PERJETA

Antineoplastic Monoclonal Antibodies Targeting HER2/neu

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: No longer considered a hazardous drug by NIOSH.
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
Low
Administer routine antiemetic prophylaxis prior to treatment.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Do not administer pertuzumab without concomitant treatment with a trastuzumab product.
When used in combination with trastuzumab and docetaxel, administer pertuzumab, trastuzumab, and docetaxel in sequential order.
If a dose of pertuzumab is delayed or missed and it has been less than 6 weeks since the previous dose, give 420 mg IV as soon as possible. Do not wait until the next planned dose.
If a dose of pertuzumab is delayed or missed and it has been 6 weeks or longer since the previous dose, re-administer the initial dose of 840 mg IV, then 3 weeks later, resume 420 mg IV every 3 weeks.
 
Dilution and Preparation:
Withdraw the calculated dose of pertuzumab from the vial and add to 250 mL of 0.9% Sodium Chloride Injection in a PVC or non-PVC polyolefin infusion bag. Do not dilute with 5% Dextrose Injection.
Mix the diluted solution by gentle inversion; do not shake.
The diluted solution may be stored at 2 to 8 degrees Celsius for up to 24 hours.
 
Intravenous Infusion:
Administer the diluted solution immediately if possible.
Do not administer as an IV push or bolus.
Give the first dose of 840 mg over 60 minutes and subsequent 420 mg doses over 30 to 60 minutes.
Monitor for infusion-related reactions for 60 minutes following an 840 mg dose or for 30 minutes following a 420 mg dose.
Slow or interrupt the infusion if an infusion-associated reaction occurs; discontinue immediately if a hypersensitivity reaction occurs.[50557]

neutropenia / Delayed / 0.9-57.0
leukopenia / Delayed / 2.0-19.0
anemia / Delayed / 1.0-17.0
diarrhea / Early / 0-12.0
thrombocytopenia / Delayed / 0-12.0
vomiting / Early / 0-5.0
heart failure / Delayed / 1.0-4.0
fatigue / Early / 0.9-4.0
elevated hepatic enzymes / Delayed / 0-4.0
nausea / Early / 0-3.0
dyspnea / Early / 0-3.0
peripheral neuropathy / Delayed / 0-3.0
rash / Early / 0-2.0
anorexia / Delayed / 0-2.0
asthenia / Delayed / 1.0-2.0
peripheral edema / Delayed / 0-1.0
dyspepsia / Early / 0-1.0
dizziness / Early / 0-1.0
headache / Early / 0-1.0
fever / Early / 0-1.0
infusion-related reactions / Rapid / 0-1.0
infection / Delayed / 0-1.0
epistaxis / Delayed / 0-1.0
myalgia / Early / 0-1.0
arthralgia / Delayed / 0-0.9
palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / 0-0.5
dysgeusia / Early / 0-0.5
constipation / Delayed / 0-0.5
abdominal pain / Early / 0-0.5
cough / Delayed / 0-0.5
paresthesias / Delayed / 0-0.5
bone pain / Delayed / 0-0.5
insomnia / Early / 0-0.3
radiation recall reaction / Delayed / 0-0.3
hot flashes / Early / 0-0.2
alopecia / Delayed / 0-0.1
pruritus / Rapid / 0-0.1
xerosis / Delayed / 0-0.1
pharyngitis / Delayed / 0-0.1
cytokine release syndrome / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
pleural effusion / Delayed / Incidence not known
teratogenesis / Delayed / Incidence not known
fetal death / Delayed / Incidence not known
tumor lysis syndrome (TLS) / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known

stomatitis / Delayed / 5.0-26.0
antibody formation / Delayed / 0.3-3.0
hypokalemia / Delayed / 2.0
hyperuricemia / Delayed / Incidence not known
hyperphosphatemia / Delayed / Incidence not known

lacrimation / Early / 0.9-18.0
gastroesophageal reflux / Delayed / 0-12.0
back pain / Delayed / 0-10.0
chills / Rapid / 1.0

Use pertuzumab with caution in patients with a history of cardiac disease or heart failure. Decreases in left ventricular ejection fraction (LVEF) and left ventricular dysfunction have been reported with drugs that block HER2 activity, including pertuzumab; pertuzumab has not been studied in patients with a pretreatment LVEF less than 50%, a prior history of congestive heart failure (CHF), patients who had LVEF decreases to less than or equal to 50% during prior trastuzumab therapy, or conditions that could impair left ventricular function such as uncontrolled hypertension, recent myocardial infarction, serious cardiac arrhythmias requiring treatment, or a cumulative prior anthracycline exposure to greater than 360 mg/m2 of doxorubicin (or equivalent). Patients treated with prior anthracyclines or who have received prior radiation therapy to the chest may be at an increased risk. Assess LVEF prior to starting treatment with pertuzumab and every 12 weeks during treatment (once during neoadjuvant therapy). For patients with early breast cancer, the LVEF should be 55% or higher prior to starting pertuzumab therapy, and 50% or higher in patients who received prior anthracycline therapy. For patients with metastatic breast cancer, the LVEF should be 50% or higher before starting treatment with pertuzumab. If the LVEF decreases during therapy, an interruption or discontinuation of therapy may be necessary. Discontinue pertuzumab treatment for a confirmed clinically significant decrease in left ventricular function.[50557]

Based on its mechanism of action, fetal harm including intrauterine fetal death and birth defects may occur when pertuzumab is administered during pregnancy; monitoring for oligohydramnios is recommended if a patient is exposed during pregnancy or within 7 months of conception. If oligohydramnios occurs, fetal testing should be done that is appropriate for gestational age and is consistent with community standards of care. Pregnancy should be avoided by females during pertuzumab therapy and for 7 months after the last dose of pertuzumab in combination with trastuzumab; women who become pregnant during this time frame should be apprised of the potential hazard to the fetus. Healthcare professionals and patients should report any pregnancy during therapy or within 7 months of completion of therapy to the pregnancy pharmacovigilance program at Genentech (1-888-835-2555). Postmarketing, oligohydramnios and oligohydramnios sequence (manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death) occurred in pregnant women who received another HER2/neu receptor antagonist (trastuzumab) during pregnancy. In an animal study, oligohydramnios, delayed fetal kidney development, and embryo-fetal death occurred in pregnant cynomolgus monkeys who had a pertuzumab maximal exposure (Cmax) of 2.5 to 20 times greater than the recommended human dose.[50557]

Counsel patients about the reproductive risk and contraception requirements during pertuzumab treatment. Pertuzumab can be teratogenic if taken by the mother during pregnancy or within 7 months of conception. Females should avoid pregnancy and use effective contraception during pertuzumab treatment and for at least 7 months after treatment with pertuzumab in combination with trastuzumab. Verify the pregnancy status of a female patient prior to initiating pertuzumab therapy; females of reproductive potential should undergo pregnancy testing prior to initiation of pertuzumab. Women who become pregnant while receiving pertuzumab should be apprised of the potential hazard to the fetus and encouraged to enroll in the MotHER Pregnancy Registry (1-800-690-6720 or www.motherpregnancyregistry.com); additionally, healthcare providers and patients should report pertuzumab exposure to the pregnancy pharmacovigilance program at Genentech (1-888-835-2555).

PERJETA

Rx

HER2/neu-receptor antagonist monoclonal antibody
For the treatment of neoadjuvant, adjuvant, and metastatic HER2-positive breast cancer
Black box warning for cardiomyopathy and against use during pregnancy; effective contraception necessary

840 mg IV over 60 minutes, plus trastuzumab (8 mg/kg IV over 90 minutes) and docetaxel (75 mg/m2 IV) on day 1 of cycle 1. Beginning 3 weeks later with cycle 2, give pertuzumab 420 mg IV over 30 to 60 minutes IV, plus trastuzumab (6 mg/kg IV) and docetaxel (75 mg/m2 IV, or escalated to 100 mg/m2 IV if first dose was well tolerated) on day 1, every 3 weeks; in the clinical trial, docetaxel was continued for at least a total of 6 cycles and pertuzumab/trastuzumab were administered until disease progression or unacceptable toxicity. Pertuzumab and trastuzumab can be given in any order; however, both agents should be given PRIOR TO the docetaxel infusion. Observe closely for infusion-related reactions for 60 minutes after the first pertuzumab infusion and for 30 minutes after subsequent infusions; do not start other infusions until after this observation period. Do not administer pertuzumab without trastuzumab; withhold or discontinue pertuzumab therapy if trastuzumab is withheld or discontinued. In a multicenter, double-blind, placebo-controlled trial of patients with HER2-positive metastatic breast cancer (CLEOPATRA), treatment with pertuzumab, trastuzumab, and docetaxel significantly improved progression-free survival (18.5 months vs. 12.4 months) compared with trastuzumab and docetaxel alone. Overall survival was also significantly improved in the pertuzumab arm (56.5 months vs. 40.8 months).

840 mg IV over 60 minutes on day 1, plus trastuzumab (8 mg/kg IV over 90 minutes on day 1). Three weeks later, give pertuzumab 420 mg IV over 30 to 60 minutes and trastuzumab (6 mg/kg IV over 30 to 90 minutes) every 3 weeks for a total of 3 to 6 cycles as part of one of the following treatment regimens: Four preoperative cycles of pertuzumab in combination with trastuzumab and docetaxel with 3 postoperative cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC); Three or four preopoerative cycles of FEC alone followed by 3 or 4 preoperative cycles of pertuzumab in combination with docetaxel and trastuzumab; Six preoperative cycles of pertuzumab in combination with docetaxel, carboplatin, and trastuzumab (TCH); Four preoperative cycles of dose-dense doxorubicin and cyclophosphamide (ddAC) alone followed by 4 preoperative doses of pertuzumab in combination with paclitaxel and trastuzumab. After surgery, give IV pertuzumab and trastuzumab every 3 weeks to complete 1 year of therapy (up to 18 cycles). Pertuzumab and trastuzumab can be given in any order; however, both agents should be given PRIOR to the taxane infusion in patients receiving a taxane-containing regimen. In patients receiving an anthracycline-containing regimen, pertuzumab and trastuzumab should be given following completion of the anthracycline. Observe closely for infusion-related reactions for 60 minutes after the first pertuzumab infusion and for 30 minutes after subsequent infusions; do not start other infusions until after this observation period. Do not administer pertuzumab without trastuzumab; withhold or discontinue pertuzumab therapy if trastuzumab is withheld or discontinued.

840 mg IV over 60 minutes on day 1, plus trastuzumab (8 mg/kg IV over 90 minutes on day 1). Three weeks later, give pertuzumab 420 mg IV over 30 to 60 minutes and trastuzumab (6 mg/kg IV over 30 to 90 minutes) every 3 weeks for a total of 1 year (up to 18 cycles) or until disease recurrence or unmanageable toxicity. Give with standard anthracycline- and/or taxane-based chemotherapy for early breast cancer. Pertuzumab and trastuzumab can be given in any order; however, both agents should be given before the taxane in taxane-containing regimens. Give pertuzumab and trastuzumab after the completion of the anthracycline dose in anthracycline-containing regimens. Observe closely for infusion-related reactions after the first pertuzumab infusion for 60 minutes and for 30 minutes after subsequent infusions; do not start other therapy until after this observation period. Do not administer pertuzumab without trastuzumab; withhold or discontinue pertuzumab therapy if trastuzumab is withheld or discontinued. Patients with HER2-positive early breast cancer were randomized to adjuvant treatment with either pertuzumab or placebo in combination with trastuzumab and standard chemotherapy (i.e., FEC or FAC followed by docetaxel or paclitaxel; AC followed by docetaxel or paclitaxel; or docetaxel in combination with carboplatin) in a multicenter, randomized, double-blind clinical trial (APHINITY; n = 4,804); after completion of chemotherapy, patients received radiotherapy and/or hormone therapy per investigator's discretion. After a median of 74 months of follow-up, the 6-year rate of invasive disease-free survival (IDFS) significantly improved in patients who received pertuzumab compared with placebo in the intent-to-treat population (91% vs. 88%). In patients with node-positive disease, the 6-year IDFS rate was also significantly improved (88% vs. 83%); 6-year IDFS was 95% versus 94.9%, respectively, in patients with node-negative disease. Overall survival at 6-years was 95% in the pertuzumab arm compared with 94% in the placebo arm.

840 mg IV over 60 minutes on day 1, plus trastuzumab; hyaluronidase (600 mg trastuzumab and 10,000 units hyaluronidase (5 mL) subcutaneously over approximately 2 to 5 minutes). Three weeks later, give pertuzumab 420 mg IV over 30 to 60 minutes and trastuzumab; hyaluronidase (600 mg trastuzumab and 10,000 units hyaluronidase (5 mL) subcutaneously over approximately 2 to 5 minutes) every 3 weeks for a total of 3 to 6 cycles as part of one of the following treatment regimens: Four preoperative cycles of pertuzumab in combination with trastuzumab; hyaluronidase and docetaxel with 3 postoperative cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC); Three or four preopoerative cycles of FEC alone followed by 3 or 4 preoperative cycles of pertuzumab in combination with docetaxel and trastuzumab; hyaluronidase; Six preoperative cycles of pertuzumab in combination with docetaxel, carboplatin, and trastuzumab; hyaluronidase (TCH); Four preoperative cycles of dose-dense doxorubicin and cyclophosphamide (ddAC) alone followed by 4 preoperative doses of pertuzumab in combination with paclitaxel and trastuzumab; hyaluronidase. After surgery, give IV pertuzumab and trastuzumab; hyaluronidase every 3 weeks to complete 1 year of therapy (up to 18 cycles). Pertuzumab and trastuzumab; hyaluronidase can be given in any order; however, both agents should be given PRIOR to the taxane infusion in patients receiving a taxane-containing regimen. In patients receiving an anthracycline-containing regimen, pertuzumab and trastuzumab; hyaluronidase should be given following completion of the anthracycline. Observe closely for infusion-related reactions for 60 minutes after the first pertuzumab infusion and for 30 minutes after subsequent infusions; do not start other infusions until after this observation period. Do not administer pertuzumab without trastuzumab; hyaluronidase; withhold or discontinue pertuzumab therapy if trastuzumab; hyaluronidase is withheld or discontinued.

840 mg IV over 60 minutes on day 1, plus trastuzumab; hyaluronidase (600 mg trastuzumab and 10,000 units hyaluronidase (5 mL) subcutaneously over approximately 2 to 5 minutes). Three weeks later, give pertuzumab 420 mg IV over 30 to 60 minutes and trastuzumab; hyaluronidase (600 mg trastuzumab and 10,000 units hyaluronidase (5 mL) subcutaneously over approximately 2 to 5 minutes) every 3 weeks for a total of 1 year (up to 18 cycles) or until disease recurrence or unmanageable toxicity. Give with standard anthracycline- and/or taxane-based chemotherapy for early breast cancer. Pertuzumab and trastuzumab; hyaluronidase can be given in any order; however, both agents should be given before the taxane in taxane-containing regimens. Give pertuzumab and trastuzumab; hyaluronidase after the completion of the anthracycline dose in anthracycline-containing regimens. Observe closely for infusion-related reactions after the first pertuzumab infusion for 60 minutes and for 30 minutes after subsequent infusions; do not start other therapy until after this observation period. Do not administer pertuzumab without trastuzumab; hyaluronidase; withhold or discontinue pertuzumab therapy if trastuzumab; hyaluronidase is withheld or discontinued.

840 mg IV over 60 minutes, plus trastuzumab; hyaluronidase (600 mg trastuzumab and 10,000 units hyaluronidase (5 mL) subcutaneously over approximately 2 to 5 minutes) and docetaxel (75 mg/m2 IV) on day 1 of cycle 1. Beginning 3 weeks later with cycle 2, give pertuzumab 420 mg IV over 30 to 60 minutes IV, plus trastuzumab; hyaluronidase (600 mg trastuzumab and 10,000 units hyaluronidase (5 mL) subcutaneously over approximately 2 to 5 minutes) and docetaxel (75 mg/m2 IV, or escalated to 100 mg/m2 IV if first dose was well tolerated) on day 1, every 3 weeks; in the clinical trial, docetaxel was continued for at least a total of 6 cycles and pertuzumab/trastuzumab were administered until disease progression or unacceptable toxicity. Pertuzumab and trastuzumab; hyaluronidase can be given in any order; however, both agents should be given PRIOR TO the docetaxel infusion. Observe closely for infusion-related reactions for 60 minutes after the first pertuzumab infusion and for 30 minutes after subsequent infusions; do not start other infusions until after this observation period. Do not administer pertuzumab without trastuzumab; hyaluronidase; withhold or discontinue pertuzumab therapy if trastuzumab; hyaluronidase is withheld or discontinued. In a multicenter, double-blind, placebo-controlled trial of patients with HER2-positive metastatic breast cancer (CLEOPATRA), treatment with pertuzumab, trastuzumab, and docetaxel significantly improved progression-free survival (18.5 months vs. 12.4 months) compared with trastuzumab and docetaxel alone. Overall survival was also significantly improved in the pertuzumab arm (56.5 months vs. 40.8 months).

Specific guidelines for dosage adjustments in hepatic impairment are not available.

CrCL 30 mL/min or higher: No dosage adjustment needed.
CrCL less than 30 mL/min: Limited pharmacokinetic data; recommendations for dosage adjustment are not available.

Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.

PERJETA Intravenous Inj Sol: 1mL, 30mg

840 mg IV initially, then 420 mg IV every 3 weeks.

840 mg IV initially, then 420 mg IV every 3 weeks.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Pertuzumab is a humanized recombinant IgG1 monoclonal antibody that binds to the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor-2 (HER2) protein. It blocks ligand-dependent heterodimerization of HER2 and other epidermal growth factor receptors including HER3 and HER4. Two intracellular signaling pathways, mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase (PI3K), are inhibited resulting in cell growth arrest and apoptosis. Pertuzumab also demonstrates antibody-dependent cell-mediated cytotoxicity. Pertuzumab differs from trastuzumab in where it binds to HER2; pertuzumab binds to the dimerization domain and trastuzumab binds in the juxtamembrane region. Combining pertuzumab with trastuzumab has demonstrated enhanced antitumor activity in HER2-amplified breast cancer in xenograft models. Additionally, combination therapy may reduce trastuzumab resistance.

Pertuzumab is administered as an intravenous infusion. At doses of 2 to 25 mg/kg, pertuzumab has linear pharmocokinetics.The median pertuzumab clearance was 0.24 L/day and the median half-life was 18 days in a pharmacokinetic analysis of 481 patients.

In a pharmacokinetic analysis of 481 patients who received pertuzumab 840 mg IV followed 3 weeks later by pertuzumab maintenance with 420 mg IV every 3 weeks, the steady-state concentration was reached following the first maintenance dose.

Based on its mechanism of action, fetal harm including intrauterine fetal death and birth defects may occur when pertuzumab is administered during pregnancy; monitoring for oligohydramnios is recommended if a patient is exposed during pregnancy or within 7 months of conception. If oligohydramnios occurs, fetal testing should be done that is appropriate for gestational age and is consistent with community standards of care. Pregnancy should be avoided by females during pertuzumab therapy and for 7 months after the last dose of pertuzumab in combination with trastuzumab; women who become pregnant during this time frame should be apprised of the potential hazard to the fetus. Healthcare professionals and patients should report any pregnancy during therapy or within 7 months of completion of therapy to the pregnancy pharmacovigilance program at Genentech (1-888-835-2555). Postmarketing, oligohydramnios and oligohydramnios sequence (manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death) occurred in pregnant women who received another HER2/neu receptor antagonist (trastuzumab) during pregnancy. In an animal study, oligohydramnios, delayed fetal kidney development, and embryo-fetal death occurred in pregnant cynomolgus monkeys who had a pertuzumab maximal exposure (Cmax) of 2.5 to 20 times greater than the recommended human dose.[50557]