KADCYLA 160mg (TRASTUZUMAB EMATASINE) POWDER FOR CONCENTRATE FOR SOLUTION

Indications

• HER2-positive breast cancer
• Metastatic breast cancer
• Locally advanced breast cancer

Dosage

Children: Refer to the BNF for Children or specific pediatric oncology guidelines for dosing information, as pediatric dosing may differ significantly from adult dosing.

Adults: Refer to specific clinical guidelines or the prescribing information for adult dosing recommendations, as it may vary based on individual patient factors and treatment protocols.

Mechanism of action

Ematasine works by binding to the HER2 receptor, which is overexpressed in certain breast cancers. The drug-antibody complex is internalized by the cancer cell, where the cytotoxic agent is released, leading to apoptosis or programmed cell death. This targeted mechanism increases the efficacy of the treatment while reducing systemic toxicity.

Pharmacodynamics

The pharmacodynamics of ematasine involve its ability to selectively target HER2-overexpressing cells, leading to enhanced therapeutic effects against tumors that express this receptor. The cytotoxic component acts by disrupting microtubule formation, which is essential for cell division, thereby inhibiting tumor growth and proliferation.

Pharmacokinetics

Ematasine exhibits a variable pharmacokinetic profile, influenced by factors such as the patient's metabolism and the presence of HER2 expression in tumors. Following administration, the drug's half-life and its distribution in tissues can vary. It undergoes hepatic metabolism and is primarily excreted via the liver. The pharmacokinetics are essential to monitor for potential toxicity and therapeutic effectiveness.

Contra-indications

• Hypersensitivity to ematasine or any of its components
• Severe hepatic impairment
• Concomitant use with other agents known to cause severe myelosuppression

Adverse effects

• Nausea
• Vomiting
• Fatigue
• Anemia
• Thrombocytopenia
• Neutropenia
• Peripheral neuropathy
• Pulmonary toxicity
• Cardiac toxicity

Interactions

• May interact with other myelosuppressive agents
• Caution with drugs that prolong QT interval
• May enhance the toxicity of other chemotherapeutic agents

Precautions

• Monitor complete blood counts regularly
• Assess liver function prior to and during treatment
• Use caution in patients with pre-existing lung disease
• Evaluate cardiac function before initiating treatment

Pregnancy

Ematasine is contraindicated in pregnancy due to its potential teratogenic effects and harm to fetal development. Women of childbearing potential should use effective contraception during treatment.

Breast-feeding

It is unknown whether ematasine is excreted in human milk. Caution is advised, and breastfeeding is not recommended during treatment.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Injectable solution for intravenous use

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.