Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands
Lartruvo is indicated in combination with doxorubicin for the treatment of adult patients with advanced soft tissue sarcoma who are not amenable to curative treatment with surgery or radiotherapy and who have not been previously treated with doxorubicin (see section 5.1).
Olaratumab therapy must be initiated and supervised by physicians experienced in oncology. Patients should be monitored during the infusion for signs and symptoms of infusion-related reactions (IRRs) in a setting with available resuscitation equipment (see section 4.4).
The recommended dose of olaratumab is 15 mg/kg administered by intravenous infusion on days 1 and 8 of each 3 week cycle until disease progression or unacceptable toxicity. Lartruvo is administered in combination with doxorubicin for up to 8 cycles of treatment, followed by Lartruvo monotherapy in patients whose disease has not progressed. Doxorubicin is given on day 1 of each cycle following the Lartruvo infusion.
Premedication with an H1 antagonist (e.g., diphenhydramine) and dexamethasone (or equivalent medicinal products) should be given, intravenously, 30–60 minutes prior to the olaratumab doses on days 1 and 8 of cycle 1 in all patients. For subsequent cycles, premedication with an H1 antagonist (e.g., diphenhydramine) should be given intravenously 30–60 minutes prior to each dose of olaratumab.
For patients who experience Grade 1 or 2 IRR, the infusion should be interrupted and paracetamol, H1 antagonist and dexamethasone (or equivalent medicinal products) administered as needed. For all subsequent infusions, premedication with the following (or equivalent medicinal products) diphenhydramine hydrochloride (intravenously), paracetamol, and dexamethasone, should be given.
In the event that intravenous administration of an H1 antagonist is not possible, equivalent alternative premedication should be given (e.g. oral diphenhydramine hydrochloride at least 90 minutes prior to the infusion).
For dose adjustment recommendations related to doxorubicin, refer to the current doxorubicin prescribing information.
Recommendations for the management of olaratumab IRRs are provided in table 1.
Table 1 – Management recommendations for infusion-related reactions (IRRs)
| Toxicity gradea | Management recommendations (any occurrence) |
|---|---|
| Grade 1-2 | Stop the infusion |
| Paracetamol, H1 antagonist and dexamethasone should be administered as needed (see premedication section) | |
| Once the reaction has resolved, resume infusion at a 50 % decreased infusion rateb | |
| Monitor patient for worsening of condition | |
| For subsequent infusions, please see premedication section | |
| Grade 3-4 | Immediately and permanently discontinue treatment with olaratumab (see section 4.4). |
a Grade per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03
b Once the infusion rate has been reduced for a Grade 1 or 2 infusion-related reaction, it is recommended that the lower infusion rate be utilized for all subsequent infusions. The infusion duration should not exceed 2 hours.
For serious Grade ≥3 non-haematologic toxicity deemed related to olaratumab, the dose of olaratumab should be withheld until toxicity is ≤ Grade 1 or has returned to pretreatment baseline. For subsequent infusions, the dose should be reduced to 12 mg/kg for serious Grade 3 toxicities and to 10 mg/kg for Grade 4 toxicities. If a Grade 3 toxicity recurs despite the dose reduction, the dose should be reduced further to 10 mg/kg. In case of recurrence of a Grade 4 toxicity, treatment with olaratumab should be permanently discontinued.
If neutropenic fever/infection or Grade 4 neutropenia lasting longer than 1 week occurs, administration of olaratumab should be temporarily discontinued until the absolute neutrophil count is 1,000/µL or higher and then the dose of olaratumab should be resumed at the reduced dose of 12 mg/kg. If neutropenic fever/infection or Grade 4 neutropenia lasting longer than 1 week recurs despite dose reduction, the dose should be reduced further to 10 mg/kg.
Data on very elderly patients (>75 years) are very limited (see sections 4.8 and 5.1). No dose reductions other than those recommended for the general patient population are necessary.
There have been no formal studies with olaratumab in patients with renal impairment. PopPK data suggest that no dose adjustments are required in patients with mild or moderate renal impairment. There are no data regarding olaratumab administration in patients with severe renal impairment (calculated creatinine clearance <30 mL/min) (see section 5.2).
There have been no formal studies with olaratumab in patients with hepatic impairment. PopPK data suggest that no dose adjustments are required in patients with mild hepatic impairment. There are very limited data regarding olaratumab administration in patients with moderate hepatic impairment. There are no data in patients with severe hepatic impairment (see section 5.2).
The safety and efficacy of olaratumab in children aged 0 to 18 years of age have not yet been established. No data are available.
After dilution in sodium chloride 9 mg/mL (0.9 %) solution for injection, olaratumab is administered as an intravenous infusion over approximately 60 minutes. In order to accommodate larger infusion volumes that may be needed for patients requiring higher doses, the duration of infusion should be increased such that the maximum infusion rate of 25 mg/minute is not exceeded.
For instructions on dilution of the medicinal product before administration, see section 6.6.
There is no experience with Lartruvo overdose in human clinical trials. Lartruvo has been administered in a Phase 1 study up to 20 mg/kg on days 1 and 8 of a 21 day cycle without reaching a maximum tolerated dose. In case of overdose, use supportive therapy. There is no known antidote to Lartruvo overdose.
Unopened vial: 2 years.
After dilution: This product is preservative free. From a microbiological point of view the prepared dosing solution should be used immediately. If not used immediately, the dosing solution should be stored under refrigeration for up to 24 hours at 2°C to 8°C and up to an additional 8 hours at room temperature (up Medicinal product no longer authorised to 25°C) assuming dilution has taken place in controlled and validated aseptic conditions. Storage times include the duration of infusion.
Store in a refrigerator (2°C-8°C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.
For storage conditions after dilution of the medicinal product, see section 6.3.
19 mL solution in a vial (Type I glass) with a chlorobutyl elastomeric stopper, an aluminium seal and a polypropylene cap.
50 mL solution in a vial (Type I glass) with a chlorobutyl elastomeric stopper, an aluminium seal and a polypropylene cap.
Pack of 1 vial of 19 mL.
Pack of 2 vials of 19 mL.
Pack of 1 vial of 50 mL.
Not all pack sizes may be marketed.
The infusion solution should be prepared using aseptic technique to ensure the sterility of the prepared solution.
Each vial is intended for single use only. Do not shake the vial. The content of the vials should be inspected for particulate matter and discolouration (the concentrate for solution for infusion should be clear to slightly opalescent and colourless to slightly yellow without visible particles) prior to administration. If particulate matter or discolouration is identified, the vial must be discarded. The dose and volume of olaratumab needed should be calculated to prepare the infusion solution. Vials contain 190 mg or 500 mg as a 10 mg/mL solution of olaratumab. Only use sodium chloride 9 mg/mL (0.9 %) solution for injection as a diluent.
Based on the calculated volume of olaratumab, the corresponding volume of sodium chloride 9 mg/mL (0.9 %) solution for injection should be removed from the prefilled 250 mL intravenous container. The calculated volume of olaratumab should be aseptically transferred to the intravenous container. The final total volume in the container should be 250 mL. The container should be gently inverted to ensure adequate mixing. DO NOT FREEZE OR SHAKE the infusion solution.
The calculated volume of olaratumab should be aseptically transferred into an empty intravenous infusion container. A sufficient quantity of sodium chloride 9 mg/mL (0.9 %) solution for injection should be added to the container to make the total volume 250 mL. The container should be gently inverted to ensure adequate mixing. DO NOT FREEZE OR SHAKE the infusion solution.
Administer via an infusion pump. A separate infusion line must be used and the line must be flushed with sodium chloride 9 mg/mL (0.9 %) solution for injection at the end of the infusion.
Any unused portion of olaratumab left in a vial should be discarded, as the product contains no antimicrobial preservatives.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
