per current practice guidelines.
| ICANS Grade * | Defining Symptoms | IMDELLTRA Dosage Modifications | Management |
|---|---|---|---|
| |||
| Grade 1 * | ICE score 7-9 † with no depressed level of consciousness. |
|
|
| Grade 2 * | ICE score 3-6 † and/or mild somnolence awaking to voice. |
|
|
| Grade 3 * | ICE score 0-2 † and/or depressed level of consciousness awakening only to tactile stimulus and/or any clinical seizure focal or generalized that resolves rapidly or nonconvulsive seizures on EEG that resolve with intervention and/or Focal or local edema on neuroimaging. |
|
|
| Grade 4 * | ICE score 0 † (patient is unarousable and unable to perform ICE) and/or Stupor or coma and/or Life-threatening prolonged seizure (> 5 minutes) or repetitive clinical or electrical seizures without return to baseline in between and/or diffuse cerebral edema on neuroimaging, decerebrate or decorticate posturing or papilledema, cranial nerve VI palsy, or Cushing's triad. |
|
|
| Adverse Reactions | Severity * | Dosage Modification † |
|---|---|---|
| ||
| Cytopenias [see Warnings and Precautions (5.3)] | Grade 3 or Grade 4 Neutropenia | Withhold IMDELLTRA until recovery to ≤Grade 2. Consider administration of granulocyte colony stimulating factor (G-CSF). Permanently discontinue if recovery to ≤Grade 2 does not occur within 3 weeks. |
| Recurrent Grade 4 Neutropenia | Permanently discontinue IMDELLTRA | |
| Febrile neutropenia | Withhold IMDELLTRA until neutropenia recovers to ≤Grade 2 and fever resolves. | |
| Hemoglobin <8 g/dL | Withhold IMDELLTRA until hemoglobin is ≥8 g/dL. | |
| Grade 3 or Grade 4 Decreased platelet count | Withhold IMDELLTRA until platelet count is ≤Grade 2 and no evidence of bleeding. Permanently discontinue if recovery to ≤Grade 2 does not occur within 3 weeks. | |
| Recurrent Grade 4 Decreased platelet count | Permanently discontinue IMDELLTRA. | |
| Infections [see Warnings and Precautions (5.4)] | All Grades | Withhold IMDELLTRA in the step-up phase in patients until infection resolves. |
| Grade 3 | Withhold IMDELLTRA during the treatment phase until infection improves to ≤Grade 1 †. | |
| Grade 4 | Permanently discontinue IMDELLTRA. | |
| Hepatotoxicity [see Warnings and Precautions (5.5)] | Grade 3 Increased ALT or AST or bilirubin | Withhold IMDELLTRA until adverse events improve to ≤ Grade 1. |
| Grade 4 Increased ALT or AST or bilirubin | Permanently discontinue IMDELLTRA. | |
| AST or ALT > 3 × ULN with total bilirubin > 2 × ULN in the absence of alternative causes | Permanently discontinue IMDELLTRA. | |
| Other Adverse Reactions [see Adverse Reactions (6.1)] | Grade 3 or 4 | Withhold IMDELLTRA until recovery to ≤Grade 1 or baseline. Consider permanently discontinuing if adverse reaction does not resolve within 28 days. Consider permanent discontinuation for Grade 4 events. |
Preparation
Material Compatibility Information
- IV bags composed of ethyl vinyl acetate (EVA), polyolefin, and polyvinyl chloride, (PVC) have been shown to be compatible with IMDELLTRA at the specified administration conditions.
- IV line and catheter materials composed of polyolefin, PVC, and polyurethane have been shown to be compatible with IMDELLTRA at the specified administration conditions.
- The use of Closed System Transfer Device (CSTD) is not recommended due to potential wrong dose medication error risk. Amgen has not performed compatibility testing of vial adaptor CSTDs with IMDELLTRA.
Step 1: Reconstitute IMDELLTRA with Sterile Water for Injection
- Table 8 provides the required amount of sterile water for injection required to reconstitute IMDELLTRA 1 mg and 10 mg vials.
Do not use IV Solution Stabilizer (IVSS) to reconstitute IMDELLTRA.
The IV Solution Stabilizer (IVSS) is used to coat the intravenous bag prior to addition of reconstituted IMDELLTRA to prevent adsorption of IMDELLTRA to IV bags and IV tubing.
| IMDELLTRA Vial Strength | Amount of Sterile Water for Injection Needed to Reconstitute IMDELLTRA | Resulting Concentration |
|---|---|---|
| ||
| 1 mg | 1.3 mL | 0.9 mg/mL |
| 10 mg | 4.4 mL | 2.4 mg/mL |
- Using a needle and syringe filled with the required amount of sterile water, inject the sterile water against the glass vial. Avoid injecting the water directly onto the powder to prevent foaming.
- Gently swirl the contents to mix. Do not shake.
- Inspect parenteral drug products for particulate matter and discoloration prior to administration. Inspect that the solution is clear to opalescent, colorless to slightly yellow. Do not use if the solution is cloudy or has particulates.
- Further dilute reconstituted IMDELLTRA.
- The reconstituted IMDELLTRA must be further diluted within 4 hours of reconstitution or discarded.
Prepare the infusion bag: Steps 2 to 5
Step 2 : Withdraw 0.9% Sodium Chloride for Injection
- Using a 250 mL prefilled bag of 0.9% Sodium Chloride for Injection, withdraw the amount of sodium chloride specified in Table 9 and discard.
| IMDELLTRA Vial Strength | IMDELLTRA Dose | Volume of 0.9% Sodium Chloride to Withdraw From 250 mL IV Bag |
|---|---|---|
| 1 mg | 1 mg | 14 mL |
| 10 mg | 10 mg | 17 mL |
Step 3: Add IV Solution Stabilizer to the infusion bag
- Inject 13 mL of IV Solution Stabilizer (IVSS) into the 250 mL 0.9% Sodium Chloride infusion bag, see Table 10.
- Gently mix the contents of the infusion bag to avoid foaming. Do not shake.
| IMDELLTRA Vial Strength | IMDELLTRA Dose | Volume of IV Solution Stabilizer (IVSS) to Add to IV Bag |
|---|---|---|
| 1 mg | 1 mg | 13 mL |
| 10 mg | 10 mg | 13 mL |
Step 4: Dilute the reconstituted IMDELLTRA into the infusion bag
- Transfer the required volume of reconstituted IMDELLTRA listed in Table 11 to the infusion bag (containing IV Solution Stabilizer).
NOTE: the final concentrations for the different strength vials are NOT the same following reconstitution and further dilution.
| IMDELLTRA Vial Strength | IMDELLTRA Dose | Volume of Reconstituted IMDELLTRA to Add to 250 mL IV Bag |
|---|---|---|
| 1 mg | 1 mg | 1.1 mL |
| 10 mg | 10 mg | 4.2 mL |
- Gently mix the contents of the bag. Do not shake.
Step 5: Remove air from IV bag
Remove air from the prepared IV bag using an empty syringe to avoid foaming.
Step 6: Prime IV tubing
- Prime intravenous tubing with either 0.9% Sodium Chloride for Injection or with the final prepared product.
- See Table 12 for maximum storage time of prepared IMDELLTRA infusion.
Prepared IMDELLTRA Infusion Bag Storage Requirements
- Administer reconstituted and diluted IMDELLTRA immediately.
- Table 12 displays the maximum storage time for the prepared IMDELLTRA infusion bag.
- Maximum storage time includes total duration from the time of reconstitution of the vial of IMDELLTRA to the end of the infusion.
| Room Temperature 20°C to 25°C (68°F to 77°F) | Refrigerated 2°C to 8°C (36°F to 46°F) | |
|---|---|---|
| Prepared IMDELLTRA Infusion Bag | 8 hours | 7 days |
| ||
For injection: 1 mg of white to slightly yellow lyophilized powder in a single-dose vial for reconstitution and further dilution.
For injection: 10 mg of white to slightly yellow lyophilized powder in a single-dose vial for reconstitution and further dilution.
Pregnancy
Risk Summary
Based on its mechanism of action, IMDELLTRA may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on the use of IMDELLTRA in pregnant women to inform a drug-associated risk.
In an animal reproduction study, a murine surrogate molecule administered intravenously to pregnant mice crossed the placental barrier.
Tarlatamab-dlle causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance.
Human immunoglobulin G (IgG) and proteins comprising IgG-derived fragment crystallizable (Fc) domains are known to cross the placental barrier; therefore, IMDELLTRA has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% - 4% and 15% - 20%, respectively.
Data
Animal Data
Animal reproduction studies have not been conducted with tarlatamab-dlle. In an embryo-fetal developmental toxicity study, a murine surrogate molecule was administered intravenously to pregnant mice during the period of organogenesis. The surrogate molecule crossed the placental barrier and did not cause maternal toxicity, embryo-fetal toxicity or teratogenicity.
Lactation
Risk Summary
There are no data on the presence of tarlatamab-dlle in human milk or the effects on the breastfed child or on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to IMDELLTRA are unknown. Because of the potential for serious adverse reactions in a breastfed child, advise patients not to breastfeed during treatment with IMDELLTRA and for 2 months after the last dose.
Females and Males of Reproductive Potential
IMDELLTRA may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Pregnancy Testing
Verify pregnancy status of females of reproductive potential prior to initiating IMDELLTRA.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with IMDELLTRA and for 2 months after the last dose.
Pediatric Use
The safety and effectiveness of IMDELLTRA have not been established in pediatric patients.
Geriatric Use
Of the 187 patients with SCLC who received IMDELLTRA 10 mg as a single agent, 54% were 65 years of age or older and 12% were 75 years of age or older. No overall differences in IMDELLTRA pharmacokinetics, or safety were observed between older patients (≥ 65 years of age) and younger patients. Clinical studies of IMDELLTRA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.
None.