Severe diarrhoea (acute and delayed):
Acute cholinergic diarrhoea: Occurs during or shortly after infusion — may present with sweating, abdominal cramping, and lacrimation.
→ Treat immediately with atropine 0.25–1 mg IV/SC (unless contraindicated).
Delayed diarrhoea: Occurs >24 hours after administration (median onset 5–6 days).
→ Can be life-threatening due to dehydration, electrolyte imbalance, and sepsis.
→ Loperamide is the treatment of choice; monitor closely.
→ Hospitalize if diarrhoea is persistent (>48 h) or accompanied by fever or neutropenia.
Myelosuppression (neutropenia, thrombocytopenia, anaemia):
Dose-limiting toxicity.
Delay or reduce dose if neutrophils <1.5 ×10⁹/L or platelets <100 ×10⁹/L.
Risk of infection and sepsis increases with Grade 3–4 neutropenia — monitor CBC prior to each cycle.
Neutropenic sepsis:
May be fatal; requires immediate broad-spectrum antibiotics and supportive care.
Delay subsequent cycles until full recovery.
Hepatotoxicity:
Elevated liver enzymes and bilirubin may occur.
Do not initiate if bilirubin >1.5 × ULN.
Monitor LFTs before each cycle.
Pulmonary toxicity:
Interstitial pneumonitis and pulmonary fibrosis reported (rare).
Stop immediately if new dyspnoea or pulmonary infiltrates appear.
Genetic risk (UGT1A1 polymorphism):
Patients homozygous for UGT1A1*28 allele have increased risk of severe neutropenia and diarrhoea.
Dose reduction may be required in these patients.
Pregnancy and lactation:
Contraindicated — teratogenic and embryotoxic.
Effective contraception required during and for ≥6 months after treatment.
Generic name: Irinotecan hydrochloride trihydrate
Brand name: Iritero®
Drug class: Topoisomerase I inhibitor (camptothecin derivative)
Formulation: Concentrate for IV infusion (solution for dilution)
Strength: 20 mg/mL
Mechanism of Action:
Prodrug converted in the liver by carboxylesterases to SN-38, a potent topoisomerase I inhibitor that prevents DNA religation, leading to double-strand breaks and apoptosis in rapidly dividing tumour cells.
Oncology indications:
Metastatic colorectal cancer (mCRC)
In combination with 5-fluorouracil (5-FU) and folinic acid (FOLFIRI regimen) in first-line therapy.
As monotherapy in patients with disease progression after 5-FU-based chemotherapy.
Use only under supervision of a physician experienced in cytotoxic chemotherapy.
IV infusion only (do not administer as IV bolus).
Regimens:
Monotherapy: 350 mg/m² IV infusion over 30–90 min every 3 weeks.
Combination therapy (FOLFIRI): 180 mg/m² IV infusion every 2 weeks with folinic acid and 5-FU.
Premedication: Antiemetic and atropine (for acute cholinergic symptoms).
Hydration: Adequate hydration essential during and after infusion.
No dose adjustment for mild renal impairment.
Dose adjustments:
Hepatic impairment:
Bilirubin 1.5–3 × ULN → reduce dose to 200 mg/m².
3 × ULN → contraindicated.
Performance status ≥2: Use cautiously or avoid.
Neutropenia or thrombocytopenia: Delay treatment until recovery.
Severe diarrhoea or febrile neutropenia: Reduce dose by 15–20% for future cycles.
Hepatic enzyme elevation: Adjust based on bilirubin and AST/ALT levels.
Persistent toxicity (Grade ≥3): Discontinue permanently.
Avoid with:
CYP3A4 inducers (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital) — ↓ irinotecan efficacy.
CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) — ↑ toxicity.
St John’s Wort — contraindicated.
Neuromuscular blockers: Enhanced neuromuscular blockade possible.
Live vaccines: Contraindicated during and after therapy.
Hypersensitivity to irinotecan or excipients
Chronic inflammatory bowel disease or bowel obstruction
Severe hepatic impairment (bilirubin >3 × ULN)
Poor performance status (ECOG ≥2 for monotherapy, ≥3 for combination)
Pregnancy and breastfeeding
Before and during therapy:
CBC with differential before each cycle
Liver function tests (ALT, AST, bilirubin)
Renal function
Bowel pattern and hydration status
Vital signs during infusion (for cholinergic symptoms)
UGT1A1 genotype if available in high-risk patients
| Frequency | Adverse Effect | Management |
|---|---|---|
| Very common (>10%) | Diarrhoea, nausea, vomiting, neutropenia, anaemia, alopecia, fatigue | Loperamide, antiemetics, hydration, supportive care |
| Common (1–10%) | Infection, mucositis, abdominal pain, anorexia, elevated LFTs | Symptomatic management, antibiotics if febrile |
| Uncommon (<1%) | Pulmonary infiltrates, hypersensitivity reactions, ileus | Stop treatment, supportive care |
| Rare | Interstitial lung disease, renal failure, thromboembolic events | Discontinue permanently |
Elderly: Higher risk of severe toxicity; close monitoring required.
Hepatic impairment: Reduce dose; contraindicated if bilirubin >3 × ULN.
Renal impairment: Use with caution; not studied in severe cases.
Pregnancy/Lactation: Contraindicated.
UGT1A1 poor metabolisers: Consider lower starting dose.
Continue until:
Disease progression, or
Completion of planned chemotherapy regimen, or
Unacceptable toxicity.
Stop immediately if:
Grade 4 diarrhoea, neutropenic sepsis, or severe hepatic injury
Pulmonary toxicity or allergic reaction
Persistent Grade ≥3 toxicity despite dose adjustment
https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2023/11/Final_PI_Iritero_Applicant.pdf
| Trade Name | |
|---|---|
| Drug Class | Topoisomerase I Inhibitors |
| Cost | |
| Company | |
|---|---|
| Drug Rep | Admin |
| Indications | |
| Dosage |
No indications found.