irinotecan liposomal

Action and Spectrum

Actions and Spectrum: 

irinotecan liposomal is a medication used to treat certain types of cancer. It is a liposomal formulation of the chemotherapy drug irinotecan, designed to improve its delivery and efficacy. Here’s some information on the action and spectrum of irinotecan liposomal: 

Action: irinotecan liposomal works by inhibiting the enzyme topoisomerase I, which is involved in DNA replication and repair. By inhibiting this enzyme, irinotecan liposomal interferes with ability of the cancer cells to replicate and divide. This ultimately leads to cell death and the inhibition of tumor growth. 

Liposomal Delivery: The liposomal formulation of irinotecan helps improve its delivery to cancer cells. Liposomes are tiny, spherical vesicles composed of lipids (fats) that can encapsulate drugs. They act as carriers, allowing the drug to reach its target more effectively. In the case of irinotecan liposomal, the liposomes help protect the drug from degradation and enhance its circulation in the body, allowing for a more targeted and controlled release at the tumor site. 

Spectrum: irinotecan liposomal is primarily used to treat advanced metastatic colorectal cancer (mCRC) that has progressed despite prior chemotherapy. It is often employed as a second-line treatment option for patients who have failed previous therapies, such as fluoropyrimidines, oxaliplatin, and targeted therapies like anti-EGFR (epidermal growth factor receptor) antibodies. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Pyrexia, grades 1-4 (23%) 

Diminished appetite, grades 1-4 (44%) 

Vomiting, grades 1-4 (52%) 

Alopecia, grades 1-4 (14%) 

Nausea, grades 1-4 (51%) 

Early diarrhea, grades 1-4 (30%) 

Neutropenia, grades 3-4 (20%) 

Late diarrhea, grades 1-4 (43%) 

Weight loss, grades 1-4 (17%) 

Diarrhea, grades 1-4 (59%) 

Stomatitis, grades 1-4 (32%) 

Fatigue or asthenia, grades 1-4 (56%) 

Lymphopenia, grades 3-4 (27%) 

Vomiting, grades 3-4 (11%) 

Fatigue or asthenia, grades 3-4 (21%) 

Diarrhea grades 3-4 (13%) 

1-10% 

Anemia, grades 3-4 (6%) 

Hypokalemia, grades 3-4 (2%) 

Nausea, grades 3-4 (8%) 

Stomatitis, grades 3-4 (4%) 

Increased ALT, grades 3-4 (6%) 

Weight loss, grades 3-4 (2%) 

Late diarrhea, grades 3-4 (3%) 

Alopecia, grades 3-4 (1%) 

Dehydration (4-8%) 

Thrombocytopenia, grades 3-4 (2%) 

Cholinergic reactions, other than diarrhea (4.5%) 

Gastroenteritis (3%) 

Infusion reactions (3%) 

Hyponatremia, grades 3-4 (5%) 

Hypophosphatemia, grades 3-4 (4%) 

Sepsis (3-4%) 

Neutropenic fever/neutropenic sepsis (3%) 

Hypocalcemia, grades 3-4 (1%) 

Hypoalbuminemia, grades 3-4 (2%) 

IV catheter-related infection (3%) 

Hypocalcemia, grades 3-4 (1%) 

Pyrexia, grades 3-4 (2%) 

Black Box Warning

Black Box Warning: 

The black box warning for irinotecan liposomal primarily focuses on the risk of neutropenic sepsis. This severe infection can occur when the white blood cell count (specifically the neutrophil) becomes too low. Neutropenic sepsis can be life-threatening and requires immediate medical attention. 

Another potential side effect of irinotecan liposomal is diarrhea, which will be severe and can lead to dehydration if not properly managed. Diarrhea can occur during treatment with irinotecan liposomal and may require prompt intervention to prevent complications. 

It’s key to note that the information provided here is typical information and should not be considered a substitute for professional medical advice. Suppose you have concerns about irinotecan liposomal or its potential side effects. In that case, I recommend consulting with a healthcare professional or your prescribing physician who can provide detailed and personalized information based on your medical history and current condition. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

irinotecan liposomal has several contraindications, which are specific situations or conditions in which medication use is not recommended. Some of the contraindications associated with irinotecan liposomal include: 

• Hypersensitivity: irinotecan liposomal should not be used in individuals with known hypersensitivity or allergic reactions to irinotecan or any of the components of the formulation. 
• Severe bone marrow suppression: The medication should not be administered to patients with severe bone marrow suppression, as it can further suppress bone marrow function and lead to complications such as severe neutropenia, anemia, and thrombocytopenia. 
• Severe diarrhea: irinotecan liposomal is contraindicated in patients with severe diarrhea, as it can exacerbate the condition. Before initiating treatment, managing any existing diarrhea appropriately is essential. 
• Gilbert’s syndrome: irinotecan liposomal should be used cautiously in individuals with Gilbert’s syndrome, a genetic disorder affecting the liver’s ability to process bilirubin.  

Caution 

some general cautions that may apply: 

• Myelosuppression: irinotecan liposomal can cause bone marrow suppression, leading to low blood cell counts, including white blood cells, red blood cells, and platelets. Close monitoring of blood counts is necessary during treatment, and caution should be exercised in patients with pre-existing bone marrow dysfunction. 
• Gastrointestinal Toxicity: irinotecan liposomal may cause gastrointestinal side effects such as diarrhea, nausea, vomiting, and abdominal pain. These symptoms should be managed appropriately with medications and supportive care. Severe diarrhea may require interruption or discontinuation of treatment. 
• Hepatic Impairment: The liver plays a significant role in the metabolism of irinotecan liposomal. Patients with pre-existing liver dysfunction should be closely monitored, and dose adjustments may be necessary.  
• Renal Impairment: irinotecan liposomal is primarily eliminated through the liver, and the impact of renal impairment on its pharmacokinetics is less clear. However, caution should still be exercised in patients with severe renal impairment, and dose adjustments may be required. 
• Interactions: irinotecan liposomal may interact with other medications, including those metabolized by liver enzymes such as CYP3A4. Reviewing the patient’s medication profile and considering potential drug interactions before initiating treatment is important. 

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk is Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

irinotecan liposomal is a liposomal formulation of the chemotherapy drug irinotecan. The pharmacology of irinotecan liposomal is based on the pharmacological properties of irinotecan itself and the liposomal delivery system.  

• irinotecan liposomal exerts its anticancer effects through the active metabolite SN-38, formed by the enzymatic conversion of irinotecan in the liver. SN-38 inhibits the enzyme topoisomerase I, damaging DNA and interfering with DNA replication and transcription. This ultimately leads to cancer cell death. 
• Liposomal Delivery: The liposomal formulation of irinotecan helps enhance drug delivery and efficacy. Liposomes are small, lipid-based vesicles that encapsulate the drug, protecting it from degradation and improving its stability and circulation. The liposomes can accumulate preferentially in tumor tissues due to the increased permeability and retention (EPR) effect, allowing for localized drug release and prolonged exposure to cancer cells. 

Pharmacodynamics: 

Mechanism of action: irinotecan liposomal exerts its anticancer effects through the same mechanism of action as conventional irinotecan. The liposomal formulation of irinotecan does not alter its mechanism of action. Here’s an overview of the mechanism of action of irinotecan and how it applies to irinotecan liposomal: 

• Inhibition of Topoisomerase I: irinotecan liposomal works by inhibiting the enzyme topoisomerase I. Topoisomerase I is responsible for regulating DNA supercoiling and unwinding during DNA replication and transcription. irinotecan, the active component of irinotecan liposomal, binds to the topoisomerase I-DNA complex, preventing the re-ligation of DNA strands. 
• Formation of Topoisomerase I-DNA Cleavage Complex: Upon binding to the topoisomerase I-DNA complex, irinotecan stabilizes the complex and prevents the resealing of DNA strands. This leads to the formation of irreversible topoisomerase I-DNA cleavage complexes. 
• DNA Damage and Cell Death: The formation of topoisomerase I-DNA cleavage complexes interferes with DNA replication and transcription processes. When the cells attempt to repair the damaged DNA, the cleavage complexes result in the formation of DNA double-strand breaks, which are highly cytotoxic. These DNA breaks trigger apoptosis (programmed cell death) and inhibit cancer cell proliferation. 

Pharmacokinetics: 

Absorption 

irinotecan liposomal is administered intravenously, bypassing the need for absorption. 

Distribution 

After intravenous administration, irinotecan liposomal distributes throughout the body. The liposomes containing the drug allow for improved distribution and prolonged circulation in the bloodstream. The enhanced permeability and retention effect (EPR effect) facilitates irinotecan liposomal distribution to tumor tissues, which allows liposomes to accumulate preferentially in the tumor microenvironment. 

Metabolism 

irinotecan liposomal is metabolized primarily in the liver. Within the liver, the liposomes release irinotecan, which is subsequently converted by the enzyme carboxylesterase into its active metabolite, SN-38. SN-38 is the primary mediator of irinotecan’s anticancer effects. SN-38 is metabolized by glucuronidation, primarily mediated by the enzyme UGT1A1, to an inactive form called SN-38 glucuronide. 

Elimination and Excretion 

The elimination of irinotecan liposomal and its metabolites occurs primarily through the biliary route, excreted through the bile into the gastrointestinal tract. Once in the gastrointestinal tract, some SN-38 glucuronides can be reconverted back into the active SN-38 form by bacterial β-glucuronidase enzymes. A portion of the drug and its metabolites may be eliminated in the feces. In contrast, a smaller portion may undergo enterohepatic circulation, where it is reabsorbed from the gut back into the bloodstream. A minor portion of the drug is eliminated in the urine. 

Adminstartion

Administration: 

Intravenous administration 

irinotecan liposomal is administered through intravenous infusion directly into a vein. The specific administration details may vary depending on the individual patient, prescribed dosage, and healthcare provider’s instructions. It is typically administered in a healthcare facility under the guidance of physician experienced in chemotherapy medications. 

Here are some general guidelines regarding the administration of irinotecan liposomal: 

• Healthcare Setting: irinotecan liposomal is typically administered in a hospital, clinic, or infusion center equipped to handle chemotherapy treatments. This allows for proper monitoring and immediate medical intervention if needed. 
• Dosage: The healthcare provider determines the dosage of irinotecan liposomal based on various factors such as the patient’s body surface area, overall health status, and the specific cancer being treated. The medication is available in pre-dosed vials, and the prescribed dose is calculated based on these factors. 
• Intravenous Infusion: irinotecan liposomal is administered as a slow intravenous infusion. The infusion is usually given over a specified duration, often ranging from 90 minutes to 120 minutes. The exact infusion time may vary depending on the specific protocol or treatment plan established by the healthcare provider. 
• Pre-Medication: Patients may sometimes receive pre-medications before administering irinotecan liposomal. These pre-medications can help prevent or minimize potential side effects, such as hypersensitivity reactions or nausea. Common pre-medications may include corticosteroids, antihistamines, and antiemetics. 
• Monitoring and Follow-up: Patients are closely monitored for any signs of adverse reactions or complications during and after the administration of irinotecan liposomal. This includes regular vital sign assessments, blood tests to monitor blood cell count values and liver function, and evaluation of any infusion-related reactions. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: irinotecan liposomal 

Pronounced: [ EYE-ri-noe-TEE-kan-LYE-poe-SOE-mal ] 

Why do we use irinotecan liposomal? 

irinotecan liposomal is used to treat advanced metastatic colorectal cancer (mCRC) that has progressed despite prior chemotherapy. It is typically indicated for patients who have failed or are intolerant to fluoropyrimidine-based chemotherapy, oxaliplatin, and targeted therapies like anti-EGFR (epidermal growth factor receptor) antibodies. 

irinotecan liposomal is often employed as a second-line treatment option, either as monotherapy or combined with other anticancer agents, such as 5-fluorouracil and leucovorin. It is used when cancer generally spreads to other body parts and is no longer responsive to initial treatment regimens. 

The liposomal formulation of irinotecan is designed to improve the drug’s delivery and enhance its efficacy by encapsulating it in liposomes. This allows for better drug distribution and prolonged release in the body, potentially leading to improved treatment outcomes. 

It’s important to note that the specific use of irinotecan liposomal may vary depending on factors such as the patient’s overall health, disease characteristics, and the healthcare provider’s assessment. Treatment decisions should be generally made in consultation with a healthcare professional who can consider the patient’s situation and provide the most appropriate recommendations.