ADCETRIS

Indications

• Hodgkin lymphoma
• Anaplastic large cell lymphoma
• Other CD30-expressing malignancies

Dosage

Children: Refer to the BNF for Children for dosing information specific to pediatric patients.

Adults: Refer to the BNF for specific dosing guidelines based on the indication and patient characteristics.

Mechanism of action

Brentuximab vedotin binds to CD30 on the surface of tumor cells, leading to internalization of the drug-antibody complex. Once internalized, the cytotoxic agent, monomethyl auristatin E (MMAE), is released, which disrupts microtubule formation, ultimately resulting in cell cycle arrest and apoptosis of CD30-positive cells.

Pharmacodynamics

The pharmacodynamics of brentuximab vedotin involve its selective targeting of CD30-positive cells, which allows for effective tumor cell elimination with reduced systemic toxicity compared to traditional chemotherapeutics. Its efficacy has been demonstrated in clinical trials, resulting in significant tumor reduction and improved survival rates in patients with relapsed or refractory disease.

Pharmacokinetics

Brentuximab vedotin exhibits a mean half-life of approximately 4 days, with distribution primarily occurring in the vascular space and tissues. The drug is metabolized by proteolytic enzymes, and its clearance is primarily through the reticuloendothelial system. Renal impairment may affect the pharmacokinetics, and dosage adjustments may be necessary based on individual patient factors.

Contra-indications

• Hypersensitivity to brentuximab vedotin or any of its components
• Active infection
• Severe pulmonary toxicity history

Adverse effects

• Peripheral neuropathy
• Neutropenia
• Anemia
• Thrombocytopenia
• Nausea
• Vomiting
• Fatigue
• Infection risk increase

Interactions

• Increased risk of pulmonary toxicity with bleomycin
• Carbamazepine may decrease the effects of brentuximab vedotin
• Rifampicin may decrease the effects of brentuximab vedotin

Precautions

• Monitor blood counts regularly due to risk of myelosuppression
• Evaluate for signs of infection prior to administration
• Use caution in patients with history of lung disease

Pregnancy

Brentuximab vedotin is not recommended during pregnancy due to potential risks to the fetus. Women of childbearing potential should use effective contraception during treatment.

Breast-feeding

It is not known whether brentuximab vedotin is excreted in human milk. Caution is advised.

Storage

Store at 2 to 8 degrees Celsius. Protect from light. Do not freeze.

Formulations

• Brentuximab vedotin 50 mg/10 mL solution for injection

Indications

• Hodgkin lymphoma
• Anaplastic large cell lymphoma

Dosage

Children: Refer to the BNF for Children for guidance on dosing in paediatric patients, as this may vary based on age, weight, and clinical condition.

Adults: Refer to the BNF for specific dosing recommendations based on individual patient factors and treatment protocols.

Mechanism of action

Vedotin targets CD30, a cell surface protein that is overexpressed in certain malignancies, such as Hodgkin lymphoma and anaplastic large cell lymphoma. The monoclonal antibody component binds to CD30 on the surface of cancer cells, facilitating internalization of the drug. Once inside the cell, the cytotoxic agent is released, leading to disruption of microtubule function, ultimately resulting in cell cycle arrest and apoptosis.

Pharmacodynamics

Vedotin exhibits dose-dependent cytotoxicity against CD30-expressing cells. Its mechanism involves the inhibition of microtubule assembly, which is crucial for mitosis and cellular integrity. The compound's selectivity for CD30-positive cells helps to limit toxicity to normal cells, contributing to its therapeutic efficacy in targeted cancer treatment.

Pharmacokinetics

After intravenous administration, vedotin distributes widely in the body, with a volume of distribution that suggests extensive tissue binding. The drug is metabolized primarily by proteolytic cleavage, resulting in the release of the cytotoxic payload. Elimination occurs mainly through the hepatobiliary route, with a half-life that supports dosing intervals based on clinical needs. Monitoring may be required to assess clearance and potential accumulation in patients with altered liver function.

Pregnancy

There is limited data on the use of vedotin in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known if vedotin is excreted in human breast milk. Caution should be exercised when administering vedotin to a nursing woman.

Storage

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