irinotecan

Contraindicated in:

Hypersensitivity;
Hereditary fructose intolerance (contains sorbitol);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Previous pelvic or abdominal irradiation or age ≥65 yr (↑ risk of myelosuppression);
Presence of infection, underlying bone marrow depression, or concurrent chronic illness;
History of prior pelvic/abdominal irradiation and serum bilirubin >1–2 mg/dL (initial dose ↓ recommended);
Hepatic impairment;
Previous severe myelosuppression or diarrhea (reinstitute at lower dose following resolution);
Homozygous for UGT1A1*28 [*28/*28] or UGT1A1*6 [*6/*6] alleles or compound heterozygous for UGT1A1*28 or UGT1A1*6 [*6/*28] alleles (poor UGT1A1 metabolizers) or heterozygous for either the UGT1A1*28 or UGT1A1*6 alleles (*1/*28, *1/*6) (intermediate UGT1A1 metabolizers) (↑ risk of severe or life-threatening neutropenia);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children;
Geri: ↑sensitivity to adverse effects (myelosuppression) in older adults; initiate at lower dose.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, vasodilation

Derm: alopecia, rash, sweating

EENT: rhinitis

F and E: dehydration

GI: abdominal pain/cramping, anorexia, constipation, diarrhea, dyspepsia, flatulence, nausea, stomatitis, vomiting, weight loss, ↑liver enzymes, abdominal enlargement, colonic ulceration

GU: ↓fertility, menstrual abnormalities

Hemat: anemia, neutropenia, THROMBOCYTOPENIA

Local: injection site reactions

MS: back pain

Neuro: dizziness, headache, insomnia, weakness.

Resp: coughing, dyspnea, INTERSTITIAL LUNG DISEASE (ILD)

Misc: chills, fever, INFECTION

Interactions ⬆ ⬇

Drug-drug:

↑bone marrow depression may occur with other antineoplastics or radiation therapy.
Strong CYP3A4 inhibitors, including ketoconazole, clarithromycin, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, and voriconazole, and strong UGT1A1 inhibitors, including atazanavir and gemfibrozil, may ↑ levels and risk of toxicity of irinotecan and its active metabolite; discontinue ≥1 wk before initiating irinotecan.
Phenobarbital, phenytoin, carbamazepine, rifampin, or rifabutin may ↓ levels of irinotecan and its active metabolite; consider using an alternative anticonvulsant at least 2 wk before initiating irinotecan.
Laxatives should be avoided; diarrhea may be ↑.
Diuretics↑ risk of dehydration; may discontinue during therapy.
Dexamethasone may ↑ risk of hyperglycemia and lymphocytopenia.
Prochlorperazine given on the same day as irinotecan may risk of akathisia.
May ↓ antibody response to and ↑ risk of adverse reactions from live-virus vaccines.

Drug-Natural Products:

St. John's wort↓ levels of irinotecan and the active metabolite; discontinue ≥2 wk before initiating irinotecan.

Availability ⬆ ⬇

(Generic available)

Solution for injection: 20 mg/mL

Route/Dosage ⬆ ⬇

Other regimens are used; careful modification required for all levels of toxicity/tolerance.

Single Agent

IV (Adults ): Weekly dosage schedule: 125 mg/m² once weekly for 4 wk, followed by a 2-wk rest period. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered. Once-every-3-wk schedule: 350 mg/m² once every 3 wk. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered.
IV Geriatric Patients >70 yr): Weekly dosage schedule: 125 mg/m² once weekly for 4 wk, followed by a 2-wk rest period. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered. Once-every-3-wk schedule: 300 mg/m² once every 3 wk. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered.
IV (Adults Homozygous for UGT1A1*28 [*28/*28] or UGT1A1*6 [*6/*6] Alleles or Compound Heterozygous for UGT1A1*28 or UGT1A1*6 [*6/*28] Alleles): Weekly dosage schedule: 100 mg/m² once weekly for 4 wk, followed by a 2-wk rest period. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered. Once-every-3-wk schedule: 300 mg/m² once every 3 wk. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered.

Hepatic Impairment

IV (Adults ): Bilirubin 1–2 mg/dL and history of prior pelvic/abdominal irradiation:Weekly dosage schedule: Initiate therapy at lower dose (100 mg/m²); once weekly for 4 wk, followed by a 2-wk rest period. Cycle may be repeated with dose adjusted as tolerated. Once-every-3-wk schedule: 300 mg/m² once every 3 wk. Cycle may be repeated with dose adjusted as tolerated.

As Part of Combination Therapy With Leucovorin and 5-Fluorouracil

IV (Adults ): Regimen 1 (Bolus regimen): 125 mg/m² once weekly for 4 wk, followed by a 2-wk rest period. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered; Regimen 2 (Infusional regimen): 180 mg/m² every 2 wk for 3 doses, followed by a 3-wk rest period. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered.
IV (Adults Homozygous for UGT1A1*28 [*28/*28] or UGT1A1*6 [*6/*6] Alleles or Compound Heterozygous for UGT1A1*28 or UGT1A1*6 [*6/*28] Alleles): Regimen 1 (Bolus regimen): 100 mg/m² once weekly for 4 wk, followed by a 2-wk rest period. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered; Regimen 2 (Infusional regimen): 150 mg/m² every 2 wk for 3 doses, followed by a 3-wk rest period. Cycle may be repeated using doses that depend on patient tolerance and degree of toxicity encountered.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Interferes with DNA synthesis by inhibiting the enzyme topoisomerase.

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Protein Binding: Irinotecan: 30–68%; SN-38 (active metabolite): 95%.

Metabolism/Excretion: Converted by the liver to SN-38, its active metabolite, which is metabolized by the liver by UDP-glucuronosyl 111 transferase 1A1 (UGT1A1) and CYP3A4. Small amounts excreted by kidneys.

Half-Life: 6 hr.

Time/Action Profile ⬆ ⬇

(hematologic effects)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	21–29 days	27–34 days

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Instruct patient to report occurrence of diarrhea to health care provider immediately if diarrhea occurs for 1st time during treatment; black or bloody stools; symptoms of dehydration such as light-headedness, dizziness, or faintness; inability to take fluids by mouth due to nausea or vomiting; or inability to get diarrhea under control within 24 hr. Diarrhea may be accompanied by severe dehydration and electrolyte imbalance. It may be life-threatening; treat promptly. Loperamide may be used for treatment up to 48 hr.
Instruct patient to monitor their temperature and to notify health care provider promptly if fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to monitor temperature frequently and use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or take products containing aspirin or other NSAIDs.
Instruct patient to notify nurse of pain at injection site immediately.
Instruct patient to notify health care provider if vomiting, fainting, or dizziness occurs.
Discuss with patient possibility of hair loss. Explore methods of coping.
Instruct patient not to receive any vaccinations without consulting health care provider.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected, to use highly effective contraception during and for 6 mo after last dose of therapy, and to avoid breastfeeding during therapy and for 7 days after final dose. Advise men with female partners of reproductive potential to use condoms during and for 3 mo after last dose. May impair female and male infertility.

section name header

Indications ⬇

Contraind./Precautions ⬆ ⬇