Generic
Irinotecan Hydrochloride Trihydrate
8 brands available in the market
At a glance
Irinotecan Hydrochloride Trihydrate is used for the treatment of colon and rectal cancer, as first-line therapy in combination with 5-fluorouracil and leucovorin, or as second-line therapy after failure of fluorouracil-based therapy.
Description
Irinotecan is a derivative of Camptothecin that interacts specifically with the enzyme topoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strand breaks. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks, disrupting DNA replication and causing cell death.
Indications
- Metastatic colorectal cancer (first-line with 5-fluorouracil and leucovorin)
- Metastatic colorectal cancer after failure of fluorouracil-based therapy
Therapeutic class
Cytotoxic Chemotherapy
Pharmacological class
Topoisomerase I Inhibitor
Pharmacology
Irinotecan is a derivative of Camptothecin. Camptothecins interact specifically with the enzyme topoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strand breaks. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks, disrupting DNA replication and causing cell death.
Mechanism of action
Binds to topoisomerase I-DNA complex to prevent religation of single-strand breaks, disrupting DNA replication and causing cancer cell death.
Dosage
Adult Dose (IV Infusion):
- Combination Therapy (Weekly): 125 mg/m2 (90 min infusion) on days 1, 8, 15, 22; then 2 weeks off
- Combination Therapy (Every 3 Weeks): 350 mg/m2 (30-90 min infusion) every 3 weeks
- Combination Therapy (6-week cycle, infusional 5-FU/LV): 180 mg/m2 on days 1, 15, 29
- Combination Therapy (6-week cycle, bolus 5-FU/LV): 125 mg/m2 on days 1, 8, 15, 22
Child Dose: Not recommended
Administration
Administered under physician supervision as IV infusion (30-90 minutes); do not self administer; antiemetic premedication required; atropine treatment should be considered for cholinergic symptoms.
Missed dose
If you miss a dose, please consult your doctor.
Side effects
Common Side Effects (>30%):
- Nausea, vomiting
- Abdominal pain
- Diarrhea (early and late)
- Constipation
- Anorexia
- Mucositis
- Neutropenia, leukopenia
- Anemia, thrombocytopenia
- Asthenia, pain, fever, infection
- Alopecia
Serious: Grade 3-4 late diarrhea (23-31%), neutropenic fever (3%), sepsis
Precautions & warnings
Precautions:
- Irinotecan may decrease alertness, affect vision or make you feel sleepy and dizzy; do not drive if symptoms occur
- Early diarrhea (during or shortly after infusion): transient; prevent/treat with atropine
- Late diarrhea (>24 hours): can be life-threatening; may lead to dehydration, electrolyte imbalance, or sepsis
- Myelosuppression: deaths due to sepsis following severe neutropenia reported
- Patients homozygous for UGT1A1*28 allele are at increased risk for neutropenia
Contraindications
Contraindications:
- Known hypersensitivity to irinotecan or its excipients
Drug interactions
Drug Interactions:
- Diuretics increase risk of dehydration secondary to vomiting/diarrhea
- Prophylactic dexamethasone may enhance lymphocytopenia
- Prochlorperazine may increase incidence of akathisia
- St. John's wort, ketoconazole may reduce irinotecan exposure
Food interactions
Food Interactions: It is not known whether it is safe to consume alcohol with Irinotecan; consult your doctor.
Use in pregnancy
Use in Pregnancy: Category D; can cause fetal harm; unsafe during pregnancy; may be used in life-threatening situations if benefits outweigh risks.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Unsafe during breastfeeding; data suggests drug may cause toxicity to baby; radiolabeled irinotecan appeared in rat milk within 5 minutes.
Pediatric use
Effectiveness in pediatric patients has not been established; not recommended.
Geriatric use
Patients >65 years should be closely monitored (greater risk of early and late diarrhea); starting dose for patients 70 years and older for once-every-3-week schedule: 300 mg/m2.
Renal / hepatic impairment
Renal Impairment: Influence of renal impairment has not been evaluated; caution required; not recommended for patients on dialysis.
Hepatic Impairment: Clearance is diminished in hepatic impairment while exposure to SN-38 is increased; caution required.
Overdose effects
Overdose: Overdose effects mainly myelosuppression and severe diarrhea; provide symptomatic supportive treatment; no specific antidote.
Storage conditions
Store at controlled room temperature 15° to 30°C; protect from light; keep vial in carton until time of use.
Chemical structure
Irinotecan Hydrochloride Trihydrate