Early and late forms of diarrhea can occur. Early diarrhea may be accompanied by cholinergic symptoms which may be prevented or ameliorated by atropine. Late diarrhea can be life-threatening and should be treated promptly with loperamide. Monitor patients with diarrhea and give fluid and electrolytes as needed. Institute antibiotic therapy if patients develop ileus, fever, or severe neutropenia. Interrupt irinotecan and reduce subsequent doses if severe diarrhea occurs.
Severe myelosuppression may occur.
Note: A reduction in the starting dose by at least one dose level should be considered for prior pelvic/abdominal radiotherapy, performance status of ≥2, or known homozygosity for UGT1A1*28 allele. Consider prophylaxis with oral third generation cephalosporins (McGregor 2012; McNall-Knapp 2010), and/or atropine IV or SubQ for treatment in patients with cholinergic symptoms (eg, increased salivation, diaphoresis, abdominal cramping) or diarrhea. Details concerning dosage in combination regimens should also be consulted. Irinotecan (conventional) and irinotecan (liposomal) are NOT interchangeable. Dosing differs between formulations; verify intended product and dose prior to preparation and administration.
Neuroblastoma, refractory or palliative: Limited data available: Children ≥2 years and Adolescents: IV: 50 mg/m2 over 1 hour once daily on days 1 to 5 (5 doses), in combination with temozolomide; repeat cycle every 21 days (Kushner 2005)
Solid tumor or CNS tumor; refractory or relapsed (low-dose, protracted schedule): Limited data available: Children ≥2 years and Adolescents: IV: 15 mg/m2 over 1 hour once daily on days 1 to 5 (5 doses) and days 8 to 12 (5 doses) of a 28-day treatment cycle; in the trial, a maximum dose of 30 mg/dose was reported; may repeat cycle if tolerated in combination with temozolomide and vincristine (McNall-Knapp 2010)
Solid tumor or CNS tumor; refractory or relapsed: Limited data available: Children and Adolescents:
Daily regimen:
IV: Children ≥2 years and Adolescents: 50 mg/m2 over 1 hour once daily on days 1 to 5 (5 doses) as a single agent; repeat cycle every 21 days (Kushner 2005); some protocols include combination with temozolomide (Morganstern 2013)
Oral: Children and Adolescents: 90 mg/m2 once daily on days 1 to 5 (5 doses) repeat every 3 weeks; in combination with vincristine and temozolomide (Wagner 2010a)
Weekly regimen (Bomgaars 2006):
Heavily pretreated patients (eg, ≥2 prior chemotherapy regimens): IV: 125 mg/m2/dose once weekly for 4 weeks over 90 minutes, repeat cycle every 6 weeks
Less-heavily pretreated patients (≤2 prior chemotherapy regimens): IV: 160 mg/m2/dose once weekly for 4 weeks over 90 minutes, repeat cycle every 6 weeks
Rhabdomyosarcoma, refractory or metastatic: Limited data available: Children and Adolescents: IV: 50 mg/m2 once daily for 5 days (maximum dose: 100 mg/dose) on protocol specific weeks (Mascarenhas 2010; Weigel 2016)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients; specific recommendations for pediatric patients are limited. Refer to specific protocol for management in pediatric patients if available. See tables for adult dosage recommendations.
It is recommended that new courses begin only after the granulocyte count recovers to ≥1,500/mm3, the platelet counts recover to ≥100,000/mm3, and treatment-related diarrhea has fully resolved. Depending on the patient's ability to tolerate therapy, adult doses should be adjusted in increments of 25 to 50 mg/m2. Treatment should be delayed 1 to 2 weeks to allow for recovery from treatment-related toxicities. If the patient has not recovered after a 2-week delay, consider discontinuing irinotecan. See tables for adult dosage recommendations.
Toxicity NCI GradeB (Value) |
During a Cycle of Therapy |
At Start of Subsequent Cycles of Therapy (After Adequate Recovery), Compared to Starting Dose in Previous CycleA | |
---|---|---|---|
Weekly |
Weekly |
Once Every 3 Weeks | |
AAll dose modifications should be based on the worst preceding toxicity. | |||
BNational Cancer Institute Common Toxicity Criteria (version 1.0). | |||
CExcludes alopecia, anorexia, asthenia. | |||
No toxicity |
Maintain dose level |
↑ 25 mg/m2 up to a maximum dose of 150 mg/m2 |
Maintain dose level |
Neutropenia | |||
1 (1,500 to 1,999/mm3) |
Maintain dose level |
Maintain dose level |
Maintain dose level |
2 (1,000 to 1,499/mm3) |
↓ 25 mg/m2 |
Maintain dose level |
Maintain dose level |
3 (500 to 999/mm3) |
Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/m2 |
↓ 25 mg/m2 |
↓ 50 mg/m2 |
4 (<500/mm3) |
Omit dose until resolved to ≤ grade 2, then ↓ 50 mg/m2 |
↓ 50 mg/m2 |
↓ 50 mg/m2 |
Neutropenic Fever (grade 4 neutropenia and ≥ grade 2 fever) |
Omit dose until resolved, then ↓ 50 mg/m2 |
↓ 50 mg/m2 |
↓ 50 mg/m2 |
Other Hematologic Toxicities |
Dose modifications for leukopenia, thrombocytopenia, and anemia during a course of therapy and at the start of subsequent courses of therapy are also based on NCI toxicity criteria and are the same as recommended for neutropenia above. | ||
Diarrhea | |||
1 (2-3 stools/day >pretreatment) |
Maintain dose level |
Maintain dose level |
Maintain dose level |
2 (4-6 stools/day >pretreatment) |
↓ 25 mg/m2 |
Maintain dose level |
Maintain dose level |
3 (7-9 stools/day > pretreatment) |
Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/m2 |
↓ 25 mg/m2 |
↓ 50 mg/m2 |
4 (≥10 stools/day > pretreatment) |
Omit dose until resolved to ≤ grade 2, then ↓ 50 mg/m2 |
↓ 50 mg/m2 |
↓ 50 mg/m2 |
Other Nonhematologic ToxicitiesC | |||
Grade 1 |
Maintain dose level |
Maintain dose level |
Maintain dose level |
Grade 2 |
↓ 25 mg/m2 |
↓ 25 mg/m2 |
↓ 50 mg/m2 |
Grade 3 |
Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/m2 |
↓ 25 mg/m2 |
↓ 50 mg/m2 |
Grade 4 |
Omit dose until resolved to ≤ grade 2, then ↓ 50 mg/m2 |
↓ 50 mg/m2 |
↓ 50 mg/m2 |
There are no pediatric specific dosage adjustments; refer to individual protocols; use with caution. Dialysis: Based on experience in adult patients, avoiding use or dosing adjustment suggested.
There are no pediatric specific dosage adjustments; refer to individual protocols. Based on experience in adult patients, dosing adjustment suggested.
(For additional information see "Irinotecan (conventional): Drug information")
Note: A reduction in the starting dose by at least one dose level should be considered for prior pelvic/abdominal radiotherapy, performance status of 2, or known homozygosity for UGT1A1*28 allele (subsequent dosing/adjustments should be based on individual tolerance). Irinotecan (conventional) and irinotecan (liposomal) are NOT interchangeable. Dosing differs between formulations; verify intended product and dose prior to preparation and administration.
Premedications: Consider premedication of atropine 0.25 to 1 mg IV or SubQ in patients with cholinergic symptoms (eg, increased salivation, rhinitis, miosis, diaphoresis, abdominal cramping) or early-onset diarrhea. Irinotecan is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
Colorectal cancer, metastatic (single-agent therapy): IV:
Weekly regimen: 125 mg/m2 over 90 minutes on days 1, 8, 15, and 22 of a 6-week treatment cycle (may adjust upward to 150 mg/m2 if tolerated).
Adjusted dose level -1: 100 mg/m2
Adjusted dose level -2: 75 mg/m2
Further adjust to 50 mg/m2 (in decrements of 25 to 50 mg/m2) if needed
Once-every-3-week regimen: 350 mg/m2 over 90 minutes, once every 3 weeks
Adjusted dose level -1: 300 mg/m2
Adjusted dose level -2: 250 mg/m2
Further adjust to 200 mg/m2 (in decrements of 25 to 50 mg/m2) if needed
Colorectal cancer, metastatic (in combination with fluorouracil and leucovorin): IV: Six-week (42-day) cycle:
Regimen 1: 125 mg/m2 over 90 minutes on days 1, 8, 15, and 22; to be given in combination with bolus leucovorin and fluorouracil (leucovorin administered immediately following irinotecan; fluorouracil immediately following leucovorin).
Adjusted dose level -1: 100 mg/m2
Adjusted dose level -2: 75 mg/m2
Further adjust if needed in decrements of ~20%
Regimen 2: 180 mg/m2 over 90 minutes on days 1, 15, and 29; to be given in combination with infusional leucovorin and bolus/infusion fluorouracil (leucovorin administered immediately following irinotecan; fluorouracil immediately following leucovorin).
Adjusted dose level -1: 150 mg/m2
Adjusted dose level -2: 120 mg/m2
Further adjust if needed in decrements of ~20%
Colorectal cancer, metastatic (off-label dosing): IV: FOLFOXIRI regimen: 165 mg/m2 over 1 hour once every 2 weeks (in combination with oxaliplatin, leucovorin, and fluorouracil) (Falcone 2007).
Cervical cancer, recurrent or metastatic (off-label use): IV: 125 mg/m2 over 90 minutes once weekly for 4 consecutive weeks followed by a 2-week rest during each 6-week treatment cycle (Verschraegen 1997).
CNS tumor, recurrent glioblastoma (off-label use): IV: 125 mg/m2 over 90 minutes once every 2 weeks (in combination with bevacizumab). NOTE: In patients taking concurrent antiseizure enzyme-inducing medications irinotecan dose was increased to 340 mg/m2 (Friedman 2009; Vredenburgh 2007).
Esophageal cancer, metastatic or locally advanced (off-label use): IV: 65 mg/m2 over 90 minutes days 1, 8, 15, and 22 of a 6-week treatment cycle (in combination with cisplatin) (Ajani 2002; Ilson 1999) or 180 mg/m2 over 90 minutes every 2 weeks (in combination with leucovorin and fluorouracil) (Guimbaud 2014) or 250 mg/m2 every 3 weeks (in combination with capecitabine) (Leary 2009; Moehler 2010).
Ewing sarcoma, recurrent or progressive (off-label use): IV: 20 mg/m2 days 1 to 5 and days 8 to 12 every 3 weeks (in combination with temozolomide) (Casey 2009).
Gastric cancer, metastatic or locally advanced (off-label use): IV: 150 mg/m2 (as a single agent) on days 1 and 15 of a 4-week treatment cycle (Hironaka 2013) or 65 mg/m2 over 90 minutes days 1, 8, 15, and 22 of a 6-week treatment cycle (in combination with cisplatin) (Ajani 2002) or 70 mg/m2 over 90 minutes on days 1 and 15 of a 4-week treatment cycle (in combination with cisplatin) for up to 6 cycles (Park 2005) or 180 mg/m2 over 90 minutes every 2 weeks (in combination with leucovorin and fluorouracil) (Bouche 2004; Guimbaud 2014) or 250 mg/m2 every 3 weeks (in combination with capecitabine) (Moehler 2010).
Non-small cell lung cancer, advanced (off-label use): IV: 60 mg/m2 days 1, 8, and 15 every 4 weeks (in combination with cisplatin) (Ohe 2007).
Ovarian cancer, recurrent, platinum- and taxane-resistant (off-label use): IV: 100 mg/m2 days 1, 8, and 15 every 4 weeks (as a single-agent) for up to 6 cycles (Matsumoto 2006).
Pancreatic cancer, advanced or metastatic (off-label use): IV: FOLFIRINOX regimen: 180 mg/m2 over 90 minutes every 2 weeks (in combination with oxaliplatin, leucovorin, and fluorouracil) (Conroy 2005; Conroy 2011).
Pancreatic cancer, potentially curable, adjuvant therapy (off-label use): Note: American Society of Clinical Oncology (ASCO) guidelines recommend 6 months of adjuvant therapy if recovery is complete; if preoperative chemotherapy therapy was received, a total of 6 months of adjuvant therapy (including the preoperative regimen) is recommended (ASCO [Khorana 2019]).
mFOLFIRINOX regimen: IV: 150 mg/m2 every 2 weeks (in combination with fluorouracil, leucovorin, and oxaliplatin; modified FOLFIRINOX regimen) for 24 weeks (Conroy 2018). According to ASCO guidelines, mFOLFIRINOX is the preferred first-line adjuvant regimen for potentially curable disease (ASCO [Khorana 2019]).
Small cell lung cancer, extensive stage (off-label use): IV: 60 mg/m2 days 1, 8, and 15 every 4 weeks (in combination with cisplatin) (Noda 2002) or 65 mg/m2 days 1 and 8 every 3 weeks (in combination with cisplatin) (Hanna 2006) or 175 mg/m2 day 1 every 3 weeks (in combination with carboplatin) (Hermes 2008) or 50 mg/m2 days 1, 8 and 15 every 4 weeks (in combination with carboplatin) (Schmittel 2006). According to ASCO guidelines, platinum-based therapy (cisplatin or carboplatin) in combination with either etoposide or irinotecan for 4 to 6 cycles is recommended over other regimens for extensive stage disease (Rudin 2015).
Small cell lung cancer, limited stage (off-label use): IV: Consolidation therapy (administer after induction cisplatin, etoposide, and radiation therapy): 60 mg/m2 days 1, 8, and 15 every 3 to 4 weeks (in combination with cisplatin) for 3 cycles (Kubota 2014). Additional studies are necessary to further define the role of irinotecan in the treatment of limited stage disease.
Unknown primary adenocarcinoma (off-label use): IV: 100 mg/m2 days 1 and 8 every 3 weeks (in combination with gemcitabine) for 4 to 6 cycles (Hainsworth 2010).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Renal impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.
Dialysis: Use in patients with dialysis is not recommended by the manufacturer; however, literature suggests reducing weekly dose from 125 mg/m2 to 50 mg/m2 and administer after hemodialysis or on nondialysis days (Janus 2010).
Manufacturer's labeling:
Liver metastases with normal hepatic function: No dosage adjustment necessary.
Bilirubin >ULN to ≤2 mg/dL: Consider reducing initial dose by one dose level
Bilirubin >2 mg/dL: Use is not recommended
Alternate recommendations: The following adjustments have also been recommended:
Bilirubin 1.5 to 3 mg/dL: Administer 75% of dose (Floyd 2006)
Bilirubin 1.51 to 3 times ULN: Reduce dose from 350 mg/m2 every 3 weeks to 200 mg/m2 every 3 weeks (Raymond 2002)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as hydrochloride:
Generic: 40 mg/2 mL (2 mL); 100 mg/5 mL (5 mL); 300 mg/15 mL (15 mL)
Solution, Intravenous, as hydrochloride [preservative free]:
Camptosar: 40 mg/2 mL (2 mL); 100 mg/5 mL (5 mL); 300 mg/15 mL (15 mL)
Generic: 40 mg/2 mL (2 mL); 100 mg/5 mL (5 mL); 300 mg/15 mL (15 mL); 500 mg/25 mL (25 mL)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Camptosar: 20 mg/mL (2 mL, 5 mL, 15 mL)
Generic: 20 mg/mL (2 mL, 5 mL, 15 mL, 25 mL)
Irinotecan is associated with a moderate emetic potential (Basch 2011; Dupuis 2011; Roila 2010).
Parenteral: IV infusion: Infuse usually over 90 minutes; some pediatric protocols infuse the dose over 1 hour (Kushner 2005; McNall-Knapp 2010); consult specific protocol. Higher incidence of cholinergic symptoms (increased salivation, rhinitis, miosis, diaphoresis, abdominal cramping) have been reported with more rapid infusion rates; consider prophylaxis with oral cephalosporin antibiotics or rescue atropine for acute-onset diarrhea.
IV: Administer by IV infusion, usually over 90 minutes.
Premedications: Irinotecan is associated with a moderate emetic potential (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]); premedication with dexamethasone and a 5-HT3 blocker is recommended 30 minutes prior to administration; prochlorperazine may be considered for subsequent use (if needed). Consider atropine 0.25 to 1 mg IV or SubQ as premedication for or treatment of cholinergic symptoms (eg, increased salivation, rhinitis, miosis, diaphoresis, abdominal cramping) or early onset diarrhea.
Diarrhea management: The recommended regimen to manage late diarrhea is loperamide 4 mg orally at onset of late diarrhea, followed by 2 mg every 2 hours (or 4 mg every 4 hours at night) until 12 hours have passed without a bowel movement. If diarrhea recurs, then repeat administration. Loperamide should not be used for more than 48 consecutive hours.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Store intact vials at 15°C to 30°C (59°F to 86°F). Protect from light; retain vials in original carton until use. Solutions diluted in NS may precipitate if refrigerated. Solutions diluted in D5W are stable for 24 hours at room temperature or 48 hours under refrigeration at 2°C to 8°C (36°F to 46°F), although the manufacturer recommends use within 24 hours if refrigerated, or within 4 to 12 hours (manufacturer dependent; refer to specific prescribing information) at room temperature (including infusion time) only if prepared under strict aseptic conditions (eg, laminar flow hood). Do not freeze.
Extemporaneously prepared oral solutions (pediatric): Undiluted commercially available injectable solution prepared in oral syringes is stable for 21 days under refrigeration (Wagner 2010).
Treatment of metastatic carcinoma of the colon or rectum (FDA approved in adults); has also been used in the treatment of refractory solid tumor, neuroblastoma, or CNS tumor and refractory or metastatic rhabdomyosarcoma
Conventional formulation (Camptosar) may be confused with the liposomal formulation (Onivyde)
Irinotecan (conventional) may be confused with irinotecan (liposomal), topotecan
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Irinotecan (conventional) and irinotecan (liposomal) are NOT interchangeable. Dosing differs between formulations; verify intended product and dose prior to preparation and administration.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency of adverse reactions reported for single-agent use of irinotecan only. In limited pediatric experience, dehydration (often associated with severe hypokalemia and hyponatremia) was among the most significant grade 3/4 adverse events, with a frequency up to 29%. In addition, grade 3/4 infection was reported in 24%.
>10%:
Cardiovascular: Vasodilation (9% to 11%)
Central nervous system: Cholinergic syndrome (47%; includes diaphoresis, flushing, increased peristalsis, lacrimation, miosis, rhinitis, sialorrhea), pain (23% to 24%), dizziness (15% to 21%), insomnia (19%), headache (17%), chills (14%)
Dermatologic: Alopecia (46% to 72%), diaphoresis (16%), skin rash (13% to 14%)
Endocrine & metabolic: Weight loss (30%), dehydration (15%)
Gastrointestinal: Diarrhea (late: 83% to 88%, grades 3/4: 14% to 31%; early: 43% to 51%, grades 3/4: 7% to 22%), nausea (70% to 86%), abdominal pain (57% to 68%), vomiting (62% to 67%), abdominal cramps (57%), anorexia (44% to 55%), constipation (30% to 32%), mucositis (30%), flatulence (12%), stomatitis (12%)
Hematologic & oncologic: Anemia (60% to 97%; grades 3/4: 5% to 7%), leukopenia (63% to 96%, grades 3/4: 14% to 28%), thrombocytopenia (96%, grades 3/4: 1% to 4%), neutropenia (30% to 96%; grades 3/4: 14% to 31%)
Hepatic: Increased serum bilirubin (84%), increased serum alkaline phosphatase (13%)
Infection: Infection (14%)
Neuromuscular & skeletal: Weakness (69% to 76%), back pain (14%)
Respiratory: Dyspnea (22%), cough (17% to 20%), rhinitis (16%)
Miscellaneous: Fever (44% to 45%)
1% to 10%:
Cardiovascular: Edema (10%), hypotension (6%), thromboembolism (5%)
Central nervous system: Drowsiness (9%), confusion (3%)
Gastrointestinal: Abdominal distention (10%), dyspepsia (10%)
Hematologic & oncologic: Febrile neutropenia (grades 3/4: 2% to 6%), hemorrhage (grades 3/4: 1% to 5%), neutropenic infection (grades 3/4: 1% to 2%)
Hepatic: Increased serum AST (10%), ascites (grades 3/4: ≤9%), jaundice (grades 3/4: ≤9%)
Respiratory: Pneumonia (4%)
<1%, postmarketing, and/or case reports: Acute renal failure, anaphylactoid reaction, anaphylaxis, angina pectoris, arterial thrombosis, bradycardia, cardiac arrhythmia, cerebral infarction, cerebrovascular accident, circulatory shock, colitis, deep vein thrombophlebitis, dysarthria, embolism, gastrointestinal hemorrhage, gastrointestinal obstruction, hepatomegaly, hiccups, hyperglycemia, hypersensitivity reaction, hyponatremia, immune thrombocytopenia, increased amylase, increased serum ALT, increased serum lipase, interstitial pulmonary disease, intestinal obstruction, intestinal perforation, ischemic colitis, ischemic heart disease, lymphocytopenia, megacolon, muscle cramps, myocardial infarction, pancreatitis, paresthesia, peripheral vascular disease, pulmonary embolism; pulmonary toxicity (includes dyspnea, fever, reticulonodular infiltrates on chest x-ray), renal insufficiency, syncope, thrombophlebitis, thrombosis, typhlitis (including neutropenic typhlitis), ulcer, ulcerative colitis, vertigo
Known hypersensitivity to irinotecan or any component of the formulation
Canadian labeling: Additional contraindications (not in the US labeling): Coadministration with azole antifungals (ketoconazole, fluconazole, itraconazole); patients with hereditary fructose intolerance
Concerns related to adverse effects:
• Bone marrow suppression: [US Boxed Warning]: May cause severe myelosuppression. Deaths due to sepsis following severe neutropenia have been reported. Complications due to neutropenia should be promptly managed with antibiotics. Therapy should be temporarily withheld if neutropenic fever occurs or if the absolute neutrophil count is <1,000/mm3; reduce the dose upon recovery to an absolute neutrophil count ≥1,000/mm3. Patients who have previously received pelvic/abdominal radiation therapy have an increased risk of severe bone marrow suppression; the incidence of grade 3 or 4 neutropenia was higher in patients receiving weekly irinotecan who have previously received pelvic/abdominal radiation therapy. Concurrent radiation therapy is not recommended with irinotecan (based on limited data).
• Diarrhea: [US Boxed Warning]: Severe diarrhea may be dose-limiting and potentially fatal; early-onset and late-onset diarrhea may occur. Early diarrhea occurs during or within 24 hours of receiving irinotecan and is characterized by cholinergic symptoms; may be prevented or treated with atropine. Late diarrhea may be life-threatening and should be promptly treated with loperamide. Antibiotics may be necessary if patient develops ileus, fever, or severe neutropenia. Interrupt treatment and reduce subsequent doses for severe diarrhea. Early diarrhea is generally transient and rarely severe; cholinergic symptoms may include increased salivation, rhinitis, miosis, diaphoresis, flushing, abdominal cramping, and lacrimation; bradycardia may also occur. Cholinergic symptoms may occur more frequently with higher irinotecan doses. Late diarrhea occurs more than 24 hours after treatment, which may lead to dehydration, electrolyte imbalance, or sepsis. Late diarrhea may be complicated by colitis, ulceration, bleeding, ileus, obstruction, or infection; cases of megacolon and intestinal perforation have been reported. The median time to onset for late diarrhea is 5 days with every 3 week irinotecan dosing and 11 days with weekly dosing. Advise patients to have loperamide readily available for the treatment of late diarrhea. Patients with diarrhea should be carefully monitored and treated promptly; may require fluid and electrolyte therapy. Bowel function should be returned to baseline for at least 24 hours prior to resumption of weekly irinotecan dosing. Avoid diuretics and laxatives in patients experiencing diarrhea.
• Extravasation: Irinotecan is an irritant. Avoid extravasation; if extravasation occurs, the manufacturer recommends flushing the external site with sterile water and applying ice.
• Gastrointestinal toxicity: Irinotecan is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (POGO [Dupuis 2011]; ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
• Hepatitis B virus screening: The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
• Hypersensitivity: Severe hypersensitivity reactions (including anaphylaxis) have occurred. Monitor closely; discontinue therapy if hypersensitivity occurs.
• Pulmonary toxicity: Fatal cases of interstitial pulmonary disease (IPD)-like events have been reported with single-agent and combination therapy. Risk factors for pulmonary toxicity include preexisting lung disease, use of pulmonary toxic medications, radiation therapy, and colony-stimulating factors. Patients with risk factors should be monitored for respiratory symptoms before and during irinotecan treatment. Promptly evaluate progressive changes in baseline pulmonary symptoms or any new-onset pulmonary symptoms (eg, dyspnea, cough, fever). Discontinue all chemotherapy if IPD is diagnosed.
• Renal toxicity: Renal impairment and acute renal failure have been reported, possibly due to dehydration secondary to diarrhea. Use with caution in patients with renal impairment; not recommended in patients on dialysis.
• Thromboembolism: Thromboembolic events have been reported.
Disease-related concerns:
• Bowel obstruction: Patients with bowel obstruction should not be treated with irinotecan until resolution of obstruction.
• Hepatic impairment: Use with caution in patients with hepatic impairment; exposure to the active metabolite (SN-38) is increased; toxicities may be increased. Patients with even modest elevations in total serum bilirubin levels (1 to 2 mg/dL) have a significantly greater likelihood of experiencing first-course grade 3 or 4 neutropenia than those with bilirubin levels that were <1 mg/dL. Patients with abnormal glucuronidation of bilirubin, such as those with Gilbert syndrome, may also be at greater risk of myelosuppression when receiving therapy with irinotecan. Use caution when treating patients with known hepatic dysfunction or hyperbilirubinemia; dosage adjustments should be considered.
Concurrent drug therapy issues:
• Drug-drug interactions: CYP3A4 enzyme inducers may decrease exposure to irinotecan and SN-38 (active metabolite); enzyme inhibitors may increase exposure. For use in patients with CNS tumors (off-label use), selection of antiseizure medications that are not enzyme inducers is preferred.
Special populations:
• Elderly: Patients >65 years of age are at greater risk for early and late diarrhea. A dose reduction is recommended for patients ≥70 years of age receiving the every-3-week regimen.
• Patients homozygous/heterozygous for the UGT1A1*28 allele: Patients homozygous for the UGT1A1*28 allele are at increased risk of neutropenia; consider reducing the initial dose by at least one dose level for both single-agent and combination regimens. Heterozygous carriers of the UGT1A1*28 allele may also be at increased neutropenic risk; however, most patients have tolerated normal starting doses. A test is available for clinical determination of UGT phenotype, although a dose reduction is already recommended in patients who have experienced toxicity.
• Pelvic/abdominal radiation recipients: Use with caution in patients who have previously received pelvic/abdominal radiation; may increase risk of severe myelosuppression.
• Performance status: Higher rates of hospitalization, neutropenic fever, thromboembolism, first-cycle discontinuation, and early mortality were observed in patients with a performance status of 2 than in patients with a performance status of 0 or 1.
Dosage form specific issues:
• Conventional vs liposomal formulation dosing: Irinotecan (conventional) and irinotecan (liposomal) are NOT interchangeable. Dosing differs between formulations; verify intended product and dose prior to preparation and administration.
• Sorbitol: Product contains sorbitol; do not use in patients with hereditary fructose intolerance.
Other warnings/precautions:
• Appropriate use: Except as part of a clinical trial, use in combination with the fluorouracil and leucovorin administered for 4 or 5 consecutive days every 4 weeks (“Mayo Clinic” regimen) is not recommended due to increased toxicity.
In pediatric patients, provide antibiotic support if patient develops persistent diarrhea (grade 3 or 4), ileus, fever, sepsis, or severe neutropenia; cefixime (8 mg/kg/day, maximum dose: 400 mg) has been used in children as prophylaxis for diarrhea beginning 5 days prior to irinotecan therapy and continued throughout course (Wagner 2008); cefpodoxime (10 mg/kg/day divided twice daily, maximum dose: 200 mg) has also been used (McNall-Knapp 2010; Wagner 2010).
Substrate of BCRP/ABCG2, CYP3A4 (major), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (minor), UGT1A1; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Atazanavir: May increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Risk X: Avoid combination
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: In the US, after receipt of the single dose COVID-19 adenovirus vector vaccine (Janssen), administer an additional 2nd dose using an mRNA COVID-19 vaccine, at least 28 days after the primary vaccine dose, in patients taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan Products. Management: Avoid administration of strong CYP3A4 inducers during irinotecan treatment, and substitute non-CYP3A4 inducing agents at least 2 weeks prior to irinotecan initiation, whenever possible. If combined, monitor for reduced irinotecan efficacy. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, the serum concentration of SN-38 may be increased. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Irinotecan Products. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Management: Avoid administration of strong CYP3A4 inhibitors during and within 1 week prior to irinotecan administration, unless no therapeutic alternatives to these agents exist. If combined, monitor closely for increased irinotecan toxicities. Risk D: Consider therapy modification
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Itraconazole: May increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Risk X: Avoid combination
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Ketoconazole (Systemic): May increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. Risk X: Avoid combination
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Mitapivat: May decrease the serum concentration of UGT1A1 Substrates. Risk C: Monitor therapy
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sacituzumab Govitecan: Irinotecan Products may enhance the adverse/toxic effect of Sacituzumab Govitecan. Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
St John's Wort: May decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. St John's Wort may decrease the serum concentration of Irinotecan Products. Management: Avoid administration of St John's wort during irinotecan treatment, and consider substituting non-CYP3A4 inducing agents at least 2 weeks prior to irinotecan initiation, whenever possible. If combined, monitor for reduced irinotecan efficacy. Risk D: Consider therapy modification
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Telotristat Ethyl: May decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Risk C: Monitor therapy
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tobacco (Smoked): May decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Risk C: Monitor therapy
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
UGT1A1 Inhibitors: May increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be increased. UGT1A1 Inhibitors may increase the serum concentration of Irinotecan Products. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Contains sorbitol; do not use in patients with hereditary fructose intolerance.
Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use highly effective contraception during therapy and for 6 months after the last irinotecan dose. Males with female partners of reproductive potential should use condoms during therapy and for 3 months after the last dose of irinotecan.
Menstrual cycle changes and impairment of female fertility may occur with irinotecan therapy.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to irinotecan may cause fetal harm.
Information related to the use of irinotecan (conventional) during pregnancy is limited (Cirillo 2012; Taylor 2009).
Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential should use highly effective contraception during therapy and for 6 months after the last irinotecan dose. Males with female partners of reproductive potential should use condoms during therapy and for 3 months after the last dose of irinotecan.
Menstrual cycle changes and impairment of female fertility may occur with irinotecan therapy.
Signs of diarrhea and dehydration, serum electrolytes, serum BUN and creatinine; infusion site for signs of inflammation; CBC with differential and platelet count, hemoglobin, liver function tests, and serum bilirubin
A test is available for genotyping of UGT1A1; however, guidelines for use are not established and not recommended; in patients who have experienced toxicity, a dose reduction is recommended
Irinotecan and its active metabolite (SN-38) bind reversibly to topoisomerase I-DNA complex preventing religation of the cleaved DNA strand. This results in the accumulation of cleavable complexes and double-strand DNA breaks. As mammalian cells cannot efficiently repair these breaks, cell death consistent with S-phase cell cycle specificity occurs, leading to termination of cellular replication.
Distribution:
Children and Adolescents: ~37 L/m2 (range: 15.2 to 77 L/m2) (Ma 2000); distributes to pleural fluid, sweat, and saliva
Adults: 33 to 150 L/m2
Protein binding, plasma: Predominantly albumin; Irinotecan: 30% to 68%, SN-38 (active metabolite): ~95%
Metabolism: Primarily hepatic to SN-38 (active metabolite) by carboxylesterase enzymes; may also undergo CYP3A4-mediated metabolism to inactive metabolites (one of which may be hydrolyzed to release SN-38). SN-38 undergoes conjugation by UDP-glucuronosyl transferase 1A1 (UGT1A1) to form a glucuronide metabolite. SN-38 is increased by UGT1A1*28 polymorphism (10% of North Americans are homozygous for UGT1A1*28 allele).
Bioavailability: Median: 9%; increased in presence of gefitinib (median: 42%) (Furman 2009)
Half-life elimination:
Children and Adolescents (Ma 2000): Irinotecan: 2.66 hours (range: 1.82 to 4.47 hours); SN-38 (active metabolite): 1.58 hours (range: 0.29 to 8.28 hours)
Adults: Irinotecan: 6 to 12 hours; SN-38: ~10 to 20 hours
Time to peak:
Irinotecan: Oral: Children and Adolescents: 3 hours (Wagner 2010a)
SN-38: Following 90-minute infusion: ~1 hour
Excretion: Urine: Irinotecan (11% to 20%), metabolites (SN-38 <1%, SN-38 glucuronide, 3%)
Hepatic function impairment: Cl of irinotecan is decreased and exposure to the active metabolite (SN-38) is increased proportional to the degree of hepatic impairment.
Solution (Camptosar Intravenous)
40 mg/2 mL (per mL): $16.59
100 mg/5 mL (per mL): $9.90
300 mg/15 mL (per mL): $9.10
Solution (Irinotecan HCl Intravenous)
40 mg/2 mL (per mL): $5.40 - $138.08
100 mg/5 mL (per mL): $4.32 - $138.07
300 mg/15 mL (per mL): $8.00 - $8.96
500 mg/25 mL (per mL): $7.07
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