Irinotecan

Pronunciation: (EYE-ri-noe-TEE-kan)
Class: DNA topoisomerase inhibitor

Trade Names

Camptosar
- Injection, solution 20 mg/mL, may contain sorbitol 45 mg

Pharmacology

Irinotecan is a derivative of camptothecin. Camptothecins interact specifically with the enzyme topoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strand breaks.

Pharmacokinetics

Absorption

T _max is 1 h (active metabolite). C _max and AUC _0-24 are 1,660 ng/mL and 10,200 ng•h/mL, respectively, for irinotecan 125 mg/m ² , and 3,392 ng/mL and 20,604 ng•h/mL, respectively, for irinotecan 340 mg/m ² .

Distribution

30% to 68% protein bound (irinotecan); active metabolite is approximately 95% protein bound.

Metabolism

SN-38 is the active metabolite. Metabolism occurs in the liver.

Elimination

The half-life is approximately 6 to 12 h. Approximately 10 to 20 h for the active metabolite. Primarily excreted in the urine.

Special Populations

Renal Function Impairment

Influence of renal impairment on the pharmacokinetics has not been evaluated; use with caution.

Hepatic Function Impairment

Cl of irinotecan is decreased and exposure to the active metabolite is increased proportional to the degree of hepatic impairment. Use is not recommended in patients with serum bilirubin above 2 mg/dL.

Elderly

No differences in pharmacokinetics were noted for administration of irinotecan using the weekly schedule. Pharmacokinetics of irinotecan administered once every 3 wk have not been studied; a lower starting dose for this regimen is recommended in patients 70 y of age and older.

Children

Pharmacokinetics of irinotecan and active metabolite were similar to those seen in adults.

Gender

Pharmacokinetics are not influenced by gender.

Race

Influence of race on irinotecan pharmacokinetics has not been evaluated.

Indications and Usage

Treatment of metastatic cancer of the colon or rectum as first-line therapy in combination with 5-fluorouracil and leucovorin or in patients whose disease has progressed or recurred after standard treatment with fluorouracil.

Unlabeled Uses

Cervical cancer, lung cancer (small cell or non–small cell), gastric cancer, and tumors of the CNS.

Contraindications

Known hypersensitivity to irinotecan or any of the product excipients.

Dosage and Administration

Metastatic Colon or Rectal Cancer
Adults Combination therapy Regimen 1

IV Irinotecan 125 mg/m ² over 90 min, leucovorin 20 mg/m ² bolus, and 5-fluorouracil 500 mg/m ² bolus on days 1, 8, 15, and 22. The dose of leucovorin should be administered immediately after irinotecan, with the administration of 5-fluorouracil to occur immediately after the receipt of leucovorin. The next cycle begins on day 43. Doses may be decreased by 1 dose level (irinotecan 100 mg/m ² and 5-fluorouracil 400 mg/m ² ) or 2 dose levels (irinotecan 75 mg/m ² and 5-fluorouracil 300 mg/m ² ) for toxicity.

Dosage modifications Neutropenia and other hematologic toxicities

For National Cancer Institute Common Toxicity Criteria (NCI CTC) grade 1 toxicity occurring during a cycle of chemotherapy or at the start of subsequent cycles, maintain current dose level. For grade 2 toxicity occurring during a cycle of therapy, decrease by 1 dose level; for grade 2 toxicity occurring at the start of a subsequent cycle, maintain current dose level. For grade 3 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less, and then decrease by 1 dose level; for grade 3 toxicity occurring at the start of a subsequent cycle, decrease by 1 dose level. For grade 4 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less, and then decrease by 2 dose levels; for grade 4 toxicity occurring at the start of a subsequent cycle, decrease by 2 dose levels. For patients who develop neutropenic fever, omit dose until resolved, and then decrease by 2 dose levels.

Diarrhea

For grade 1 toxicity occurring during a cycle of chemotherapy, delay dose until resolved to baseline, the resume at current dose level; for grade 1 toxicity occurring at the start of subsequent cycles, maintain current dose level. For grade 2 toxicity occurring during a cycle of therapy, omit until resolved to baseline, then decrease by 1 dose level; for grade 2 toxicity occurring at the start of a subsequent cycle, maintain current dose level. For grade 3 toxicity occurring during a cycle of therapy, omit dose until resolved to baseline, and then decrease by 1 dose level; for grade 3 toxicity occurring at the start of a subsequent cycle, decrease by 1 dose level. For grade 4 toxicity occurring during a cycle of therapy, omit dose until resolved to baseline and then decrease by 2 dose levels; for grade 4 toxicity occurring at the start of a subsequent cycle, decrease by 2 dose levels.

Other nonhematologic toxicities

For grade 1 toxicity occurring during a cycle of chemotherapy or occurring at the start of subsequent cycles, maintain current dose level. For grade 2 toxicity occurring during a cycle of therapy, omit until resolved to grade 1 or less, then decrease by 1 dose level; for grade 2 toxicity occurring at the start of a subsequent cycle, maintain current dose level. For grade 3 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less and then decrease by 1 dose level; for grade 3 toxicity occurring at the start of a subsequent cycle, decrease by 1 dose level. For grade 4 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less and then decrease by 2 dose levels; for grade 4 toxicity occurring at the start of a subsequent cycle, decrease by 2 dose levels. For mucositis/stomatitis, decrease only 5-fluorouracil.

Regimen 2

IV Irinotecan 180 mg/m ² over 90 min on days 1, 15, and 29; leucovorin 200 mg/m ² over 2 h on days 1, 2, 15, 16, 29, and 30; 5-fluorouracil 400 mg/m ² bolus on days 1, 2, 15, 16, 29, and 30; and 5-fluorouracil 600 mg/m ² infusion over 22 h on days 1, 2, 15, 16, 29, and 30. The dose of leucovorin should be administered immediately after irinotecan, with the administration of 5-fluorouracil to occur immediately after the receipt of leucovorin; 5-fluorouracil infusion follows bolus administration. The next cycle begins on day 43. Doses may be decreased by 1 dose level (irinotecan 150 mg/m ² , 5-fluorouracil 320 mg/m ² bolus, and 5-fluorouracil 480 mg/m ² infusion) or 2 dose levels (irinotecan 120 mg/m ² , 5-fluorouracil 240 mg/m ² bolus, and 5-fluorouracil 360 mg/m ² infusion) for toxicity.

Dosage modifications Neutropenia and other hematologic toxicities

For NCI CTC grade 1 toxicity occurring during a cycle of chemotherapy or at the start of subsequent cycles, maintain current dose level. For grade 2 toxicity occurring during a cycle of therapy, decrease by 1 dose level; for grade 2 toxicity occurring at the start of a subsequent cycle, maintain current dose level. For grade 3 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less, and then decrease by 1 dose level; for grade 3 toxicity occurring at the start of a subsequent cycle, decrease by 1 dose level. For grade 4 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less, and then decrease by 2 dose levels; for grade 4 toxicity occurring at the start of a subsequent cycle, decrease by 2 dose levels. For patients who develop neutropenic fever, omit dose until resolved, and then decrease by 2 dose levels.

Diarrhea

For grade 1 toxicity occurring during a cycle of chemotherapy, delay dose until resolved to baseline, the resume at current dose level; for grade 1 toxicity occurring at the start of subsequent cycles, maintain current dose level. For grade 2 toxicity occurring during a cycle of therapy, omit until resolved to baseline, then decrease by 1 dose level; for grade 2 toxicity occurring at the start of a subsequent cycle, maintain current dose level. For grade 3 toxicity occurring during a cycle of therapy, omit dose until resolved to baseline, and then decrease by 1 dose level; for grade 3 toxicity occurring at the start of a subsequent cycle, decrease by 1 dose level. For grade 4 toxicity occurring during a cycle of therapy, omit dose until resolved to baseline and then decrease by 2 dose levels; for grade 4 toxicity occurring at the start of a subsequent cycle, decrease by 2 dose levels.

Other nonhematologic toxicities

For grade 1 toxicity occurring during a cycle of chemotherapy or occurring at the start of subsequent cycles, maintain current dose level. For grade 2 toxicity occurring during a cycle of therapy, omit until resolved to grade 1 or less, then decrease by 1 dose level; for grade 2 toxicity occurring at the start of a subsequent cycle, maintain current dose level. For grade 3 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less and then decrease by 1 dose level; for grade 3 toxicity occurring at the start of a subsequent cycle, decrease by 1 dose level. For grade 4 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less and then decrease by 2 dose levels; for grade 4 toxicity occurring at the start of a subsequent cycle, decrease by 2 dose levels. For mucositis/stomatitis, decrease only 5-fluorouracil.

Single-agent therapy Weekly regimen

IV Irinotecan 125 mg/m ² over 90 min on days 1, 8, 15, and 22, followed by 2 wk of rest. Give an initial dose of irinotecan 100 mg/m ² in patients with prior pelvic or abdominal radiation or in patients with a performance status of 2. Based on response and adverse reactions, the dose may be adjusted to as high as 150 mg/m ² and as low as 50 mg/m ² , in 25 to 50 mg/m ² increments. Doses may be decreased by 1 dose level (irinotecan 100 mg/m ² ) or 2 dose levels (irinotecan 75 mg/m ² ) for toxicity.

Dosage modifications Neutropenia and other hematologic toxicities

For NCI CTC grade 1 toxicity occurring during a cycle of chemotherapy or at the start of subsequent cycles, maintain current dose level. For grade 2 toxicity occurring during a cycle of therapy, decrease irinotecan by 1 dose level; for grade 2 toxicity occurring at the start of a subsequent cycle, maintain current dose level. For grade 3 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less, and then decrease by 1 dose level; for grade 3 toxicity occurring at the start of a subsequent cycle, decrease by 1 dose level. For grade 4 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less, and then decrease by 2 dose levels; for grade 4 toxicity occurring at the start of a subsequent cycle, decrease by 2 dose levels. For patients who develop neutropenic fever during a cycle of chemotherapy, omit dose until resolved, and then decrease by 2 dose levels; for patients who develop neutropenic fever at the start of a subsequent cycle, decrease by 2 dose levels.

Diarrhea

For grade 1 toxicity occurring during a cycle of chemotherapy or at the start of subsequent cycles, maintain current dose level. For grade 2 toxicity occurring during a cycle of therapy, decrease by 1 dose level; for grade 2 toxicity occurring at the start of a subsequent cycle, maintain current dose level. For grade 3 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less, and then decrease by 1 dose level; for grade 3 toxicity occurring at the start of a subsequent cycle, decrease by 1 dose level. For grade 4 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less and then decrease by 2 dose levels; for grade 4 toxicity occurring at the start of a subsequent cycle, decrease by 2 dose levels.

Other nonhematologic toxicities

For grade 1 toxicity occurring during a cycle of chemotherapy or occurring at the start of subsequent cycles, maintain current dose level. For grade 2 toxicity occurring during a cycle of therapy or at the start of a subsequent cycle, decrease by 1 dose level. For grade 3 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less and then decrease by 1 dose level; for grade 3 toxicity occurring at the start of a subsequent cycle, decrease by 1 dose level. For grade 4 toxicity occurring during a cycle of therapy, omit dose until resolved to grade 2 or less and then decrease by 2 dose levels; for grade 4 toxicity occurring at the start of a subsequent cycle, decrease by 2 dose levels.

Once-every-3-wk regimen

IV Irinotecan 350 mg/m ² over 90 min once every 3 wk. Give an initial dose of irinotecan 300 mg/m ² every 21 days in patients 70 y of age and older, patients with prior pelvic or abdominal radiation, or patients with a performance status of 2. Based on adverse reactions, the dose may be decreased in 50 mg/m ² increments to a minimum of 200 mg/m ² . Doses may be decreased by 1 dose level (irinotecan 300 mg/m ² ) or 2 dose levels (irinotecan 250 mg/m ² ) for toxicity.

Dosage modifications Neutropenia and other hematologic toxicities

For NCI CTC grade 1 or 2 toxicity occurring at the start of subsequent cycles, maintain current dose level. For grade 3 or 4 toxicity or neutropenic fever occurring at the start of a subsequent cycle, decrease by 1 dose level.

Diarrhea

For grade 1 or 2 toxicity occurring at the start of subsequent cycles, maintain current dose level. For grade 3 or 4 toxicity occurring at the start of a subsequent cycle, decrease by 1 dose level.

Other nonhematologic toxicities

For grade 1 toxicity occurring at the start of subsequent cycles, maintain current dose level. For grade 2, 3, or 4 toxicity occurring at the start of a subsequent cycle, decrease by 1 dose level.

Dosage Adjustment for UGT1A1∗28 Homozygous Patients

Consider a decrease in the starting dose of irinotecan of at least 1 dose level (eg, 100 mg/m ² for combination therapy regimen 1 and single-agent weekly regimen, 150 mg/m ² for combination therapy regimen 2, and 300 mg/m ² for the once-every-3-wk regimen).

Dosage Adjustment for Hepatic Function Impairment/Previous Abdominal or Pelvic Irradiation Once-weekly regimen

Dose should be 125 mg/m ² if serum bilirubin is less than 1 mg/dL. If bilirubin concentration is 1 to 2 mg/dL, dose should be 100 mg/m ² . Irinotecan is not recommended if bilirubin is more than 2 mg/dL.

Every-21-day regimen

Dose should be 350 mg/m ² if serum bilirubin is less than 1 mg/dL. If bilirubin concentration is 1 to 2 mg/dL, dose should be 300 mg/m ² . Irinotecan is not recommended if bilirubin is more than 2 mg/dL.

General Advice

Administer as an IV infusion over 90 min.
Dilute in dextrose 5% injection or sodium chloride 0.9% injection to a final concentration of 0.12 to 2.8 mg/mL.
Use of gloves is recommended. If contact with the skin occurs, wash immediately and thoroughly with soap and water. If contact with the mucous membranes occurs, flush thoroughly with water.
Do not add other drugs to the infusion solution.
Patients should return to pretreatment bowel function without requiring antidiarrheal medications for at least 24 h before the next chemotherapy administration. A new cycle should not begin until the granulocyte count has recovered to 1,500/mm ³ or more, platelet count has recovered to 100,000 mm ³ or more, and treatment-related diarrhea is fully resolved. Treatment should be delayed 1 to 2 wk to allow for recovery from treatment-related toxicities; if the patient has not recovered after a 2-wk delay, consider discontinuing therapy.

Storage/Stability

Store vials between 59° and 86°F; protect from light. Use solutions diluted with dextrose 5% injection within 6 h if stored between 59° and 86°F or within 24 h if stored refrigerated between 36° and 46°F. Solutions diluted in sodium chloride 0.9% injection should be stored between 59° and 86°F and used within 6 h; do not refrigerate these solutions.

Drug Interactions

Antineoplastics

Irinotecan adverse reactions (eg, diarrhea, myelosuppression) would possibly be exacerbated by other antineoplastics having similar adverse reactions. Closely monitor for irinotecan adverse reactions.

CYP3A4 inducers (ie, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John's wort)

Exposure to irinotecan and its active metabolite (SN-38) may be reduced when given concomitantly with CYP3A4 enzyme-inducing anticonvulsants. For patients requiring anticonvulsant treatment, consider substituting a nonenzyme-inducing anticonvulsant at least 2 wk prior to initiation of irinotecan therapy. Coadministration with St. John's wort is contraindicated. Discontinue St. John's wort at least 2 wk prior to the first cycle of irinotecan.

CYP3A4 inhibitors (ie, atazanavir, ketoconazole)

Coadministration may increase irinotecan and its active metabolite (SN-38). Patients should discontinue ketoconazole at least 1 wk prior to initiating irinotecan. Coadministration with ketoconazole is contraindicated. Avoid concomitant use with atazanavir. Close clinical and laboratory monitoring are warranted when administering ritonavir-boosted lopinavir with IV irinotecan.

Depolarizing neuromuscular blocking agents (ie, succinylcholine)

Irinotecan has anticholinesterase activity, which may prolong the neuromuscular-blocking effects of succinylcholine.

Dexamethasone

It is possible that coadministration of dexamethasone and irinotecan may enhance the likelihood of lymphocytopenia. Dexamethasone given as emetic prophylaxis can contribute to hyperglycemia in some patients.

Diuretics (eg, furosemide)

Consider withholding diuretics during dosing with irinotecan and during periods of active vomiting or diarrhea because of the potential risk of dehydration secondary to irinotecan-induced vomiting and diarrhea.

Laxatives

Laxative therapy during irinotecan therapy may increase the severity of diarrhea, but this has not been studied.

Nondepolarizing neuromuscular blocking agents (eg, vecuronium)

Irinotecan may antagonize the neuromuscular blockage of nondepolarizing neuromuscular-blocking agents.

Palifermin

Coadministration of palifermin and irinotecan within the same 24-h time period may increase the severity and duration of oral mucositis. Palifermin should not be administered within 24 h before, during, or 24 h after administration of irinotecan.

Prochlorperazine

The incidence of akathisia in clinical trials was greater (8.5%) when prochlorperazine was administered on the same day as irinotecan than when these drugs were given on separate days (1.3%).

Vaccines, live

The risk of live vaccine–induced adverse reactions may be increased by coadministration of irinotecan. The use of live vaccines in patients receiving irinotecan is not recommended under most circumstances and should be deferred.

Adverse Reactions

Cardiovascular

Flushing/vasodilation (11%); thromboembolic reactions (5%); hypotension (2%); bradycardia; myocardial ischemic events (postmarketing).

CNS

Asthenia (76%); dizziness (21%); insomnia (19%); headache (17%); somnolence (9%); confusion (3%); paresthesia (postmarketing).

Dermatologic

Alopecia (60%); sweating (16%); rash (14%); cutaneous signs (2%).

GI

Late diarrhea (88%); nausea (86%); abdominal pain (68%); vomiting (67%); anorexia (55%); early diarrhea (51%); constipation (32%); mucositis (30%); grade 3 diarrhea (16%); grade 4 diarrhea (14%); flatulence, stomatitis (12%); abdominal enlargement, dyspepsia (10%); intestinal perforation, megacolon, symptomatic pancreatitis or asymptomatic elevated pancreatic enzymes, ulcerative and ischemic colitis complicated by bleeding, ileus, infection, obstruction, and ulceration (postmarketing).

Genitourinary

Renal impairment, including acute renal failure, circulatory failure, or hypotension (postmarketing).

Hematologic

Anemia (97%); leukopenia, neutropenia, thrombocytopenia (96%); grade 3 neutropenia (19%); grade 4 neutropenia (12%); neutropenic fever (6%); hemorrhage (5%); neutropenic infection (2%).

Hypersensitivity

Hypersensitivity reactions, including severe anaphylactic or anaphylactoid reactions (postmarketing).

Metabolic-Nutritional

Body weight decreased (30%); dehydration (15%); alkaline phosphatase increased (13%); AST increased, edema (10%); hyponatremia, increased ALT, amylase, and lipase (postmarketing).

Respiratory

Dyspnea (22%); cough (20%); rhinitis (16%); pneumonia (4%).

Miscellaneous

Increased bilirubin (84%); fever (45%); pain (24%); back pain, chills, infection (14%); fever with grade 3 or 4 neutropenia (4%); infection with grade 3 or 4 neutropenia (2%); cholinergic symptoms (eg, flushing, increased salivation, intestinal hyperperistalsis, lacrimation, miosis, rhinitis); hiccups, muscular contraction, transient dysarthria (postmarketing).

Precautions

Warnings

Diarrhea

Irinotecan injection can induce early and late forms of diarrhea, which may be severe and appear to be mediated by different mechanisms. Early diarrhea may be accompanied by cholinergic symptoms (eg, diaphoresis, flushing, increased salivation, interstitial hyperperistalsis, lacrimation, miosis, rhinitis), which can cause abdominal cramping. Early diarrhea and other cholinergic symptoms may be ameliorated by atropine. Late diarrhea can be life-threatening because it may be prolonged and lead to dehydration, electrolyte imbalance, or sepsis. Late diarrhea should be promptly treated with loperamide.

Myelosuppression

Severe myelosuppression may occur.

Monitor

Monitor WBC with differential, hemoglobin, and platelet count before each dose. Carefully monitor patients with diarrhea and give fluid and electrolyte replacement if they become dehydrated or antibiotic therapy if they develop fever, ileus, or severe neutropenia. Carefully monitor patients who have previously received pelvic/abdominal radiation.

Pregnancy

Category D . May cause fetal harm.

Lactation

Undetermined. Breast-feeding should be discontinued during therapy with irinotecan.

Children

Safety and efficacy not established.

Elderly

Exercise particular caution in monitoring the effects of irinotecan in elderly patients (ie, 65 y of age and older).

Hypersensitivity

Hypersensitivity reactions, including severe anaphylactic or anaphylactoid reactions, have been observed.

Renal Function

Use with caution. Not recommended for use in patients on dialysis.

Hepatic Function

Use of irinotecan in patients with significant hepatic impairment has not been established. Irinotecan is not recommended if bilirubin is more than 2 mg/dL.

Special Risk Patients

It has been noted that patients with modestly elevated baseline serum total bilirubin levels (1 to 2 mg/dL) have had a significantly greater likelihood of experiencing first-course grade 3 or 4 neutropenia than those with bilirubin levels that were less than 1 mg/dL. Patients with a baseline performance status of 2 had higher rates of hospitalization, neutropenic fever, thromboembolism, first-cycle treatment discontinuation, and early death in clinical trials. Avoid use in patients with severe bone marrow failure. Do not use in patients with bowel obstruction.

Colitis/Ileus

Cases of colitis complicated by bleeding, ileus, infection, and ulceration have been observed. Patients experiencing ileus should receive prompt antibiotic support.

Extravasation

Local irritation or phlebitis may occur. Refer to the institution-specific protocol.

Irradiation

Patients who have previously received pelvic/abdominal irradiation are at an increased risk of severe myelosuppression following irinotecan administration.

Premedication

Irinotecan is emetogenic. Premedication with antiemetics is recommended.

Prophylaxis of cholinergic symptoms

Consider administration of atropine in patients experiencing cholinergic symptoms.

Pulmonary toxicity

Interstitial pulmonary disease–like events, including fatalities, have been reported.

Renal effects

Rare cases of renal impairment and acute renal failure have been identified, usually in patients who became volume-depleted from severe vomiting or diarrhea.

Sorbitol

This product may contain sorbitol; do not use in patients with hereditary fructose intolerance.

Thromboembolism

Thromboembolic reactions have been observed.

Toxic deaths

Do not use in combination with the “Mayo Clinic” regimen of 5-fluorouracil/leucovorin because of reports of increased toxicity, including toxic deaths. Use irinotecan as recommended.

UGT1A1 activity

Patients who are homozygous for the UGT1A1∗28 allele (UGT1A1 7/7 genotype) are at increased risk for neutropenia.

Vaccines

Avoid administration of live vaccines; killed or inactivated vaccines may be administered, but response may be diminished.

Overdosage

Symptoms

Diarrhea, neutropenia.

Patient Information

Inform patients and caregivers of the expected toxic effects of irinotecan, particularly of its GI manifestations, such as nausea, vomiting, and diarrhea. Instruct each patient to have loperamide readily available and to begin treatment for late diarrhea (generally occurring more than 24 h after administration) at the first episode of poorly formed or loose stools or the earliest onset of bowel movements more frequent than normally expected for the patient. One dosage regimen for loperamide is 4 mg at the first onset of late diarrhea and then 2 mg every 2 h until the patient is diarrhea-free for at least 12 h. Inform patients that they may take 4 mg loperamide every 4 h during the night. Instruct patients to notify health care provider if diarrhea occurs. Premedication with loperamide is not recommended.
Advise patients to avoid the use of drugs with laxative properties because of the potential for exacerbation of diarrhea. Instruct patients to contact the health care provider to discuss any laxative use.
Advise patients to consult health care provider if they experience black or bloody stools; diarrhea for the first time during treatment; fever or evidence of infection; inability to get diarrhea under control within 48 h; inability to take fluids by mouth because of nausea or vomiting; or symptoms of dehydration, such as dizziness, faintness, or light-headedness.
Warn patients about the potential for dizziness or visual disturbances, which may occur within 24 h following the administration of irinotecan. Advise patients not to drive or operate machinery if these symptoms occur.
Alert patients to the possibility of alopecia.