Pertuzumab-Trastuzumab-Hyaluronidase

Pertuzumab-Trastuzumab-Hyaluronidase is a combination medication indicated for neoadjuvant treatment of adults with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (EBC) (either more than 2 cm in diameter or node-positive as part of a complete treatment regimen for early breast cancer. It is also indicated in combination with 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.

• Pertuzumab-Trastuzumab-Hyaluronidase is available under the following different brand names: Phesgo, pertuzumab-trastuzumab-hyaluronidase-zzxf.

Common side effects of Pertuzumab-Trastuzumab-Hyaluronidase include:

• hair loss
• nausea
• diarrhea
• anemia
• weakness
• low white blood cell count (neutropenia)
• fatigue
• rash
• numbness and tingling of extremities
• constipation
• vomiting
• muscle pain
• joint pain
• decreased appetite
• insomnia

Serious side effects of Pertuzumab-Trastuzumab-Hyaluronidase include:

• a new or worsening cough or shortness of breath (even while at rest)
• fast or pounding heartbeats
• severe headache, blurred vision, pounding in the neck or ears
• swelling in the face or lower legs
• rapid weight gain (more than 5 pounds in 24 hours)
• a light-headed feeling
• low white blood cell counts--fever, mouth sores, skin sores, sore throat, cough, trouble breathing
• low red blood cells (anemia)--pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands, and feet

Rare side effects of Pertuzumab-Trastuzumab-Hyaluronidase include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injectable solution

• 600 mg/600 mg/30,000 units/10 mL
• 1,200 mg/600 mg/30,000 units/15 mL

Early breast cancer

Adult dosage

• Neoadjuvant treatment
  • Treated with IV pertuzumab and trastuzumab within 6 weeks: 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC initially and then every 3 weeks for subsequent administrations
  • Treated with IV pertuzumab and trastuzumab greater than 6 weeks: 1,200 mg pertuzumab/600 mg trastuzumab/30,000 units hyaluronidase SC initially followed by 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC every 3 weeks for subsequent administrations
  • Administer for 3-6 cycles as part of a treatment regimen for EBC
  • Following surgery
    • Continue to receive Pertuzumab-Trastuzumab-Hyaluronidase to complete 1 year of treatment (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first
    • Refer to the prescribing information for pertuzumab, administered in combination with trastuzumab and chemotherapy, for recommended dose and dosage modifications
• Adjuvant treatment
  • Treated with IV pertuzumab and trastuzumab within 6 weeks: 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC initially and then every 3 weeks for subsequent administrations
  • Treated with IV pertuzumab and trastuzumab greater than 6 weeks: 1,200 mg pertuzumab/600 mg trastuzumab/30,000 units hyaluronidase SC initially followed by 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC every 3 weeks for subsequent administrations
  • Administer for a total of 1 year (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first
  • For taxane-based regimens: Start on Day 1

Metastatic breast cancer

Adult dosage

• Treated with IV pertuzumab and trastuzumab within 6 weeks: 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC initially and then every 3 weeks for subsequent administrations
• Treated with IV pertuzumab and trastuzumab greater than 6 weeks: 1,200 mg pertuzumab/600 mg trastuzumab/30,000 units hyaluronidase SC initially followed by 600 mg pertuzumab/600 mg trastuzumab/20,000 units hyaluronidase SC every 3 weeks for subsequent administrations
• When administered with Phesgo, start with docetaxel is 75 mg/m2 IV initially; may escalate the dose to 100 mg/m2 IV every 3 weeks if the initial dose is well tolerated
• Continue until disease progression or unmanageable toxicity, whichever occurs first
• Refer to the prescribing information for pertuzumab, administered in combination with trastuzumab and chemotherapy, for recommended dose and dosage modifications

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Pertuzumab-Trastuzumab-Hyaluronidase has severe interactions with no other drugs
• Pertuzumab-Trastuzumab-Hyaluronidase has serious interactions with the following drugs:
  • axicabtagene ciloleucel
  • beclomethasone, inhaled
  • brexucabtagene autoleucel
  • ciltacabtagene autoleucel
  • daunorubicin
  • doxorubicin
  • doxorubicin liposomal
  • epirubicin
  • etrasimod
  • idarubicin
  • palifermin
• Pertuzumab-Trastuzumab-Hyaluronidase has moderate interactions with at least 67 other drugs
• Pertuzumab-Trastuzumab-Hyaluronidase has minor interactions with the following drugs:
  • bupivacaine
  • mepivacaine
  • prilocaine
  • ropivacaine

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity to pertuzumab, trastuzumab, hyaluronidase, or any of its excipients

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Pertuzumab-Trastuzumab-Hyaluronidase?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Pertuzumab-Trastuzumab-Hyaluronidase?”

Cautions

• Hypertension, arrhythmias, left ventricular cardiac dysfunction, disabling cardiac failure, cardiomyopathy, and cardiac death may occur
• May cause fetal harm when administered to a pregnant woman
• Serious and fatal pulmonary toxicity reported
• May cause exacerbation of chemotherapy-induced neutropenia
• Severe administration-related reactions, including hypersensitivity, anaphylaxis, and events with fatal outcomes, have been associated with IV pertuzumab and trastuzumab
• Drug interaction overview
  • Patients who receive anthracycline after stopping Phesgo may be at increased risk of cardiac dysfunction because of the long washout period of Phesgo
  • If possible, avoid anthracycline-based therapy for up to 7 months after stopping Phesgo
  • If anthracyclines are used, carefully monitor cardiac function

Pregnancy and Lactation

• May cause fetal harm when administered to a pregnant woman
• In postmarketing reports, the use of IV trastuzumab during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death
• Verify pregnancy status of women of reproductive potential before initiation
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for 7 months after the last dose
  • Clinical considerations
  • Monitor women who received treatment during pregnancy or within 7 months before conception for oligohydramnios
  • If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care
  • Pregnancy pharmacovigilance program
  • If administered during pregnancy, or if a patient becomes pregnant during treatment or within 7 months following the last dose, healthcare providers and patients should immediately report exposure to Genentech at 1-888-835-2555
• Lactation
  • No information available on the presence of pertuzumab, trastuzumab, or hyaluronidase in human milk, the effects on the breastfed infant, or milk production
  • Published data suggest that human IgG is present in human milk but does not enter neonatal and infant circulation in substantial amounts
  • Trastuzumab was present in the milk of lactating cynomolgus monkeys but was not associated with neonatal toxicity
  • Consider that the elimination half-life of pertuzumab and trastuzumab washout period is 7 months when considering the mother’s clinical need for treatment