Pertuzumab

🔴 RED FLAG (IMPORTANT) INFORMATION

(Most critical safety and prescribing information)

• Cardiotoxicity (↓ LVEF, heart failure) can occur, especially when combined with trastuzumab and chemotherapy → baseline and regular LVEF monitoring is mandatory.

• Severe infusion-related reactions and anaphylaxis, including fatal cases, have been reported → must be administered in a setting with full resuscitation facilities.

• Febrile neutropenia risk is increased when used with trastuzumab and docetaxel, particularly in the first 3 cycles.

• Pregnancy is contraindicated — can cause embryo-foetal death and severe foetal harm.

• Breastfeeding is contraindicated.

• If trastuzumab is discontinued, pertuzumab must also be discontinued.

• Contains sucrose — caution in patients with diabetes and contraindicated in rare hereditary sugar intolerance disorders.

1. BASIC INFORMATION

• Generic name: Pertuzumab

• Brand name: PERJETA®

• Drug class: Monoclonal antibody (anti-HER2)

• Formulation: Concentrate for solution for IV infusion

• Strength: 420 mg / 14 mL vial (30 mg/mL)

• Route: Intravenous infusion

• Scheduling status: S4

2. INDICATIONS

HER2-positive breast cancer

Metastatic / locally recurrent unresectable disease

• In combination with trastuzumab and docetaxel

• For patients not previously treated with anti-HER2 therapy or chemotherapy for metastatic disease

Early breast cancer

• Neoadjuvant treatment:

  • Locally advanced, inflammatory, or early disease (>2 cm or node-positive)

• Adjuvant treatment:

  • High-risk HER2-positive breast cancer

3. DOSING & ADMINISTRATION

Standard dosing (with trastuzumab ± chemotherapy)

• Loading dose:

  • 840 mg IV over 60 minutes

• Maintenance dose:

  • 420 mg IV every 3 weeks over 30–60 minutes

Administration notes

• Must be diluted and given as IV infusion only

• Do NOT give as IV push or bolus

• Observe patient:

  • 60 minutes after first infusion

  • 30 minutes after subsequent infusions

• Pertuzumab and trastuzumab:

  • Given sequentially

  • Can be given in any order

  • Administer before taxane chemotherapy

4. DOSE MODIFICATIONS

• Dose reductions are NOT recommended

• Management is by:

  • Treatment interruption

  • Permanent discontinuation if required

Cardiac dysfunction

• Withhold pertuzumab and trastuzumab if LVEF declines significantly

• Consider permanent discontinuation if LVEF does not recover

Infusion reactions

• Slow or interrupt infusion

• Permanently discontinue for severe hypersensitivity or anaphylaxis

5. CO-MEDICATIONS

• Mandatory combinations:

  • Trastuzumab

  • Chemotherapy (e.g. docetaxel; anthracycline-based regimens in early breast cancer)

• If docetaxel is discontinued, pertuzumab + trastuzumab may continue (metastatic setting)

6. CONTRAINDICATIONS

• Hypersensitivity to pertuzumab or excipients

• Pregnancy

• Breastfeeding

7. MONITORING REQUIREMENTS

Cardiac monitoring

• LVEF assessment:

  • Baseline

  • Every ~12 weeks during treatment

• Higher risk if:

  • Prior anthracyclines

  • Prior chest radiotherapy

Clinical monitoring

• Infusion reactions

• Signs of heart failure

• Diarrhoea and mucositis

• Signs of infection or febrile neutropenia

8. SIDE EFFECTS

Very common (≥30%)

• Diarrhoea

• Alopecia

• Nausea

• Fatigue

• Neutropenia

• Vomiting

Common

• Febrile neutropenia

• Anaemia

• Rash

• Mucositis

• Peripheral neuropathy

• Decreased appetite

• Headache

Serious

• Left ventricular dysfunction / heart failure

• Severe infusion reactions

• Anaphylaxis

• Febrile neutropenia

• Interstitial lung disease

• Tumour lysis syndrome (post-marketing)

9. DRUG INTERACTIONS

• No clinically significant pharmacokinetic interactions with:

  • Trastuzumab

  • Docetaxel

  • Paclitaxel

  • Carboplatin

  • Gemcitabine

  • Erlotinib

  • Capecitabine

10. USE IN SPECIAL POPULATIONS

• Pregnancy: Contraindicated; effective contraception required during treatment and for 6 months after last dose

• Breastfeeding: Contraindicated

• Elderly (≥65 years): No dose adjustment required

• Renal impairment: No adjustment for mild–moderate impairment; limited data in severe impairment

• Hepatic impairment: Not studied

• Paediatric patients: Not indicated

11. DURATION OF USE / WHEN TO STOP

Metastatic breast cancer

• Continue until:

  • Disease progression, or

  • Unmanageable toxicity

Early breast cancer

• Neoadjuvant: 3–6 cycles (depending on regimen)

• Adjuvant: Continue with trastuzumab to complete 1 year total therapy (maximum 18 cycles)

Stop permanently if:

• Severe cardiac dysfunction

• Life-threatening hypersensitivity or infusion reaction

12. TOXICITY MANAGEMENT (SIMPLIFIED)

Cardiac toxicity

• Withhold pertuzumab + trastuzumab

• Repeat LVEF assessment

• Discontinue if no recovery

Infusion reactions

• Slow or stop infusion

• Supportive treatment

• Permanently discontinue if severe

Neutropenia / febrile neutropenia

• Symptomatic management

• Monitor closely during early cycles

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2023/02/Perjeta-PI_18Oct2022.pdf