Trastmab 440

Indications

• Vaccination
• Antibiotic therapy
• Hormone replacement therapy
• Enzyme replacement therapy
• Immunotherapy

Dosage

Children: Refer to specific drug information for dosing guidelines, as this varies widely based on the active ingredient and indication.

Adults: Refer to specific drug information for dosing guidelines, as this varies widely based on the active ingredient and indication.

Mechanism of action

Lyophilization itself does not have a mechanism of action, as it is a preservation technique rather than a pharmacologically active process. The mechanism of action of the lyophilized drug will depend on the specific active pharmaceutical ingredient (API) that has been lyophilized. For example, if the lyophilized drug is a vaccine, its mechanism may involve the stimulation of the immune response through the introduction of antigens.

Pharmacodynamics

The pharmacodynamics of a lyophilized drug will vary based on the specific formulation and active ingredients. Generally, once reconstituted, the pharmacodynamic properties will reflect those of the non-lyophilized form. Factors such as bioavailability, receptor binding, and the drug's effects on physiological systems will be determined by the specific drug's characteristics.

Pharmacokinetics

The pharmacokinetics of a lyophilized drug will also depend on the specific API. Once reconstituted, the drug's absorption, distribution, metabolism, and excretion (ADME) profile will align with that of the non-lyophilized version. The freeze-drying process is designed to minimize degradation, maintaining the pharmacokinetic properties of the drug post-reconstitution.

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised when administering during breastfeeding. The effects on a nursing infant are not known.

Storage

Store in a cool, dry place. Protect from light and moisture. Follow specific storage recommendations for individual formulations.

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.