irinotecan hydrochloride trihydrate: clinical use

Prescribing considerations

• Restrict administration to specialist cytotoxic chemotherapy units with rapid access to treatment of diarrhoea, neutropenic sepsis and infusion reactions.
• Assess performance status, bowel symptoms, marrow reserve, hepatic function, previous abdominal or pelvic radiotherapy and ability to follow urgent diarrhoea instructions.
• Consider reduced UGT1A1 activity when assessing severe neutropenia and diarrhoea risk; genotyping may help selected patients but does not predict all toxicity.
• Review fertility preservation where relevant.
• Ask specifically about hereditary fructose intolerance because the selected formulation contains sorbitol.

Contraindications and cautions

• Chronic inflammatory bowel disease or bowel obstruction
• Hypersensitivity to irinotecan or an excipient
• Breastfeeding
• Bilirubin above the product-defined limit
• Severe bone-marrow failure
• WHO performance status above the licensed limit
• Concurrent St John's wort
• Concurrent live attenuated vaccines

Monitoring

• Full blood count and urgent assessment of fever or suspected infection.
• Liver function; impaired bilirubin clearance increases exposure and toxicity risk.
• Diarrhoea, hydration and electrolytes.
• Nausea, vomiting, mucosal toxicity and nutritional status.
• Respiratory symptoms in patients with pulmonary risk factors.
• Infusion site inflammation or extravasation.

Clinical pharmacology

A camptothecin-derived prodrug converted by carboxylesterases to SN-38. Both compounds inhibit topoisomerase I, producing replication-associated single-strand DNA lesions. SN-38 is inactivated mainly through UGT1A1-mediated glucuronidation; CYP3A-dependent metabolism also contributes.

Formulation and product differences

• Clear, colourless to pale-yellow concentrate requiring dilution before intravenous use.
• Preservative-free, single-use cytotoxic preparation; remaining solution must be discarded safely.
• Contains sorbitol and is essentially sodium-free.
• Protect vials from light and do not freeze.

Solution for infusion

Route: Intravenous

Strengths: 1.5 mg/mL, 20 mg/mL, 40 mg, 100 mg, 300 mg