Canri (Irinotecan)

Uses

Canri (Irinotecan) Injection is used for a component of first-line therapy in combination with 5-fluorouracil (5-FU) and leucovorin (LV) for patients with metastatic carcinoma of the colon or rectum.

Canri (Irinotecan) is used for patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy.

Canri (Irinotecan) is also used to associated treatment for these conditions: Esophageal Cancers, Ewing's Sarcoma, Glioblastomas, Malignant Neoplasm of Pancreas, Malignant Neoplasm of Stomach, Metastatic Colorectal Carcinoma, Non-Small Cell Lung Carcinoma (NSCLC), Ovarian Cancer, Rhabdomyosarcomas, Small Cell Lung Cancer (SCLC), Recurrent, IV-B Cervical cancer, Recurrent, metastatic Colorectal carcinoma, Refractory, metastatic Pancreatic adenocarcinoma

How Canri (Irinotecan) works

Canri (Irinotecan) inhibits the action of topoisomerase I. Canri (Irinotecan) prevents religation of the DNA strand by binding to topoisomerase I-DNA complex. The formation of this ternary complex interferes with the moving replication fork, which induces replication arrest and lethal double-stranded breaks in DNA. As a result, DNA damage is not efficiently repaired and apoptosis (programmed cell death) occurs.

Dosage

Canri (Irinotecan) dosage

Administer as a 90-minute intravenous infusion followed by LV and 5-FU. A reduction in the starting dose by one dose level may be considered for patients with any of the following conditions: prior pelvic/abdominal radiotherapy, performance status of 2, or increased bilirubin levels.

Refractory colorectal malignancies: 125 mg/m2 once wkly for 4 wk, followed by a 2 wk rest period.

Metastatic colorectal cancer: As 1st line treatment: 125 mg/m2 on days 1,8,15 and 22 of a 6-wk cycle.

Side Effects

Anemia, Leukopenia, Neutropenia,Thrombocytopenia, Elevated bilirubin, Diarrhea, Nausea, Asthenia, Abdominal pain, Vomiting , Alopecia, Fever, Constipation, Anorexia, Mucositis, Pain, Dyspnea, Cough, Dizziness, Infection, Rash, Abdominal fullness, AST increased , Dyspepsia, Edema, Ascites/jaundice, Vasodilation, Thromboembolism, Hypotension, Neutropenic fever, Headache, Insomnia, Orthostatic hypotension

Toxicity

Gastrointestinal complications, such as nausea, vomiting, abdominal cramping, diarrhea, and infection.

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.

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.

Food Interaction

Canri (Irinotecan) Drug Interaction

Moderate: dexamethasone, dexamethasoneMinor: prochlorperazine, prochlorperazineUnknown: lorazepam, lorazepam, bevacizumab, bevacizumab, diphenhydramine, diphenhydramine, hydromorphone, hydromorphone, fentanyl, fentanyl, acetaminophen, acetaminophen, cholecalciferol, cholecalciferol, ondansetron, ondansetron

Canri (Irinotecan) Disease Interaction

Major: myelosuppressionModerate: hepatic dysfunction, renal impairment, interstitial lung disease

Volume of Distribution

The volume of distribution of terminal elimination phase is 110 L/m^2 when a dose of 125 mg/m^2 is given to patients with solid tumours. The volume of distribution of terminal elimination phase is 234 L/m^2 when a dose of 340 mg/m^2 is given to patients with solid tumours.

Elimination Route

The maximum plasma concentration (Cmax) when a dose of 125 mg/m^2 is given to patients with solid tumours is 1660 ng/mL. The AUC (0-24) is 10,200 ng·h/mL. The Cmax when a dose of 340 mg/m^2 is given to patients with solid tumours is 3392 ng/mL. The AUC (0-24) is 20,604 ng·h/mL.

Half Life

The half life of irinotecan is about 6 - 12 hours. The terminal elimination half-life of the active metabolite, SN-38 is 10 - 20 hours.

Clearance

• 13.3 L/h/m^2 [Dose of 125 mg/m^2, patients with solid tumours]
• 13.9 L/h/m^2 [Dose of 340 mg/m^2, patients with solid tumours]

Elimination Route

The cumulative biliary and urinary excretion of irinotecan and its metabolites (SN-38 and SN-38 glucuronide) over a period of 48 hours following administration of irinotecan in two patients ranged from approximately 25% (100 mg/m2) to 50% (300 mg/m2).

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Contraindication

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

Storage Condition

Store at controlled room temperature 15° to 30°C. Protect from light. Keep the vial in the carton until the time of use.

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