Posology : מינונים

2 DOSAGE AND ADMINISTRATION
2.1 Patient Selection
Select patients for the treatment of platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer with ELAHERE based on the presence of FRα tumor expression.

2.2 Recommended Dosage
The recommended dosage of ELAHERE is 6 mg/kg adjusted ideal body weight (AIBW) administered once every 3 weeks (21-day cycle) as an intravenous infusion until disease progression or unacceptable toxicity [see Dosage and Administration (2.5)]. Dosing based on AIBW reduces exposure variability for patients who are either under or overweight.
The total dose of ELAHERE is calculated based on each patient’s AIBW using the following formula: AIBW = Ideal Body Weight (IBW [kg]) + 0.4*(Actual weight [kg] – IBW) Female IBW [kg] = 0.9*height[cm] – 92

2.3 Premedication and Required Eye Care
Premedication
Administer the premedications in Table 1 prior to each infusion of ELAHERE to reduce the incidence and severity of infusion related reactions (IRRs), nausea, and vomiting.
Table 1: Premedication Prior to Each ELAHERE Infusion
Premedication              Route of Administration     Examples (or equivalent)    Administration Time Prior to ELAHERE
Infusion
Corticosteroid             intravenous                 dexamethasone 10 mg Antihistamine              oral or intravenous         diphenhydramine 25 mg to 50 mg                       At least 30 minutes prior
Antipyretic                oral or intravenous         acetaminophen 325 mg to 650 mg
Antiemetic                 oral or intravenous         5-HT3 serotonin receptor    Before each dose and antagonist or appropriate   thereafter as needed alternatives

Consider additional premedications including corticosteroids the day prior to ELAHERE administration for patients who experienced IRRs.
Ophthalmic Exams and Premedication
Ophthalmic Exam: Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated.
Ophthalmic Topical Steroids: The use of ophthalmic topical steroids is recommended. The initial prescription and renewals of any corticosteroid medication should be made only after examination with a slit lamp.
Administer one drop of ophthalmic topical steroids in each eye 6 times daily starting the day prior to each infusion until day 4; then administer one drop in each eye 4 times daily for days 5-8 of each cycle of ELAHERE [see Warnings and Precautions (5.1)].
Lubricating Eye Drops: The use of lubricating eye drops at least four times daily and as needed is recommended during treatment with ELAHERE. Instruct patients to use lubricating eye drops and advise to wait at least 10 minutes after ophthalmic topical steroid administration before instilling lubricating eye drops [see Warnings and Precautions (5.1)].

2.4 Dosage Modifications
Table 2 provides dose reduction levels and Table 3 provides dosage modifications for ELAHERE due to adverse reactions.
Table 2: Dosage Reduction Schedule
ELAHERE Dose Levels
First Dose Reduction                                   5 mg/kg AIBW once every 3 weeks (21-day cycle) Second Dose Reduction                                  4 mg/kg AIBW once every 3 weeks (21-day cycle) * * Permanently discontinue in patients who cannot tolerate 4 mg/kg AIBW.
Table 3: Dosage Modifications for Adverse Reactions
Severity of Adverse
Adverse Reaction                                                 Dosage Modification Reaction*
Nonconfluent superficial
Monitor.
keratitis
Confluent superficial keratitis, a cornea
Withhold until improved or resolved, then maintain at
Keratitis/Keratopathy             epithelial defect, or 3-line same dose level or consider dose reduction.
[see Warnings and                 or more loss in best
Precautions (5.1) and             corrected visual acuity
Adverse Reactions (6.1)]          Corneal ulcer or stromal opacity or best corrected      Withhold until improved or resolved, then reduce by one distance visual acuity         dose level.
20/200 or worse
Corneal perforation            Permanently discontinue.
Grade 1/ Rare cell in
Monitor.
anterior chamber
Uveitis                           Grade 2/ 1-2+ Cell or          Withhold until Grade 1 or less, then maintain dose at [see Warnings and                 Flare in anterior chamber      same dose level.
Precautions (5.1) and
Adverse Reactions (6.1)]          Grade 3/ 3+ Cell or Flare      Withhold until Grade 1 or less, then reduce dose by one in anterior chamber            dose level.
Grade 4/ Hypopyon              Permanently discontinue.

Pneumonitis                       Grade 1                        Monitor.
[see Warnings and                                                Withhold until Grade 1 or less, then maintain at same Grade 2
Precautions (5.2) and                                            dose level or consider dose reduction.
Adverse Reactions (6.1)]          Grade 3 or 4                   Permanently discontinue.
Peripheral Neuropathy                                            Withhold until Grade 1 or less, then reduce by one dose Grade 2
[see Warnings and                                                level.
Precautions (5.3) and
Adverse Reactions (6.1)]          Grade 3 or 4                   Permanently discontinue.

Grade 1                        Maintain infusion rate.
•   Interrupt infusion and administer supportive treatment.
Infusion-Related
•   After recovery from symptoms, resume the infusion at
Reactions/Hypersensitivity
50% of the previous rate, and if no further symptoms
[see Adverse Reactions (6.1)] Grade 2                                appear, increase rate as appropriate until infusion is completed [see Dosage and Administration (2.5)].
•   Administer additional premedication for future cycles
[see Dosage and Administration (2.3)].
Severity of Adverse
Adverse Reaction                                               Dosage Modification Reaction*
•   Immediately stop infusion and administer supportive treatment.
•   Advise patient to seek emergency treatment and
Grade 3 or 4 immediately notify their healthcare provider if the infusion-related symptoms recur.
•   Permanently discontinue.
Hematological                                                  Withhold until Grade 1 or less, then resume at one lower Grade 3 or 4
[see Adverse Reactions (6.1)]                                  dose level.
Withhold until Grade 1 or less, then resume at one lower
Other Adverse Reactions       Grade 3 dose level.
[see Adverse Reactions (6.1)]
Grade 4                          Permanently discontinue.
*
Unless otherwise specified, National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

2.5 Instructions for Preparation and Administration
Preparation
•    ELAHERE is a hazardous drug. Follow applicable special handling and disposal procedures.
•    Calculate the dose (mg) (based on the patient’s AIBW), total volume (mL) of solution required, and the number of vials of ELAHERE needed [see Recommended Dosage (2.2) and Dose Modifications (2.4)]. More than one vial will be needed for a full dose.
•    Remove the vials of ELAHERE from the refrigerator and allow to warm to room temperature.
•    Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. ELAHERE is a clear to slightly opalescent, colorless solution.
•    Gently swirl and inspect each vial prior to withdrawing the calculated dose volume of ELAHERE.
Do not shake the vial.
•    Using aseptic technique, withdraw the calculated dose volume of ELAHERE for subsequent dilution.
•    ELAHERE contains no preservatives and is intended for single-dose only. Discard any unused drug remaining in the vial.
Dilution
•    ELAHERE must be diluted prior to administration with 5% Dextrose Injection to a final concentration of 1 mg/mL to 2 mg/mL.
•    ELAHERE is incompatible with 0.9% Sodium Chloride Injection. ELAHERE must not be mixed with any other drugs or intravenous fluids.
•    Determine the volume of 5% Dextrose Injection required to achieve the final diluted drug concentration. Either remove excess 5% Dextrose Injection from a prefilled intravenous bag or add the calculated volume of 5% Dextrose Injection to a sterile empty intravenous bag. Then add the calculated dose volume of ELAHERE to the intravenous bag.
•    Gently mix the diluted drug solution by slowly inverting the bag several times to assure uniform mixing. Do not shake or agitate.
•   If the diluted infusion solution is not used immediately, store solution either at room temperature (25°C) for no more than 8 hours (including infusion time), or under refrigeration at 2°C to 8°C for no more than 12 hours. If refrigerated, allow the infusion bag to reach room temperature prior to administration. After refrigeration, administer diluted infusion solutions within 8 hours (including infusion time).
•   Do not freeze prepared infusion solution.
Administration
•   Inspect the ELAHERE intravenous infusion bag visually for particulate matter and discoloration prior to administration.
•   Administer pre-medications prior to ELAHERE administration [see Premedication and Prophylactic Regimen (2.3)].
•   Administer ELAHERE as an intravenous infusion only, using a 0.2 or 0.22 µm polyethersulfone (PES) in-line filter. Do not substitute other membrane materials.
•   Administer the initial dose as an intravenous infusion at the rate of 1 mg/min. If well tolerated after 30 minutes at 1 mg/min, the infusion rate can be increased to 3 mg/min. If well tolerated after 30 minutes at 3 mg/min, the infusion rate can be increased to 5 mg/min.
•   If no infusion-related reactions occur with the previous dose, subsequent infusions should be started at the maximally tolerated rate and may be increased up to a maximum infusion rate of 5 mg/min, as tolerated.
•   Following the infusion, flush the intravenous line with 5% Dextrose Injection to ensure delivery of the full dose. Do not use any other intravenous fluids for flushing.