Irinotecan liposomal

Mechanism of Action

Binds to topoisomerase-1

Topoisomerase-1 relieves torsional strain in DNA by inducing single-strand breaks

Irinotecan and its active metabolite SN-38 bind reversibly to the topoisomerase-1 DNA complex and prevent re-ligation of the single-strand breaks, leading to exposure time-dependent double-strand DNA damage and cell death

Absorption

Peak plasma concentration: 37.2 mcg/mL; 5.4 ng/mL (SN-38)

AUC: 1364 h·mcg/mL; 620 h·mcg/mL (SN-3

Distribution

Vd: 4.1 L; 95% remains encapsulated

Metabolism

Metabolism of irinotecan liposome has not been evaluated

Irinotecan is subject to extensive metabolic conversion by various enzyme systems, including esterases to form the active metabolite SN-38, and UGT1A1 mediating glucuronidation of SN-38 to form the inactive glucuronide metabolite SN-38G

Irinotecan can also undergo CYP3A4-mediated oxidative metabolism to several inactive oxidation products, one of which can be hydrolyzed by carboxylesterase to release SN-38

Elimination

Half-life: 25.8 hr; 67.8 hr (SN-38)

Clearance: 0.2 L/hr

Excretion: 11-20% urine (SN-38 <1%); 25-50% cumulative biliary and urinary (parent drug and metabolites over 48 hr

Pharmacogenomics

Homozygous for UGT1A1*28 allele

• Individuals who are homozygous for the UGT1A1*28 allele are at increased risk for neutropenia from irinotecan HCL
• In clinical trials, patients homozygous for the UGT1A1*28 allele (N=7) were initiated on irinotecan liposomal (Onivyde) at a reduced dose of 50 mg/m² in combination with 5-fluorouracil/leucovorin
• The frequency of grade 3 or 4 neutropenia in these patients (2 of 7 [28.6%]) was similar to the frequency in patients not homozygous for the UGT1A1*28 allele who received a starting dose of irinotecan liposomal of 70 mg/m² (30 of 110 [27.3%])

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about irinotecan, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

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 brief summary of general information about irinotecan. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using irinotecan.

Review Date: October 4, 2017

(eye rye no TEE kan lye po SO mal)

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

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)]

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

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.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience mouth sores, lack of appetite, alopecia, or weight loss. Have patient report immediately to prescriber diarrhea, signs of infection, signs of fluid and electrolyte problems (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), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), signs of a severe pulmonary disorder (lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse), bruising, bleeding, loss of strength and energy, black, tarry, or bloody stools, severe nausea, or vomiting (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience,and judgment in diagnosing, treating, and advising patients.

Applies to irinotecan liposomal: intravenous solution

Along with its needed effects, irinotecan liposomal may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking irinotecan liposomal:

• Confusion
• decreased urination
• diarrhea (severe)
• dizziness
• dry mouth
• fainting
• fever
• lightheadedness
• rapid breathing
• sunken eyes
• thirst
• unusual tiredness or weakness
• wrinkled skin

• Black, tarry stools
• chest pain or discomfort
• chills
• confusion
• cough
• fast heartbeat
• lightheadedness, dizziness, or fainting
• lower back or side pain
• painful or difficult urination
• pale skin
• rapid, shallow breathing
• shortness of breath
• slow or irregular heartbeat
• sore throat
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising

• Difficulty with breathing or swallowing
• hives, itching, or skin rash
• nausea
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• reddening of the skin, especially around the ears
• tightness in the chest

Some side effects of irinotecan liposomal may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Decreased appetite
• hair loss or thinning of the hair
• lack or loss of strength
• vomiting
• weight loss

• Abdominal or stomach pain
• feeling of warmth
• increased sweating
• runny nose
• sneezing
• stuffy nose
• tearing of the eyes
• watering of the mouth
• weakness

Data not available

Data not available