GLIRIN 100MG

Indications

• Colorectal cancer
• Small cell lung cancer
• Gastric cancer
• Pancreatic cancer

Dosage

Children: Paediatric dosing is not well established and should be guided by clinical protocols and the BNF for Children.

Adults: Dosing of irinotecan is typically individualized based on the specific cancer type, treatment regimen, and patient tolerance. Refer to established treatment protocols for specific dosing recommendations.

Mechanism of action

Irinotecan is metabolized to its active form, SN-38, which inhibits topoisomerase I. This enzyme is crucial for DNA replication and transcription as it introduces single-strand breaks in DNA. By stabilizing the topoisomerase I-DNA complex, irinotecan prevents the re-ligation of DNA strands, resulting in DNA damage and subsequent cell death.

Pharmacodynamics

The cytotoxic effects of irinotecan are primarily due to its ability to interfere with DNA replication in cancer cells. The drug has a biphasic elimination profile, with an initial rapid distribution phase followed by a slower elimination phase. The pharmacodynamic response is influenced by the degree of DNA damage and the repair capacity of the tumor cells, which can vary significantly among individuals.

Pharmacokinetics

Irinotecan is administered intravenously and is rapidly converted to its active metabolite, SN-38, which has a longer half-life than the parent compound. The drug is extensively metabolized in the liver primarily by the enzyme UGT1A1. The elimination half-life of irinotecan is approximately 6 to 12 hours, while SN-38 can persist longer in circulation. Excretion occurs mainly through feces, with a smaller percentage eliminated via urine.

Contra-indications

• Severe hypersensitivity to irinotecan or any of its components
• Severe bone marrow depression
• Severe hepatic impairment
• Diarrhea not controlled by medication

Adverse effects

• Diarrhea
• Nausea and vomiting
• Myelosuppression, including neutropenia
• Fatigue
• Alopecia
• Abdominal pain
• Infection
• Dehydration
• Sepsis
• Febrile neutropenia

Interactions

• CYP3A4 inhibitors and inducers may alter irinotecan metabolism
• Concurrent use of other myelosuppressive agents may increase the risk of bone marrow suppression
• Antidiarrheal agents like loperamide may be used cautiously to manage diarrhea

Precautions

• Monitor blood counts regularly due to the risk of myelosuppression
• Ensure adequate hydration to prevent dehydration from diarrhea
• Assess liver function prior to and during treatment
• Caution in patients with a history of gastrointestinal obstruction or inflammatory bowel disease

Pregnancy

Irinotecan is classified as category D. It may cause fetal harm and should be avoided during pregnancy unless the benefits outweigh the risks.

Breast-feeding

It is not known if irinotecan is excreted in human milk. Caution is advised if the drug is administered to a nursing mother.

Storage

Store at room temperature, protected from light. Once diluted, the solution should be used immediately or can be stored for a limited time as specified by local guidelines.

Formulations

• Irinotecan injection for intravenous use