ENHERTU 100 MG POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

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

• Metastatic breast cancer in patients with HER2 overexpression who have received at least two prior chemotherapy regimens, including an anthracycline and a taxane.
• Metastatic gastric cancer in patients with HER2-positive tumors who have not received prior treatment for this condition.

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines in paediatric patients, as specific doses are not provided in the BNF.

Adults: The recommended dosage for adults is typically 8 mg/kg as a loading dose, followed by 6 mg/kg every three weeks, administered via intravenous infusion or subcutaneous injection.

Mechanism of action

Trastuzumab binds specifically to the extracellular domain of the human epidermal growth factor receptor 2 (HER2), leading to inhibition of HER2-mediated signaling pathways, including the PI3K/AKT and MAPK pathways. This blockade reduces cell proliferation and induces apoptosis in HER2-overexpressing cells. Additionally, trastuzumab enhances antibody-dependent cellular cytotoxicity (ADCC) through immune effector cells.

Pharmacodynamics

Trastuzumab demonstrates a dose-dependent effect on inhibiting the growth of HER2-positive cancer cells. Its clinical efficacy is primarily associated with its ability to target HER2 overexpression, leading to decreased tumor growth and improved survival rates in patients with HER2-positive breast and gastric cancers. Common side effects include infusion-related reactions, gastrointestinal disturbances, and increased risk of infections.

Pharmacokinetics

Trastuzumab has a terminal half-life of approximately 5 to 8 days after the initial intravenous administration. It is distributed widely, with a volume of distribution typically around 2-3 L/kg. Metabolism occurs via proteolytic degradation, primarily in the reticuloendothelial system. The clearance is affected by the patient's body size and HER2 expression levels, and it is excreted mainly through the lymphatic system.

Contra-indications

• Severe dyspnoea at rest
• Symptomatic heart failure
• Uncontrolled arrhythmias

Adverse effects

• Abdominal pain
• Alopecia
• Anaemia
• Appetite decreased
• Arthralgia
• Asthenia
• Constipation
• Cough exacerbated
• Decreased leucocytes
• Diarrhoea
• Dyspnoea
• Electrolyte imbalance
• Fever
• Headache
• Hyperbilirubinaemia
• Hyperhidrosis
• Hypogammaglobulinaemia
• Increased risk of infection
• Infusion related reaction
• Malaise
• Mucositis
• Muscle spasms
• Nasal congestion
• Nausea
• Neutropenia
• Pain
• Paresthesia
• Peripheral oedema
• Sepsis
• Skin reactions
• Taste altered
• Thrombocytopenia
• Vomiting
• Weight decreased

Interactions

• Anthracyclines: Severe (increases risk of cardiotoxicity)
• Anthracyclines + trastuzumab-emtansine: Severe (increases risk of cardiotoxicity)
• Cobicistat + trastuzumab-emtansine: Severe (increases exposure)
• Idelalisib + trastuzumab-emtansine: Severe (increases exposure)
• Clarithromycin + trastuzumab-emtansine: Severe (increases exposure)
• Anthracyclines + trastuzumab-deruxtecan: Unknown (increases risk of cardiotoxicity)

Precautions

• Monitor for cardiac function before each treatment cycle and throughout therapy
• Females of childbearing potential should use effective contraception during treatment and for at least 3 months after last treatment

Pregnancy

Use is not recommended during pregnancy. If exposed, monitor the infant for B-cell depletion.

Breast-feeding

It is not known if trastuzumab is excreted in human milk. Caution should be exercised.