Pertuzumab

• HER2-Positive Breast Cancer:
• In combination with trastuzumab and chemotherapy for neoadjuvant treatment of early-stage HER2-positive breast cancer.
• In combination with trastuzumab and chemotherapy for metastatic or locally advanced HER2-positive breast cancer.
• Off-label Uses:
• Used in combination regimens for HER2-positive gastric or gastroesophageal junction adenocarcinoma in selected clinical settings.

• Route: Intravenous infusion only.
• Adult Dosage for Breast Cancer:
• Loading dose: 840 mg IV over 60 minutes on Day 1.
• Maintenance dose: 420 mg IV over 30–60 minutes every 3 weeks thereafter.
• Duration: Continue until disease progression or unacceptable toxicity.
• Dose Adjustments:
• No specific dosing adjustments for renal impairment.
• Use with caution in severe hepatic impairment.
• Infusion rate may be slowed or interrupted if infusion-related reactions occur.
• Pediatric Use: Safety and efficacy not established.

Pertuzumab is a recombinant humanized monoclonal antibody that binds specifically to the extracellular dimerization domain (subdomain II) of the human epidermal growth factor receptor 2 (HER2). By blocking HER2 heterodimerization with other HER family receptors (HER1, HER3, HER4), pertuzumab inhibits ligand-dependent signaling pathways essential for tumor cell growth and survival. This blockade also triggers antibody-dependent cellular cytotoxicity (ADCC), enhancing immune-mediated tumor cell killing.

• Absorption: Complete bioavailability via intravenous administration.
• Distribution: Volume of distribution approximately 3–4 liters, mainly confined to plasma and extracellular fluids.
• Metabolism: Catabolized by proteolytic enzymes into small peptides and amino acids; not metabolized by CYP450 enzymes.
• Elimination half-life: Approximately 18 days.
• Excretion: Eliminated through reticuloendothelial system; not excreted unchanged in urine or feces.

• Pregnancy: FDA Category D — evidence of fetal risk from animal studies; use only if benefits outweigh risks.
• Lactation: Unknown if excreted in human milk. Breastfeeding not recommended during treatment and for at least 6 months after last dose due to potential serious adverse effects in nursing infants.

• Class: Antineoplastic agent
• Subclass: Monoclonal antibody targeting HER2 receptor

• Hypersensitivity to pertuzumab or any excipients.
• Severe cardiac dysfunction; use cautiously due to risk of cardiotoxicity.

• Cardiotoxicity: Monitor left ventricular ejection fraction (LVEF) at baseline and periodically. Avoid if baseline LVEF <50%.
• Infusion-related reactions: Monitor during and after infusion; symptoms include fever, chills, rash, hypotension.
• Pregnancy risk: Use effective contraception during and after therapy.
• Diarrhea: Common and may require management.
• Neutropenia: Monitor blood counts regularly; risk of infection.
• Hypersensitivity: Rare anaphylaxis may occur; emergency measures should be available.

• Common: Diarrhea, alopecia, nausea, fatigue, rash, neutropenia, peripheral neuropathy.
• Serious: Cardiac dysfunction (e.g., reduced LVEF, congestive heart failure), severe infusion reactions, severe neutropenia with infection risk.

• No known CYP450 enzyme interactions due to monoclonal antibody nature.
• Caution with other cardiotoxic drugs (e.g., anthracyclines).
• No documented drug-food or drug-alcohol interactions.

• FDA approvals confirm use in neoadjuvant and metastatic HER2-positive breast cancer settings.
• NCCN and ESMO guidelines recommend pertuzumab plus trastuzumab and chemotherapy as first-line therapy for HER2-positive metastatic breast cancer.
• No new major safety warnings; emphasis remains on cardiac monitoring and management of infusion reactions.

• Store refrigerated at 2°C to 8°C (36°F to 46°F).
• Do not freeze or shake.
• Protect from light; keep in original carton until use.
• Use immediately after dilution; do not store diluted solutions for prolonged periods.