HERCEPTIN POWDER FOR INJECTION 440 MG/VIAL [SIN11028P]

Product Info

HERCEPTIN POWDER FOR INJECTION 440 MG/VIAL

[SIN11028P]

2.1 Therapeutic Indications
Herceptin IV and Herceptin SC
Metastatic Breast Cancer (MBC)
Herceptin is indicated for the treatment of patients with metastatic breast cancer who have tumors that overexpress HER2:

1. as monotherapy for the treatment of those patients who have received one or more chemotherapy regimens for their metastatic disease

2. in combination with paclitaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease

3. in combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormone-receptor positive metastatic breast cancer, not previously treated with Herceptin. This indication is based on data from one Phase III trial which studied the use of Herceptin in combination with anastrozole (see 3.1.2 Clinical / Efficacy Studies – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Experience with other aromatase inhibitors is limited.

Early Breast Cancer (EBC)
Herceptin is indicated for the treatment of patients with HER2 positive early breast cancer.

• following surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (if applicable) (see section 3.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• following adjuvant chemotherapy with doxorubicin and cyclophosphamide, in combination with paclitaxel or docetaxel.

• in combination with adjuvant chemotherapy consisting of docetaxel and carboplatin.

• in combination with neoadjuvant chemotherapy followed by adjuvant Herceptin therapy, for locally advanced (including inflammatory) disease or tumours > 2 cm in diameter (see sections 2.4 and 3.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Herceptin should only be used in patients whose tumours have either HER2 overexpression or HER2 gene amplification as determined by an accurate and validated assay.

Herceptin IV only
Metastatic Gastric Cancer (MGC)
Herceptin in combination with capecitabine or 5-fluorouracil and cisplatin is indicated for the treatment of patients with HER2 positive metastatic adenocarcinoma of the stomach or gastro-esophageal junction who have not received prior anti-cancer treatment for their metastatic disease.

Herceptin should only be used in patients with metastatic gastric cancer whose tumours have HER2 overexpression as defined by IHC2+ and a confirmatory FISH+ result, or IHC 3+, as determined by an accurate and validated assay.

2.2 Dosage and Administration
General
HER2 testing is mandatory prior to initiation of Herceptin therapy.

Substitution by any other biological medicinal product requires the consent of the prescribing physician.

The safety and efficacy of alternating or switching between Herceptin and products that are biosimilar but not deemed interchangeable to Herceptin has not been established. Therefore, the benefit/risk of alternating or switching need to be carefully considered.

Herceptin should be administered by a qualified health care professional.

It is important to check the product labels to ensure that the correct formulation (Herceptin IV or Herceptin SC) is being administered to the patient as prescribed.

Switching treatment between Herceptin IV and Herceptin SC and vice versa, using a three-weekly (q3w) dosing regimen, was investigated in study MO22982 (see section 2.6.1 Undesirable Effects / Clinical Trials – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

In order to prevent medication errors it is important to check the vial labels to ensure that the drug being prepared and administered is Herceptin (trastuzumab) and not Kadcyla (trastuzumab emtansine).

Herceptin IV (see section 4. Pharmaceutical Particulars – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information):
Herceptin IV is not to be used for subcutaneous administration and should be administered as intravenous infusion.

Do not administer as an intravenous push or bolus.

Metastatic breast cancer
Weekly schedule:

Loading dose: The recommended initial loading dose is 4 mg/kg body weight Herceptin IV administered as a 90-minute intravenous infusion. Patients should be observed for fever and chills or other infusion-associated symptoms (see 2.6 Undesirable effects – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Interruption of the infusion may help control such symptoms. The infusion may be resumed when symptoms abate.

Subsequent doses: The recommended weekly dose of Herceptin IV is 2 mg/kg body weight. If the prior dose was well tolerated, the dose can be administered as a 30-minute infusion. Patients should be observed for fever and chills or other infusion-associated symptoms (see 2.6 Undesirable effects – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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

3-weekly schedule:
Alternatively the following loading and subsequent doses are recommended for monotherapy and in combination with paclitaxel or an aromatase inhibitor.

Initial Herceptin IV loading dose of 8 mg/kg body weight, followed by 6 mg/kg body weight 3 weeks later and then 6 mg/kg repeated at 3-weekly intervals administered as infusions over approximately 90 minutes. If the initial loading dose was well tolerated, the subsequent doses can be administered as a 30-minute infusion.

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

Alternative weekly schedule:
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.

Metastatic Gastric Cancer
3-weekly schedule:
Herceptin IV is administered at an initial loading dose of 8 mg/kg body weight, followed by 6 mg/kg body weight 3 weeks later and then 6 mg/kg repeated at 3-weekly intervals administered as infusions over approximately 90 minutes. If the initial loading dose is well tolerated, the subsequent doses can be administered as a 30-minute infusion (See section 3.1 for chemotherapy combination dosing – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Herceptin SC (see section 4. Pharmaceutical Particulars – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information):
Herceptin SC is not to be used for intravenous administration and must be administered as a subcutaneous injection only.
No loading dose is required.
The recommended fixed dose of Herceptin SC is 600 mg every three weeks irrespective of the patient’s body weight. The injection site should be alternated between the left and right thigh. New injections should be given at least 1 inch/2.5 cm from the previous site on healthy skin and never into areas where the skin is red, bruised, tender, or hard. During the treatment course with Herceptin SC, other medications for SC administration should preferably be injected at different sites.
When administering Herceptin SC vial, the dose should be administered over 2–5 minutes every three weeks. In the pivotal trial (BO22227) Herceptin subcutaneous formulation was administered in the neoadjuvant-adjuvant setting in patients with early breast cancer. The preoperative chemotherapy regimen consisted of docetaxel (75mg/m²) followed by FEC (5-FU, epirubicin and cyclophosphamide) at standard doses. See section 3.1.2 Clinical / Efficacy Studies for chemotherapy combination dosing – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Duration of treatment
In clinical studies, patients with metastatic breast cancer or metastatic gastric cancer were treated with Herceptin until progression of disease or unmanageable toxicity. Patients with early breast cancer should be treated for 1 year or until disease recurrence or unmanageable toxicity, whichever occurs first. Extending treatment in EBC beyond one year is not recommended (see section 3.1.2 Clinical / Efficacy Studies – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

For instructions for use and handling refer to Section 4.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Dose modification
If the patient develops an infusion-related reaction (IRR), the infusion rate of Herceptin IV may be slowed or interrupted (see section 2.4 Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
No reductions in the dose of Herceptin were made during clinical trials. Patients may continue Herceptin therapy during periods of reversible, chemotherapy-induced myelosuppression, but they should be monitored carefully for complications of neutropenia during this time. The specific instructions to reduce or hold the dose of chemotherapy should be followed.

Missed doses
If the patient has missed a dose of Herceptin IV 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 Herceptin IV maintenance doses 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 Herceptin IV by more than one week, a reloading dose of Herceptin IV should be administered over approximately 90 minutes (weekly regimen: 4 mg/kg; 3-weekly regimen: 8 mg/kg) as soon as possible. Subsequent Herceptin IV 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.
If one dose of Herceptin SC is missed, it is recommended to administer the next 600 mg dose (i.e. the missed dose) as soon as possible. The interval between subsequent Herceptin SC doses should not be less than three weeks.

2.2.1 Special Dosage Instructions
Geriatric use
Data suggest that the disposition of Herceptin is not altered based on age or serum creatinine (see Pharmacokinetics in special populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). In clinical trials, patients ≥ 65 years of age did not receive reduced doses of Herceptin. Dedicated pharmacokinetic studies in the elderly and those with renal or hepatic impairment have not been carried out. However in a population pharmacokinetic analysis, age and renal impairment were not shown to affect Herceptin disposition.

Paediatric use
The safety and efficacy of Herceptin in paediatric patients < 18 years of age have not been established.

2.3 Contraindications
Patients with known hypersensitivity to Herceptin, murine proteins, hyaluronidase or to any other component of the product. Patients with severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.