Perjeta
Pertuzumab · Injection, Solution, Concentrate · Intravenous
Uses
1 INDICATIONS AND USAGE PERJETA is a HER2/neu receptor antagonist indicated for: Use in combination with trastuzumab and docetaxel for treatment of adults with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. ( 1.1 ) Use in combination with trastuzumab and chemotherapy as neoadjuvant treatment of adults 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. ( 1.2 , 2.2 , 14.2 ) adjuvant treatment of adults with HER2-positive early breast cancer at high risk of recurrence ( 1.2 , 2.2 , 14.3 ) 1.1 Metastatic Breast Cancer (MBC) PERJETA is indicated for use in combination with trastuzumab and docetaxel for the treatment of adults with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease [see Dosage and Administration (2.2) and Clinical Studies (14.1) ] . 1.2 Early Breast Cancer (EBC) PERJETA is indicated for use in combination with trastuzumab and chemotherapy for the neoadjuvant treatment of adults 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 [see Dosage and Administration (2.2) and Clinical Studies (14.2) ] . the adjuvant treatment of adults with HER2-positive early breast cancer at high risk of recurrence [see Dosage and Administration (2.2) and Clinical Studies (14.3) ] .
Dosage and administration
For intravenous infusion only. Do not administer as an intravenous push or bolus. ( 2.5 ) HER2 testing: Perform using FDA-approved tests by laboratories with demonstrated proficiency. ( 2.1 ) The initial PERJETA 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. ( 2.3 ) MBC: Administer PERJETA, trastuzumab or trastuzumab hyaluronidase-oysk, and docetaxel every 3 weeks. ( 2.3 ) Neoadjuvant: Administer PERJETA, trastuzumab or trastuzumab hyaluronidase-oysk, and chemotherapy preoperatively every 3 weeks for 3 to 6 cycles. ( 2.3 ) Adjuvant: Administer PERJETA, trastuzumab or trastuzumab hyaluronidase-oysk, and chemotherapy postoperatively every 3 weeks for a total of 1 year (up to 18 cycles). ( 2.3 ) 2.1 Evaluation and Testing Before Initiating Perjeta Assess left ventricular ejection fraction (LVEF) prior to initiation of PERJETA and at regular intervals during treatment [see Boxed Warning , Dosage and Administration (2.4) , Warnings and Precautions (5.1) ]. Verify the pregnancy status of females of reproductive potential prior to the initiation of PERJETA [see Warnings and Precautions (5.2) , Use in Specific Populations (8.1 , 8.3) ]. 2.2 Patient Selection Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens [see Indications and Usage (1) and Clinical Studies (14) ] . Assessment of HER2 protein overexpression and HER2 gene amplification should be performed using FDA-approved tests specific for breast cancer by laboratories with demonstrated proficiency. Information on the FDA-approved tests for the detection of HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda.gov/CompanionDiagnostics. Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results. 2.3 Recommended Dosage and Administration The initial dose of PERJETA is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks by a dose of 420 mg administered as an intravenous infusion over 30 to 60 minutes. When administered with PERJETA, the recommended initial dose of trastuzumab is 8 mg/kg administered as a 90-minute intravenous infusion, followed every 3 weeks by a dose of 6 mg/kg administered as an intravenous infusion over 30 to 90 minutes. When administered with PERJETA, the recommended initial dose of trastuzumab hyaluronidase-oysk is 600 mg/10,000 units (600 mg trastuzumab and 10,000 units hyaluronidase) administered subcutaneously over approximately 2 to 5 minutes once every three weeks irrespective of the patient's body weight. Administer PERJETA, trastuzumab or trastuzumab hyaluronidase-oysk, and taxane sequentially. PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk can be given in any order. Administer taxane after PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk. An observation period of 30 to 60 minutes is recommended after each PERJETA infusion and before commencement of any subsequent administration of trastuzumab or trastuzumab hyaluronidase-oysk, or taxane [see Warnings and Precautions (5.3) ]. In patients receiving an anthracycline-based regimen, administer PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk after completion of the anthracycline. Metastatic Breast Cancer (MBC) When administered with PERJETA, the recommended initial dose of docetaxel is 75 mg/m 2 administered as an intravenous infusion. The dose may be escalated to 100 mg/m 2 administered every 3 weeks if the initial dose is well tolerated. Neoadjuvant Treatment of Breast Cancer Administer PERJETA every 3 weeks for 3 to 6 cycles as part of one of the following treatment regimens [see Clinical Studies (14.2 , 14.3) ] : Four preoperative cycles of PERJETA in combination with trastuzumab or trastuzumab hyaluronidase-oysk and docetaxel followed by 3 postoperative cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) Three or four preoperative cycles of FEC alone followed by 3 or 4 preoperative cycles of PERJETA in combination with docetaxel and trastuzumab or trastuzumab hyaluronidase-oysk Six preoperative cycles of PERJETA in combination with docetaxel, carboplatin, and trastuzumab (TCH) or trastuzumab hyaluronidase-oysk (escalation of docetaxel above 75 mg/m 2 is not recommended) Four preoperative cycles of dose-dense doxorubicin and cyclophosphamide (ddAC) alone followed by 4 preoperative cycles of PERJETA in combination with paclitaxel and trastuzumab or trastuzumab hyaluronidase-oysk Following surgery, administer PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk to complete 1 year of treatment (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first. Adjuvant Treatment of Breast Cancer As part of a regimen including standard anthracycline- and/or taxane-based chemotherapy, administer PERJETA in combination with trastuzumab or trastuzumab hyaluronidase-oysk every 3 weeks for a total of 1 year (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first. Administer PERJETA on Day 1 of the first taxane-containing cycle [see Clinical Studies (14.3) ] . 2.4 Important Dosing Considerations Missed Dose The recommended dosage modifications for delayed or missed doses are listed in Table 1 . Table 1: Recommendations for Delayed or Missed Doses Time between two sequential doses PERJETA Trastuzumab (intravenous) Trastuzumab hyaluronidase-oysk < 6 weeks Administer PERJETA 420 mg intravenously as soon as possible. Do not wait until the next planned dose. Administer trastuzumab 6 mg/kg intravenously as soon as possible. Do not wait until the next planned dose.
Dosage forms and strengths
Injection: 420 mg/14 mL (30 mg/mL) clear to slightly opalescent and colorless to pale brown solution in a single-dose vial Injection: 420 mg/14 mL (30 mg/mL) solution in a single-dose vial. ( 3 )
Contraindications
4 CONTRAINDICATIONS PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients [see Warnings and Precautions (5.4)]. PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients. ( 4 )
Warnings and precautions
Infusion-Related Reactions: PERJETA can cause serious infusion reactions, including fatal events: Monitor for signs and symptoms. If a significant infusion-associated reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies. ( 5.3 ) Hypersensitivity Reactions/Anaphylaxis: PERJETA can cause hypersensitivity reactions, including anaphylaxis: Monitor for signs and symptoms, including angioedema. If a severe hypersensitivity reaction/anaphylaxis occurs, discontinue the infusion immediately and administer appropriate medical therapies. ( 5.4 ) 5.1 Left Ventricular Dysfunction PERJETA can cause left ventricular dysfunction, including symptomatic heart failure. Decreases in LVEF have been reported with drugs that block HER2 activity, including PERJETA. Assess LVEF prior to initiation of PERJETA and at regular intervals during treatment to ensure that LVEF is within normal limits. If the LVEF declines and has not improved, or has declined further at the subsequent assessment, consider permanent discontinuation of PERJETA and trastuzumab [see Dosage Modification for Adverse Reactions (2.5) ] . In the PERJETA-treated patients with MBC in CLEOPATRA, left ventricular dysfunction occurred in 4% of patients and symptomatic left ventricular systolic dysfunction (LVSD) (congestive heart failure) occurred in 1% of patients. Patients who received prior anthracyclines or prior radiotherapy to the chest area may be at higher risk of decreased LVEF or left ventricular dysfunction. In patients receiving PERJETA as a neoadjuvant treatment in combination with trastuzumab and docetaxel in NeoSphere, LVEF decline > 10% and a drop to < 50% occurred in 8% of patients and left ventricular dysfunction occurred in 3% of patients. LVEF recovered to ≥ 50% in all these patients. In patients receiving neoadjuvant PERJETA in TRYPHAENA, LVEF decline > 10% and a drop to < 50% occurred in 7% of patients treated with PERJETA plus trastuzumab and FEC followed by PERJETA plus trastuzumab and docetaxel, 16% of patients treated with PERJETA plus trastuzumab and docetaxel following FEC, and 11% of patients treated with PERJETA in combination with TCH. Left ventricular dysfunction occurred in 6% of patients treated with PERJETA plus trastuzumab and FEC followed by PERJETA plus trastuzumab and docetaxel, 4% of patients treated with PERJETA plus trastuzumab and docetaxel following FEC, and 3% of patients treated with PERJETA in combination with TCH. Symptomatic LVSD occurred in 4% of patients treated with PERJETA plus trastuzumab and docetaxel following FEC, 1% of patients treated with PERJETA in combination with TCH, and none of the patients treated with PERJETA plus trastuzumab and FEC followed by PERJETA plus trastuzumab and docetaxel. LVEF recovered to ≥ 50% in all but one patient. In patients receiving neoadjuvant PERJETA in BERENICE, in the neoadjuvant period, LVEF decline ≥ 10% and a drop to < 50% as measured by ECHO/MUGA assessment occurred in 7% of patients treated with PERJETA plus trastuzumab and paclitaxel following ddAC, and 2% of patients treated with PERJETA plus trastuzumab and docetaxel following FEC. Ejection fraction decreased (asymptomatic LVD) occurred in 7% of patients treated with PERJETA plus trastuzumab and paclitaxel following ddAC and 4% of the patients treated with PERJETA plus trastuzumab and docetaxel following FEC in the neoadjuvant period. Symptomatic LVSD (NYHA Class III/IV Congestive Heart Failure) occurred in 2% of patients treated with PERJETA plus trastuzumab and paclitaxel following ddAC and none of the patients treated with PERJETA plus trastuzumab and docetaxel following FEC in the neoadjuvant period. In patients receiving adjuvant PERJETA in APHINITY, the incidence of symptomatic heart failure (NYHA Class III/IV) with a LVEF decline ≥ 10% and a drop to < 50% was 0.6%. Of the patients who experienced symptomatic heart failure, 47% of PERJETA-treated patients had recovered (defined as 2 consecutive LVEF measurements above 50%) at the data cutoff. The majority of the events (86%) were reported in anthracycline-treated patients. Asymptomatic or mildly symptomatic (NYHA Class II) declines in LVEF ≥ 10% and a drop to < 50% were reported in 3% of PERJETA-treated patients, of whom 80% recovered at the data cutoff. PERJETA has not been studied in patients with a pretreatment LVEF value of < 50%, a prior history of CHF, decreases in LVEF to < 50% during prior trastuzumab therapy, or conditions that could impair left ventricular function such as uncontrolled hypertension, recent myocardial infarction, serious cardiac arrhythmia requiring treatment or a cumulative prior anthracycline exposure to > 360 mg/m 2 of doxorubicin or its equivalent. 5.2 Embryo-Fetal Toxicity Based on its mechanism of action and findings in animal studies, PERJETA can cause fetal harm when administered to a pregnant woman. PERJETA is a HER2/neu receptor antagonist. Cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death have been reported with use of another HER2/neu receptor antagonist (trastuzumab) during pregnancy. In an animal reproduction study, administration of pertuzumab to pregnant cynomolgus monkeys during the period of organogenesis resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal death at exposures 2.5 to 20 times the exposure in humans at the recommended dose, based on C max . Verify the pregnancy status of females of reproductive potential prior to the initiation of PERJETA. Advise pregnant women and females of reproductive potential that exposure to PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception can result in fetal harm, including embryo-fetal death or birth defects.
Side effects
The following adverse reactions are discussed in greater detail in other sections of the label: Left Ventricular Dysfunction [see Warnings and Precautions (5.1) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.2) ] Infusion-Related Reactions [see Warnings and Precautions (5.3) ] Hypersensitivity Reactions/Anaphylaxis [see Warnings and Precautions (5.4) ] Metastatic Breast Cancer The most common adverse reactions (> 30%) with PERJETA in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy. ( 6.1 ) Neoadjuvant Treatment of Breast Cancer The most common adverse reactions (> 30%) with PERJETA in combination with trastuzumab and docetaxel were alopecia, diarrhea, nausea, and neutropenia. ( 6.1 ) The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel when given for 3 cycles following 3 cycles of FEC were fatigue, alopecia, diarrhea, nausea, vomiting, and neutropenia. ( 6.1 ) The most common adverse reactions (>30%) with PERJETA in combination with docetaxel, carboplatin, and trastuzumab (TCH) were fatigue, alopecia, diarrhea, nausea, vomiting, neutropenia, thrombocytopenia, and anemia. ( 6.1 ) The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and paclitaxel when given for 4 cycles following 4 cycles of ddAC were nausea, diarrhea, alopecia, fatigue, constipation, peripheral neuropathy, and headache. ( 6.1 ) The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel when given for 4 cycles following 4 cycles of FEC were diarrhea, nausea, alopecia, asthenia, constipation, fatigue, mucosal inflammation, vomiting, myalgia, and anemia. ( 6.1 ) Adjuvant Treatment of Breast Cancer The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and chemotherapy were diarrhea, nausea, alopecia, fatigue, peripheral neuropathy and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Metastatic Breast Cancer (MBC) CLEOPATRA The safety of PERJETA in combination with trastuzumab and docetaxel was evaluated in a randomized trial (CLEOPATRA) in patients with HER2-positive metastatic breast cancer [see Clinical Studies (14.1) ] . Patients received either PERJETA administered at an initial dose of 840 mg followed by 420 mg every 3 weeks thereafter or placebo in combination with trastuzumab (initial dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks thereafter) and docetaxel (75 mg/m2 by intravenous infusion every 3 weeks for 6 cycles). The median duration of study treatment was 18.1 months for patients in the PERJETA-treated group. Permanent discontinuation of PERJETA, trastuzumab, and docetaxel due to adverse reactions occurred in 6% of patients. Adverse reactions that led to permanent discontinuation of PERJETA, trastuzumab, and docetaxel in >1% of patients were left ventricular dysfunction. The safety profile of PERJETA remained unchanged with an additional 2.75 years of follow-up (median total follow-up of 50 months) in CLEOPATRA. The most common adverse reactions (> 30%) with PERJETA in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy. The most common Grade 3 – 4 adverse reactions (> 2%) were neutropenia, febrile neutropenia, leukopenia, diarrhea, peripheral neuropathy, anemia, asthenia, and fatigue. An increased incidence of febrile neutropenia was observed for Asian patients in both treatment arms compared with patients of other races and from other geographic regions. Among Asian patients, the incidence of febrile neutropenia was higher in the pertuzumab-treated group (26%) compared with the placebo-treated group (12%). Table 3 summarizes the adverse reactions in CLEOPATRA that occurred ≥ 10% of patients in the PERJETA-treated group. Table 3: Adverse Reactions (≥ 10%) in Patients Who Received PERJETA in Combination with Trastuzumab and Docetaxel in CLEOPATRA Adverse Reactions PERJETA + trastuzumab + docetaxel n=407 % Placebo + trastuzumab + docetaxel n=397 % All Grades % Grades 3 – 4 % All Grades % Grades 3 – 4 % Gastrointestinal disorders Diarrhea 67 8 46 5 Nausea 42 1 42 0.5 Vomiting 24 1 24 2 Stomatitis 19 0.5 15 0.3 Constipation 15 0 25 1 Skin and subcutaneous tissue disorders Alopecia 61 0 60 0.3 Rash 34 0.7 24 0.8 Nail disorder 23 1 23 0.3 Pruritus 14 0 10 0 Dry skin 11 0 4 0 Blood and lymphatic system disorders Neutropenia 53 49 50 46 Anemia 23 2 19 4 Leukopenia 18 12 20 15 Febrile neutropenia In this table this denotes an adverse reaction that has been reported in association with a fatal outcome 14 13 8 7 General disorders and administration site conditions Fatigue 37 2 37 3 Mucosal inflammation 28 1 20 1 Asthenia 26 2 30 2 Peripheral edema 23 0.5 30 0.8 Pyrexia 19 1 18 0.5 Nervous system disorders Neuropathy peripheral 32 3 34 2 Headache 21 1 17 0.5 Dysgeusia 18 0 16 0 Dizziness 13 0.5 12 0 Metabolism and nutrition disorders Decreased appetite 29 2 26 2 Musculoskeletal and connective tissue disorders Myalgia 23 1 24 0.8 Arthralgia 15 0.2 16 0.8 Infections and infestations Upper respiratory tract infection 17 0.7 13 0 Nasopharyngitis 12 0 13 0.3 Respiratory, thoracic, and mediastinal disorders Dyspnea 14 1 16 2 Eye disorders Lacrimation increased 14 0 14 0 Psychiatric disorders Insomnia 13 0 13 0 Clinically relevant adverse reactions in < 10% of patients in the PERJETA-treated group in CLEOPATRA included paronychia (7%).
Use in specific populations
Females and Males of Reproductive Potential: Verify the pregnancy status of females prior to initiation of PERJETA. ( 8.3 ) 8.1 Pregnancy If PERJETA is administered during pregnancy, or if a patient becomes pregnant while receiving PERJETA or within 7 months following the last dose of PERJETA in combination with trastuzumab, health care providers and patients should immediately report PERJETA exposure to Genentech at 1-888-835-2555. Risk Summary Based on its mechanism of action and findings in animal studies, PERJETA can cause fetal harm when administered to a pregnant woman. There are no available data on the use of PERJETA in pregnant women. However, in post-marketing reports, use of another HER2/neu receptor antagonist (trastuzumab) during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In an animal reproduction study, administration of pertuzumab to pregnant cynomolgus monkeys during the period of organogenesis resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal deaths at clinically relevant exposures that were 2.5 to 20-fold greater than exposures in humans receiving the recommended dose, based on C max [see Data ]. Apprise the patient of the potential risks to a fetus. There are clinical considerations if PERJETA in combination with trastuzumab is used during pregnancy or within 7 months prior to conception [see Clinical Considerations ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Monitor women who received PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care. Data Animal Data Pregnant cynomolgus monkeys were treated on Gestational Day (GD)19 with loading doses of 30 to 150 mg/kg pertuzumab, followed by bi-weekly doses of 10 to 100 mg/kg. These dose levels resulted in clinically relevant exposures of 2.5 to 20-fold greater than exposures in humans receiving the recommended dose, based on C max . Intravenous administration of pertuzumab from GD19 through GD50 (period of organogenesis) was embryotoxic, with dose-dependent increases in embryo-fetal death between GD25 to GD70. The incidences of embryo-fetal loss were 33, 50, and 85% for dams treated with bi-weekly pertuzumab doses of 10, 30, and 100 mg/kg, respectively (2.5 to 20-fold greater than the recommended human dose, based on C max ). At Caesarean section on GD100, oligohydramnios, decreased relative lung and kidney weights, and microscopic evidence of renal hypoplasia consistent with delayed renal development were identified in all pertuzumab dose groups. Pertuzumab exposure was reported in offspring from all treated groups, at levels of 29% to 40% of maternal serum levels at GD100. 8.2 Lactation Risk Summary There is no information regarding the presence of pertuzumab in human milk, the effects on the breastfed infant or the effects on milk production. Published data suggest that human IgG is present in human milk but does not enter the neonatal and infant circulation in substantial amounts. Consider the developmental and health benefits of breast feeding along with the mother's clinical need for PERJETA treatment and any potential adverse effects on the breastfed child from PERJETA or from the underlying maternal condition. This consideration should also take into account the elimination half-life of pertuzumab and the trastuzumab wash out period of 7 months . 8.3 Females and Males of Reproductive Potential Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to the initiation of PERJETA. Contraception Females Based on the mechanism of action and animal data, PERJETA can cause embryo-fetal harm when administered during pregnancy. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of PERJETA in combination with trastuzumab [see Use in Specific Populations (8.1) ]. 8.4 Pediatric Use The safety and effectiveness of PERJETA have not been established in pediatric patients. 8.5 Geriatric Use In CLEOPATRA, NeoSphere, TRYPHAENA, BERENICE, and APHINITY, 464 patients who received PERJETA were ≥ 65 years of age and 47 were ≥ 75 years of age. The incidence of adverse reactions was increased in patients aged ≥ 65 years of age compared to patients aged < 65 years of age for decreased appetite, anemia, decreased weight, asthenia, dysgeusia, peripheral neuropathy, and hypomagnesemia. No overall differences in efficacy of PERJETA were observed in patients aged ≥ 65 and <65 years of age. Clinical studies did not include sufficient numbers of patients aged ≥ 75 years to determine if these patients respond differently than younger patients. Based on a population pharmacokinetic analysis, no significant difference was observed in the pharmacokinetics of pertuzumab between patients < 65 years (n=306) and patients ≥ 65 years (n=175). 8.6 Renal Impairment Dose adjustments of PERJETA are not needed in patients with mild (creatinine clearance [CLcr] 60 to 90 mL/min) or moderate (CLcr 30 to 60 mL/min) renal impairment. No dose adjustment can be recommended for patients with severe renal impairment (CLcr less than 30 mL/min) because of the limited pharmacokinetic data available [see Clinical Pharmacology (12.3) ] .
Pregnancy
8.1 Pregnancy If PERJETA is administered during pregnancy, or if a patient becomes pregnant while receiving PERJETA or within 7 months following the last dose of PERJETA in combination with trastuzumab, health care providers and patients should immediately report PERJETA exposure to Genentech at 1-888-835-2555. Risk Summary Based on its mechanism of action and findings in animal studies, PERJETA can cause fetal harm when administered to a pregnant woman. There are no available data on the use of PERJETA in pregnant women. However, in post-marketing reports, use of another HER2/neu receptor antagonist (trastuzumab) during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In an animal reproduction study, administration of pertuzumab to pregnant cynomolgus monkeys during the period of organogenesis resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal deaths at clinically relevant exposures that were 2.5 to 20-fold greater than exposures in humans receiving the recommended dose, based on C max [see Data ]. Apprise the patient of the potential risks to a fetus. There are clinical considerations if PERJETA in combination with trastuzumab is used during pregnancy or within 7 months prior to conception [see Clinical Considerations ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Monitor women who received PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care. Data Animal Data Pregnant cynomolgus monkeys were treated on Gestational Day (GD)19 with loading doses of 30 to 150 mg/kg pertuzumab, followed by bi-weekly doses of 10 to 100 mg/kg. These dose levels resulted in clinically relevant exposures of 2.5 to 20-fold greater than exposures in humans receiving the recommended dose, based on C max . Intravenous administration of pertuzumab from GD19 through GD50 (period of organogenesis) was embryotoxic, with dose-dependent increases in embryo-fetal death between GD25 to GD70. The incidences of embryo-fetal loss were 33, 50, and 85% for dams treated with bi-weekly pertuzumab doses of 10, 30, and 100 mg/kg, respectively (2.5 to 20-fold greater than the recommended human dose, based on C max ). At Caesarean section on GD100, oligohydramnios, decreased relative lung and kidney weights, and microscopic evidence of renal hypoplasia consistent with delayed renal development were identified in all pertuzumab dose groups. Pertuzumab exposure was reported in offspring from all treated groups, at levels of 29% to 40% of maternal serum levels at GD100.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of PERJETA have not been established in pediatric patients.
Geriatric use
8.5 Geriatric Use In CLEOPATRA, NeoSphere, TRYPHAENA, BERENICE, and APHINITY, 464 patients who received PERJETA were ≥ 65 years of age and 47 were ≥ 75 years of age. The incidence of adverse reactions was increased in patients aged ≥ 65 years of age compared to patients aged < 65 years of age for decreased appetite, anemia, decreased weight, asthenia, dysgeusia, peripheral neuropathy, and hypomagnesemia. No overall differences in efficacy of PERJETA were observed in patients aged ≥ 65 and <65 years of age. Clinical studies did not include sufficient numbers of patients aged ≥ 75 years to determine if these patients respond differently than younger patients. Based on a population pharmacokinetic analysis, no significant difference was observed in the pharmacokinetics of pertuzumab between patients < 65 years (n=306) and patients ≥ 65 years (n=175).
Description
Pertuzumab is a recombinant humanized monoclonal antibody and HER2/neu receptor antagonist that targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2). Pertuzumab is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture. Pertuzumab has an approximate molecular weight of 148 kDa. PERJETA (pertuzumab) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale brown solution for intravenous infusion. Each single-dose vial contains 420 mg of pertuzumab,glacial acetic acid (9.2 mg), histidine (43.5 mg), polysorbate 20 (2.8 mg), and sucrose (575.1 mg) with a pH of 6.
Mechanism of action
12.1 Mechanism of Action 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 (ADCC). While pertuzumab alone inhibited the proliferation of human tumor cells, the combination of pertuzumab and trastuzumab augmented anti-tumor activity in HER2-overexpressing xenograft models.
How supplied
How Supplied PERJETA (pertuzumab) injection is supplied as a 420 mg/14 mL (30 mg/mL) single-dose vial containing sterile, preservative-free, clear to slightly opalescent, colorless to pale brown solution. NDC 50242-145-01. Storage and Handling Store vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton until time of use to protect from light. Do not freeze. Do not shake. DO NOT FREEZE. DO NOT SHAKE.
Storage
Storage and Handling Store vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton until time of use to protect from light. Do not freeze. Do not shake. DO NOT FREEZE. DO NOT SHAKE.
Patient information
Left Ventricular Dysfunction Advise patients to contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness [ see Warnings and Precautions (5.1) ]. Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential that exposure to PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception can result in fetal harm [ see Warnings and Precautions (5.2) ] . Advise female patients to contact their healthcare provider with a known or suspected pregnancy [see Use in Specific Populations (8.1) ]. Encourage women who are exposed to PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception to report their pregnancy to Genentech [see Use in Specific Populations (8.1) ]. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of PERJETA in combination with trastuzumab [see Use in Specific Populations (8.3) ]. Hypersensitivity and Anaphylaxis Advise patients to contact their healthcare provider immediately and to report any symptoms of hypersensitivity or anaphylaxis including angioedema, breathing problems, or chest pain [see Warnings and Precautions (5.4) ].
Label text from the FDA structured product label by Genentech, Inc. (revised Apr 30, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Pertuzumab in 1 product
Perjeta NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50242-145 | Pertuzumab 30 mg/mL Injection, Solution, Concentrate | Genentech, Inc. | BLA |
Frequently asked questions
What is Perjeta used for?
1 INDICATIONS AND USAGE PERJETA is a HER2/neu receptor antagonist indicated for: Use in combination with trastuzumab and docetaxel for treatment of adults with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. ( 1.1 ) Use in combination with trastuzumab and chemotherapy as neoadjuvant treatment of adults with…
What are the side effects of Perjeta?
The following adverse reactions are discussed in greater detail in other sections of the label: Left Ventricular Dysfunction [see Warnings and Precautions (5.1) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.2) ] Infusion-Related Reactions [see Warnings and Precautions (5.3) ] Hypersensitivity Reactions/Anaphylaxis [see Warnings and Precautions (5.4) ] Metastatic Breast Cancer The most… See the full label for the complete list.
Who makes Perjeta?
Perjeta is listed by 1 labeler in the FDA NDC directory, including Genentech, Inc..