Pertuza(Pertuzumab)

Therapeutic Group: Oncology

Presentation

Pertuza 420: Each vial contains Pertuzumab INN 420 mg in 14 ml solution for IV infusion

Description

Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular

dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2).

Pertuzumab targets the extracellular dimerization domain (Subdomain II) of the human epidermal

growth factor receptor 2 protein (HER2) and, thereby, blocks ligand-dependent heterodimerization of

HER2 with other HER family members, including EGFR, HER3, and HER4. As a result, Pertuzumab

inhibits ligand-initiated intracellular signaling through two major signal pathways, mitogen-activated

protein (MAP) kinase, and phosphoinositide 3-kinase (PI3K). Inhibition of these signaling pathways

can result in cell growth arrest and apoptosis, respectively. In addition, Pertuzumab mediates

antibody-dependent cell-mediated cytotoxicity

Indications

Pertuzumab is a HER2/neu receptor antagonist indicated for:

- Use in combination with Trastuzumab and docetaxel for treatment of patients with HER2-positive

metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy

for metastatic disease

- Use in combination with Trastuzumab and docetaxel as neoadjuvant treatment of patients with

HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2

cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer.

This indication is based on demonstration of an improvement in pathological complete response

rate. No data are available demonstrating improvement in event-free survival or overall survival.

Limitations of Use:

The safety of Pertuzumab as part of a doxorubicin-containing regimen has not been established

The safety of Pertuzumab administered for greater than 6 cycles for early breast cancer has not been

established.

Dosage & Administration

For intravenous infusion only. It should not be administered as an intravenous push or bolus
The initial Pertuzumab dose is 840 mg administered as a 60-minute intravenous infusion, followed
every 3 weeks thereafter by 420 mg administered as a 30 to 60 minute intravenous infusion
MBC: Pertuzumab should be administered with Trastuzumab and Docetaxel by intravenous infusion
every 3 weeks
Neoadjuvant: Pertuzumab should be administered with Trastuzumab and Docetaxel by intravenous
infusion preoperatively every 3 weeks for 3 to 6 cycles
Instruction of Uses
Pertuzumab should be administered as an intravenous infusion only. It should not be administered as
an intravenous push or bolus. Pertuzumab should not be used with other drugs.

Side Effects

- Left Ventricular Dysfunction: Pertuzumab can result in subclinical and clinical cardiac failure
manifesting as CHF, and decreased LVEF. Evaluate cardiac function prior to and during treatment.
Discontinue Pertuzumab treatment for a confirmed clinically significant decrease in left ventricular
function
- Embryo-fetal Toxicity: Exposure to Pertuzumab can result in embryo-fetal death and birth defects.
Studies in animals have resulted in oligohydramnios, delayed renal development, and death.
Patients should be advised of these risks and the need for effective contraception.
Metastatic Breast Cancer
The most common adverse reactions (> 30%) with Pertuzumab in combination with Trastuzumab
and Docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral
neuropathy.
Neoadjuvant Treatment of Breast Cancer:
The most common adverse reactions (> 30%) with Pertuzumab in combination with Trastuzumab
and Docetaxel were alopecia, diarrhea, nausea, and neutropenia
The most common adverse reactions (>30%) with Pertuzumab in combination with Trastuzumab
and Docetaxel when given for 3 cycles following 3 cycles of fluorouracil, epirubicin, and cyclophosphamide
(FEC) were fatigue, alopecia, diarrhea, nausea, vomiting, and neutropenia
The most common adverse reactions (>30%) with Pertuzumab in combination with Docetaxel,
Carboplatin, and Trastuzumab (TCH) were fatigue, alopecia, diarrhea, nausea, vomiting,
neutropenia, thrombocytopenia, and anemia

Precautions

Left Ventricular Dysfunction: LVEF should be monitored and dosing should be withheld as appropriate
Embryo-fetal toxicity: Fetal harm can occur when administered to a pregnant woman
Infusion-Related Reactions: Should be monitored for signs and symptoms. If a significant
infusion-associated reaction occurs, the infusion should be slowed or interrupted and appropriate
medical therapies should be administered
Hypersensitivity Reactions/Anaphylaxis: Should be monitored for signs and symptoms. If a severe
hypersensitivity reaction/anaphylaxis occurs, the infusion should be discontinued immediately and
appropriate medical therapies should be administered

Use in Pregnancy & Lactation

Pregnancy Category D
There are no adequate and well-controlled studies of Pertuzumab in pregnant women. If Pertuzumab
is administered during pregnancy or if a patient becomes pregnant while receiving Pertuzumab or
within 7 months following the last dose of Pertuzumab in combination with Trastuzumab, the patient
should be apprised of the potential hazard to the fetus
Lactation
It is not known whether Pertuzumab is excreted in human milk, but human IgG is excreted in human
milk. Because many drugs are secreted in human milk and because of the potential for serious
adverse actions in nursing infants from Pertuzumab a decision should be made whether to discontinue
nursing, or discontinue drug, taking into account the elimination half-life of Pertuzumab and the
importance of the drug to the mother
Pediatric Use
Safety and effectiveness of Pertuzumab have not been established in pediatric patients.

Drug Interaction

Patients who receive anthracycline after stopping Pertuzumab may be at increased risk of cardiac
dysfunction because of Pertuzumab’s long wash out period. If possible, physicians should avoid
anthracycline-based therapy for up to 7 months after stopping Pertuzumab. If anthracyclines are
used, the patient’s cardiac function should be monitored carefully.

Commercial Pack

Pertuza 420 IV infusion: Each box contains 1 vial of Pertuzumab 420 mg