trastuzumab-hyaluronidase-oysk, Herceptin Hylecta trastuzumab/hyaluronidase

Action and Spectrum

Actions and Spectrum: 

Actions: 

• Targeted HER2 Inhibition: trastuzumab, the monoclonal antibody component of trastuzumab/hyaluronidase, binds to the HER2 receptors on cancer cells. Doing so inhibits the signaling pathways that promote cell growth and division. This action helps to slow down or halt the progression of HER2-positive cancer. 
• Immune-Mediated Cytotoxicity: trastuzumab can stimulate immune responses through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). These mechanisms involve recruiting immune cells to recognize and destroy HER2-positive cancer cells, further contributing to the anti-cancer effects of trastuzumab. 

Spectrum: 

• HER2-Positive Breast Cancer: trastuzumab/hyaluronidase is indicated for treating HER2-positive early-stage breast cancer and advanced (metastatic) breast cancer. It is combined with chemotherapy or as a single agent, depending on the treatment regimen. trastuzumab/hyaluronidase has demonstrated efficacy in reducing the risk of cancer recurrence, improving overall survival, and controlling the progression of HER2-positive breast cancer. 
• HER2-Positive Stomach (Gastric) Cancer: trastuzumab/hyaluronidase is also approved for treating HER2-positive advanced or metastatic stomach (gastric) or gastroesophageal junction cancer. It is combined with chemotherapy to improve overall survival and delay disease progression in this subset of gastric cancers. 

Drug Interaction

Adverse Reaction

Adverse reactions 

Frequency defined 

>10% 

Alopecia (63%) 

Nausea (49%) 

Diarrhea (34%) 

Rash (26%) 

Fatigue (46%) 

Neutropenia (44%) 

Upper respiratory tract infection (24%) 

Vomiting (23%) 

Peripheral neuropathy (20%) 

Decreased appetite (20%) 

Arthralgia (18%) 

Headache (17%) 

Stomatitis (21%) 

Myalgia (21%) 

Nail disorder (14%) 

Abdominal pain (14%) 

Flushing (14%) 

Anemia (12%) 

Cough (12%) 

Edema (14%) 

Pyrexia (13%) 

Dyspepsia (11%) 

Back pain (11%) 

Incision site complication (11%) 

Leukopenia (11%) 

1-10% 

Mucosal inflammation (10%) 

Dizziness (10%) 

Dysgeusia (10%) 

Injection site reactions (10%) 

Pain in extremities (10%) 

Pruritus (9%) 

Hypersensitivity (7%) 

Febrile neutropenia (6%) 

Skin discoloration (9%) 

Pain (8%) 

Dyspnea (7%) 

Hypertension (8%) 

Erythema (7%) 

Bone pain (6%) 

Epistaxis (6%) 

Abnormal liver function tests (6%) 

Arrhythmia (5%) 

Urinary tract infection (4%) 

Febrile neutropenia (6%) 

Leukopenia (5%) 

Pain (5%) 

Nasal inflammation/discomfort (5%) 

Alopecia (1.3%) 

Nausea (1.3%) 

Diarrhea (2.7%) 

Hypertension (2.4%) 

Hypersensitivity (1%) 

Abnormal liver function tests (1%) 

Vomiting (1%) 

Upper respiratory tract infection (1%) 

Back pain (1%) 

<1% 

Erythema 

Fatigue 

Headache 

Dizziness 

Cough 

Mucosal inflammation 

Anemia 

Rash 

Stomatitis 

Bone pain 

Pain 

Flushing 

Decreased appetite 

Black Box Warning

Black Box Warning: 

The drug may lead to clinical/subclinical cardiac failure, embryo-fetal toxicity, and pulmonary toxicity.

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• Hypersensitivity 

Caution 

• Cardiac dysfunction 
• Pulmonary toxicity 
• Infusion reactions 
• Pregnancy  
• Breastfeeding 
• Hepatic & renal impairment 
• Pre-existing infection 

Pregnancy / Lactation

Pregnancy consideration:  

No adequate data are available regarding the usage of the drug during pregnancy.  

Breastfeeding warnings:  

No data on the drug’s effect on the infant during breastfeeding is available. 

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 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: No data is available for the drug under this category. 

Pharmacology

Pharmacology  

trastuzumab: 

• trastuzumab binds to the HER2 receptors on the cancer cells, thereby blocking the signals that promote cancer cell growth and division. 
• trastuzumab can also elicit an immune response by recruiting the body’s immune system to recognize and destroy the cancer cells. 
• Additionally, trastuzumab can inhibit the shedding of the extracellular domain of the HER2 receptor, which may have a role in tumor growth. 

hyaluronidase: 

• hyaluronidase is an enzyme that breaks down hyaluronic acid, a natural component of the extracellular matrix in tissues. 
• By breaking down hyaluronic acid, hyaluronidase increases tissue permeability and diffusion, allowing improved drug distribution within the tissues. 
• In the context of trastuzumab/hyaluronidase, the hyaluronidase component facilitates the dispersion and absorption of trastuzumab within the subcutaneous tissue, enhancing its delivery and bioavailability

Pharmacodynamics 

trastuzumab 

• trastuzumab binds to the HER2 receptors on the cancer cells, thereby blocking the signals that promote cancer cell growth and division. 
• trastuzumab can also elicit an immune response by recruiting the body’s immune system to recognize and destroy the cancer cells. 
• Additionally, trastuzumab can inhibit the shedding of the extracellular domain of the HER2 receptor, which may have a role in tumor growth. 

hyaluronidase 

• hyaluronidase is an enzyme responsible for breaking down hyaluronic acid. 
• By breaking down hyaluronic acid, hyaluronidase increases tissue permeability and diffusion, allowing improved drug distribution within the tissues. 
• In the context of trastuzumab/hyaluronidase, the hyaluronidase component facilitates the dispersion and absorption of trastuzumab within the subcutaneous tissue, enhancing its delivery and bioavailability.

Pharmacokinetics 

trastuzumab 

Absorption 

trastuzumab is administered intravenously or subcutaneously. Intravenous administration ensures complete and immediate bioavailability, while subcutaneous administration allows for sustained release into systemic circulation. 

Distribution 

trastuzumab has a large volume of distribution, indicating extensive distribution into tissues. It primarily targets HER2-positive cancer cells but can also be found in normal tissues expressing HER2, such as the heart. 

Metabolism 

trastuzumab is not extensively metabolized in the body. It undergoes catabolism into small peptides and amino acids. 

Elimination and Excretion 

trastuzumab is eliminated through proteolytic degradation and clearance mechanisms. The primary elimination pathway is via receptor-mediated endocytosis followed by intracellular degradation. The elimination half-life of trastuzumab is approximately 4-6 days. 

hyaluronidase 

Absorption 

hyaluronidase is administered subcutaneously alongside trastuzumab to improve its dispersion and absorption. It facilitates the breakdown of hyaluronic acid, allowing for enhanced drug distribution within the subcutaneous tissue. 

Distribution 

hyaluronidase is distributed throughout the tissues due to its enzymatic activity, which acts on the hyaluronic acid in the extracellular matrix. 

Metabolism 

hyaluronidase is metabolized in various tissues through enzymatic processes. 

Elimination and Excretion 

hyaluronidase is eliminated through both renal and hepatic routes. The elimination half-life of hyaluronidase is relatively short, typically within hours. 

Adminstartion

Administration 

The injection is administered subcutaneously, which means it is injected just beneath the skin rather than into a muscle or vein. 

• The healthcare provider may pinch the skin to create a fold, making inserting the needle into the subcutaneous tissue easier.
• The needle is inserted at a 45-degree angle into the subcutaneous tissue.
• The medication is injected slowly and steadily.

Patient Information Leaflet

Patient information leaflet 

Generic Name: trastuzumab/hyaluronidase 

Pronounced: tras-TOO-zoo-mab HYE-al-ure-ON-i-dase  

Why do we use trastuzumab/hyaluronidase? 

trastuzumab/hyaluronidase is a medication used to treat certain breast and stomach cancers. It is a combination therapy that consists of trastuzumab, a monoclonal antibody, and hyaluronidase, an enzyme.