Onivyde Pegylated Liposomal (Irinotecan)
Liposomal topoisomerase I inhibitor for metastatic pancreatic cancer
Onivyde pegylated liposomal is a chemotherapy medicine containing the active substance irinotecan enclosed in tiny fat particles called liposomes. It is used to treat adults with metastatic pancreatic cancer, either as first-line therapy or after gemcitabine-based treatment has failed. The liposomal delivery system allows the drug to accumulate in tumors and release slowly, providing a sustained anticancer effect.
Quick Facts
Key Takeaways
- Onivyde pegylated liposomal is a liposomal form of irinotecan approved for metastatic pancreatic adenocarcinoma, used in combination with other chemotherapy agents.
- It is administered as an intravenous infusion over at least 90 minutes every two weeks in a hospital setting by trained oncology professionals.
- The most important side effects to watch for are severe diarrhea, neutropenia (low white blood cells), and infusion-related allergic reactions.
- This liposomal formulation must not be substituted for conventional irinotecan, as the two have different dosing, pharmacokinetics, and safety profiles.
- Patients should avoid grapefruit and grapefruit juice during treatment, and inform their physician about all current medications due to significant drug interactions.
What Is Onivyde Pegylated Liposomal and What Is It Used For?
Onivyde pegylated liposomal is an innovative anticancer treatment specifically designed for the management of metastatic adenocarcinoma of the pancreas. Pancreatic cancer is one of the most aggressive malignancies, and metastatic disease — meaning the cancer has spread beyond the pancreas to other parts of the body — represents an advanced stage that requires systemic chemotherapy to control tumor growth and improve patient outcomes.
The active substance in Onivyde pegylated liposomal is irinotecan, which belongs to a class of anticancer agents known as topoisomerase I inhibitors. Topoisomerase I is an essential enzyme that cancer cells need to unwind and replicate their DNA. By blocking this enzyme, irinotecan causes irreversible breaks in the DNA strands during cell division, which prevents cancer cells from reproducing and ultimately leads to their death.
What makes Onivyde pegylated liposomal unique is its liposomal delivery system. The irinotecan molecules are encapsulated within pegylated liposomes — microscopic spheres made of lipid bilayers coated with polyethylene glycol (PEG). This coating helps the liposomes circulate in the bloodstream for longer periods and avoid rapid clearance by the immune system. The liposomes are designed to exploit the enhanced permeability and retention (EPR) effect found in many tumors, where leaky blood vessels allow the liposomes to accumulate preferentially in tumor tissue. Once inside the tumor, the liposomes gradually release irinotecan, providing a sustained drug concentration at the site where it is needed most.
Indications and Combination Regimens
Onivyde pegylated liposomal is authorized for two distinct clinical settings in metastatic pancreatic adenocarcinoma:
- First-line treatment: For patients who have not received prior chemotherapy for metastatic disease, Onivyde pegylated liposomal is given in combination with oxaliplatin, 5-fluorouracil (5-FU), and leucovorin. This regimen, known as NALIRIFOX, has shown improved overall survival compared to other standard-of-care regimens in clinical trials.
- Second-line treatment: For patients whose cancer has progressed after gemcitabine-based therapy, Onivyde pegylated liposomal is combined with 5-fluorouracil and leucovorin. The NAPOLI-1 clinical trial demonstrated that this combination significantly extended overall survival compared to 5-FU/leucovorin alone in gemcitabine-refractory patients.
It is important to understand that Onivyde pegylated liposomal is not used as a single agent (monotherapy). It is always part of a combination chemotherapy regimen, and your oncologist will determine the most appropriate treatment plan based on your disease stage, overall health, and prior treatment history.
What Should You Know Before Taking Onivyde Pegylated Liposomal?
Contraindications
There are specific situations where Onivyde pegylated liposomal must not be used. These absolute contraindications are in place to protect patients from potentially life-threatening adverse events:
- Severe allergy (hypersensitivity): You must not receive Onivyde pegylated liposomal if you have a known severe allergy to irinotecan or any of the other ingredients in the formulation. Allergic reactions during infusion can range from mild (rash, itching) to life-threatening anaphylaxis.
- Breastfeeding: Women who are breastfeeding must not receive this medicine. Irinotecan and its metabolites may pass into breast milk and could harm the nursing infant. Breastfeeding must not be resumed until at least one month after the last dose.
Warnings and Precautions
Before starting treatment, it is essential that your healthcare team is fully informed about your medical history. The following conditions or circumstances require special attention and may affect how your treatment is managed:
- Liver problems or jaundice: Irinotecan is metabolized in the liver, and impaired liver function can significantly alter drug levels in the body, increasing the risk of toxicity. Your doctor will perform liver function tests before starting treatment and may adjust your dose accordingly.
- Lung disease: Pre-existing lung conditions may increase the risk of pulmonary complications, including pneumonitis (inflammation of the lungs), which has been reported with irinotecan-based therapies.
- Previous colony-stimulating factor use or radiation therapy: If you have previously received growth factors to boost blood cell counts or have undergone radiation therapy, your risk of severe bone marrow suppression may be increased.
- Vaccinations: Several types of vaccines, particularly live vaccines, are contraindicated during chemotherapy because your immune system is suppressed. Discuss any planned vaccinations with your oncologist before starting treatment.
- Sodium-restricted diet: Onivyde pegylated liposomal contains 33.1 mg of sodium per vial (approximately 1.65% of the WHO recommended maximum daily intake for adults). Patients on a sodium-restricted diet should take this into account.
- Sudden breathlessness, flushing, headache, rash, or hives during or shortly after the infusion
- Fever, chills, or other signs of infection
- Severe or persistent diarrhea that cannot be controlled after 12–24 hours
- Sudden pain or swelling in a limb, chest pain, or difficulty breathing (possible blood clot)
Diarrhea Management
Diarrhea is one of the most clinically significant side effects of irinotecan-based therapies and can become severe if not managed promptly. There are two distinct forms that may occur:
- Early-onset diarrhea (cholinergic syndrome): Occurring during or shortly after the infusion, accompanied by sweating, abdominal cramping, and excessive salivation. This is managed with atropine.
- Late-onset diarrhea: Occurring more than 24 hours after the infusion, which can be severe and prolonged. At the first sign of watery stools, begin drinking large amounts of fluids (water, clear broths, electrolyte solutions) and contact your doctor immediately. Your doctor may prescribe loperamide, but this should not be used for more than 48 consecutive hours. If diarrhea persists, seek medical attention urgently.
Pregnancy and Breastfeeding
Onivyde pegylated liposomal can cause serious harm to an unborn baby. Women of childbearing potential must use effective contraception during treatment and for at least seven months after the last dose. Men receiving this treatment should use condoms during therapy and for at least four months afterward.
If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, you must inform your doctor before receiving this treatment. The potential risks to the fetus versus the benefits of treatment will need to be carefully discussed.
Breastfeeding is strictly contraindicated during treatment with Onivyde pegylated liposomal and for at least one month after the last dose. The active substance and its metabolites may be excreted in breast milk and could pose a risk to the nursing infant.
Regarding fertility, patients should discuss potential effects on reproductive capacity with their oncologist before initiating treatment. Options for fertility preservation may be available and should be considered prior to starting chemotherapy.
Driving and Using Machines
Onivyde pegylated liposomal may impair your ability to drive and operate machinery. Common side effects such as drowsiness, dizziness, and fatigue can affect concentration and reaction times. Avoid driving, operating heavy machinery, or performing tasks requiring full alertness if you experience these symptoms.
How Does Onivyde Pegylated Liposomal Interact with Other Drugs?
Drug interactions are a critical consideration with Onivyde pegylated liposomal because irinotecan is metabolized by liver enzymes, particularly CYP3A4 and UGT1A1. Medications that induce or inhibit these enzymes can substantially change irinotecan blood levels, potentially leading to either reduced effectiveness or increased toxicity.
Drugs That Decrease Irinotecan Levels (CYP3A4 Inducers)
The following medications can reduce the concentration of irinotecan in your body, potentially making the treatment less effective. Your oncologist will need to assess whether dose adjustments or alternative medications are necessary:
| Drug | Therapeutic Use | Interaction Mechanism |
|---|---|---|
| Phenytoin | Seizures and epilepsy | Induces CYP3A4, reduces irinotecan levels |
| Phenobarbital | Seizures and epilepsy | Induces CYP3A4, reduces irinotecan levels |
| Carbamazepine | Seizures and epilepsy | Induces CYP3A4, reduces irinotecan levels |
| Rifampicin | Tuberculosis | Potent CYP3A4 inducer, significantly reduces irinotecan |
| Rifabutin | Tuberculosis | CYP3A4 inducer, reduces irinotecan levels |
| St. John's Wort | Mild depression and anxiety (herbal) | Potent CYP3A4 inducer, must be avoided |
Drugs That Increase Irinotecan Levels (CYP3A4 Inhibitors)
The following medications can increase irinotecan concentrations, raising the risk of severe toxicity including neutropenia and diarrhea. If co-administration is unavoidable, close monitoring and possible dose reductions may be required:
| Drug | Therapeutic Use | Interaction Mechanism |
|---|---|---|
| Ketoconazole | Fungal infections | Inhibits CYP3A4, increases irinotecan levels |
| Itraconazole | Fungal infections | Inhibits CYP3A4, increases irinotecan levels |
| Voriconazole | Fungal infections | Inhibits CYP3A4, increases irinotecan levels |
| Clarithromycin | Bacterial infections | Inhibits CYP3A4, increases irinotecan levels |
| HIV protease inhibitors (ritonavir, atazanavir, lopinavir, etc.) | HIV infection | Strong CYP3A4 inhibition, significant increase in irinotecan |
| Regorafenib | Certain cancers | Inhibits CYP3A4, increases irinotecan exposure |
| Gemfibrozil | High cholesterol/lipids | Inhibits UGT1A1, increases active metabolite SN-38 |
| Nefazodone | Depression | Inhibits CYP3A4, increases irinotecan levels |
Food Interactions
Grapefruit and grapefruit juice must be avoided during treatment with Onivyde pegylated liposomal. Grapefruit contains compounds that inhibit CYP3A4 in the gut wall, which can increase irinotecan absorption and blood levels, potentially leading to more severe side effects.
Other Important Interactions
Inform your oncologist if you are receiving or have recently received any other chemotherapy agents, radiation therapy, or the antifungal agent flucytosine. Concurrent or recent treatment with these therapies may increase the risk of bone marrow suppression and other serious adverse effects.
What Is the Correct Dosage of Onivyde Pegylated Liposomal?
Onivyde pegylated liposomal is exclusively administered by healthcare professionals who are trained in cancer chemotherapy. It is given as an intravenous (IV) drip infusion, meaning the medicine is slowly delivered into a vein over a period of at least 90 minutes. It must never be given as a rapid bolus injection or as an undiluted solution.
Adults
The dose of Onivyde pegylated liposomal is individualized based on the patient's body surface area and the specific treatment regimen being used. Your oncologist will calculate the appropriate dose for you. Treatment cycles are repeated every two weeks (14 days).
First-Line Treatment (NALIRIFOX Regimen)
For patients who have not previously received chemotherapy for metastatic pancreatic cancer, the following sequence is used on each treatment day:
- Onivyde pegylated liposomal (IV infusion over at least 90 minutes)
- Oxaliplatin (IV infusion)
- Leucovorin (IV infusion)
- 5-Fluorouracil (IV infusion)
This cycle is repeated every 14 days.
Second-Line Treatment (After Gemcitabine)
For patients whose cancer has progressed after gemcitabine-based therapy:
- Onivyde pegylated liposomal (IV infusion over at least 90 minutes)
- Leucovorin (IV infusion)
- 5-Fluorouracil (IV infusion)
This cycle is repeated every 14 days.
Dose Adjustments
In certain situations, your doctor may need to reduce your dose or extend the interval between treatments. Blood tests are performed before each cycle to monitor your blood cell counts, liver function, and kidney function. Dose modifications may be necessary if you experience:
- Severe neutropenia (very low white blood cell count)
- Severe or prolonged diarrhea
- Significant changes in liver or kidney function
- Other severe adverse reactions
Children and Adolescents
Onivyde pegylated liposomal is not recommended for use in children and adolescents under 18 years of age. The safety and efficacy in this population have not been established.
Premedication
Before receiving Onivyde pegylated liposomal, you may be given premedication to prevent nausea and vomiting (antiemetics). If you experienced cholinergic syndrome (sweating, abdominal cramps, salivation, and early diarrhea) during a previous infusion, additional premedication with atropine may be administered to reduce or prevent these symptoms in subsequent cycles.
Overdose
Since Onivyde pegylated liposomal is prepared and administered exclusively by healthcare professionals in a controlled clinical setting, overdose is unlikely. However, if an inadvertent overdose occurs, the patient will be monitored closely for signs of toxicity, particularly severe neutropenia, diarrhea, and dehydration, and supportive care will be provided as needed.
What Are the Side Effects of Onivyde Pegylated Liposomal?
Like all chemotherapy medicines, Onivyde pegylated liposomal can cause side effects, although not everyone will experience them. Some side effects can be serious and require immediate medical attention. Your oncology team will prescribe supportive medications to help manage these effects and will monitor you closely throughout treatment.
- Swelling under the skin (angioedema) or signs of anaphylaxis: sudden breathlessness, flushing, nausea, headache, rash, hives, itching, swelling around the eyes, or chest tightness during or after infusion
- Fever, chills, or other signs of infection (may need urgent treatment)
- Severe persistent diarrhea (watery and frequent stools)
The following side effects have been reported with Onivyde pegylated liposomal, organized by how frequently they occur:
Very Common
May affect more than 1 in 10 people
- Diarrhea (loose, watery, frequent stools)
- Nausea and vomiting
- Abdominal pain
- Mouth sores (stomatitis)
- Mucositis (inflammation of the digestive tract lining)
- Low white blood cell count (neutropenia, leukopenia)
- Low red blood cell count (anemia)
- Low platelet count (thrombocytopenia)
- Low electrolyte levels (potassium, magnesium)
- Weight loss and decreased appetite
- Dehydration
- Fatigue and general weakness
- Edema (fluid retention/swelling)
- Fever
- Hair loss (alopecia)
- Dizziness
- Peripheral neuropathy (numbness, tingling in hands/feet)
- Altered taste (dysgeusia)
Common
May affect up to 1 in 10 people
- Low lymphocyte count (lymphopenia)
- Low blood sugar (hypoglycemia)
- Low albumin levels in blood
- Elevated liver enzymes (ALT, AST, GGT)
- Elevated alkaline phosphatase and bilirubin
- Elevated creatinine (impaired kidney function)
- Gastroenteritis, colitis, flatulence, constipation
- Gastroesophageal reflux, dysphagia, hemorrhoids, dry mouth
- Chills, insomnia, blurred vision, headache
- Infusion reactions (breathlessness, flushing, chest tightness)
- Rapid heart rate (tachycardia)
- Dry skin, rash, hand-foot syndrome, hyperpigmentation
- Cholinergic syndrome (sweating, salivation, abdominal cramps)
- Tremor, sensory disturbances
- Oral candidiasis, febrile neutropenia, pneumonia, urinary tract infection
- Septic shock
- Hypotension (low blood pressure)
- Thromboembolism (blood clots), pulmonary embolism
- Hoarseness, shortness of breath, hiccups, nosebleed
- Acute kidney injury
- Muscle weakness, muscle pain
Uncommon
May affect up to 1 in 100 people
- Pancytopenia (low counts of all blood cell types)
- Hemolytic anemia (excessive breakdown of red blood cells)
- Elevated troponin I (indicates heart damage)
- Esophageal inflammation, rectal inflammation, paralytic ileus
- Anal incontinence, rectal bleeding, oral ulcers
- Dental caries, gum disease, tongue disorders
- Angioedema, allergic reactions to active substance
- Conjunctivitis, reduced visual acuity, vertigo
- Cerebral hemorrhage, ischemic stroke, transient ischemic attack
- Loss of smell (anosmia), loss of taste (ageusia)
- Seizures, excessive drowsiness, cognitive impairment
- Syncope (fainting), confusion, depression
- Biliary sepsis, hepatitis, cholestasis
- Angina, myocardial infarction, QT prolongation
- Hypertension, phlebitis, hematoma
- Pneumonitis, interstitial lung disease, atelectasis
- Clostridium difficile infection, herpes simplex
- Bullous dermatitis, psoriasis, urticaria
- Hypothermia, influenza-like symptoms
Reporting Side Effects
If you experience any side effects, including those not listed above, inform your healthcare provider. Reporting suspected adverse reactions helps regulatory authorities continuously monitor the benefit-risk profile of medicines. In the European Union, adverse reactions can be reported through the national reporting system of each member state. In the United States, you can report side effects to the FDA MedWatch program.
How Should You Store Onivyde Pegylated Liposomal?
Proper storage of Onivyde pegylated liposomal is essential to maintain its efficacy and safety. As this is a hospital-administered medicine, storage is managed by pharmacy professionals, but understanding these requirements provides important context:
- Storage temperature: Store in a refrigerator at 2°C to 8°C (36°F to 46°F).
- Do not freeze: Freezing can damage the liposomal structure and compromise drug integrity.
- Light protection: Keep the vial in the outer carton to protect from light.
- Shelf life: Do not use after the expiry date stated on the carton and vial (EXP). The expiry date refers to the last day of that month.
- Keep out of reach of children.
After Dilution
Once the concentrate has been diluted with 5% glucose solution or 0.9% sodium chloride solution for infusion, the prepared dispersion should be used as soon as possible. However, if immediate use is not feasible:
- Room temperature (15–25°C): The diluted solution may be stored for up to 6 hours.
- Refrigerated (2–8°C): The diluted solution may be stored for up to 24 hours.
- The diluted solution must be protected from light and must not be frozen.
Unused medicine should not be disposed of via household waste or wastewater. Return any unused medication to a pharmacy for safe disposal. These measures help protect the environment from cytotoxic contamination.
What Does Onivyde Pegylated Liposomal Contain?
Active Substance
The active substance is irinotecan, present as the sucrosofate salt encapsulated within a pegylated liposomal mixture. Each 10 mL vial of concentrate contains 43 mg of irinotecan (as anhydrous free base), giving a concentration of 4.3 mg/mL.
Other Ingredients (Excipients)
The liposomal membrane and supporting formulation consist of the following inactive ingredients:
- DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) – a phospholipid forming the liposomal bilayer
- Cholesterol – stabilizes the liposomal membrane
- MPEG-2000-DSPE (N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine) – provides the PEG coating that extends circulation time
- Sucrose octasulfate – trapping agent for irinotecan inside the liposomes
- HEPES buffer (2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid)
- Sodium chloride
- Water for injections
Appearance and Packaging
Onivyde pegylated liposomal is supplied as a white to slightly yellowish, opaque, isotonic liposomal dispersion in a glass vial. Each carton contains one vial of 10 mL concentrate.
Sodium Content
This medicine contains 33.1 mg sodium per vial, which is equivalent to approximately 1.65% of the WHO recommended maximum daily intake of 2 g sodium for adults. This should be taken into account by patients on a sodium-restricted diet.
Marketing Authorization Holder
Onivyde pegylated liposomal is manufactured by Ipsen Pharma Biotech (France) and Les Laboratoires Servier Industrie (France). The marketing authorization is held by Les Laboratoires Servier, Suresnes, France. Further information about this medicine is available from the European Medicines Agency (EMA) and national medicines agencies.
Frequently Asked Questions About Onivyde Pegylated Liposomal
References
This article is based on the following peer-reviewed sources and official regulatory documents:
- European Medicines Agency (EMA). Onivyde pegylated liposomal – Summary of Product Characteristics (SmPC). Last updated November 2024. Available from: www.ema.europa.eu
- Wainberg ZA, Melisi D, Macarulla T, et al. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. The Lancet. 2023;402(10409):1272-1281. doi:10.1016/S0140-6736(23)01366-1
- Wang-Gillam A, Li CP, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. The Lancet. 2016;387(10018):545-557. doi:10.1016/S0140-6736(15)00986-1
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Pancreatic Adenocarcinoma. Version 1.2025.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List. 2023.
- Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. New England Journal of Medicine. 2018;379(25):2395-2406. doi:10.1056/NEJMoa1809775
- U.S. Food and Drug Administration (FDA). Onivyde Prescribing Information. Available from: www.fda.gov
About the Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising board-certified physicians with specializations in oncology, clinical pharmacology, and internal medicine. Our editorial process follows international medical guidelines and the GRADE evidence framework to ensure accuracy and clinical relevance.
Content authored by specialist physicians with clinical experience in oncology and cancer pharmacotherapy. All medical claims are supported by peer-reviewed evidence at the highest available level.
Independently reviewed by the iMedic Medical Review Board. All content is cross-referenced with EMA SmPC, FDA prescribing information, NCCN guidelines, and current medical literature.
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