Your activity: 26 p.v.
your limit has been reached. plz Donate us to allow your ip full access, Email: sshnevis@outlook.com

Irinotecan (conventional): Drug information

Irinotecan (conventional): Drug information
(For additional information see "Irinotecan (conventional): Patient drug information" and see "Irinotecan (conventional): Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Diarrhea:

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.

Bone marrow suppression:

Severe myelosuppression may occur.

Brand Names: US
  • Camptosar
Brand Names: Canada
  • Camptosar [DSC]
Pharmacologic Category
  • Antineoplastic Agent, Camptothecin;
  • Antineoplastic Agent, Topoisomerase I Inhibitor
Dosing: Adult

Note: A reduction in the starting dose by at least 1 dose level should be considered for prior pelvic/abdominal radiotherapy or performance status of 2 (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.

Reduced UGT1A1 activity:Consider a dose reduction in the starting irinotecan dose by at least 1 dose level for patients known to be homozygous for the UGT1A1*28 or *6 alleles (*28/*28, *6/*6) or compound heterozygous for the UGT1A1*28 and *6 alleles (*6/*28); base subsequent dosing modifications on individual tolerance.

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

Colorectal cancer, metastatic, single-agent therapy:

Weekly regimen: IV: 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: IV: 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, combination therapy

Colorectal cancer, metastatic, combination therapy:

In combination with fluorouracil and leucovorin:

Regimen 1: IV: 125 mg/m2 over 90 minutes on days 1, 8, 15, and 22 of a 6-week cycle; 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: IV: 180 mg/m2 over 90 minutes on days 1, 15, and 29 of a 6-week cycle; 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%.

FOL FOXIRI regimen (off-label dosing): IV: 165 mg/m2 over 1 hour once every 2 weeks (in combination with oxaliplatin, leucovorin, and fluorouracil) (Falcone 2007).

Cervical cancer, recurrent or metastatic

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

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

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

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

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

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

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

Pancreatic cancer, advanced or metastatic (off-label use): FOLFIRINOX regimen: IV: 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

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

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

Small cell lung cancer, limited stage (off-label use): Consolidation therapy (administer after induction cisplatin, etoposide, and radiation therapy): IV: 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

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.

Dosing: Kidney Impairment: Adult

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).

Dosing: Hepatic Impairment: Adult

Manufacturer's labeling:

Liver metastases with normal hepatic function: No dosage adjustment necessary.

Bilirubin >ULN to ≤2 mg/dL: Consider reducing initial dose by 1 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).

Dosing: Pediatric

(For additional information see "Irinotecan (conventional): Pediatric 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. 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. Irinotecan is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (POGO [Dupuis 2011]). 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

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

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

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.

Colorectal Cancer: Single-Agent Schedule: Recommended Adult Dosage ModificationsA

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

Dosing: Kidney Impairment: Pediatric

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.

Dosing: Hepatic Impairment: Pediatric

There are no pediatric specific dosage adjustments; refer to individual protocols. Based on experience in adult patients, dosing adjustment suggested.

Dosing: Older Adult

Weekly dosing schedule: No dosing adjustment is recommended

Every 3-week dosing colorectal cancer schedule: Recommended initial dose is 300 mg/m2/dose for patients ≥70 years

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate chemotherapy dosing in adults with cancer with a BMI ≥30 kg/m2 : Utilize patient's actual body weight (full weight) for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]).

Dosing: Adjustment for Toxicity: Adult

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, 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.

Colorectal Cancer: Single-Agent Schedule: Recommended Dosage Modificationsa

Toxicity grade (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

a All dose modifications should be based on the worst preceding toxicity.

b Excludes alopecia, anorexia, asthenia.

No toxicity

Maintain dose level

↑ 25 mg/m2 up to a maximum dose of 150 mg/m2

Maintain dose level

Neutropenia

Grade 1 (1,500 to 1,999/mm3)

Maintain dose level

Maintain dose level

Maintain dose level

Grade 2 (1,000 to 1,499/mm3)

↓ 25 mg/m2

Maintain dose level

Maintain dose level

Grade 3 (500 to 999/mm3)

Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/m2

↓ 25 mg/m2

↓ 50 mg/m2

Grade 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

Patients with diarrhea should be carefully monitored and treated promptly; may require fluid and electrolyte therapy. Avoid diuretics and laxatives in patients experiencing diarrhea. Advise patients to have loperamide readily available for the treatment of late diarrhea. Delay weekly irinotecan until bowel function has returned to baseline for at least 24 hours (without antidiarrheals).

Grade 1 (2 to 3 stools/day > pretreatment)

Maintain dose level

Maintain dose level

Maintain dose level

Grade 2 (4 to 6 stools/day > pretreatment)

↓ 25 mg/m2

Maintain dose level

Maintain dose level

Grade 3 (7 to 9 stools/day > pretreatment)

Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/m2

↓ 25 mg/m2

↓ 50 mg/m2

Grade 4 (≥10 stools/day > pretreatment)

Omit dose until resolved to ≤ grade 2, then ↓ 50 mg/m2

↓ 50 mg/m2

↓ 50 mg/m2

Other nonhematologic toxicitiesb

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

Colorectal Cancer: Combination Schedules: Recommended Dosage Modificationsa

Toxicity grade (value)

During a cycle of therapy

At the start of subsequent cycles of therapy (after adequate recovery), compared to the starting dose in the previous cyclea

a All dose modifications should be based on the worst preceding toxicity.

b Excludes alopecia, anorexia, asthenia.

No toxicity

Maintain dose level

Maintain dose level

Neutropenia

Grade 1 (1,500 to 1,999/mm3)

Maintain dose level

Maintain dose level

Grade 2 (1,000 to 1,499/mm3)

↓ 1 dose level

Maintain dose level

Grade 3 (500 to 999/mm3)

Omit dose until resolved to ≤ grade 2, then ↓ 1 dose level

↓ 1 dose level

Grade 4 (<500/mm3)

Omit dose until resolved to ≤ grade 2, then ↓ 2 dose levels

↓ 2 dose levels

Neutropenic fever (grade 4 neutropenia and ≥ grade 2 fever)

Omit dose until resolved, then ↓ 2 dose levels

Other hematologic toxicities

Dose modifications for leukopenia or thrombocytopenia 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

Patients with diarrhea should be carefully monitored and treated promptly; may require fluid and electrolyte therapy. Avoid diuretics and laxatives in patients experiencing diarrhea. Advise patients to have loperamide readily available for the treatment of late diarrhea. Delay weekly irinotecan until bowel function has returned to baseline for at least 24 hours (without antidiarrheals).

Grade 1 (2 to 3 stools/day > pretreatment)

Delay dose until resolved to baseline, then give same dose

Maintain dose level

Grade 2 (4 to 6 stools/day > pretreatment)

Omit dose until resolved to baseline, then ↓ 1 dose level

Maintain dose level

Grade 3 (7 to 9 stools/day > pretreatment)

Omit dose until resolved to baseline, then ↓ by 1 dose level

↓ 1 dose level

Grade 4 (≥10 stools/day > pretreatment)

Omit dose until resolved to baseline, then ↓ 2 dose levels

↓ 2 dose levels

Other nonhematologic toxicitiesb

Grade 1

Maintain dose level

Maintain dose level

Grade 2

Omit dose until resolved to ≤ grade 1, then ↓ 1 dose level

Maintain dose level

Grade 3

Omit dose until resolved to ≤ grade 2, then ↓ 1 dose level

↓ 1 dose level

Grade 4

Omit dose until resolved to ≤ grade 2, then ↓ 2 dose levels

↓ 2 dose levels

Mucositis and/or stomatitis

Decrease only fluorouracil, not irinotecan

Decrease only fluorouracil, not irinotecan

Hypersensitivity reaction: Discontinue irinotecan if hypersensitivity develops.

Pulmonary toxicity: Interrupt chemotherapy and evaluate for progressive changes in baseline pulmonary symptoms or any new-onset pulmonary symptoms (eg, dyspnea, cough, fever). Discontinue all chemotherapy and manage as clinically indicated if interstitial pulmonary disease is diagnosed.

Dosage Forms: US

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)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Camptosar: 20 mg/mL ([DSC])

Generic: 20 mg/mL (2 mL, 5 mL, 25 mL)

Solution, Intravenous, as hydrochloride:

Generic: 100 mg/5 mL (5 mL); 500 mg/25 mL (25 mL)

Administration: Adult

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 loperamide administration. Loperamide should not be used for more than 48 consecutive hours.

Administration: Pediatric

Irinotecan is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (POGO [Dupuis 2011]).

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.

Hazardous Drugs Handling Considerations

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).

Use: Labeled Indications

Colorectal cancer, metastatic: Treatment of metastatic carcinoma of the colon or rectum, either as first-line therapy (in combination with fluorouracil and leucovorin), or for recurrent or progressive disease following initial fluorouracil-based treatment.

Use: Off-Label: Adult

Cervical cancer (recurrent or metastatic); CNS tumor, (recurrent glioblastoma); Esophageal cancer (metastatic or locally advanced); Ewing sarcoma (recurrent or progressive); Gastric cancer (metastatic or locally advanced); Non-small cell lung cancer (advanced); Ovarian cancer (recurrent); Pancreatic cancer (advanced or metastatic); Pancreatic cancer, potentially curable, adjuvant therapy; Small cell lung cancer (extensive stage); Small cell lung cancer (limited stage); Unknown primary adenocarcinoma

Medication Safety Issues
Sound-alike/look-alike issues:

Conventional formulation (Camptosar) may be confused with the liposomal formulation (Onivyde)

Irinotecan (conventional) may be confused with irinotecan (liposomal), sacituzumab govitecan, topotecan

High alert medication:

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.

Administration issues:

Irinotecan (conventional) and irinotecan (liposomal) are NOT interchangeable. Dosing differs between formulations; verify intended product and dose prior to preparation and administration.

Adverse Reactions

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

Contraindications

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

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Irinotecan may cause severe myelosuppression. Deaths due to sepsis following severe neutropenia have been reported. Complications due to neutropenia should be promptly managed with antibiotics. 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: 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. 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.

• Extravasation: Irinotecan is an irritant. Avoid extravasation; if extravasation occurs, the manufacturer recommends flushing the external site with sterile water and applying ice.

• Hypersensitivity: Severe hypersensitivity reactions (including anaphylaxis) have occurred.

• Pulmonary toxicity: Fatal cases of interstitial pulmonary disease–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.

• Renal toxicity: Renal impairment and acute renal failure have been reported, possibly due to dehydration secondary to diarrhea.

Disease-related concerns:

• Bowel obstruction: Patients with bowel obstruction should not be treated with irinotecan until resolution of obstruction.

• Hepatic impairment: Exposure to the active metabolite (SN-38) is increased in hepatic impairment; 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.

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:

• Older adult: 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.

• Pelvic/abdominal radiation recipients: 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.

• Reduced UGT1A1 activity: Patients homozygous for either the UGT1A1*28 or *6 alleles (*28/*28, *6/*6) or who are compound or double heterozygous for the UGT1A1*28 and *6 alleles (*6/*28) are at increased risk of severe or life-threatening neutropenia with irinotecan due to poor metabolism of UGT1A1; UGT1A1-poor metabolizers have increased systemic exposure to SN-38 (active metabolite). Patients who are heterozygous for either the UGT1A1*28 or *6 alleles (*1/*28, *1/*6) are intermediate metabolizers and may also be at increased risk of severe or life-threatening neutropenia.

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.

Warnings: Additional Pediatric Considerations

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).

Metabolism/Transport Effects

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

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). 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: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. 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

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). 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

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

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

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). 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

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

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. 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 combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. 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/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). 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

Reproductive Considerations

Verify pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant should use highly effective contraception during therapy and for 6 months after the last irinotecan dose. Patients with partners who could become pregnant 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.

Pregnancy Considerations

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).

Breastfeeding Considerations

Irinotecan and its metabolites are present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy and for 7 days after the last irinotecan dose.

Dietary Considerations

Contains sorbitol; do not use in patients with hereditary fructose intolerance.

Monitoring Parameters

CBC with differential, platelet count, and hemoglobin with each dose; bilirubin, electrolytes (with severe diarrhea). Verify pregnancy status prior to use (in patients who could become pregnant). Monitor for cholinergic reactions; monitor bowel movements and hydration status. Monitor for signs/symptoms of pulmonary toxicity (particularly in patients with risk factors such as preexisting lung disease, use of pulmonary toxicity medications, radiation therapy, and colony-stimulating factors); promptly evaluate progressive changes in baseline pulmonary symptoms or any new-onset pulmonary symptoms (eg, dyspnea, cough, fever). Monitor for hypersensitivity reactions; monitor infusion site for signs of inflammation and avoid extravasation.

Consider UGT1A1 genotype testing for the *28 and *6 alleles to determine UGT1A1 metabolizer status; closely monitor for neutropenia during and after treatment with irinotecan.

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.

Mechanism of Action

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.

Pharmacokinetics

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 oxidative metabolism to several 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 AUC is increased in patients who are homozygous for either the UGT1A1*28 or *6 alleles, or who are compound heterozygous for these alleles.

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%)

Pharmacokinetics: Additional Considerations

Hepatic function impairment: Clearance of irinotecan is decreased and exposure to the active metabolite (SN-38) is increased proportional to the degree of hepatic impairment.

Pricing: US

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

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Actatecan (ID);
  • Ai Li (CN);
  • Calmtop (KR);
  • Campto (AE, AT, BE, BF, BG, BH, BJ, CH, CI, CN, CY, CZ, EE, EG, ES, ET, FR, GB, GH, GM, GN, GR, HK, HN, HR, ID, IE, IL, IT, JO, JP, KE, KR, LB, LR, LU, MA, ML, MR, MT, MU, MW, MY, NE, NG, NL, PK, PL, PT, RO, RU, SA, SC, SD, SG, SI, SK, SL, SN, TH, TN, TR, TW, TZ, UG, VN, ZA, ZM);
  • Camptosar (AR, AU, BO, BR, CL, CO, CR, DO, GT, MX, NI, NZ, PA, PE, PR, QA, SV, UY, VE);
  • Camtecan (KR);
  • Canri (CZ);
  • Efixano (PY);
  • Etoniri (MX);
  • Herocan (TW);
  • Imocam (VN);
  • Imtus (TH, ZW);
  • Indotecan (KR);
  • Innocan (TW);
  • Irenax (TW);
  • Irican (PH, TW);
  • Iricip (LK);
  • Irino (LK, TH);
  • Irinocyt (CO);
  • Irinogen (EC, PY);
  • Irinokabi (NO, SE);
  • Irinoll (TH);
  • Irinomedac (DE);
  • Irinotel (EG, ET, IN, JO, LK, TH, ZW);
  • Irinotesin (HK, PH, SG, TH);
  • Irinox (BD, SG);
  • Iritecan (KR);
  • Irnocam (MY);
  • Irocan (ZW);
  • Irotin (BD);
  • Itoxaril (EC);
  • Linatecan (PE);
  • Lritecin (KR);
  • Pipetecan (AR);
  • Romisan (ID);
  • Terican (MX);
  • Topotecin (JP);
  • Trinotecan (EG, LB)


For country code abbreviations (show table)
  1. <800> Hazardous Drugs–Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Ajani JA, Baker J, Pisters PW, et al, “CPT-11 Plus Cisplatin in Patients With Advanced, Untreated Gastric or Gastroesophageal Junction Carcinoma: Results of a Phase II Study,” Cancer, 2002, 94(3):641-6. [PubMed 11857295]
  3. Bagatell R, London WB, Wagner LM, et al, "Phase II Study of Irinotecan and Temozolomide in Children With Relapsed or Refractory Neuroblastoma: A Children's Oncology Group Study," J Clin Oncol, 2011, 29(2):208-13. [PubMed 21115869]
  4. Balaban EP, Mangu PB, Khorana AA, et al. Locally advanced, unresectable pancreatic cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2016;34(22):2654-2668. doi: 10.1200/JCO.2016.67.5561. [PubMed 27247216]
  5. Bomgaars L, Kerr J, Berg S, et al, "A Phase I Study of Irinotecan Administered on a Weekly Schedule in Pediatric Patients," Pediatr Blood Cancer, 2006, 46(1):50-5. [PubMed 15768380]
  6. Bomgaars LR, Bernstein M, Krailo M, et al, "Phase II Trial of Irinotecan in Children With Refractory Solid Tumors: A Children's Oncology Group Study," J Clin Oncol, 2007, 25(29):4622-7. [PubMed 17925558]
  7. Bouché O, Raoul JL, Bonnetain F, et al, “Randomized Multicenter Phase II Trial of a Biweekly Regimen of Fluorouracil and Leucovorin (LV5FU2), LV5FU2 Plus Cisplatin, or LV5FU2 Plus Irinotecan in Patients With Previously Untreated Metastatic Gastric Cancer: A Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803,” J Clin Oncol, 2004, 22(21):4319-28. [PubMed 15514373]
  8. Camptosar (irinotecan) [prescribing information]. New York, NY: Pharmacia & Upjohn Co; January 2022.
  9. Camptostar (irinotecan) [product monograph] Kirkland, Quebec, Canada: Pfizer Canada ULC; February 2022.
  10. Casey DA, Wexler LH, Merchant MS, et al, “Irinotecan and Temozolomide for Ewing Sarcoma: The Memorial Sloan-Kettering Experience,” Pediatr Blood Cancer, 2009, 53(6):1029-34. [PubMed 19637327]
  11. Chen G, Huynh M, Fehrenbacher L, et al, “Phase II Trial of Irinotecan and Carboplatin for Extensive or Relapsed Small-Cell Lung Cancer,” J Clin Oncol, 2009, 27(9):1401-4. [PubMed 19204194]
  12. Cirillo M, Musola M, Cassandrini PA, Lunardi G, Venturini M. Irinotecan during pregnancy in metastatic colon cancer. Tumori. 2012;98(6):155e-157e. [PubMed 23389374]
  13. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825. [PubMed 21561347]
  14. Conroy T, Hammel P, Hebbar M, et al; Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379(25):2395-2406. doi: 10.1056/NEJMoa1809775. [PubMed 30575490]
  15. Conroy T, Paillot B, François E, et al, “Irinotecan Plus Oxaliplatin and Leucovorin-Modulated Fluorouracil in Advanced Pancreatic Cancer--A Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer Study,” J Clin Oncol, 2005, 23(6):1228-1236. [PubMed 15718320]
  16. Cosetti M, Wexler LH, Calleja E, et al, “Irinotecan for Pediatric Solid Tumors: The Memorial Sloan-Kettering Experience,” J Pediatr Hematol Oncol, 2002, 24(2):101-5. [PubMed 11990694]
  17. Dupuis LL, Boodhan S, Sung L, et al. Guideline for the classification of the acute emetogenic potential of antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer. 2011;57(2):191-198.
  18. Falcone A, Ricci S, Brunetti I, et al, “Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) as First-Line Treatment for Metastatic Colorectal Cancer: The Gruppo Oncologico Nord Ovest,” J Clin Oncol, 2007, 25(13):1670-6. [PubMed 17470860]
  19. Floyd J, Mirza I, Sachs B, et al, “Hepatotoxicity of Chemotherapy,” Semin Oncol, 2006, 33(1):50-67. [PubMed 16473644]
  20. Friedman HS, Prados MD, Wen PY, et al, “Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma,” J Clin Oncol, 2009, 27(28):4733-40. [PubMed 19720927]
  21. Fuchs CS, Moore MR, Harker G, et al. Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer. J Clin Oncol. 2003;21(5):807-814. doi: 10.1200/JCO.2003.08.058. [PubMed 12610178]
  22. Furman WL, Navid F, Daw NC, et al, "Tyrosine Kinase Inhibitor Enhances the Bioavailability of Oral Irinotecan in Pediatric Patients With Refractory Solid Tumors," J Clin Oncol, 2009, 27(27):4599-604. [PubMed 19687340]
  23. Gajjar A, Chintagumpala MM, Bowers DC, et al, “Effect of Intrapatient Dosage Escalation of Irinotecan on Its Pharmacokinetics in Pediatric Patients Who Have High-Grade Gliomas and Receive Enzyme-Inducing Anticonvulsant Therapy,” Cancer, 2003, 97(9 Suppl):2374-80. [PubMed 12712459]
  24. Griggs JJ, Bohlke K, Balaban EP, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J Clin Oncol. 2021;39(18):2037-2048. doi:10.1200/JCO.21.00471 [PubMed 33939491]
  25. Guimbaud R, Louvet C, Ries P, et al. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Federation Francophone de Cancerologie Digestive, Federation Nationale des Centres de Lutte Contre le Cancer, and Groupe Cooperateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014;32(31):3520-3526. [PubMed 25287828]
  26. Hainsworth JD, Spigel DR, Clark BL, et al. Paclitaxel/carboplatin/etoposide versus gemcitabine/irinotecan in the first-line treatment of patients with carcinoma of unknown primary site: a randomized, phase III Sarah Cannon Oncology Research Consortium Trial. Cancer J. 2010;16(1):70-75. doi: 10.1097/PPO.0b013e3181c6aa89. [PubMed 20164695]
  27. Hanna N, Bunn PA Jr, Langer C, et al, “Randomized Phase III Trial Comparing Irinotecan/Cisplatin With Etoposide/Cisplatin in Patients With Previously Untreated Extensive-Stage Disease Small-Cell Lung Cancer,” J Clin Oncol, 2006, 24(13):2038-43. [PubMed 16648503]
  28. Hermes A, Bergman B, Bremnes R, et al, “Irinotecan Plus Carboplatin Versus Oral Etoposide Plus Carboplatin in Extensive Small-Cell Lung Cancer: A Randomized Phase III Trial,” J Clin Oncol, 2008, 26(26):4261-7. [PubMed 18779613]
  29. Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO guideline update. J Clin Oncol. 2020;38(24):2782-2797. doi:10.1200/JCO.20.01296 [PubMed 32658626]
  30. Hironaka S, Ueda S, Yasui H, et al. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013; 31(35):4438-4444. [PubMed 24190112]
  31. Hirose T, Horichi, N, Ohmori T, et al, “Phase II Study of Irinotecan and Carboplatin in Patients With the Refractory or Relapsed Small Cell Lung Cancer,” Lung Cancer, 2003, 40(3):333-8. [PubMed 12781433]
  32. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  33. Ilson DH, Saltz L, Enzinger P, et al, “Phase II Trial of Weekly Irinotecan Plus Cisplatin in Advanced Esophageal Cancer,” J Clin Oncol, 1999, 17(10):3270-5. [PubMed 10506629]
  34. Janus N, Thariat J, Boulanger H, et al, “Proposal for Dosage Adjustment and Timing of Chemotherapy in Hemodialyzed Patients,” Ann Oncol, 2010, 21(7):1395-403. [PubMed 20118214]
  35. Khorana AA, McKernin SE, Berlin J, et al. Potentially curable pancreatic adenocarcinoma: ASCO clinical practice guideline update. J Clin Oncol. 2019;37(23):2082-2088. doi: 10.1200/JCO.19.00946. [PubMed 31180816]
  36. Kubota K, Hida T, Ishikura S, et al. Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited-stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised phase 3 study. Lancet Oncol. 2014;15(1):106-113. doi: 10.1016/S1470-2045(13)70511-4. [PubMed 24309370]
  37. Kushner BH, Kramer K, Modak S, et al, "Five-Day Courses of Irinotecan as Palliative Therapy for Patients With Neuroblastoma," Cancer, 2005, 103(4):858-62. [PubMed 15637685]
  38. Leary A, Assersohn L, Cunningham D, et al, “A Phase II Trial Evaluating Capecitabine and Irinotecan as Second Line Treatment in Patients With Oesophago-Gastric Cancer Who Have Progressed On, or Within 3 Months of Platinum-Based Chemotherapy,” Cancer Chemother Pharmacol, 2009, 64(3):455-62. [PubMed 19104814]
  39. Ma MK, Zamboni WC, Radomski KM, et al, "Pharmacokinetics of Irinotecan and Its Metabolites SN-38 and APC in Children With Recurrent Solid Tumors After Protracted Low-Dose Irinotecan," Clin Cancer Res, 2000, 6(3):813-9. [PubMed 10741701]
  40. Marsh S and McLeod HL, “Pharmacogenetics of Irinotecan Toxicity,” Pharmacogenomics, 2004, 5(7):835-43. [PubMed 15469406]
  41. Mascarenhas L, Lyden ER, Breitfeld PP, et al. Randomized phase II window trial of two schedules of irinotecan with vincristine in patients with first relapse or progression of rhabdomyosarcoma: a report from the Children's Oncology Group. J Clin Oncol. 2010;28(30):4658-4663. doi: 10.1200/JCO.2010.29.7390. [PubMed 20837952]
  42. Mathijssen RH, van Alphen RJ, Verweij J, et al, “Clinical Pharmacokinetics and Metabolism of Irinotecan (CPT-11),” Clin Cancer Res, 2001, 7(8):2182-94. [PubMed 11489791]
  43. Matsumoto K, Katsumata N, Yamanaka Y, et al. The safety and efficacy of the weekly dosing of irinotecan for platinum- and taxanes-resistant epithelial ovarian cancer. Gynecol Oncol. 2006;100(2):412-416. [PubMed 16298422]
  44. McGregor LM, Stewart CF, Crews KR, et al, "Dose Escalation of Intravenous Irinotecan Using Oral Cefpodoxime: A Phase I Study in Pediatric Patients With Refractory Solid Tumors," Pediatr Blood Cancer, 2012, 58(3):372-9. [PubMed 21509928]
  45. McNall-Knapp RY, Williams CN, Reeves EN, et al, "Extended Phase I Evaluation of Vincristine, Irinotecan, Temozolomide, and Antibiotic in Children With Refractory Solid Tumors," Pediatr Blood Cancer, 2010, 54(7):909-15. [PubMed 20405511]
  46. Moehler M, Kanzler S, Geissler M, et al, “A Randomized Multicenter Phase II Study Comparing Capecitabine With Irinotecan or Cisplatin in Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction,” Ann Oncol. 2010;21(1):71-77. [PubMed 19605504]
  47. Morgan C, Tillett T, Braybrooke J, et al. Management of Uncommon Chemotherapy-Induced Emergencies. Lancet Oncol. 2011;12(8):806-814. [PubMed 21276754]
  48. Morgenstern DA, Baruchel S, Irwin MS. Current and future strategies for relapsed neuroblastoma: challenges on the road to precision therapy. J Pediatr Hematol Oncol. 2013;35(5):337-347. [PubMed 23703550]
  49. Noda K, Nishiwaki Y, Kawahara M, et al, “Irinotecan Plus Cisplatin Compared With Etoposide Plus Cisplatin for Extensive Small-Cell Lung Cancer,” N Engl J Med, 2002, 346(2):85-91. [PubMed 11784874]
  50. Ohe Y, Ohashi Y, Kubota K, et al, “Randomized Phase III Study of Cisplatin Plus Irinotecan Versus Carboplatin Plus Paclitaxel, Cisplatin Plus Gemcitabine, and Cisplatin Plus Vinorelbine for Advanced Non-Small-Cell Lung Cancer: Four-Arm Cooperative Study in Japan,” Ann Oncol, 2007, 18(2):317-23. [PubMed 17079694]
  51. Pappo AS, Lyden E, Breitfeld P, et al, "Two Consecutive Phase II Window trials of Irinotecan Alone or in Combination With Vincristine for the Treatment of Metastatic Rhabdomyosarcoma: The Children's Oncology Group," J Clin Oncol, 2007, 25(4):362-9. [PubMed 17264331]
  52. Park SH, Choi EY, Bang SM, et al, “Salvage Chemotherapy With Irinotecan and Cisplatin in Patients With Metastatic Gastric Cancer Failing Both 5-Fluorouracil and Taxanes,” Anticancer Drugs, 2005, 16(6):621-5. [PubMed 15930889]
  53. Pillot GA, Read WL, Hennenfent KL, et al, “A Phase II Study of Irinotecan and Carboplatin in Advanced Non-Small Cell Lung Cancer With Pharmacogenomic Analysis: Final Report,” J Thorac Oncol, 2006, 1(9):972-8. [PubMed 17409981]
  54. Raymond E, Boige V, Faivre S, et al, “Dosage Adjustment and Pharmacokinetic Profile of Irinotecan in Cancer Patients With Hepatic Dysfunction,” J Clin Oncol, 2002, 20(21):4303-12. [PubMed 12409328]
  55. Roila F, Molassiotis A, Herrstedt J, et al; participants of the MASCC/ESMO Consensus Conference. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol. 2016;27(suppl 5):v119-v133. doi: 10.1093/annonc/mdw270. [PubMed 27664248]
  56. Rothenberg ML, Eckardt JR, Kuhn JG, et al, "Phase II Trial of Irinotecan in Patients With Progressive or Rapidly Recurrent Colorectal Cancer," J Clin Oncol, 1996, 14(4):1128-35. [PubMed 8648367]
  57. Rudin CM, Ismaila N, Hann CL, et al. Treatment of small-cell lung cancer: American Society of Clinical Oncology endorsement of the American College of Chest Physicians Guideline. J Clin Oncol. 2015;33(34):4106-4111. [PubMed 26351333]
  58. Schmittel A, Fischer von Weikersthal L, Sebastian M, et al, “A Randomized Phase II Trial of Irinotecan Plus Carboplatin Versus Etoposide Plus Carboplatin Treatment in Patients With Extended Disease Small-Cell Lung Cancer,” Ann Oncol, 2006, 17(4):663-7. [PubMed 16423848]
  59. Sohal DPS, Kennedy EB, Cinar P, et al. Metastatic pancreatic cancer: ASCO guideline update. J Clin Oncol. Published online August 5, 2020. doi:10.1200/JCO.20.01364 [PubMed 32755482]
  60. Taylor J, Amanze A, Di Federico E, Verschraegen C. Irinotecan use during pregnancy. Obstet Gynecol. 2009;114(2 Pt 2):451-452. [PubMed 19622957]
  61. Toffoli G, Cecchin E, Corona G, et al, “The Role of UGT1A1*28 Polymorphism in the Pharmacodynamics and Pharmacokinetics of Irinotecan in Patients With Metastatic Colorectal Cancer,” J Clin Oncol, 2006, 24(19):3061-8. [PubMed 16809730]
  62. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 5, 2016.
  63. van der Bol JM, Loos WJ, de Jong FA, et al, “Effect of Omeprazole on the Pharmacokinetics and Toxicities of Irinotecan in Cancer Patients: A Prospective Cross-Over Drug-Drug Interaction Study,” Eur J Cancer, 2011, 47(6):831-8. [PubMed 21216137]
  64. van der Bol JM, Mathijssen RH, Loos WJ, et al, “Cigarette Smoking and Irinotecan Treatment: Pharmacokinetic Interaction and Effects on Neutropenia,” J Clin Oncol, 2007, 25(19):2719-26. [PubMed 17563393]
  65. Vassal G, Couanet D, Stockdale E, et al, "Phase II Trial of Irinotecan in Children With Relapsed or Refractory Rhabdomyosarcoma: A Joint Study of the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group," J Clin Oncol, 2007, 25(4):356-61. [PubMed 17264330]
  66. Verschraegen CF, Levy T, Kudelka AP, et al, “Phase II Study of Irinotecan in Prior Chemotherapy-Treated Squamous Cell Carcinoma of the Cervix,” J Clin Oncol, 1997, 5(2):625-31. [PubMed 9053486]
  67. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al, “Bevacizumab Plus Irinotecan in Recurrent Glioblastoma Multiforme,” J Clin Oncol, 2007, 25(30):4722-9. [PubMed 17947719]
  68. Wagner LM, "Oral Irinotecan for Treatment of Pediatric Solid Tumors: Ready for Prime Time?" Pediatr Blood Cancer, 2010, 54(5):661-2. [PubMed 20108333]
  69. Wagner LM, Crews KR, Stewart CF, et al, "Reducing Irinotecan-Associated Diarrhea in Children," Pediatr Blood Cancer, 2008, 50(2):201-7. [PubMed 17570704]
  70. Wagner LM, McAllister N, Goldsby RE, et al, "Temozolomide and Intravenous Irinotecan for Treatment of Advanced Ewing Sarcoma," Pediatr Blood Cancer, 2007, 48(2):132-9. [PubMed 16317751]
  71. Wagner LM, Perentesis JP, Reid JM, et al, "Phase I Trial of Two Schedules of Vincristine, Oral irinotecan, and Temozolomide (VOIT) for Children With Relapsed or Refractory Solid Tumors: A Children's Oncology Group Phase I Consortium Study," Pediatr Blood Cancer, 2010a, 54(4):538-45. [PubMed 20049936]
  72. Walker SE, Law S, and Puodziunas A, “Simulation of Y-Site Compatibility of Irinotecan and Leucovorin at Room Temperature in 5% Dextrose in Water in 3 Different Containers,” Can J Hosp Pharm, 2005, 58(4): 212-22.
  73. Weigel BJ, Lyden E, Anderson JR, et al. Intensive multiagent therapy, including dose-compressed cycles of ifosfamide/etoposide and vincristine/doxorubicin/cyclophosphamide, irinotecan, and radiation, in patients with high-risk rhabdomyosarcoma: a report from the Children's Oncology Group. J Clin Oncol. 2016;34(2):117-122. doi: 10.1200/JCO.2015.63.4048. [PubMed 26503200]
Topic 8573 Version 450.0