Generic Name

Irinotecan Hydrochloride Trihydrate

Precaution

Early diarrhea is usually transient and infrequently severe. It may be accompanied by cholinergic symptoms of rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, and intestinal hyperperistalsis that can cause abdominal cramping. Bradycardia may also occur. Late diarrhea can be life threatening since it may be prolonged and may lead to dehydration, electrolyte imbalance, or sepsis.Late diarrhea can be complicated by colitis, ulceration, bleeding, ileus, obstruction, and infection. Cases of megacolon and intestinal perforation have been reported. Lactation: not known if excreted in breast milk, do not nurse

Indication

Carcinoma of the colon or rectum

Contra Indication

Patients with a known hypersensitivity to the drug or its excipients.

Dose

N/A

Side Effect

>10% Anemia (>90%),Leukopenia (>90%),Neutropenia (>90%),Thrombocytopenia (>90%),Elevated bilirubin (88%),Diarrhea (85%),Nausea (79%),Asthenia (70%),Abdominal pain (63%),Vomiting (60%),Alopecia (43%),Fever (42%),Constipation (41%),Anorexia (34%),Mucositis (32%),Pain (31%),Dyspnea (28%),Cough (27%),Dizziness (23%),Infection (22%),Rash (19%) 1-10% Abdominal fullness (10%),AST increased (10%),Dyspepsia (10%),,Edema (10%),Ascites/jaundice (9%),Vasodilation (9%),Thromboembolism (9%),Hypotension (6%),Neutropenic fever (2-6%) Frequency Not Defined Headache,Insomnia,Orthostatic hypotension Potentially Fatal: Fatal sepsis due to myelosuppression; severe, chronic diarrhoea.

Pregnancy Category

Mode of Action

Irinotecan, a derivative of camptothecin, works by inhibiting the enzyme topoisomerase I thereby interfering with the coiling and uncoiling of DNA during replication and causing irreparable damage.

Interaction

Diuretics increase risks of dehydration secondary to vomiting/diarrhoea; prophylactic dexamethasone as an antiemetic may enhance lymphocytopenia; prochlorperazine may increase incidence of akathisia; antineoplastic agents (myelosuppression and diarrhoea). St John's wort, ketoconazole may reduce irinotecan exposure.

Pregnancy Category Note

N/A

Adult Dose

Intravenous Colorectal Cancer Indicated as first-line therapy (with 5-fluorouracil and leucovorin) for metastatic colorectal cancer (CRC); it is also indicated for CRC that has recurred or progressed following intial fluorouracil-based therapy Monotherapy Patients should be premedicated with antiemetic agents Atropine treatment should be considered in patients that experience cholinergic symptoms Regimen 1 (Weekly): 125 mg/m² IV infusion over 90 minutes on days 1, 8, 15, 22, then 2 weeks off, then repeat Regimen 2 (Once Every 3 Weeks): 350 mg/sq.meter IV infusion over 30-90 minutes q3Weeks Adjust dose per protocol Combination therapy Patients should be premedicated with antiemetic agents Atropine treatment should be considered in patients that experience cholinergic symptoms Regimen 1 (6 week cycle with infusional 5-fluorouracil/ leucovorin): 180 mg/m² IV infusion over 30-90 minutes once on days 1, 15, and 29 IV (infuse over 30-90 min), followed by infusion with leucovorin and 5-fluorouracil; next cycle begins on day 43 Regimen 2 (6 week cycle with bolus 5-fluorouracil/ leucovorin): 125 mg/sq.meter on days 1, 8, 15, and 22 (infuse over 90 min), followed by bolus doses of leucovorin and 5-fluorouracil Adjust dose per protocol Hepatic impairment: Dose reduction may be necessary.

Child Dose

Not recommended

Renal Dose

N/A

Administration

Reconstitution: Dilute in 5% dextrose injection (preferred) or 0.9% sodium chloride injection to a final concentration of 0.12-2.8 mg/ml.