Herceptin Hylecta is a combination of two drugs: Trastuzumab and Hyaluronidase. Trastuzumab is a monoclonal antibody that binds to the extracellular domain of human epidermal growth factor receptor 2 protein (HER-2) cells. Hyaluronidase increases the absorption of trastuzumab when administered subcutaneously.

Trastuzumab and Hyaluronidase (Herceptin Hylecta) Uses:

• Breast cancer, adjuvant treatment:

  • It is used as adjuvant treatment of HER2 overexpressing node-positive or node-negative i.e ER or PR negative or with one high-risk feature, in adults with breast cancer, as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel.
  • It is also given as part of a treatment regimen with docetaxel and carboplatin. It is administered as a single agent following multi-modality anthracycline-based therapy.

• Metastatic Breast cancer:

  • It can also be used as a first-line treatment of HER2-overexpressing metastatic breast cancer in combination with paclitaxel in adults.
  • It is used as a single-agent treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease.
  • However, its limitations of use include selectivity of patients for trastuzumab treatment based on an approved companion diagnostic test for tumor specimen for HER2 overexpression or HER2 gene amplification.

Trastuzumab and Hyaluronidase (Herceptin Hylecta) Dose in Adults

It is noted that do not substitute trastuzumab or hyaluronidase with IV trastuzumab products (eg, conventional trastuzumab or ado-trastuzumab emtansine). However, no loading dose is required.

Trastuzumab and Hyaluronidase (Herceptin Hylecta) Dose in the adjuvant treatment of Breast cancer, HER2+:

• SubQ: It is given as trastuzumab 600 mg/hyaluronidase 10,000 units once every 3 weeks for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first.
• Administer in combination with doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel. It can also be given in combination with docetaxel and carboplatin, or as a single agent following multi-modality anthracycline-based therapy.

Trastuzumab and Hyaluronidase (Herceptin Hylecta) Dose in the treatment of metastatic Breast cancer, HER2+:

• SubQ: It is administered as trastuzumab 600 mg/hyaluronidase 10,000 units once every 3 weeks in combination with paclitaxel or as a single agent following one or more chemotherapy regimens for metastatic disease, until disease progression or unacceptable toxicity has occurred.

  • Missed doses:

    • If one dose is missed, administer the missed dose as soon as possible. The period between subsequent trastuzumab/hyaluronidase doses should not be less than 3 weeks.

Dose in Children:

Not indicated.

Trastuzumab and Hyaluronidase Pregnancy Category: N

• [US Boxed Warning]Trastuzumab/hyaluronidase can cause oligohydramnios or oligohydramnios in pregnancy. This can manifest as pulmonary hypoplasia and skeletal abnormalities and even neonatal death.
• Effective contraception should be discussed with patients.
• Exposure during pregnancy has been associated with adverse fetal outcomes.
• Before you start the treatment, it is important to get rid of any pregnancy.
• Effective contraception should be used by women of reproductive age during treatment, and at least seven months after the last trastuzumab/hyaluronidase dosage.
• For more information, see individual monographs.

Use of Trastuzumab or hyaluronidase during breastfeeding

• It is unknown if breast milk contains it.
• Trastuzumab, a humanized immunoglobulin, is available.
• Many immunoglobulins can be secreted in milk.
• Therefore, studies suggest that breastfeeding decisions should be made in light of both the benefits and risks for the mother as well as the advantages to the child.
• Before you decide to start breastfeeding, it is necessary for your body to completely cleanse itself for 7 months.
• For more information, see individual monographs.

Dose in Kidney Disease:

The dose adjustments in renal disease has not yet been studied.

Dose in Liver disease:

The dose adjustments in liver dysfunction is not yet studied.

Common Side Effects of Trastuzumab and Hyaluronidase (Herceptin Hylecta):

• Cardiovascular:

  • Edema
  • Flushing

• Central Nervous System:

  • Fatigue
  • Peripheral Neuropathy
  • Headache
  • Peripheral Sensory Neuropathy

• Dermatologic:

  • Alopecia
  • Skin Rash
  • Nail Disease

• Gastrointestinal:

  • Nausea
  • Diarrhea
  • Vomiting
  • Stomatitis
  • Decreased Appetite
  • Abdominal Pain
  • Constipation
  • Dyspepsia

• Hematologic & Oncologic:

  • Neutropenia
  • Anemia
  • Leukopenia

• Immunologic:

  • Antibody Development

• Local:

  • Injection Site Reaction
  • Incisional Pain

• Neuromuscular & Skeletal:

  • Asthenia
  • Arthralgia
  • Myalgia
  • Limb Pain
  • Back Pain

• Respiratory:

  • Upper Respiratory Tract Infection
  • Cough
  • Dyspnea

• Miscellaneous:

  • Radiation Injury
  • Fever

Less Common Side Effects of Trastuzumab and Hyaluronidase (Herceptin Hylecta):

• Cardiovascular:

  • Hypertension
  • Cardiac Arrhythmia
  • Reduced Ejection Fraction
  • Left Ventricular Dysfunction
  • Palpitations
  • Tachycardia
  • Cardiac Failure

• Central Nervous System:

  • Dizziness
  • Pain
  • Insomnia
  • Paresthesia

• Dermatologic:

  • Skin Discoloration
  • Erythema Of Skin
  • Pruritus
  • Cellulitis

• Endocrine & Metabolic:

  • Hot Flash
  • Menstrual Disease
  • Amenorrhea

• Gastrointestinal:

  • Dysgeusia

• Genitourinary:

  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Febrile Neutropenia
  • Granulocytopenia

• Hepatic:

  • Abnormal Hepatic Function Tests

• Hypersensitivity:

  • Hypersensitivity Reaction
  • Anaphylaxis

• Infection:

  • Viral Infection

• Local:

  • Erythema At Injection Site
  • Pain At Injection Site

• Neuromuscular & Skeletal:

  • Musculoskeletal Pain
  • Ostealgia

• Respiratory:

  • Epistaxis
  • Nasal Discomfort
  • Rhinitis

Contraindications to Trastuzumab and Hyaluronidase (Herceptin Hylecta):

The literature does not mention any contraindications.

Warnings and precautions

• Cardiomyopathy [US Boxed Warning]

  • After treatment, cardiomyopathy can lead to heart failure.
  • Patients who received trastuzumab/hyaluronidase in combination with anthracycline-containing chemotherapy regimens had the highest incidence and severity.
  • Before performing echocardiography, it is important to evaluate the LVEF.
  • Trazuzumab/hyaluronidase should be stopped in patients who are receiving adjuvant treatment.
  • Patients with metastatic malignancy should receive trastuzumab/hyaluronidase. This will result in a clinically significant decrease of left ventricular function.
  • Trastuzumab/hyaluronidase may cause left-ventricular cardiac dysfunction, arrhythmias and hypertension, disabling heart failure, cardiomyopathy, sudden cardiac death, and disabling cardiac function.
  • Asymptomatic decrease in left ventricular Ejection Fraction (LVEF) may be caused by Trastuzumab/hyaluronidase. This could lead to subclinical cardiac failure.
  • Trazuzumab/hyaluronidase can also cause heart problems such as tachycardia and palpitations.
  • Patients who receive trastuzumab in combination with chemotherapy or as a single agent have a 4-to 6-fold increase in the incidences of symptomatic myocardial disease compared to those who don't.
  • Trazuzumab given in combination with an anthracycline has the highest absolute incidence
  • Clinical trials showed similar rates of symptomsatic myocardial dysfunction in intravenous trastuzumab/hyaluronidase as well as trastuzumab/hyaluronidase.
  • Trazuzumab/hyaluronidase should be stopped if there is a greater than 16% absolute drop in LVEF compared to pretreatment values, or a LVEF value that falls below the institutional limits of normal, and a LVEF decrease greater than 10% compared to pretreatment values.
  • Safety of continuing or resuming trastuzumab/hyaluronidase in the presence of left ventricular dysfunction due to trastuzumab has not been established.
  • Patients who are treated with anthracycline following the discontinuation of trastuzumab/hyaluronidase could also be at higher risk for cardiac dysfunction.
  • A thorough cardiac assessment should be performed, including a history and physical exam, as well as a LVEF assessment by either echocardiogram (or MUGA scan).
  • LVEF should first be evaluated at baseline before trastuzumab/hyaluronidase initiation. Then, every 3 months after trastuzumab/hyaluronidase treatment is completed, and then every 4 week if trastuzumab/hyaluronidase has been withheld due to significant left ventricular dysfunction. Finally, every 6 months for at most 2 years after trastuzumab/hyaluronidase has been used in adjuvant therapy.
  • ASCO has created guidelines to monitor and prevent cardiac dysfunction in adult cancer survivors.
  • The following guidelines state that there is an increased risk of developing cardiac disease from trastuzumab:
    • Trastuzumab by itself and any of the following factors: Multiple cardiovascular risk factor (>=2 risk factors), such as smoking, hypertension or diabetes, and older age (>=60) during or after treatment for cancer or impaired cardiac function (eg borderline low LVEF [50%-555%], history MI, moderate or greater valvular disease, etc.) before or during treatment.
    • If used in a sequential therapy, treatment with a lower dose of anthracycline (eg doxorubicin 250m2/m2, epirubicin 600 mg/m2) and trastuzumab.
  • ASCO guidelines recommend that patients with cancer undergo a thorough assessment. This includes a history, physical examination, screening for cardiovascular disease risk factors like hypertension, diabetes and dyslipidemia.
  • It is possible to cause cardiac problems. Pre-treatment echocardiography should also be done.
  • Before attempting potentially cardiotoxic therapies, it is important to manage modifiable risk factors such as smoking, diabetes, hypertension, and obesity.
  • An echocardiogram may be recommended for patients with signs and symptoms of cardiac dysfunction. An echocardiogram may not be possible if the patient is not able to obtain one.
  • A referral to a cardiologist is possible if necessary.
  • Patients with metastatic breast carcinoma receiving trastuzumab may benefit from routine echocardiographic surveillance.

• Hypersensitivity

  • Tratuzumab/hyaluronidase has been associated with severe hypersensitivity reactions including anaphylaxis.
  • Patients suffering from dyspnea at home due to advanced malignancy complications and/or comorbidities could be at greater risk for a serious or fatal adverse reaction.
  • Grade 3 and 4 reactions are rare. A small percentage of patients required permanent discontinuation because of hypersensitivity or anaphylaxis.
  • After IV trastuzumab treatment, serious and even fatal reactions were reported.
  • Be aware of systemic hypersensitivity reactions, especially with the initial dose.
  • Tratuzumab/hyaluronidase should be permanently withheld from patients who have severe anaphylaxis.
  • You should have immediate access to emergency equipment and medications for anaphylaxis.
  • Premedication should be considered with an analgesic or antipyretic before you begin trastuzumab/hyaluronidase treatment in patients who have experienced a reversible Grade 1 or 2 hypersensitivity reaction.

• Pulmonary toxicities: [US Boxed Warning]

  • Trastuzumab can cause serious and fatal pulmonary toxicities.
  • Trazuzumab/hyaluronidase administration is usually followed by symptoms.
  • Trastuzumab/hyaluronidase should be stopped for anaphylaxis and angioedema.
  • Keep an eye on patients until all symptoms are resolved.
  • Pulmonary toxicities include dyspnea and interstitial pneumonitis.
  • Patients suffering from symptomatic intrinsic lung disease or extensive pulmonary tumour involvement (dyspnea at rest) are more likely to be diagnosed with severe pulmonary toxicities.

Trastuzumab and hyaluronidase (subcutaneous): Drug Interaction

Monitoring parameters:

• Assess the patient for the presence of human epidermal growth hormone 2 (HER2), HER2 gene amplification and overexpression by validated immunohistochemistry.
• Before treatment for women with reproductive potential, it is important to have a pregnancy test.
• Assess left ventricular efficacy (LVEF) at baseline and every 3 months after treatment completion. If the component of adjuvant therapies is used, every 6 months for at most 2 years.
• Monitor LVEF every 4 weeks if treatment is stopped due to significant LVEF dysfunction.
• Pay attention to signs and symptoms of hypersensitivity, cardiomyopathy, and/or lung toxicity.

Additional monitoring of the heart:

• A comprehensive assessment is required before treatment. This includes a history, physical exam, screening for cardiovascular disease risk factors like hypertension, diabetes and dyslipidemia.
• An echocardiogram should be performed for patients with signs or symptoms of cardiac dysfunction. If an echocardiogram cannot or is not possible, a cardiac MRI or MUGA scan can be used to determine serum cardiac biomarkers.
• Patients with metastatic breast carcinoma receiving trastuzumab may benefit from routine echocardiographic surveillance.

How to administer Trastuzumab and Hyaluronidase (Herceptin Hylecta)?

SubQ

• Subcutaneously administer for 2-5 minutes.
• Only for subcutaneous use. A health care professional should administer the doses.
• Alternate where you are going to inject between your left and right thighs. Apply new injections to healthy skin no more than 2.5 cm from the original site. Do not inject into areas that are red, bruised or tender or where scars or moles exist.
• You should not give other subcutaneous drugs at the same site as trastuzumab/hyaluronidase.
• Avoid clogging your needle by attaching the injection needle immediately before administering. Then adjust the volume to 5 mL.

You should always check the label to make sure the correct product is being used. Tratuzumab/hyaluronidase and conventional trastuzumab products are all different products.

Mechanism of action of Trastuzumab and Hyaluronidase (Herceptin Hylecta):

• Trastuzumab, a monoclonal anti-body that binds to extracellular domains of the human epidermal Growth Factor 2 protein (HER-2), mediates antibody dependent cellular cytotoxicity through inhibiting proliferation of cells with HER-2 overexpression.
• Hyaluronidase increases subcutaneous trastuzumab absorption and dispersion rate by temporarily depolymerizing hyaluronan. The temporary depolymerization causes a temporary increase in the permeability subcutaneous tissue. At the recommended doses, the hyaluronidase works locally and transiently; the subcutaneous tissues are re-permeabilized within 24 to 48 hours.

Bioavailability:

• Absolute: Trastuzumab: SubQ: 0.77

Time to peak:

• Trastuzumab: SubQ: ~3 days.

Excretion:

• Trastuzumab: SubQ: In most patients, trastuzumab is estimated to reach concentrations of <1 mcg/mL by 7 months following the last trastuzumab/ hyaluronidase dose.

International Brand Names of Trastuzumab and hyaluronidase:

• Herceptin Hylecta
• Herceptin SC

Trastuzumab and Hyaluronidase Brand Names in Pakistan:

No Brands Available in Pakistan.