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.
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.
Note: Irinotecan (liposomal) is associated with a moderate emetic potential (ASCO [Hesketh 2020]). 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.
CrCl 30 to 89 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, a population pharmacokinetic analysis showed no effect on total SN-38 exposure in patients with mild to moderate renal impairment.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (insufficient data).
Bilirubin >ULN: There are no dosage adjustments provided in the manufacturer's labeling (there is no recommended dose); use with caution. No data are available regarding use in patients with bilirubin >2 mg/dL.
Refer to adult dosing.
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
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)]
No
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)]
Irinotecan (liposomal) is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]).
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.
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).
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 (PS) of 0 or 1, a relatively favorable comorbidity profile, preference for aggressive therapy, a suitable support system, and access to a chemotherapy port/infusion pump management service who received an alternative (gemcitabine-based) first-line therapy. Irinotecan (liposomal) may be added to fluorouracil (with proactive dose/schedule adjustments to minimize toxicities) as second-line therapy for patients with a PS of 2 or a comorbidity profile prohibiting more aggressive therapy (ASCO [Sohal 2020]).
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]).
Liposomal formulation (Onivyde) may be confused with the conventional formulation (Camptosar)
Irinotecan (liposomal) may be confused with irinotecan (conventional), topotecan
Onivyde may be confused with Oncaspar, Opdivo
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 (liposomal) and irinotecan (conventional) are NOT interchangeable. Dosing differs between formulations; verify intended product and dose prior to preparation and administration.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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%)
Severe hypersensitivity to irinotecan (liposomal), irinotecan hydrochloride, or any component of the formulation
Canadian labeling (additional contraindications not in the US labeling): Breastfeeding
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 (ASCO [Hesketh 2020]). Stomatitis also commonly occurs.
• Hepatitis B virus screening: 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.
• 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.
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
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
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
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
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: In the US, after receipt of the single dose COVID-19 adenovirus vector vaccine (Janssen), administer an additional 2nd dose using an mRNA COVID-19 vaccine, at least 28 days after the primary vaccine dose, in patients taking immunosuppressive therapies. 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: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. 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
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
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
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
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
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
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
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
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 post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
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
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of 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 Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
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
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): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). 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
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.
Based on the mechanism of action as well as animal data using irinotecan (conventional), irinotecan (liposomal) may cause fetal harm if administered during pregnancy.
It is not known if irinotecan (liposomal) is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy or for one month following the last dose.
Complete blood counts on days 1 and 8 of each cycle and as clinically indicated; bilirubin, electrolytes (with severe diarrhea). Hepatitis B virus screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning systemic anticancer therapy (ASCO [Hwang 2020]). Monitor bowel movements (diarrhea episodes) and hydration status; monitor for signs/symptoms of pulmonary toxicity or hypersensitivity reactions
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
Protein binding: <1%
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).
Half-life elimination: Total irinotecan: ~26 hours; SN-38: ~68 hours
Excretion: Urine: Irinotecan hydrochloride (11% to 20%), metabolites (SN-38 <1%, SN-38 glucuronide, 3%)
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.
Injection (Onivyde Intravenous)
43 mg/10 mL (per mL): $309.96
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