pertuzumab

pertuzumab

Perjeta

Pharmacologic class: Recombinant humanized monoclonal antibody

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Box Warning

• Exposure to pertuzumab can result in embryo-fetal death and birth defects. Studies in animals have resulted in oligohydramnios, delayed renal development, and death. Advise patients of these risks and the need for effective contraception.

Action

Targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor (EGRF) 2 protein (HER2) and thereby blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGRF, HER3, and HER4. As a result, pertuzumab inhibits ligand-initiated intracellular signaling through two major signal pathways, mitogen-activated protein kinase and phosphoinositide 3-kinase. Inhibition of these signaling pathways can result in cell growth arrest and apoptosis, respectively. In addition, pertuzumab mediates antibody-dependent cell-mediated cytotoxicity.

Availability

Solution for injection: 420 mg/14-ml single-use vial

Indications and dosages

➣ HER2-positive metastatic breast cancer in patients who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease

Adults: Initially, 840 mg by 60-minute I.V. infusion, followed by 420 mg over 30 to 60 minutes by I.V. infusion q 3 weeks thereafter. When administered with trastuzumab, recommended initial dose of trastuzumab is 8 mg/kg by 90-minute I.V. infusion, followed by 6 mg/kg over 30 to 90 minutes by I.V. infusion q 3 weeks thereafter. When administered with docetaxel, recommended initial dose of docetaxel is 75 mg/m² by I.V. infusion; may escalate to 100 mg/m² q 3 weeks if initial dose is well tolerated.

Dosage adjustment

• Left ventricular ejection fraction (LVEF) less than 40% or LVEF of 40% to 45% with a 10% or greater absolute decrease below pretreatment values

Contraindications

None

Precautions

Use cautiously in:

• pregnant and breastfeeding patients

• children (safety and efficacy not established).

Administration

• Be aware that HER2 testing should be performed for selection of patients appropriate for treatment with this drug.

• Assess LVEF before starting drug.

• Verify pregnancy status before starting drug.

☞ Administer as an I.V. infusion only. Don't give as an I.V. push or bolus.

• Withdraw appropriate volume of drug solution from vial(s). Dilute in a 250-ml normal saline solution-in only PVC or non-PVC polyolefin infusion bag. Mix diluted solution by gentle inversion. Don't shake and don't mix with other drugs. Don't use dextrose (5%) solution.

• Administer immediately once prepared. If diluted infusion solution isn't used immediately, it can be stored at 2° C to 8° C (36° F to 46° F) for up to 24 hours.

☞ Observe patient closely for 60 minutes after first infusion. If significant infusion-associated reaction occurs, slow or interrupt infusion and administer appropriate medical therapies. Discontinue drug immediately if patient develops a serous hypersensitivity reaction.

• Be aware that drug should be withheld or discontinued if trastuzumab treatment is withheld or discontinued. If docetaxel is discontinued, treatment with pertuzumab and trastuzumab may continue.

• Be aware that pertuzumab dosage reductions aren't recommended.

Adverse reactions

CNS: headache, dizziness, fatigue, peripheral neuropathy, asthenia, insomnia

CV: left ventricular dysfunction

EENT: increased lacrimation, nasopharyngitis

GI: nausea, vomiting, diarrhea, constipation, stomatitis

Hematologic: anemia, leukopenia, neutropenia, febrile neutropenia

Musculoskeletal: myalgia, arthralgia

Respiratory: upper respiratory tract infection, dyspnea, pleural effusion

Skin: alopecia, rash, nail disorder, pruritus, dry skin, paronychia

Other: mucosal inflammation, pyrexia, dysgeusia, decreased appetite, peripheral edema, infusion and hypersensitivity reactions including anaphylaxis

Interactions

None

Patient monitoring

☞ Closely monitor patient for 30 minutes after each subsequent infusion for infusion and hypersensitivity reactions. If a significant infusion-associated reaction occurs, slow or interrupt infusion and administer appropriate medical therapies. Monitor patients carefully until complete resolution of signs and symptoms. Consider permanent discontinuation in patients with severe infusion reactions.

☞ Continue to assess LVEF at regular intervals (every 3 months) during treatment to ensure LVEF is within institution's normal limits. If LVEF is less than 40%, or is 40% to 45% with a 10% or greater absolute decrease below pretreatment value, withhold pertuzumab and trastuzumab and repeat LVEF assessment within approximately 3 weeks. Discontinue pertuzumab and trastuzumab if LVEF hasn't improved or has declined further, unless benefits to patient outweigh risks.

• Monitor women who become pregnant during pertuzumab therapy for oligohydramnios. If oligohydramnios occurs, perform fetal testing appropriate for gestational age and consistent with community standards of care.

Patient teaching

☞ Tell patient to immediately report fever, chills, fatigue, headache, vomiting, weakness, rash, muscle pain, leg swelling, or shortness of breath.

• Advise female patient of childbearing potential to use effective contraception while receiving this drug and for 6 months after last dose.

• Advise breastfeeding patient that she should decide whether to discontinue breastfeeding or discontinue drug, taking into account importance of drug for her treatment.

• As appropriate, review all other significant and life-threatening adverse reactions mentioned above.

McGraw-Hill Nurse's Drug Handbook, 7th Ed. Copyright © 2013 by The McGraw-Hill Companies, Inc. All rights reserved