Version May 2024
Pertuzumab can result in subclinical and clinical cardiac failure manifesting as decreased left ventricular ejection fraction (LVEF) and congestive heart failure (CHF). Evaluate cardiac function prior to and during treatment. Discontinue pertuzumab treatment for a confirmed clinically significant decrease in left ventricular function.
Exposure to pertuzumab can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception.
Note: Actively manage modifiable cardiac risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) before initiating treatment (Ref). Observe patients for 30 to 60 minutes after each pertuzumab infusion and before subsequent doses of trastuzumab products or docetaxel. Do not substitute pertuzumab (IV) with pertuzumab/trastuzumab/hyaluronidase (SUBQ).
Breast cancer, metastatic, HER2+: IV: 840 mg over 60 minutes followed by a maintenance dose of 420 mg over 30 to 60 minutes every 3 weeks until disease progression or unacceptable toxicity (in combination with trastuzumab [or trastuzumab/hyaluronidase] and docetaxel) (Ref).
Breast cancer, early HER2+, adjuvant treatment: IV: 840 mg over 60 minutes followed by a maintenance dose of 420 mg over 30 to 60 minutes every 3 weeks for a total of 1 year (up to 18 cycles) or until disease progression or unacceptable toxicity (whichever occurs first); as part of a combination regimen containing trastuzumab (or trastuzumab/hyaluronidase) and including standard anthracycline- and/or taxane-based therapy; pertuzumab and trastuzumab (or trastuzumab/hyaluronidase) should begin on day 1 of the first taxane-containing cycle (Ref).
Breast cancer, early HER2+, neoadjuvant treatment: IV: 840 mg over 60 minutes followed by a maintenance dose of 420 mg over 30 to 60 minutes every 3 weeks for 3 to 6 cycles; may be administered as one of the regimens below. Postoperatively, continue pertuzumab and trastuzumab (or trastuzumab/hyaluronidase) to complete 1 year of treatment (up to 18 cycles); refer to specific protocol for details.
Four preoperative cycles of pertuzumab, trastuzumab (or trastuzumab/hyaluronidase), and docetaxel, followed by 3 postoperative cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) (Ref) or
Three or four preoperative cycles of FEC (alone) followed by 3 or 4 preoperative cycles of pertuzumab, trastuzumab (or trastuzumab/hyaluronidase), and docetaxel (Ref) or
Six preoperative cycles of pertuzumab, trastuzumab (or trastuzumab/hyaluronidase), docetaxel, and carboplatin (Ref)
Four preoperative cycles of dose-dense doxorubicin and cyclophosphamide alone, followed by 4 preoperative cycles of pertuzumab, trastuzumab (or trastuzumab/hyaluronidase), and paclitaxel (Ref).
Missed doses or delays: If <6 weeks has elapsed, administer pertuzumab 420 mg (maintenance dose) as soon as possible; do not wait until the next planned dose. If ≥6 weeks has elapsed, readminister pertuzumab 840 mg (loading dose) over 60 minutes, and then follow with a maintenance dose of pertuzumab 420 mg (over 30 to 60 minutes) every 3 weeks thereafter.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Note: Dose reductions are not recommended for pertuzumab; if trastuzumab (or trastuzumab/hyaluronidase) is withheld, pertuzumab should also be withheld; if the trastuzumab product is discontinued, pertuzumab should be discontinued. For concomitant chemotherapy dosage adjustments, refer to individual chemotherapy drug monographs.
Infusion-related reaction: Slow or interrupt the infusion.
Serious hypersensitivity or anaphylaxis: Discontinue immediately.
Cardiotoxicity:
Metastatic breast cancer: Pretreatment left ventricular ejection fraction (LVEF) should be ≥50%.
LVEF decline to <40% or LVEF 40% to 45% with fall of ≥10% points below pretreatment values: Withhold treatment (pertuzumab and trastuzumab [or trastuzumab/hyaluronidase]) for at least 3 weeks; may resume if LVEF either returns to >45% or to 40% to 45% with fall of <10% points below pretreatment values. If LVEF declines and has not improved, or has declined further at the subsequent assessment, strongly consider discontinuing pertuzumab (and the trastuzumab product).
Early breast cancer: Pretreatment LVEF should be ≥55% (LVEF should be ≥50% after completion of anthracycline therapy [before starting pertuzumab/trastuzumab treatment]).
LVEF decline to <50% with fall of ≥10% points below pretreatment values: Withhold treatment (pertuzumab and trastuzumab [or trastuzumab/hyaluronidase]) for at least 3 weeks; may resume if LVEF either returns to ≥50% or <10% points below pretreatment values. If LVEF declines and has not improved, or has declined further at the subsequent assessment, strongly consider discontinuing pertuzumab (and the trastuzumab product).
Asymptomatic heart disease: Consider initiating heart failure medications (eg, angiotensin-converting enzyme inhibitors or an angiotensin receptor blocker, and/or beta-blockers) in patients with asymptomatic (stage B) heart disease (Ref).
Mild cardiac dysfunction: Continue treatment with close cardiovascular monitoring (Ref).
Moderate cardiac dysfunction: Consider continuing treatment with close cardiovascular monitoring. Initiation of heart failure medications is recommended (Ref).
Severe cardiac dysfunction: Interrupt treatment and utilize a multidisciplinary approach when deciding if/when to restart. Initiation of heart failure medications is recommended (Ref).
Symptomatic heart disease: Initiate heart failure medications (Ref).
Mild cardiac dysfunction: Consider a multidisciplinary approach for decisions regarding treatment interruption versus continuation (Ref).
Moderate or severe cardiac dysfunction: Interrupt treatment; consider a multidisciplinary approach for decisions regarding treatment reinitiation (Ref).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reactions reported in combination therapy with trastuzumab and docetaxel unless otherwise noted.
>10%:
Cardiovascular: Decreased left ventricular ejection fraction (8% to 16%)
Central nervous system: Fatigue (26% to 36%), headache (11% to 21%), insomnia (8% to 13%), dizziness (3% to 13%)
Dermatologic: Alopecia (52% to 65%), skin rash (11% to 34%), pruritus (4% to 14%), palmar-plantar erythrodysesthesia (11%), xeroderma (9% to 11%)
Gastrointestinal: Diarrhea (46% to 67%), nausea (39% to 53%), vomiting (13% to 36%), decreased appetite (11% to 29%), mucositis (20% to 28%), constipation (23%), stomatitis (17% to 19%; grades 3/4: <1%), dysgeusia (13% to 18%)
Hematologic & oncologic: Neutropenia (47% to 53%; grades 3/4: 43% to 49%), anemia (3% to 23%; grades 3/4: 2% to 4%), leukopenia (9% to 16%; grades 3/4: 5% to 12%), febrile neutropenia (8% to 14%; grades 3/4: 9% to 13%)
Hypersensitivity: Hypersensitivity (1% to 11%)
Neuromuscular & skeletal: Asthenia (15% to 26%), myalgia (11% to 22%), arthralgia (10% to 12%)
Respiratory: Upper respiratory tract infection (4% to 17%), epistaxis (11%)
Miscellaneous: Fever (9% to 19%), infusion reactions (13%)
1% to 10%:
Cardiovascular: Left ventricular dysfunction (3% to 4%), peripheral edema (3% to 4%)
Central nervous system: Peripheral sensory neuropathy (8%; grades 3/4: <1%), peripheral neuropathy (1%)
Dermatologic: Nail disease (7%), paronychia (1% to 7%)
Gastrointestinal: Dyspepsia (8%)
Hematologic & oncologic: Thrombocytopenia (1%)
Hepatic: Increased serum alanine aminotransferase (3%)
Ophthalmic: Increased lacrimation (4% to 5%)
Respiratory: Dyspnea (8%), nasopharyngitis (7%), oropharyngeal pain (7%), cough (5%)
<1%, postmarketing, and/or case reports: Left systolic heart failure, pleural effusion, sepsis, tumor lysis syndrome
Known hypersensitivity to pertuzumab or any component of the formulation
Concerns related to adverse effects:
• Cardiotoxicity: [US Boxed Warning]: May result in cardiac failure (clinical and subclinical) manifesting as decreased left ventricular ejection fraction (LVEF) and heart failure (HF). Assess cardiac function at baseline and at regular intervals during treatment. Discontinue for confirmed clinically significant decline in left ventricular function. Decreases in LVEF are associated with HER2 inhibitors, including pertuzumab. Patients who received prior anthracycline therapy or chest irradiation may be at an increased risk for cardiotoxicity. In studies of pertuzumab (versus placebo) in combination with trastuzumab and docetaxel for the treatment of metastatic breast cancer, the rate of cardiotoxicity (LVEF decline or symptomatic LV systolic dysfunction) was not increased in the pertuzumab group when compared to placebo. In the early breast cancer neoadjuvant setting, the incidence of LV dysfunction was higher in patients treated with pertuzumab. In the early breast cancer adjuvant setting, the incidence of symptomatic heart failure was slightly higher in patients treated with pertuzumab (most of these events were reported in anthracycline-treated patients); approximately half of the pertuzumab-treated patients who experienced symptomatic heart failure recovered. Of note, patients with pretreatment LVEF ≤50%, congestive heart failure, LVEF decreases to <50% during prior trastuzumab treatment, or conditions which could impair LV function (eg, uncontrolled hypertension, recent myocardial infarction, serious arrhythmia requiring treatment, or cumulative lifetime anthracycline exposure >360 mg/m2 doxorubicin or its equivalent) were excluded from studies. Assess LVEF at baseline and approximately every 12 weeks during treatment. Withhold pertuzumab and trastuzumab (or trastuzumab/hyaluronidase) for at least 3 weeks if LVEF declines below the threshold for metastatic or early breast cancer; repeat LVEF assessment in ~3 weeks; consider discontinuing pertuzumab (and the trastuzumab product) if LVEF has not improved or has declined further.
• GI adverse events: Diarrhea occurred more frequently in patients receiving pertuzumab in combination with trastuzumab and docetaxel, compared to patients receiving only trastuzumab and docetaxel. Diarrhea occurred more frequently in the first pertuzumab cycle and was generally grade 1 or 2; diarrhea was usually managed with loperamide and rarely required treatment delay (Swain 2017).
• Hypersensitivity: Severe hypersensitivity, including anaphylaxis has been reported; some events were fatal. Angioedema has also been reported. The overall incidence of hypersensitivity/anaphylaxis was slightly higher in the group receiving pertuzumab (compared to placebo) in combination with trastuzumab and docetaxel. Monitor for hypersensitivity. Medications and equipment for the treatment of hypersensitivity should be available for immediate use during infusion.
• Infusion reaction: Infusion reactions (either during or on the day of infusion), including fatal events, have been associated with pertuzumab. Infusion reaction was defined as hypersensitivity, anaphylactic reaction, acute infusion reaction, or cytokine release during the infusion or on the same day as the infusion; other common infusion reactions included fever, chills, fatigue, headache, weakness, myalgia, abnormal taste, and/or vomiting. Grade 3 or 4 infusion reactions occurred rarely. Monitor for 1 hour after the first infusion and for 30 minutes after subsequent infusions. For significant infusion reactions, interrupt or slow infusion rate and administer appropriate supportive management; for severe infusion reactions, consider permanently discontinuing.
Concomitant drug therapy issues:
• Chemotherapy administration: For pertuzumab, trastuzumab (or trastuzumab/hyaluronidase), and taxane combination regimens, pertuzumab and the trastuzumab product may be administered in any order; however, the taxane should be given after pertuzumab and the trastuzumab product. Pertuzumab and the trastuzumab product should be administered following completion of the anthracycline therapy in patients receiving anthracycline-based regimens.
Special populations:
• Pregnancy: [US Boxed Warning]: Exposure to pertuzumab can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception.
Dosage form specific issues:
• Do not interchange: Pertuzumab (IV) and pertuzumab/trastuzumab/hyaluronidase (SubQ) are not interchangeable. Verify product label prior to reconstitution and administration to prevent medication errors. Dosing and treatment schedules differ between pertuzumab (Perjeta) and pertuzumab/trastuzumab/hyaluronidase (Phesgo).
Other warnings/precautions:
• HER2 expression: Establish HER2 status prior to treatment. Improper assay performance (including suboptimally fixed tissue, failure to use specified reagents, deviation from assay instructions, and failure to include appropriate assay controls) may lead to unreliable results. Information on tests is available at http://www.fda.gov/CompanionDiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Perjeta: 420 mg/14 mL (14 mL)
No
Solution (Perjeta Intravenous)
420 mg/14 mL (per mL): $559.44
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Perjeta: 420 mg/14 mL (14 mL) [contains mouse (murine) and/or hamster protein]
IV: For IV infusion only, as a short infusion; infuse initial dose (840 mg) over 60 minutes; infuse maintenance dose (420 mg) over 30 to 60 minutes. Do not administer IV push or as a rapid bolus. Do not mix with other medications. Observe patients for 30 to 60 minutes after each pertuzumab infusion and before subsequent infusions of the trastuzumab product or docetaxel. Monitor for hypersensitivity reactions for 60 minutes following the initial pertuzumab infusion and for 30 minutes following subsequent infusions.
For pertuzumab, trastuzumab (or trastuzumab/hyaluronidase), and taxane combination regimens, pertuzumab and the trastuzumab product may be administered in any order; however, the taxane should be given after pertuzumab and the trastuzumab product. Pertuzumab (and the trastuzumab product) should be administered following completion of the anthracycline therapy in patients receiving anthracycline-based regimens.
Check label to ensure appropriate product is being administered; pertuzumab and pertuzumab/trastuzumab/hyaluronidase are different products and are NOT interchangeable.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Breast cancer, metastatic: Treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (in combination with trastuzumab and docetaxel) in patients who have not received prior anti-HER2 therapy or chemotherapy to treat metastatic disease.
Breast cancer, early (adjuvant): Adjuvant treatment of HER2-positive early breast cancer at high risk of recurrence (in combination with trastuzumab and chemotherapy).
Breast cancer, early (neoadjuvant): Neoadjuvant treatment of locally advanced, inflammatory, or early stage HER2-positive, breast cancer (either greater than 2 cm in diameter or node positive) in combination with trastuzumab and chemotherapy (as part of a complete treatment regimen for early breast cancer).
Perjerta may be confused with Phesgo.
Pertuzumab may be confused with ado-trastuzumab emtansine, fam-trastuzumab deruxtecan, panitumumab, pertuzumab/trastuzumab/hyaluronidase, polatuzumab vedotin, trastuzumab, trastuzumab/hyaluronidase.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
Pertuzumab (IV) is for IV administration only. Do not substitute pertuzumab/trastuzumab/hyaluronidase (SubQ) for pertuzumab (IV). Use caution during product selection, preparation, and administration.
Pertuzumab (Perjeta) may be confused with pertuzumab/trastuzumab/hyaluronidase (Phesgo).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
[US Boxed Warning]: Exposure to pertuzumab can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception.
Evaluate pregnancy status prior to treatment in females of reproductive potential; effective contraception should be used during therapy and for 7 months after the last dose of pertuzumab in combination with trastuzumab (or trastuzumab/hyaluronidase).
[US Boxed Warning]: Exposure to pertuzumab can result in embryo-fetal death and birth defects. Advise patients of these risks.
Based on the mechanism of action of pertuzumab and data from similar agents, oligohydramnios or oligohydramnios sequence may occur resulting in pulmonary hypoplasia, skeletal anomalies, and neonatal death. Monitor for oligohydramnios if exposure occurs during pregnancy or within 7 months prior to conception; conduct appropriate fetal testing if oligohydramnios occurs. Information related to inadvertent exposure to pertuzumab in combination with trastuzumab in pregnancy is limited (Yildirim 2018).
European Society for Medical Oncology (ESMO) guidelines for cancer during pregnancy recommend delaying treatment with HER2-targeted agents until after delivery in pregnant patients with HER2-positive disease (Peccatori 2013).
Advise patients to immediately report to health care provider if pregnancy is suspected during treatment. If pertuzumab exposure occurs during pregnancy or exposure to pertuzumab in combination with trastuzumab (or trastuzumab/hyaluronidase) occurs within 7 months following the last dose of pertuzumab, report the exposure to Genentech (888-835-2555).
It is not known if pertuzumab is present in breast milk.
Immunoglobulin is present in breast milk. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. The extended half-life of pertuzumab and the 7-month wash out period for trastuzumab (or trastuzumab/hyaluronidase) should be considered for decisions regarding breastfeeding after treatment is completed.
HER2 expression. Evaluate pregnancy status (prior to treatment in patients who can become pregnant). Assess LVEF at baseline, and approximately every 12 weeks during treatment (more frequently for declines). Monitor for infusion reaction, diarrhea, and hypersensitivity (monitor for hypersensitivity reactions for 60 minutes following the initial pertuzumab infusion and for 30 minutes following subsequent infusions).
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Additional cardiovascular monitoring (guideline recommendations): Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017], ESC [Lyon 2022]). Obtain a baseline echocardiography (transthoracic preferred) and repeat every 3 months during treatment (may reduce to every 4 to 6 months if normal and asymptomatic), assess more frequently if clinically indicated and obtain echocardiography within 12 months after completion; in high- and very high-risk patients, assess troponin and natriuretic peptide at baseline and consider assessing every 2 to 3 cycles, and at 3 and 12 months after completion of therapy; in low- and moderate-risk patients, consider troponin and natriuretic peptide at baseline (post-anthracycline), every 3 months and 12 months after completion of therapy (ESC [Lyon 2022]).
Pertuzumab is a recombinant humanized monoclonal antibody which targets the extracellular human epidermal growth factor receptor 2 protein (HER2) dimerization domain. Inhibits HER2 dimerization and blocks HER downstream signaling halting cell growth and initiating apoptosis. Pertuzumab binds to a different HER2 epitope than trastuzumab so that when pertuzumab is combined with trastuzumab, a more complete inhibition of HER2 signaling occurs (Baselga 2012).
Distribution: Vd: 5.12 L (Gianni 2010)
Half-life elimination: Terminal: 18 days
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