Version May 2024
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 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 (Ref).
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 (in combination with bolus leucovorin and fluorouracil; leucovorin administered immediately following irinotecan; fluorouracil immediately following leucovorin); continue until disease progression or unacceptable toxicity.
Adjusted dose level −1: 100 mg/m2.
Adjusted dose level −2: 75 mg/m2.
Further adjust if needed in decrements of ~20%.
Regimen 2 (FOLFIRI regimen): IV: 180 mg/m2 over 90 minutes on days 1, 15, and 29 of a 6-week cycle (in combination with infusional leucovorin and bolus/infusion fluorouracil; leucovorin administered immediately following irinotecan; fluorouracil immediately following leucovorin); continue until disease progression or unacceptable toxicity.
Adjusted dose level −1: 150 mg/m2.
Adjusted dose level −2: 120 mg/m2.
Further adjust if needed in decrements of ~20%.
Note: FOLFIRI regimens may also be administered in combination with bevacizumab (Ref), cetuximab (Ref), panitumumab (Ref), ramucirumab (Ref), or ziv-aflibercept (Ref); refer to protocols for further information.
FOL FOXIRI regimen (off-label dosing): IV: 165 mg/m2 over 1 hour once every 2 weeks (in combination with oxaliplatin, leucovorin, and fluorouracil); continue until disease progression or unacceptable toxicity (Ref) or 165 mg/m2 over 1 hour once every 2 weeks (in combination with oxaliplatin, leucovorin, fluorouracil, and bevacizumab) for up to 12 cycles (Ref) or 150 mg/m2 over 1 hour once every 14 days (in combination with oxaliplatin, leucovorin, fluorouracil, and panitumumab) until disease progression or resection for up to a maximum of 12 preoperative cycles; after resection, patients received the same regimen as adjuvant therapy for a total of 12 perioperative cycles (Ref).
In combination with cetuximab (off- label combination): IV: 180 mg/m2 over 30 minutes once every 2 weeks (in combination with cetuximab) until disease progression or unacceptable toxicity (Ref).
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); continue until disease progression or unacceptable toxicity.
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; continue until disease progression or unacceptable toxicity.
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
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; continue until disease progression or unacceptable toxicity (Ref).
CNS tumor, recurrent glioblastoma (off-label use): IV: 125 mg/m2 over 90 minutes once every 2 weeks (in combination with bevacizumab); continue for up to 2 years or until disease progression or unacceptable toxicity. NOTE: In the studies, the irinotecan dose was increased in patients taking concurrent antiseizure enzyme-inducing medications; refer to protocols for further information (Ref).
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); continue until disease progression or unacceptable toxicity (Ref) or 180 mg/m2 over 90 minutes every 2 weeks (in combination with leucovorin and fluorouracil); continue until disease progression or unacceptable toxicity (Ref) or 250 mg/m2 every 3 weeks (in combination with capecitabine) for up to a maximum of 24 weeks or until disease progression or unacceptable toxicity (Ref).
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); continue for up to 12 cycles (patients received a median of 7.5 cycles) (Ref).
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; continue until disease progression or unacceptable toxicity (Ref) or 65 mg/m2 over 90 minutes days 1, 8, 15, and 22 of a 6-week treatment cycle (in combination with cisplatin); continue until disease progression or unacceptable toxicity (Ref) 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 (or until disease progression or unacceptable toxicity are detected) (Ref) or 180 mg/m2 over 90 minutes every 2 weeks (in combination with leucovorin and fluorouracil); continue for at least 4 cycles or until disease progression or unacceptable toxicity (Ref) or 250 mg/m2 every 3 weeks (in combination with capecitabine); continue until disease progression or unacceptable toxicity (Ref).
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); continue for 3 or more cycles until disease progression or unacceptable toxicity (Ref).
Ovarian cancer, recurrent (off-label use):
Platinum- and taxane-resistant: IV: 100 mg/m2 days 1, 8, and 15 every 4 weeks (as a single-agent) for up to 6 cycles (Ref).
Platinum- refractory/resistant: IV: Initial: 50 mg/m2 on days 1 and 8 every 3 weeks (in combination with gemcitabine) until disease progression or unacceptable toxicity; chemotherapy doses were modified based on the presence or absence of toxicity; refer to protocol for further information (Ref).
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) until disease progression or unacceptable toxicity (12 cycles were recommended in patients who responded) (Ref).
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 (Ref).
mFOLFIRINOX regimen: IV: 150 mg/m2 every 2 weeks (in combination with fluorouracil, leucovorin, and oxaliplatin; modified FOLFIRINOX regimen) for 24 weeks (Ref). According to ASCO guidelines, mFOLFIRINOX is the preferred first-line adjuvant regimen for potentially curable disease (Ref).
Rhabdomyosarcoma, metastatic or relapsed/progressive (off-label use):
Adults <50 years of age: IV: 50 mg/m2 (maximum: 100 mg/dose) once daily for 5 days during protocol-specific weeks (in combination with ifosfamide, etoposide, vincristine, doxorubicin, cyclophosphamide, dactinomycin, and radiation; high-risk disease); protocol-specific weeks assigned were weeks 1, 4, 20, 23, 47, and 50 (refer to protocol for details) (Ref). In adult patients <21 years of age, may consider the regimen below.
Adults <21 years of age: IV: 50 mg/m2 once daily for 5 days at weeks 1 and 4 (in combination with vincristine); if complete or partial response occurs, continue 50 mg/m2 once daily for 5 days at weeks 13, 25, 34, 46, and 49 (Ref). Refer to protocol for details.
Small bowel adenocarcinoma, advanced unresectable or metastatic (off-label use): Note: Ampullary adenocarcinomas were excluded from this study (Ref).
FOLFIRI regimen (following progression on a platinum-based regimen): IV: 180 mg/m2 over 90 minutes once every 2 weeks (in combination with leucovorin and fluorouracil); continue until disease progression or unacceptable toxicity (Ref).
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) for 4 cycles (Ref) or 65 mg/m2 days 1 and 8 every 3 weeks (in combination with cisplatin) for a minimum of 4 cycles (Ref) or 175 mg/m2 day 1 every 3 weeks for 4 cycles (in combination with carboplatin) (Ref) or 50 mg/m2 days 1, 8 and 15 every 4 weeks (in combination with carboplatin); in the study, patients received a median of 4 cycles (Ref). 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 (Ref).
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 (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
Note: Irinotecan clearance is complex with extensive interpatient variability (Ref); kidney function is one consideration (Ref) in the context of additional factors influencing drug disposition and toxicity (eg, liver function, UGT1A1 genotype, liver function, concurrent medications) (Ref). Monitor patients with kidney impairment closely for development of toxicity.
IV:
CrCl ≥60 mL/minute: No dosage adjustment necessary (Ref).
CrCl 30 to <60 mL/minute: Consider initiating with 75% to 100% of the usual indication-specific dose; if starting with a reduced dose, increase if tolerated (Ref). Although the clearance of irinotecan in these patients appears unaltered, unbound fraction may be increased (Ref). Additionally, a retrospective study in which patients received 350 mg/m2 irinotecan every 3 weeks found a 2.5-times higher risk of grade 3 or 4 neutropenia in patients with CrCl 35 to 66 mL/minute compared to patients with CrCl >98 mL/minute (Ref).
CrCl <30 mL/minute: Consider initiating with 50% to 66% of the usual indication-specific dose; increase if tolerated; use with caution. The unbound AUC of SN-38 (active metabolite) is increased 4.4-fold potentially due to reduced nonrenal metabolism, and adverse effects are more likely (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):
Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV: No dosage adjustment likely to be necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Irinotecan may be partially dialyzable, SN38 (active metabolite) is not (Ref).
IV: The manufacturer does not recommend use and some studies suggest higher risk of toxicity in patients with end-stage kidney disease (ESKD) (Ref). Initial: If benefits outweigh the risks may initiate with 50% to 66% of the usual recommended dose (Ref) or given the variability in patient response, when the usual indication-specific dose is 100 to 150 mg/m2 once weekly, it may be safest to reduce the dose to 50 mg/m2 once weekly (Ref).
Doses may be increased with caution if tolerated; severe toxicity at 80 mg/m2 weekly (grade 4 neutropenia and death in a patient with UGT1A polymorphism) and 100 mg/m2 weekly (grade 4 diarrhea) has been reported (Ref). Administer after hemodialysis or on nondialysis days (Ref).
Peritoneal dialysis:
IV: The manufacturer does not recommend use and some studies suggest higher risk of toxicity in patients with ESKD (Ref). Initial: If benefits outweigh the risks may initiate with 50% to 66% of the usual recommended dose or when the usual indication-specific dose is 100 to 150 mg/m2 once weekly, it may be safest to reduce the dose to 50 mg/m2 once weekly (Ref).
Doses may be increased with caution if tolerated; severe toxicity at 80 mg/m2 weekly (grade 4 neutropenia and death in a patient with UGT1A polymorphism) and 100 mg/m2 weekly (grade 4 diarrhea) has been reported in patients with ESKD (Ref).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations. Close monitoring of response and adverse reactions (eg, diarrhea, myelosuppression) due to drug accumulation is important.
IV: Dose as for CrCl <30 mL/minute; use with caution (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations. Close monitoring of response and adverse reactions (eg, diarrhea, myelosuppression) due to drug accumulation is important.
IV: Dose as for CrCl <30 mL/minute; use with caution. When scheduled dose falls on PIRRT days, dose after PIRRT or on non-PIRRT days (Ref).
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 (Ref).
Bilirubin 1.51 to 3 times ULN: Reduce dose from 350 mg/m2 every 3 weeks to 200 mg/m2 every 3 weeks (Ref).
Weekly irinotecan dosing:
Bilirubin 1.5 to 3 times ULN and ALT/AST ≤5 times ULN or bilirubin ≤1.5 times ULN and ALT/AST >5 to 20 times ULN: Administer 60 mg/m2 (Ref).
Bilirubin >3 to 5 times ULN and ALT/AST ≤5 times ULN: Administer 50 mg/m2 (Ref).
Bilirubin 1.5 to 3 times ULN and ALT/AST >5 to 20 times ULN: Administer 40 mg/m2 (Ref).
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 (Ref).
It is recommended that new courses begin only after the granulocyte count recovers to ≥1,500/mm3, platelets 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.
|
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) |
Manage promptly with antibiotic support. | ||
|
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 |
|
Hypersensitivity reaction (anaphylactic reaction) |
Discontinue irinotecan if anaphylactic reaction occurs. | ||
|
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. | ||
|
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) |
Manage promptly with antibiotic support. | |
|
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 |
|
Hypersensitivity reaction (anaphylactic reaction) |
Discontinue irinotecan if anaphylactic reaction occurs. | |
|
Mucositis and/or stomatitis |
Decrease only fluorouracil, not irinotecan |
Decrease only fluorouracil, not irinotecan |
|
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. | |
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
(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 (Ref), 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 (Ref). 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 (Ref)
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 (Ref)
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 (Ref); some protocols include combination with temozolomide (Ref)
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 (Ref)
Weekly regimen (Ref):
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 (Ref)
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.
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.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
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).
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
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): $7.73
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.
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)
IV: Administer by IV infusion, usually over 90 minutes.
Premedications: Irinotecan is associated with a moderate emetic potential (Ref); 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: Advise patients to have loperamide readily available for management of late diarrhea. 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.
Irinotecan is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Parenteral: IV infusion: Infuse usually over 90 minutes; some pediatric protocols infuse the dose over 1 hour (Ref); 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 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).
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.
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; Rhabdomyosarcoma, metastatic or relapsed/progressive; Small bowel adenocarcinoma, advanced unresectable or metastatic; Small cell lung cancer, extensive stage; Small cell lung cancer, limited stage; Unknown primary adenocarcinoma
Conventional formulation (Camptosar) may be confused with the liposomal formulation (Onivyde)
Irinotecan (conventional) may be confused with irinotecan (liposomal), sacituzumab govitecan, 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.
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
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
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
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
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Capecitabine: Irinotecan Products may enhance the nephrotoxic effect of Capecitabine. Risk C: Monitor therapy
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
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
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). 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
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- 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 Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
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
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
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
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
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
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
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.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to irinotecan may cause fetal harm.
Outcome data following maternal use of irinotecan (conventional) during pregnancy are limited (Abellar 2009; Cirillo 2012; Kozai 2022; Taylor 2009).
The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach. In general, if chemotherapy is indicated, it should be avoided in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (ESMO [Peccatori 2013]).
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (1-877-635-4499).
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.
Contains sorbitol; do not use in patients with hereditary fructose intolerance.
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.
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.
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 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%)
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.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
