Posology : מינונים

4.2. Posology and method of administration

HER2 testing is mandatory prior to initiation of therapy (see sections 4.4 and 5.1). Ogivri treatment should only be initiated by a physician experienced in the administration of cytotoxic chemotherapy (see section 4.4), and should be administered by a healthcare professional only.

It is important to check the product labels to ensure that the correct formulation (intravenous or subcutaneous fixed dose) is being administered to the patient, as prescribed.

Ogivri intravenous formulation is not intended for subcutaneous administration and should be administered via an intravenous infusion only.

If an alternate route of administration is required, other trastuzumab products offering such an option should be used.

In order to prevent medication errors it is important to check the vial labels to ensure that the drug being prepared and administered is trastuzumab and not another trastuzumab-containing product (e.g.trastuzumab emtansine or trastuzumab deruxtecan).

Posology

Metastatic breast cancer
Weekly schedule
The recommended initial loading dose of trastuzumab is 4 mg/kg body weight. The recommended weekly maintenance dose of trastuzumab is 2 mg/kg body weight, beginning one week after the loading dose.

Administration in combination with paclitaxel or docetaxel
In the pivotal trials (H0648g, M77001), paclitaxel or docetaxel was administered the day following the first dose of trastuzumab (for dose, see the prescribing information of paclitaxel or docetaxel) and immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.

Administration in combination with an aromatase inhibitor
In the pivotal trial (BO16216) trastuzumab and anastrozole were administered from day 1. There were no restrictions on the relative timing of trastuzumab and anastrozole at administration (for dose, see the prescribing information of anastrozole or other aromatase inhibitors).

Early breast cancer
Three-weekly and weekly schedule
As a three-weekly regimen the recommended initial loading dose of trastuzumab is 8 mg/kg body weight. The recommended maintenance dose of trastuzumab at three-weekly intervals is 6 mg/kg body weight, beginning three weeks after the loading dose.

As a weekly regimen (initial loading dose of 4 mg/kg followed by 2 mg/kg every week) concomitantly with paclitaxel following chemotherapy with doxorubicin and cyclophosphamide.

See section 5.1 for chemotherapy combination dosing.

Metastatic gastric cancer
Three-weekly schedule
The recommended initial loading dose is 8 mg/kg body weight. The recommended maintenance dose at three-weekly intervals is 6 mg/kg body weight, beginning three weeks after the loading dose.

Breast cancer and gastric cancer

Duration of treatment
Patients with MBC or MGC should be treated with trastuzumab until progression of disease. Patients with EBC should be treated with trastuzumab for 1 year or until disease recurrence, whichever occurs first, extending treatment in EBC beyond one year is not recommended (see section 5.1).

Dose reduction
No reductions in the dose of trastuzumab were made during clinical trials. Patients may continue therapy during periods of reversible, chemotherapy-induced myelosuppression but they should be monitored carefully for complications of neutropenia during this time. Refer to the prescribing information of paclitaxel, docetaxel or aromatase inhibitor for information on dose reduction or delays.

If left ventricular ejection fraction (LVEF) percentage drops ≥ 10 points from baseline AND to below 50 %, treatment should be suspended and a repeat LVEF assessment performed within approximately 3 weeks. If LVEF has not improved, or has declined further, or if symptomatic congestive heart failure (CHF) has developed, discontinuation of trastuzumab should be strongly considered, unless the benefits for the individual patient are deemed to outweigh the risks. All such patients should be referred for assessment by a cardiologist and followed up.

Missed doses
If the patient has missed a dose of trastuzumab by one week or less, then the usual maintenance dose (weekly regimen: 2 mg/kg; three-weekly regimen: 6 mg/kg) should be administered as soon as possible. Do not wait until the next planned cycle. Subsequent maintenance doses should be administered 7 days or 21 days later according to the weekly or three-weekly schedules, respectively.

If the patient has missed a dose of trastuzumab by more than one week, a re-loading dose of trastuzumab should be administered over approximately 90 minutes (weekly regimen: 4 mg/kg; three-weekly regimen: 8 mg/kg) as soon as possible. Subsequent trastuzumab maintenance doses (weekly regimen: 2 mg/kg; three-weekly regimen 6 mg/kg respectively) should be administered 7 days or 21 days later according to the weekly or three-weekly schedules respectively.

Special populations
Dedicated pharmacokinetic studies in the elderly and those with renal or hepatic impairment have not been carried out. In a population pharmacokinetic analysis, age and renal impairment were not shown to affect trastuzumab disposition.

Paediatric population
There is no relevant use of trastuzumab in the paediatric population.

Method of administration
Trastuzumab loading dose should be administered as a 90-minute intravenous infusion. Do not administer as an intravenous push or bolus. Trastuzumab intravenous infusion should be administered by a healthcare provider prepared to manage anaphylaxis and an emergency kit should be available.
Patients should be observed for at least six hours after the start of the first infusion and for two hours after the start of the subsequent infusions for symptoms like fever and chills or other infusion-related symptoms (see sections 4.4 and 4.8).
Interruption or slowing the rate of the infusion may help control such symptoms. The infusion may be resumed when symptoms abate.
If the initial loading dose was well tolerated, the subsequent doses can be administered as a 30-minute infusion.

For instructions on reconstitution of the medicinal product before administration, see section 6.6.