[.
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Action/Kinetics:
The cytotoxic effect is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either irinotecan or SN-38 (its active metabolite). Conversion of irinotecan to SN-38 occurs in the liver.
t
1/2, terminal, irinotecan: About 6 hr;
t
1/2, terminal, SN-38: About 10 hr. SN-38 is 95% bound to plasma proteins.
Uses:
Metastatic carcinoma of the colon or rectum in those whose disease has recurred or progressed following 5-fluorouracil therapy.
Contraindications:
Lactation.
Special Concerns:
Clients who have previously received pelvic or abdominal irradiation are at an increased risk for severe myelosuppression when treated with irinotecan. Safety and efficacy have not been determined in children.
Side Effects:
GI: Diarrhea, N&V;, anorexia, abdominal cramping or pain, constipation, flatulence, stomatitis, dyspepsia.
Hematologic: Leukopenia, anemia, neutropenia, serious thrombocytopenia (rare).
CNS: Insomnia, dizziness.
Re
spiratory: Dyspnea, increased coughing, rhinitis, severe pulmonary events (rare).
CV: Vasodilation, flushing.
Body as a whole: Asthenia, fever, pain, headache, back pain, chills, minor infections (usually UTI), edema, abdominal enlargement.
Dermatologic: Alopecia, sweating, rashes.
Metabolic/nutritional: Decreased body weight, dehydration.
Laboratory Test Alterations:
AST, alkaline phosphatase.
Overdose Management:
Symptoms: Extension of side effects.
Treatment: Maximum supportive care to prevent dehydration due to diarrhea. Treat any infections.
Drug Interactions:
-
Antineoplastic agents /
Risk of myelosuppression and diarrhea
-
Dexamethasone /
Risk of lymphocytopenia and hyperglycemia
-
Prochlorperazine /
Risk of akathisia
How Supplied:
Injection: 20 mg/mL
Dosage
?IV Infusion
Metastatic carcinoma of the colon or rectum.
Initial: 125 mg/m
2 given as an IV infusion over 90 min once weekly for 4 weeks. This is followed by a 2-week rest period.
Subsequent dosing: Additional courses of treatment may be repeated q 6 weeks (4 weeks on therapy, 2 weeks off therapy). Doses can be adjusted to as high as 150 mg/m
2 or as low as 50 mg/m
2 in 25- to 50-mg/m
2 increments, depending on the client's tolerance. If intolerable toxicity does not occur, courses of treatment may be continued indefinitely.
NOTE: Modifications of the dosage are based on the degree of neutropenia, neutropenic fever, diarrhea, and other toxicities. Consult the package insert for specific dosage modifications.
