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Irinotecan (Liposomal)

Medically reviewed by Drugs.com. Last updated on Mar 22, 2020.

Pronunciation

(eye rye no TEE kan lye po SO mal)

Index Terms

  • Irinotecan Liposome
  • Liposomal Irinotecan
  • Liposome-Encapsulated Irinotecan Hydrochloride PEP02
  • MM-398
  • Nanoliposomal Irinotecan
  • Onivyde

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injectable, Intravenous:

Onivyde: 43 mg/10 mL (10 mL) [contains mpeg-2000-dspe (methoxy-terminated peg)]

Brand Names: U.S.

  • Onivyde

Pharmacologic Category

  • Antineoplastic Agent, Camptothecin
  • Antineoplastic Agent, Topoisomerase I Inhibitor

Pharmacology

Irinotecan (liposomal) is a topoisomerase 1 inhibitor encapsulated in a lipid bilayer (liposome). Irinotecan and its active metabolite (SN-38) bind reversibly to topoisomerase I-DNA complex preventing re-ligation 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

4.1 L; 95% of irinotecan remains liposome-encapsulated

Metabolism

Irinotecan hydrochloride: Primarily hepatic to SN-38 (active metabolite) by carboxylesterase enzymes; may also undergo CYP3A4-mediated metabolism to 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 is increased by UGT1A1*28 polymorphism (10% of North Americans are homozygous for UGT1A1*28 allele).

Excretion

Urine: Irinotecan hydrochloride (11% to 20%), metabolites (SN-38 <1%, SN-38 glucuronide, 3%)

Half-Life Elimination

Total irinotecan: ~26 hours; SN-38: ~68 hours

Protein Binding

<1%

Special Populations: Hepatic Function Impairment

Average steady-state concentrations for total SN-38 were increased by 37% in patients with baseline bilirubin concentrations of 1 to 2 mg/dL versus patients with baseline bilirubin levels <1 mg/dL.

Special Populations: Race

The average steady-state concentrations of total irinotecan and total SN-38 are 56% lower and 8% higher, respectively, in Asian patients versus white patients.

Use: Labeled Indications

Pancreatic adenocarcinoma, metastatic: Treatment of metastatic adenocarcinoma of the pancreas (in combination with fluorouracil and leucovorin) after disease progression following gemcitabine-based therapy.

Limitations of use: Irinotecan (liposomal) is not indicated as a single agent for the treatment of metastatic adenocarcinoma of the pancreas.

Guideline recommendations:

The American Society of Clinical Oncology (ASCO) guidelines for metastatic pancreatic cancer recommend fluorouracil in combination with irinotecan (liposomal) as preferred second-line therapy in patients with Eastern Cancer Cooperative Group (ECOG) performance status of 2 or a comorbidity profile prohibiting more aggressive therapy who received an alternative (gemcitabine-based) first-line therapy (ASCO [Sohal 2018]).

According to ASCO guidelines for locally advanced, unresectable pancreatic cancer, if disease progression occurs following induction with an initial systemic combination therapy regimen, treatment according to guidelines for metastatic pancreatic cancer should be offered (in appropriate patients) (ASCO [Balaban 2016]).

Contraindications

Severe hypersensitivity to irinotecan (liposomal), irinotecan hydrochloride, or any component of the formulation

Canadian labeling (additional contraindications not in the US labeling): Breastfeeding

Dosing: Adult

Note: Irinotecan (liposomal) is associated with a moderate emetic potential (Hesketh 2017). Premedicate with a corticosteroid and an antiemetic 30 minutes prior to infusion. Irinotecan (liposomal) and irinotecan (conventional) are NOT interchangeable. Dosing differs between formulations; verify intended product and dose prior to preparation and administration.

Pancreatic adenocarcinoma, metastatic: IV: 70 mg/m2 once every 2 weeks (in combination with fluorouracil and leucovorin) (Wang-Gillam 2016). Note: Reduce initial starting dose to 50 mg/m2 in patients known to be homozygous for the UGT1A1*28 allele; the dose may be increased to 70 mg/m2 as tolerated in subsequent cycles.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Note: Fluorouracil and leucovorin may also require dosage adjustment.

Hematologic toxicity: ANC <1,500/mm3 or neutropenic fever: Withhold treatment. Resume therapy when ANC ≥1,500/mm3 with a reduced dose for grade 3 or 4 neutropenia or neutropenic fever in subsequent cycles:

First occurrence: Reduce dose to 50 mg/m2 (in patients receiving 70 mg/m2); reduce dose to 43 mg/m2 in patients homozygous for UGT1A1*28 without previous increase to 70 mg/m2

Second occurrence: Reduce dose to 43 mg/m2 (in patients receiving 50 mg/m2); reduce dose to 35 mg/m2 in patients homozygous for UGT1A1*28 previously receiving 43 mg/m2

Third occurrence: Discontinue

Nonhematologic toxicity:

Anaphylactic reaction: Discontinue permanently

Diarrhea: Withhold therapy for grade 2 to 4 diarrhea. Administer IV or SubQ atropine 0.25 to 1 mg (unless clinically contraindicated) for early-onset diarrhea of any severity. Administer loperamide for late-onset diarrhea of any severity. Following recovery to ≤ grade 1 diarrhea, resume treatment at a reduced dose:

First occurrence: Reduce dose to 50 mg/m2 (in patients receiving 70 mg/m2); reduce dose to 43 mg/m2 in patients homozygous for UGT1A1*28 without previous increase to 70 mg/m2

Second occurrence: Reduce dose to 43 mg/m2 (in patients receiving 50 mg/m2); reduce dose to 35 mg/m2 in patients homozygous for UGT1A1*28 previously receiving 43 mg/m2

Third occurrence: Discontinue

Interstitial lung disease (ILD): Discontinue

Other grade 3 or 4 adverse reactions: Withhold therapy. Upon recovery to ≤ grade 1 toxicity, resume treatment at a reduced dose:

First occurrence: Reduce dose to 50 mg/m2 (in patients receiving 70 mg/m2); reduce dose to 43 mg/m2 in patients homozygous for UGT1A1*28 without previous increase to 70 mg/m2

Second occurrence: Reduce dose to 43 mg/m2 (in patients receiving 50 mg/m2); reduce dose to 35 mg/m2 in patients homozygous for UGT1A1*28 previously receiving 43 mg/m2

Third occurrence: Discontinue

Reconstitution

Withdraw appropriate dose from the vial and dilute in 500 mL D5W or NS. Mix by gentle inversion; protect diluted solution from light.

Administration

Irinotecan (liposomal) is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Hesketh 2017).

IV: Administer by IV infusion over 90 minutes. Premedicate with a corticosteroid and an antiemetic 30 minutes prior to infusion. Administer irinotecan (liposomal) prior to fluorouracil and leucovorin. Do not use in-line filters for administration.

Administer IV or SubQ atropine 0.25 to 1 mg (unless clinically contraindicated) for early onset diarrhea of any severity; initiate loperamide for late-onset diarrhea of any severity.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Solution diluted for administration in D5W or NS is stable for up to 4 hours when stored at room temperature, or up to 24 hours when refrigerated (administration should be completed within these time frames). Allow diluted solution to come to room temperature prior to administration.

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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. Avoid combination

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). 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. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan Products. Avoid combination

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

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. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

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

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Management: Consider avoiding Echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Consider therapy modification

Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Monitor therapy

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Gemfibrozil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. See separate drug interaction monographs for agents listed as exceptions. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Inebilizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. 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. 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. Consider therapy modification

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Management: Avoid use of immunosuppressants (including systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for immune-related toxicity) is unlikely to affect nivolumab efficacy. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Ozanimod: Immunosuppressants may enhance the immunosuppressive effect of Ozanimod. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). 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. Consider therapy modification

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Rifabutin: May decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. Rifabutin may decrease the serum concentration of Irinotecan Products. Monitor therapy

Rifapentine: May decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. Rifapentine may decrease the serum concentration of Irinotecan Products. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Management: Consider avoiding concomitant use of roflumilast and immunosuppressants as recommended by the Canadian product monograph. Inhaled or short-term corticosteroids are unlikely to be problematic. Consider therapy modification

Sacituzumab Govitecan: Irinotecan Products may enhance the adverse/toxic effect of Sacituzumab Govitecan. Avoid combination

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). 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. Avoid combination

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Monitor therapy

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tobacco (Smoked): May decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Tolvaptan: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Management: Avoid concomitant use of OATP1B1/1B3 substrates in patients receiving the Jynarque brand of tolvaptant. Concentrations and effects of the OATP1B1/1B3 substrate would be expected to increase with combined use. Consider therapy modification

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. Exceptions: Atazanavir; Ombitasvir, Paritaprevir, and Ritonavir; Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Avoid combination

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Management: Concomitant use of upadacitinib with potent immunosuppressants is not recommended. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Adverse Reactions

Frequency not always defined. Percentages reported as part of combination chemotherapy regimens.

Cardiovascular: Septic shock (≥2%)

Central nervous system: Fatigue (≤56%)

Dermatologic: Alopecia (14%)

Endocrine & metabolic: Hypoalbuminemia (43%), hypomagnesemia (35%), hypocalcemia (32%), hypokalemia (32%), hypophosphatemia (29%), hyponatremia (27%), weight loss (17%), dehydration (8%)

Gastrointestinal: Diarrhea (59%, grade 3/4: 13%; early onset 30%, grade 3/4: 3%; late onset 43%, grade 3/4: 9%), vomiting (52%), nausea (51%), decreased appetite (44%), stomatitis (32%), gastroenteritis (3%)

Hematologic & oncologic: Anemia (97%, grades 3/4: 6%), lymphocytopenia (81%, grades 3/4: 27%), neutropenia (52%, grades 3/4: 20%; incidence of neutropenia was higher among Asian patients), thrombocytopenia (41%, grades 3/4: 2%), febrile neutropenia (≤3%, grades 3/4: ≤3%)

Hepatic: Increased serum ALT (51%)

Hypersensitivity: Severe hypersensitivity

Infection: Sepsis (4%, grades 3/4: 3%), neutropenic sepsis (≤3%, grades 3/4: ≤3%)

Local: Catheter infection (3%)

Neuromuscular & skeletal: Weakness (≤56%)

Renal: Increased creatinine clearance (18%), acute renal failure (≥2%)

Respiratory: Pneumonia (≥2%), interstitial pulmonary disease

Miscellaneous: Fever (23%)

ALERT: U.S. Boxed Warning

Bone marrow suppression:

Fatal neutropenic sepsis occurred in 0.8% of patients receiving irinotecan (liposomal). Severe or life-threatening neutropenic fever or sepsis occurred in 3% and severe or life-threatening neutropenia occurred in 20% of patients receiving irinotecan (liposomal) in combination with fluorouracil and leucovorin. Withhold irinotecan (liposomal) for absolute neutrophil count below 1,500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment.

Gastrointestinal toxicity:

Severe diarrhea occurred in 13% of patients receiving irinotecan (liposomal) in combination with fluorouracil and leucovorin. Do not administer irinotecan (liposomal) to patients with bowel obstruction. Withhold irinotecan (liposomal) for diarrhea of grade 2 to 4 severity. Administer loperamide for late diarrhea of any severity. Administer atropine, if not contraindicated, for early diarrhea of any severity.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: [US Boxed Warning]: Fatal neutropenic sepsis occurred in nearly 1% of patients receiving irinotecan (liposomal). Severe or life-threatening neutropenic fever or sepsis occurred in 3% and severe or life-threatening neutropenia occurred in 20% of patients receiving irinotecan (liposomal) in combination with fluorouracil and leucovorin. Withhold irinotecan (liposomal) for absolute neutrophil count below 1,500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment (days 1 and 8 of each cycle and more frequently if clinically necessary). May require therapy interruption, dose reduction, and/or discontinuation. Anemia, lymphopenia, and thrombocytopenia also commonly occur. The incidence of neutropenia was higher in Asian patients (compared to white patients).

• Gastrointestinal toxicity: [US Boxed Warning]: Severe diarrhea (may be life-threatening) occurred in 13% of patients receiving irinotecan (liposomal) in combination with fluorouracil and leucovorin. Do not administer irinotecan (liposomal) to patients with bowel obstruction. Withhold irinotecan (liposomal) for diarrhea of grade 2 to 4 severity. Administer loperamide for late diarrhea of any severity. Administer atropine, if not contraindicated, for early diarrhea of any severity. Early onset diarrhea occurs within 24 hours of chemotherapy, and may cause other symptoms of cholinergic reaction. Late onset diarrhea occurs more than 24 hours following chemotherapy. Diarrhea may require therapy interruption, dosage reduction, and/or discontinuation. Irinotecan (liposomal) is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Hesketh 2017). Stomatitis also commonly occurs.

• Hypersensitivity reactions: Severe hypersensitivity reactions (including anaphylaxis) have occurred with irinotecan (conventional). Monitor closely; permanently discontinue irinotecan (liposomal) therapy if severe hypersensitivity occurs.

• Pulmonary toxicity: Irinotecan (conventional) may cause severe and fatal interstitial lung disease (ILD). Withhold irinotecan (liposomal) during diagnostic evaluation if new or progressive dyspnea, cough, or fever occurs during use. Discontinue therapy if ILD diagnosis is confirmed.

Disease-related concerns:

• Bowel obstruction: Do not administer in patients with bowel obstruction.

• Hepatic impairment: The pharmacokinetics of irinotecan (liposomal) have not been studied in patients with hepatic impairment. However, exposure to the active metabolite (SN-38) is increased in patients with hepatic impairment receiving irinotecan (conventional); toxicities may be increased.

Concurrent drug therapy issues:

• Drug-drug interactions: CYP3A4 enzyme inducers may decrease exposure to irinotecan and SN-38 (active metabolite); avoid concomitant use (substitute non-enzyme inducing therapies at least 2 weeks prior to irinotecan [liposomal] initiation). Enzyme inhibitors may increase exposure; avoid concomitant use (discontinue strong CYP3A4 inhibitors at least 1 week prior to irinotecan [liposomal] initiation).

Dosage form specific issues:

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

Monitoring Parameters

Complete blood counts on days 1 and 8 of each cycle and as clinically indicated; bilirubin, electrolytes (with severe diarrhea); bowel movements (diarrhea episodes) and hydration status; signs/symptoms of pulmonary toxicity or hypersensitivity reactions

Reproductive Considerations

Women of childbearing potential should use effective contraception while receiving treatment and avoid pregnancy for 1 month following the last dose. Males with female partners of reproductive potential should use condoms during therapy and for 4 months following the last dose.

Pregnancy Considerations

Based on the mechanism of action as well as animal data using irinotecan (conventional), irinotecan (liposomal) may cause fetal harm if administered during pregnancy.

Patient Education

What is this drug used for?

• It is used to treat pancreatic cancer.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Mouth irritation

• Mouth sores

• Lack of appetite

• Hair loss

• Weight loss

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe diarrhea

• Infection

• Fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, nausea, or vomiting.

• Kidney problems like unable to pass urine, blood in urine, change in amount of urine passed, weight gain.

• Lung problems like shortness of breath or other trouble breathing, cough that is new or worse

• Bruising

• Bleeding

• Severe loss of strength and energy

• Black, tarry, or bloody stools

• Severe nausea

• Vomiting

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.