irinotecan (Rx)

Brand and Other Names:Camptosar
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

  • 20mg/mL

Colorectal Cancer

Indicated as first-line therapy (with 5-fluorouracil and leucovorin) for metastatic colorectal cancer (CRC); it is also indicated for CRC that has recurred or progressed following initial fluorouracil-based therapy

Monotherapy

  • Patients should be premedicated with antiemetic agents
  • Atropine treatment should be considered in patients that experience cholinergic symptoms
  • Regimen 1 (Weekly): 125 mg/m² IV infusion over 90 minutes on days 1, 8, 15, 22, then 2 weeks off, then repeat  
  • Regimen 2 (Once Every 3 Weeks): 350 mg/sq.meter IV infusion over 30-90 minutes q3Weeks
  • Adjust dose per protocol

Combination therapy

  • Patients should be premedicated with antiemetic agents
  • Atropine treatment should be considered in patients that experience cholinergic symptoms
  • Regimen 1 (6 week cycle with infusional 5-fluorouracil/ leucovorin): 180 mg/m² IV infusion over 30-90 minutes once on days 1, 15, and 29 IV (infuse over 30-90 min), followed by infusion with leucovorin and 5-fluorouracil; next cycle begins on day 43  
  • Regimen 2 (6 week cycle with bolus 5-fluorouracil/ leucovorin): 125 mg/sq.meter on days 1, 8, 15, and 22 (infuse over 90 min), followed by bolus doses of leucovorin and 5-fluorouracil
  • Adjust dose per protocol

Dosage Modifications

See prescribing information for detailed recommendations for combination and single-use regimens

Patients homozygous for UGT1A1*28 allele: Precise dose reduction unknown; consider reducing dose by at least 1 level

Renal impairment

  • Not studied; use with caution
  • Dialysis: Not recommended

Hepatic impairment

  • Irinotecan clearance diminished with hepatic impairment, while exposure to active metabolite SN-38 is increased relative to that in patients with normal hepatic function
  • Caution when administering to patients with hepatic impairment
  • Hepatic dysfunction (bilirubin >2 mg/dL): Not sufficiently assessed; no recommendations for dosing can be made

Pancreatic Cancer (Orphan)

Stable nanotherapeutic encapsulated irinotecan (MM-398; pegirinotecan)

Orphan indication sponsor

  • Merrimack Pharmaceuticals, Inc., 1 Kendall Square; Cambridge, MA 02139-1670

Ovarian Cancer (Orphan)

Peg-irinotecan: Treatment of ovarian cancer

Orphan indication sponsor

  • Nektar Therapeutics; 455 Mission Bay Blvd; South San Francisco, CA 94158

Other Indications & Uses

Off-label: advanced ovarian cancer, glioblastoma multiforme, NSCLC

Not recommended

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Interactions

Interaction Checker

and irinotecan

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Anemia (>90%)

            Leukopenia (>90%)

            Neutropenia (>90%)

            Thrombocytopenia (>90%)

            Elevated bilirubin (88%)

            Diarrhea (85%)

            Nausea (79%)

            Asthenia (70%)

            Abdominal pain (63%)

            Vomiting (60%)

            Alopecia (43%)

            Fever (42%)

            Constipation (41%)

            Anorexia (34%)

            Mucositis (32%)

            Pain (31%)

            Dyspnea (28%)

            Cough (27%)

            Dizziness (23%)

            Infection (22%)

            Rash (19%)

            1-10%

            Abdominal fullness (10%)

            AST increased (10%)

            Dyspepsia (10%),

            Edema (10%)

            Ascites/jaundice (9%)

            Vasodilation (9%)

            Thromboembolism (9%)

            Hypotension (6%)

            Neutropenic fever (2-6%)

            Frequency Not Defined

            Headache

            Insomnia

            Orthostatic hypotension

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            Warnings

            Black Box Warnings

            Severe myelosuppression may occur

            Diarrhea

            • Early and late forms of diarrhea can occur
            • Early diarrhea may be accompanied by cholinergic symptoms which may be prevented or ameliorated by atropine
            • Late diarrhea can be life threatening and should be treated promptly with loperamide
            • Monitor 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

            Contraindications

            Hypersensitivity to drug or excipients

            Contains sorbitol, which is contraindicated in individuals with hereditary fructose intolerance

            Cautions

            Hyperbilirubinemia, elderly, receiving radiation therapy, abdominal/pelvic radiation history

            Outside of a clinical study, not for use in combination with a regimen of 5-FU/LV administered for 4-5 consecutive days every 4 weeks owing to increased toxicity, including toxic deaths

            Renal impairment and acute renal failure reported; usually in patients who became volume depleted from severe vomiting and/or diarrhea

            Interstitial pulmonary disease (IPD)-like events, including fatalities, have been reported (in combination and as monotherapy) for treatment of colorectal cancer and other advanced solid tumors

            Therapy can cause severe myelosuppression; bacterial, viral, and fungal infections have occurred in patients receiving therapy; manage febrile neutropenia promptly with antimicrobial support; interrupt therapy and reduce subsequent doses if necessary

            Drug is subject to photodegradation, especially in neutral and alkaline solutions

            Individuals who are homozygous for the UGT1A1*28 allele are at increased risk for neutropenia following initiation of therapy; consider dose reduction by at least 1 level for pts homozygous in the enzyme UDP-glucuronosyl transferase 1A1*28 (UGT1A1*28) variant

            Avoid pregnancy; can cause fetal harm

            Diarrhea and cholinergic reactions

            • Also see Black Box Warnings
            • Early diarrhea
              • Occurs during or shortly after infusion
              • Usually transient and infrequently severe; may be accompanied by cholinergic symptoms of rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, and intestinal hyperperistalsis that can cause abdominal cramping
              • Bradycardia may also occur
              • May be prevented or treated; consider prophylactic or therapeutic administration of atropine 0.25-1 mg IV/SC unless clinically contraindicated
              • These symptoms are expected to occur more frequently with higher irinotecan doses
            • Late diarrhea
              • Generally occurs >24 hr after administration
              • Can be life threatening since it may be prolonged and may lead to dehydration, electrolyte imbalance, or sepsis
              • Grade 3-4 late diarrhea occurred in 23-31% of patients receiving weekly dosing
              • Late diarrhea can be complicated by colitis, ulceration, bleeding, ileus, obstruction, and infection; megacolon and intestinal perforation also reported
              • Patients should have loperamide readily available to begin treatment for late diarrhea
              • Begin loperamide with first episode of poorly formed or loose stools, or the earliest onset of bowel movements more frequent than normal
              • Loperamide is not recommended to be used for more than 48 consecutive hr at the higher doses needed for treating irinotecan-induced diarrhea, owing to risk of paralytic ileus
              • Monitor and replace fluid and electrolytes; use antibiotic support for ileus, fever, or severe neutropenia
              • Delay subsequent irinotecan weekly chemotherapy until pretreatment bowel function restored (ie, ≥24 hr without antidiarrheal medication)
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            Pregnancy & Lactation

            Pregnancy Category: D

            Lactation: not known if excreted in breast milk, do not nurse

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Binds to topoisomerase I to produce double-strand breaks in DNA

            Pharmacokinetics

            Half-Life: 6-12 hr; SN-38 10-20 hr

            Pleak Plasma Concentration: 1660 ng/mL; SN-38 26.3 ng/mL

            Protein Bound: 30-68%; SN-38 95%

            Vd: 110-234 L/m²

            Metabolism: hepatic, to SN-38; SN-38 is further metabolized by UGT1A1

            Metabolites: SN-38

            Clearance: 13-14 L/hr/m²

            Excretion: urine, feces

            Pharmacogenomics

            Converted to SN-38 active metabolite; SN-38 is subsequently conjugated predominantly by the enzyme UDP-glucuronosyl transferase 1A1 (UGT1A1) to form a glucuronide metabolite

            UGT1A1 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity such as the UGT1A1*28 polymorphism

            Reduced UGT1A1 activity increases risk for neutropenia

            ~10% of North American population is homozygous for UGT1A1*28 variant; consider dose reduction in these patients

            Genetic testing laboratories

            • Genotyping tests are available through the following companies
            • ARUP Laboratories (http://www.aruplab.com/)
            • LabCorp (http://www.labcorp.com/)
            • Genzyme Genetics (http://www.genzymegenetics.com/)
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            Administration

            IV Incompatibilities

            Additive: methylprednisolone sodium succinate (10% loss in 3 hr)

            Y-site: gemcitabine

            IV Preparation

            Dilute in D5W to a final concentration of 0.12-2.8 mg/mL (most commonly in 500 mL D5W)

            NS can be used, but precipitation under refrigeration is more likely with NS, so D5W is generally preferred

            IV Administration

            Irritant

            Infuse over 90 min

            If administered in combination with fluorouracil & leucovorin, administer leucovorin immediately after irinotecan, & administer fluorouracil immediately after leucovorin

            Premedication with antiemetics (dexamethasone plus ondansetron/granisetron) is recommended, at least 30 min prior to infusion

            Atropine should be considered in pts experiencing cholinergic symptoms

            Storage

            Store at controlled room temp

            Protect from light

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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.