ADRIM INJECTION

Indications

• Breast cancer
• Lung cancer
• Leukemia
• Lymphoma
• Ovarian cancer
• Sarcomas

Dosage

Children: Refer to the BNF for Children for appropriate dosing in pediatric patients.

Adults: Refer to specific treatment guidelines or the BNF for appropriate dosing as it varies based on cancer type and treatment regimen.

Mechanism of action

Doxorubicin exerts its anticancer effects primarily through intercalation into DNA, which disrupts the structure of DNA and inhibits macromolecular biosynthesis. It also generates free radicals that contribute to cellular damage and apoptosis. Additionally, doxorubicin inhibits topoisomerase II, an enzyme crucial for DNA replication and repair, leading to DNA strand breaks.

Pharmacodynamics

The pharmacodynamics of doxorubicin involve its ability to induce apoptosis in rapidly dividing cancer cells. The drug's intercalation into the DNA helix results in inhibition of the topoisomerase II enzyme, which is essential for DNA unwinding during replication. The resultant DNA damage triggers cellular signaling pathways that lead to programmed cell death. The efficacy of doxorubicin can be influenced by factors such as tumor type and genetic mutations within the cancer cells.

Pharmacokinetics

Doxorubicin is administered intravenously and has a volume of distribution of approximately 10-20 L/m². It is extensively distributed in tissues, with high concentrations in the liver, spleen, and heart. The drug is metabolized primarily in the liver, with a half-life of approximately 20-48 hours. Doxorubicin is excreted mainly in bile, with a small percentage eliminated via the urine. The drug's clearance can be affected by liver function, necessitating dose adjustments in patients with hepatic impairment.

Contra-indications

• Hypersensitivity to doxorubicin or any of its components
• Severe myocardial insufficiency
• Previous therapy with doxorubicin or other anthracyclines at cumulative doses exceeding recommended limits
• Active infections
• Pregnancy

Adverse effects

• Cardiotoxicity
• Nausea and vomiting
• Myelosuppression
• Alopecia
• Mucositis
• Extravasation reactions
• Secondary malignancies

Interactions

• CYP3A4 inhibitors may increase doxorubicin levels
• CYP3A4 inducers may decrease doxorubicin effectiveness
• Concurrent use with other cardiotoxic agents may increase the risk of cardiac toxicity
• Anticoagulants may have altered effects

Precautions

• Monitor cardiac function regularly during treatment
• Use caution in patients with hepatic impairment
• Minimize exposure to live vaccines during therapy
• Avoid extravasation during intravenous administration

Pregnancy

Doxorubicin is contraindicated during pregnancy due to potential harm to the fetus.

Breast-feeding

Breastfeeding is not recommended during treatment with doxorubicin due to the potential for excretion in breast milk.

Storage

Store at room temperature, protected from light. Do not freeze.

Formulations

• Injectable solution
• Liposomal formulation