ENHERTY 100MG POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION (TRATUZUMAB DERUXTECAN)

Indications

• Breast cancer
• Gastric cancer
• Other solid tumors expressing HER2

Dosage

Children: There is limited data on the use of deruxtecan in pediatric populations, refer to the BNF for Children for any applicable dosing guidelines.

Adults: The dosage in adults should be based on the specific indication and patient characteristics, refer to the BNF for detailed dosing guidelines.

Mechanism of action

Deruxtecan works by binding to the human epidermal growth factor receptor 2 (HER2) on cancer cells. Upon internalization, the drug is released from the antibody, allowing the cytotoxic agent to induce cell cycle arrest and apoptosis in HER2-expressing cells.

Pharmacodynamics

The pharmacodynamics of deruxtecan involves its ability to selectively target and kill cancer cells that overexpress HER2. The cytotoxic component disrupts microtubule formation, inhibiting cell division and promoting programmed cell death. This targeted approach helps in reducing damage to normal cells and enhancing the drug's effectiveness against tumors.

Pharmacokinetics

Deruxtecan exhibits a high volume of distribution and is primarily eliminated via the liver. It undergoes metabolism which leads to the formation of active metabolites. The drug has a half-life that supports once every three-week dosing. Its pharmacokinetic profile allows for sustained exposure of cancer cells to the cytotoxic agent while limiting systemic exposure.

Contra-indications

• Hypersensitivity to deruxtecan or any of its components
• Severe hepatic impairment

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Fatigue
• Anemia
• Neutropenia
• Thrombocytopenia
• Elevated liver enzymes
• Interstitial lung disease

Interactions

• Caution with drugs that are strong CYP3A4 inducers or inhibitors
• Potential interaction with other antineoplastic agents

Precautions

• Monitor for signs and symptoms of interstitial lung disease
• Assess liver function prior to treatment and periodically during therapy
• Use caution in patients with a history of pulmonary disease

Pregnancy

Deruxtecan may cause fetal harm. It is contraindicated in pregnancy unless the potential benefit justifies the risk. Women of childbearing potential should use effective contraception during treatment and for a period after completion of therapy.

Breast-feeding

It is not known if deruxtecan is excreted in human milk. Caution should be exercised when administering to a nursing mother.

Storage

Store in a refrigerator (2 to 8 degrees Celsius). Protect from light. Do not freeze.

Formulations

• Injection, powder for concentrate for solution for infusion

Indications

• HER2-positive breast cancer
• HER2-positive gastric cancer
• Gastroesophageal junction adenocarcinoma

Dosage

Children: Refer to the BNF for Children for dosing information specific to pediatric patients, as no established pediatric dosing guidelines

Adults: Refer to specific treatment guidelines and the BNF for appropriate dosing regimens based on the type of cancer and treatment protocol.

Mechanism of action

Trastuzumab binds to the extracellular domain of the HER2 protein, preventing its dimerization and subsequent activation of downstream signaling pathways associated with cell growth and survival. This blockade inhibits the activation of key pathways such as the phosphoinositide 3-kinase (PI3K)/AKT and the mitogen-activated protein kinase (MAPK) pathways, resulting in reduced cell proliferation and increased apoptosis of HER2-overexpressing cancer cells.

Pharmacodynamics

Trastuzumab exhibits dose-dependent antitumor activity in HER2-positive breast and gastric cancers. The binding of trastuzumab to HER2 not only inhibits signaling pathways that promote cell growth but also enhances the immune response against tumor cells through mechanisms such as antibody-dependent cellular cytotoxicity (ADCC). The drug is known to have a synergistic effect when combined with chemotherapy agents, contributing to improved clinical outcomes in patients with HER2-positive cancers.

Pharmacokinetics

Trastuzumab has a half-life of approximately 5 to 8 days, which can be influenced by factors such as the presence of HER2-positive tumor burden and individual patient characteristics. The drug is administered intravenously, and its bioavailability is nearly 100% when given via this route. It is primarily eliminated through the reticuloendothelial system, with target tissues such as tumors playing a significant role in its distribution. Trastuzumab does not undergo extensive metabolism, but rather is catabolized through proteolytic pathways.

Contra-indications

• Hypersensitivity to trastuzumab or any component of the formulation
• Severe cardiac dysfunction
• History of severe infusion reactions

Adverse effects

• Infusion-related reactions (fever, chills, nausea)
• Cardiotoxicity (heart failure)
• Nausea and vomiting
• Diarrhea
• Rash
• Fatigue
• Potential for pulmonary toxicity

Interactions

• Caution when used with other cardiotoxic agents (e.g., anthracyclines)
• Avoid use with medications that may exacerbate heart failure

Precautions

• Monitor cardiac function regularly during treatment
• Be alert for signs of infusion reactions
• Caution in patients with pre-existing heart conditions

Pregnancy

Trastuzumab is classified as Category D. It should be avoided during pregnancy due to potential harm to the fetus.

Breast-feeding

There is insufficient data on the excretion of trastuzumab in human milk. Caution is advised when administering to nursing mothers.

Storage

Store in a refrigerator at 2-8°C. Do not freeze. Protect from light.

Formulations

• Trastuzumab injection (solution for intravenous use)
• Trastuzumab biosimilar formulations