pertuzumab/trastuzumab/hyaluronidase

Action and Spectrum

Mechanism of action 

pertuzumab and Trastuzumab have a synergetic effect that enhances the inhibitory effect on the HER2 protein. hyaluronidase can enhance the absorption of Pertuzumab and Trastuzumab when administered subcutaneously, allowing for a more convenient administration route for patients. 

This drug combination is used to treat early and metastatic breast cancer that is HER2-positive. It is intended to improve treatment outcomes for patients with HER2-positive breast cancer by inhibiting the activity of the HER2 protein and slowing down cancer’s progression. 

Spectrum 

hyaluronidase is an enzyme used to enhance the absorption of other drugs when administered subcutaneously. It is mostly used in combination with other drugs to treat various conditions, including but not limited to cancer, joint pain, and skin conditions. 

pertuzumab is a monoclonal antibody that targets the HER2 protein, which is overexpressed in some types of breast cancer. It is used in treating HER2-positive breast cancer, both early and metastatic, in combination with other drugs such as Trastuzumab and chemotherapy. 

trastuzumab is also a monoclonal antibody that targets the HER2 protein. It is also used in treating HER2-positive breast cancer, both early and metastatic, in combination with other drugs such as pertuzumab and chemotherapy. 

Drug Interaction

Adverse Reaction

Frequency defined:  

>10% 

Low absolute lymphocytes (89%) 

Low total leukocytes (82%) 

Low total absolute neutrophils (68%) 

High ALT (58%) 

Anemia (36%) 

Fatigue (29%) 

Stomatitis (25%) 

Arthralgia (24%) 

Neutropenia (22%) 

Radiation skin injury (19%) 

Dysgeusia (17%) 

Insomnia (17%) 

Low albumin (16%) 

Rash (16%) 

Injection site reaction (15%) 

Cough (15%) 

Pyrexia (13%) 

Procedural pain (13%) 

Low hemoglobin (90%) 

High creatinine (84%) 

Alopecia (77%) 

Nausea (60%) 

Diarrhea (60%) 

High AST (50%) 

Asthenia (31%) 

Low platelets (27%) 

Myalgia (25%) 

Constipation (22%) 

Vomiting (20%) 

Decreased appetite (17%) 

Headache (17%) 

Low potassium (17%) 

Peripheral sensory neuropathy (16%) 

Mucosal inflammation (15%) 

Dry skin (15%) 

Dyspepsia (14%) 

Dizziness (13%) 

High potassium (13%)  

1-10% 

Back pain (10%) 

High bilirubin (9%) 

Nail discoloration (9%) 

Hemorrhoids (9%) 

Leukopenia (9%) 

Peripheral edema (8%) 

Malaise (7%) 

Dermatitis (7%) 

Bone pain (7%) 

Muscle spasms (6%) 

Palmoplantar erythrodysesthesia syndrome (6%) 

Paresthesia (10%) 

Low glucose (9%) 

Erythema (9%) 

Abdominal pain (9%) 

Upper abdominal pain (8%) 

High sodium (7%) 

Febrile neutropenia (7%) 

Nail disorder (7%) 

Pain in extremities (6%) 

Musculoskeletal pain (6%) 

Influenza-like illness (5%)  

<1% 

Mucosal inflammation (0.8%) 

Decreased appetite (0.8%) 

Paresthesia (0.8%) 

Vomiting (0.8%) 

Palmoplantar erythrodysesthesia syndrome (0.8%) 

Abdominal pain (0.4%) 

High sodium (0.8%) 

High AST (0.8%) 

Decreased weight (0.8%) 

Peripheral sensory neuropathy (0.8%) 

Stomatitis (0.8%) 

Asthenia (0.4%)  

Post-marketing reports 

Immune thrombocytopenia 

Glomerulotherapy 

Tumor lysis syndrome 

Black Box Warning

Black box warning 

Phesgo (pertuzumab, Trastuzumab, and hyaluronidase-zzxf) is a medication used to treat certain types of breast cancer. The drug can cause several serious side effects, including cardiomyopathy, which can lead to subclinical and clinical cardiac failure. The incidence and severity of this side effect are highest in patients receiving Phesgo in combination with anthracycline-containing chemotherapy regimens. It is essential to evaluate cardiac function before and during treatment and to discontinue Phesgo in patients receiving adjuvant therapy and withhold it in patients with metastatic disease for a clinically significant decrease in LVEF. 

Another severe side effect of Phesgo is embryofetal toxicity. Exposure to the drug can result in embryofetal death and birth defects, including oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Patients should be advised of these risks and the need for effective contraception. 

Pulmonary toxicity is another profound side effect of Phesgo. Administration can result in severe and fatal pulmonary toxicity. Phesgo should be discontinued for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome, and patients should be monitored until symptoms resolve entirely. 

Contraindication / Caution

Contraindications 

Intolerance to hyaluronidase, pertuzumab, Trastuzumab, or any of its excipients 

Caution 

• pertuzumab and trastuzumab: Cardiac dysfunction, hypertension, arrhythmias, cardiomyopathy, disabling cardiac failure, and cardiac death have been reported. Pulmonary toxicity and exacerbation of chemotherapy-induced neutropenia have also been reported. Severe hypersensitivity reactions and fatal outcomes have been associated with IV administration. 
• hyaluronidase: Hypersensitivity reactions, including anaphylaxis, have been reported. There is a risk of injection site reactions, such as pain, redness, and swelling. 

Pregnancy / Lactation

Pregnancy consideration: may cause fetal harm when administered 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology 

Both pertuzumab and Trastuzumab are targeted therapy, and they are used to treat HER2-positive breast cancer. Hyaluronidase is an enzyme that is used to enhance the delivery of chemotherapy drugs.  

Pharmacodynamics 

pertuzumab and Trastuzumab are targeted therapy that works by inhibiting the HER2 receptor, which is overexpressed in HER2-positive breast cancer. At the same time, hyaluronidase is an enzyme used to enhance the delivery of chemotherapy drugs by increasing the permeability of the extracellular matrix. 

Pharmacokinetics 

Absorption: 

The bioavailability of both drugs is also similar, with pertuzumab having an absolute bioavailability of 0.7 and Trastuzumab having an absolute bioavailability of 0.8 when administered subcutaneously. 

Distribution: 

The distribution of pertuzumab and Trastuzumab is similar, with both having a volume of distribution of about 2.8-2.9 L when administered subcutaneously.  

Metabolism: 

The peak concentration for both drugs is four days when administered subcutaneously. 

Elimination and excretion: 

The clearance of both drugs is linear, with pertuzumab having a clearance rate of 0.2 L/day and Trastuzumab having a clearance rate of 0.1 L/day when administered subcutaneously. 

Adminstartion

Administration 

hyaluronidase is typically administered as an injection, either subcutaneously or intramuscularly. It is often used with other chemotherapy drugs to enhance their delivery to cancer cells. The dosing will depend on the specific indication and the patient’s characteristics. 

pertuzumab and Trastuzumab are both administered as intravenous infusions. pertuzumab is usually given every three weeks for about 8-12 cycles, depending on the treatment plan. Trastuzumab is usually given once every week for the first several months of treatment and then every three weeks for the remainder. The duration of treatment can vary, but it is usually for one year. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: hyaluronidase / pertuzumab / trastuzumab 

Pronounced: [ HYE-al-ure-ON-i-dase, per-TOOZ-ue-mab, and-tras-TOOZ-ue-mab ] 

Why do we use hyaluronidase / pertuzumab / trastuzumab? 

To treat HER2-positive, locally advanced, inflammatory, or early-stage breast cancer, pertuzumab, Trastuzumab, and hyaluronidase-zzxf combination injection is used first along with other cancer medications part of a comprehensive treatment plan for early breast cancer. It is also used to treat early breast cancer that is HER2-positive after an initial course of treatment since it has a high chance of recurring.