ONIVYDE PEGYLATED LIPOSOMAL 4.3 mg/mL concentrate for dispersion for infusion

Introduction

Package Leaflet: Information for the User

ONIVYDEpegylated liposomal4.3mg/ml concentrate for dispersion for infusion

irinotecan

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What ONIVYDE pegylated liposomal is and what it is used for
2. What you need to know before you use ONIVYDE pegylated liposomal
3. How to use ONIVYDE pegylated liposomal
4. Possible side effects
5. Storage of ONIVYDE pegylated liposomal
6. Contents of the pack and other information

1. What ONIVYDE pegylated liposomal is and what it is used for

What ONIVYDE pegylated liposomal is and how it works.

ONIVYDE pegylated liposomal is a cancer medicine that contains the active substance irinotecan. This active substance has been introduced into small lipid (fat) particles called liposomes.

Irinotecan belongs to a group of cancer medicines called 'topoisomerase inhibitors'. It blocks an enzyme called topoisomerase I, which takes part in the division of cellular DNA. This prevents cancer cells from multiplying and growing, and eventually causes these cells to die.

It is expected that the liposomes will accumulate inside the tumor and slowly release the medicine, allowing it to act for a longer time.

What ONIVYDE pegylated liposomal is used for

ONIVYDE pegylated liposomal is used to treat adult patients with metastatic pancreatic cancer (pancreatic cancer that has already spread to another part of the body) whose cancer has not been previously treated or whose previous treatment for cancer contained a medicine called gemcitabine.

For patients who have not been previously treated, ONIVYDE pegylated liposomal is used in combination with other cancer medicines called oxaliplatin, 5-fluorouracil, and folinic acid.

For patients previously treated with gemcitabine, ONIVYDE pegylated liposomal is used in combination with other cancer medicines called 5-fluorouracil and folinic acid.

If you have any questions about how ONIVYDE pegylated liposomal works or why you have been prescribed this medicine, ask your doctor.

2. What you need to know before you use ONIVYDE pegylated liposomal

Follow carefully all instructions given by your doctor. They may be different from the general information contained in this leaflet.

Do not use ONIVYDE pegylated liposomal:

• if you are allergic to irinotecan or any of the other ingredients of this medicine (listed in section 6).
• if you are breast-feeding.

Warnings and precautions

Tell your doctor or nurse before you are given ONIVYDE pegylated liposomal

• if you have had liver problems or jaundice.
• if you have had any lung disease or have previously received medicines (colony stimulating factors) to increase your blood cell count or radiotherapy.
• if you are taking other medicines (see section 'Other medicines and ONIVYDE pegylated liposomal').
• if you are planning to be vaccinated, as many vaccines should not be given during chemotherapy.
• if you are on a low-sodium diet, as this medicine contains sodium.

Tell your doctor or nurse immediately during treatment with ONIVYDE pegylated liposomal

• if you suddenly feel difficulty breathing, flushing, headache, skin rash or urticarial rash (itchy rash with red, inflamed bumps on the skin that appear suddenly), itching, swelling around the eyes, chest tightness or throat constriction during or shortly after infusion.
• if you have a fever, chills or other signs of infection.
• if you suffer from diarrhea with frequent liquid stools and this does not improve after 12 to 24 hours of treatment (see below).
• if you have difficulty breathing or coughing.
• if you have signs or symptoms related to a blood clot, such as sudden pain and swelling in a leg or arm, sudden onset of cough, chest pain or difficulty breathing.

What to do in case of diarrhea

As soon as the first liquid stools occur, start drinking large amounts of rehydration fluids (e.g., water, soft drinks, fizzy drinks, soup) to avoid losing too much fluid and salts from your body. Immediately consult your doctor so that they can provide you with appropriate treatment. Your doctor may give you a medicine that contains loperamide to start treatment at home, but you should not use it for more than 48 hours in a row. If soft stools persist, consult your doctor.

Blood tests and medical examinations

Before starting treatment with ONIVYDE pegylated liposomal, your doctor will perform blood tests (or other medical examinations) to determine the best starting dose for you. You will need to undergo tests (blood tests or other types) during treatment so that your doctor can monitor your blood cells and evaluate how you are responding to treatment. Your doctor may need to adjust the dose or your treatment.

Children and adolescents

ONIVYDE pegylated liposomal is not recommended for use in children and adolescents under 18 years of age.

Other medicines and ONIVYDE pegylated liposomal

Tell your doctor if you are taking, have recently taken, or might take any other medicines.

It is especially important that you inform your doctor if you have been given irinotecan before in any of its forms.

ONIVYDE pegylated liposomal must not be used instead of other irinotecan medicines, as it works differently when introduced into liposomes than when given in its free form.

Tell your doctor, pharmacist, or nurse if you are receiving, or have recently received, chemotherapy and/or radiotherapy or treatment with the antifungal medicine flucytosine.

Additionally, it is especially important that you inform your doctor if you are also taking the following medicines, as they reduce the level of irinotecan in your body:

• phenytoin, phenobarbital, or carbamazepine (medicines used to treat seizures and epilepsy).
• rifampicin and rifabutin (medicines used to treat tuberculosis).
• St. John's Wort (a herbal medicine used to treat depression and exhaustion).

It is especially important that you inform your doctor if you are also taking the following medicines, as they increase the level of irinotecan in your body:

• ketoconazole, itraconazole, or voriconazole (medicines used to treat fungal infections).
• clarithromycin (an antibiotic used to treat bacterial infections).
• indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, atazanavir (medicines for HIV infection).
• regorafenib (a medicine used to treat certain types of cancer).
• telaprevir (a medicine used to treat a liver disease called hepatitis C).
• nefazodone (a medicine used to treat depression and exhaustion).
• gemfibrozil (a medicine used to treat high levels of fats in the blood).

Using ONIVYDE pegylated liposomal with food and drinks

Avoid eating grapefruits and drinking grapefruit juice while being treated with ONIVYDE pegylated liposomal, as they may increase the level of irinotecan in your body.

Pregnancy, breast-feeding, and fertility

ONIVYDE pegylated liposomal must not be given to you if you are pregnant, as it may harm the fetus. Tell your doctor if you are pregnant or think you may be. If you plan to become pregnant, ask your doctor for advice. If you are given ONIVYDE pegylated liposomal, you must not breast-feed until one month after the last dose.

Before starting treatment with this medicine, consult your doctor about the possible risks of this medicine and the options that may preserve your ability to have children.

During treatment with ONIVYDE pegylated liposomal and for 7 months after, you must choose an effective method of birth control that is suitable for you, in order to avoid pregnancies during this period. Men must use condoms during treatment with ONIVYDE pegylated liposomal and for 4 months after completing treatment.

Tell your doctor if you are breast-feeding. ONIVYDE pegylated liposomal must not be given to you if you are breast-feeding, as it may harm the baby.

Driving and using machines

ONIVYDE pegylated liposomal may affect your ability to drive and use machines (as it can make you feel drowsy, dizzy, or exhausted). If you feel drowsy, dizzy, or exhausted, you should avoid driving, using machines, or performing other tasks that require your full attention.

ONIVYDE pegylated liposomal contains sodium

This medicine contains 33.1 mg of sodium (a major component of cooking/table salt) in each vial. This is equivalent to 1.65% of the maximum recommended daily intake of sodium for an adult.

3. How to use ONIVYDE pegylated liposomal

ONIVYDE pegylated liposomal can only be administered by healthcare professionals with experience in the administration of cancer medicines.

Follow carefully all instructions given by your doctor or nurse.

Your doctor will decide the doses that you will be given.

ONIVYDE pegylated liposomal is administered as a single dose in the form of a drip (infusion) into a vein, which must last at least 90 minutes.

If your cancer has not been previously treated, after administering ONIVYDE pegylated liposomal, you will be given three other medicines: oxaliplatin, folinic acid, and 5-fluorouracil.

If your cancer has been previously treated with a medicine called gemcitabine, once you have been given ONIVYDE pegylated liposomal, you will be given two other medicines: folinic acid and 5-fluorouracil.

Treatment will be repeated every two weeks.

In certain cases, it may be necessary to reduce the doses or prolong the administration intervals.

You may receive premedication for nausea and vomiting. If you have suffered from sweating, abdominal cramps, and salivation, as well as frequent liquid stools of early onset during previous treatments with ONIVYDE pegylated liposomal, you may receive other medicines before ONIVYDE pegylated liposomal to prevent or reduce these effects in subsequent treatment cycles.

If you have any further questions about the use of this medicine, ask your doctor or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. It is essential that you know what these adverse effects can be.

Your doctor may also prescribe other medications to help control the adverse effects.

Report immediately to your doctor or nurse if you experience any of the following serious adverse effects:

The following other adverse effects may occur:

Very Common(may affect more than 1 in 10 people)

Changes in laboratory tests

• Low levels of white blood cells (leukocytes) (neutropenia and leukopenia), low levels of red blood cells (anemia)
• Low platelet counts (thrombocytopenia)
• Low levels of salts in the body (e.g., potassium, magnesium)

Stomach and intestine

• Diarrhea (frequent and soft or watery stools)
• Nausea and vomiting
• Stomach or intestinal pain
• Mouth pain (in the mouth)
• Pain and swelling of the digestive tract lining (mucositis)

General

• Weight loss
• Lack of appetite
• Loss of body fluids (dehydration)
• General fatigue and weakness
• Abnormal fluid retention in the body that causes swelling in the affected tissues (edema)
• Fever

Skin

• Unusual hair loss

Nervous System

• Dizziness
• Nerve damage in arms and legs that causes pain or numbness, burning, and tingling (peripheral neuropathy)
• Paresthesia, a sensation like numbness, tingling
• Bad taste in the mouth

Common(may affect up to 1 in 10 people)

Changes in laboratory tests

• Low levels of a subtype of white blood cells called lymphocytes, with an important function for the immune system (lymphopenia)
• Low blood sugar levels (hypoglycemia)
• Low levels of albumin (an important body protein) in the blood
• Increased liver enzymes (alanine aminotransferase or aspartate aminotransferase or Gamma-glutamyltransferase) in blood tests
• High levels of alkaline phosphatase in the blood, a protein that contributes to certain chemical processes in the body and is found in many parts of the body. High levels of alkaline phosphatase in the blood can be a sign of liver or bone disorder.
• Increased levels of bilirubin (a yellow-orange pigment, a waste product of normal red blood cell breakdown) in other laboratory tests related to liver function
• Increased levels in other laboratory tests (increased international normalized ratio) related to blood coagulation system function
• Increased creatinine levels in the blood, a product that shows that the kidneys are not functioning properly

Stomach and intestine

• Gastroenteritis (inflammation of the stomach and intestine)
• Intestinal inflammation (colitis), enterocolitis, gas, abdominal bloating
• Indigestion
• Constipation
• Gastroesophageal reflux disease (a condition in which stomach acid rises to the esophagus)
• Difficulty swallowing (dysphagia)
• Hemorrhoids
• Dry mouth

General

• Chills
• Loss of sleep
• Abnormal reaction to the infusion that causes symptoms such as difficulty breathing, flushing, headache, chest or throat tightness.
• Rapid heartbeats
• Blurred vision
• Headache

Skin

• Itching
• Dry skin
• Skin rash
• Hand-foot syndrome: redness, swelling, and/or pain in the palms of the hands and/or the soles of the feet
• Darker skin areas (hyperpigmentation)

Nervous System

• A syndrome called "cholinergic syndrome", with sweating, salivation, and abdominal cramps
• Toxicity that causes neurological disorders
• Unpleasant and abnormal sensation to touch
• Tremors

Infections

• Infections, such as oral thrush (candidiasis), febrile neutropenia, infections related to the administration of the medication in a vein
• Potentially life-threatening complication of the body's reaction to an infection (septic shock)
• Pneumonia (lung infection)
• Urinary tract infection

Blood Vessels

• Low blood pressure (hypotension)
• Thromboembolic events, formation of a blood clot in a blood vessel (vein or artery) or obstruction of the main pulmonary artery or one of its branches (pulmonary embolism), or obstruction due to a blood clot in another part of the bloodstream (embolism).

Lungs and Airways

• Voice deterioration, hoarse voice or excessive wheezing
• Shortness of breath
• Inflammation of the nose and throat
• Hiccup
• Nosebleed

Kidney

• Sudden kidney function problems that can cause deterioration or loss of kidney function

Muscles

• Muscle weakness, muscle pain, abnormal muscle contractions

Uncommon(may affect up to 1 in 100 people)

Changes in laboratory tests

• Low levels of all types of blood cells (pancytopenia)
• Hemolytic anemia, excessive destruction of red blood cells
• Increased monocyte count, increased blood level of monocytes (a subtype of white blood cell)
• Increased troponin I level, a protein that indicates if there is heart damage
• Decreased total protein, a decrease in protein levels in the blood related to kidney or liver function or poor absorption
• Decreased renal clearance of creatinine, a decreased level of creatinine clearance, showing that the kidneys are not functioning correctly
• Excess protein in the urine
• Abnormal levels of salts in the blood
• Low chloride levels in the blood (hypochloremia)
• High levels of uric acid in the blood that cause symptoms, especially painful inflammation in the joints (gout)
• High blood sugar levels (hyperglycemia)
• Iron deficiency in the blood

Stomach and intestine

• Esophagitis (inflammation of the esophagus)
• Inflammation of the rectal mucosa (proctitis)
• Obstruction of the part of the intestine that comes out of the stomach (duodenal obstruction)
• Abnormal muscle contractions in the esophagus (esophageal spasms)
• Lack of movement of the intestinal muscles (paralytic ileus)
• Lack of control of bowel movements (anal incontinence), anal fissure, difficulty defecating (pain, straining, or obstructed defecation)
• Passage of blood through the anal canal (hematochezia)
• Rectal bleeding
• Painful ulcer in the mouth (aphthous ulcer), unpleasant and abnormal sensation in the mouth, sensations like numbness, tingling in the mouth, inflammation of the mouth corners (oral commissures), loss or erosion of mouth tissue (oral ulceration)
• Tongue disorder
• Dental caries, gum disorder, gum disease, increased tooth sensitivity, severe gum inflammation
• Stomach disorder, inflammation of the stomach lining (gastritis)
• Belching
• Diverticulitis (a disease that affects the intestine)

General

• Allergic reaction to the active substance or excipients
• Eye irritation, reduced visual acuity, conjunctivitis, redness, and discomfort in the eye
• Dizziness, sensation of spinning
• Feeling of general malaise
• General deterioration of physical health
• Red, painful, and often swollen area on a part of the body (inflammation)
• Failure of one or more organs at the same time
• Abnormalities in thermal sensation, body temperature below 35°C (hypothermia)
• Swelling of lips and face
• Flu-like symptoms, such as high fever, sore throat, runny nose, cough, and chills
• Lack of adequate nutrition
• Fluid retention around the tumor
• Excessive sweating
• Coldness in the extremities

Skin

• Urticarial hives (red, inflamed bumps)
• Toxicity that causes nail disorders, change in color of the nail plates
• Skin lesion, skin redness (erythema), dry skin, sensitive skin
• Rash with pus-filled blisters (pustular rash)
• Bullous dermatitis, skin inflammation with blisters
• Generalized exfoliative dermatitis, scaling or peeling of the skin
• Petechiae, small blood spots under the skin, and telangiectasia, small linear red blood vessels visible
• Inflammatory disease that causes red, scaly patches on the skin (psoriasis)
• Vulvar and vaginal dryness

Nervous System

• Seizure
• Bleeding in the brain (cerebral hemorrhage), sudden interruption of blood flow to the brain caused by obstruction of blood supply to a part of the brain (ischemic stroke), temporary interruption of blood flow to the brain (transient ischemic attack)
• Loss of sense of smell (anosmia), loss of taste functions of the tongue (ageusia)
• Sensation of instability or dizziness (balance disorder)
• Excessive sleepiness
• Decreased sensitivity to touch, pain, and temperature
• Limitations in cognitive function and abilities (intellectual disability) and unusual lack of energy and mental sharpness (lethargy)
• Reduced ability to memorize things
• Imminent and transient sensation of loss of consciousness (presyncope) and fainting (syncope)
• Sensation of confusion
• Neurosis (a mental disorder with high levels of anxiety) and depression

Infections

• Systemic inflammation of the body, caused by an infection of the gallbladder and bile ducts (biliary sepsis)
• Fever caused by an infection
• Bacterial infection caused by a bacterium called Clostridium difficile
• Infection of the mucous membranes (infection of the lining of body cavities)
• Boil, a bacterial infection of the hair follicles
• Laryngitis, an inflammation of the larynx
• Sinusitis, an inflammation of the paranasal sinuses
• Dental infection
• Fungal infection of the mouth
• Herpes simplex, a viral infection of the mouth (such as cold sores) or genitals
• Fungal infection of the vulva and vagina
• Anal abscess, an inflamed area around the anus where pus has accumulated

Lungs and Airways

• Decreased availability of oxygen in body tissues or increased oxygen supply to body tissues and organs
• Cough
• Nose inflammation
• Complete or partial collapse of a lung (atelectasis)
• Inflammation of the lungs (pneumonitis, interstitial lung disease)

Pain

• Pain, non-cardiac chest pain, pain in the axillary region, joint pain, back pain, bone pain, pain in a limb, pain and inflammation in several joints (polyarthritis), pain in the mouth and throat (oropharyngeal pain)
• Chest pain
• Pain in the mouth (oral paresthesia)
• Pain in the gums
• Pain while urinating

Heart and Blood Vessels

• Chest pain - Pains in the chest, jaw, and back, caused by physical exertion and due to problems with blood flow to the heart.
• Heart attack
• A strong heartbeat that can be fast or irregular
• Abnormal electrical activity of the heart that affects its rhythm (prolonged QT interval on the electrocardiogram)
• High blood pressure (hypertension)
• Inflammation of a vein (phlebitis)
• Accumulation of blood under the skin (hematoma)

Liver

• Inflammation of the bile duct, usually caused by bacteria (cholangitis)
• Inflammation of the liver as a reaction to certain substances
• Decreased bile flow from the liver due to an obstruction (cholestasis)
• Hepatocellular damage, liver inflammation with increased blood levels of transaminases, liver chemicals that indicate its function.

Reporting of Adverse Effects

If you experience any adverse effects, consult your doctor or nurse, even if they are possible adverse effects that are not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of ONIVYDE pegylated liposomal

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date that appears on the packaging and vial after EXP. The expiry date is the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C).

Do not freeze.

Keep the vial in the outer packaging to protect it from light.

Once the concentrate for infusion has been diluted with a 5% glucose injectable solution or 9 mg/ml (0.9%) sodium chloride, the dispersion should be used as soon as possible, but it can be stored at room temperature (between 15°C and 25°C) for up to 6 hours. Before use, the diluted infusion dispersion can be stored in the refrigerator (2°C-8°C) for a maximum of 24 hours. It should be protected from light and not frozen.

This medicine should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Container Content and Additional Information

Composition of ONIVYDE pegylated liposomal

• The active ingredient is irinotecan. A 10 ml vial of concentrate contains 43 mg of irinotecan anhydrous base (as a sucrose sulfate salt in a pegylated liposomal formulation).
• The other components are: 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC); cholesterol, N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (MPEG-2000-DSPE); sucrose octasulfate; 2-[4-(2-hydroxyethyl)-1-piperazinyl-(1)]ethanesulfonic acid (HEPES buffer); sodium chloride and water for injectable preparations. ONIVYDE pegylated liposomal contains sodium; if you are on a low-sodium diet, see section 2.

Appearance and Container Content of the Product

ONIVYDE pegylated liposomal is supplied as an opaque, white to slightly yellowish liposomal dispersion in a glass vial.

Each container contains a vial with 10 ml of concentrate.

Marketing Authorization Holder

Les Laboratoires Servier

50, rue Carnot

92284 Suresnes cedex

France

Manufacturer

Ipsen Pharma Biotech

Parc d’Activités du Plateau de Signes

Chemin Départemental 402

83870 Signes

France

Les Laboratoires Servier Industrie

905 Route de Saran

45520 Gidy

France

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet: September 2024

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

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This information is intended only for healthcare professionals:

Preparation and Administration of ONIVYDE pegylated liposomal

• ONIVYDE pegylated liposomal is supplied as a sterile liposomal dispersion at a concentration of 4.3 mg/ml and must be diluted prior to administration using a needle with a gauge no larger than 21. Dilute with a 5% glucose injectable solution or a 9 mg/ml (0.9%) sodium chloride injectable solution to prepare a dispersion of the corresponding dose of ONIVYDE pegylated liposomal diluted to a final volume of 500 ml. Mix the diluted dispersion by gently inverting.
• In the first-line treatment of metastatic pancreatic adenocarcinoma, ONIVYDE pegylated liposomal should be administered before oxaliplatin, followed by folinic acid, followed by 5-fluorouracil.
• In the treatment of metastatic pancreatic adenocarcinoma in patients who have progressed after gemcitabine-based therapy, ONIVYDE pegylated liposomal should be administered before folinic acid followed by 5-fluorouracil.
• ONIVYDE pegylated liposomal should not be administered as an intravenous rapid injection or as an undiluted dispersion.
• Aseptic techniques should be used during preparation of the infusion. ONIVYDE pegylated liposomal is for single use only.
• From a microbiological point of view, the product should be used as soon as possible after dilution. Before use, the diluted infusion dispersion may be stored at room temperature (between 15°C and 25°C) for up to 6 hours or in the refrigerator (2°C-8°C) for up to 24 hours. It should be protected from light and not frozen.
• Care should be taken to avoid extravasation and the infusion site should be monitored for signs of inflammation. In case of extravasation, it is recommended to wash the area with a 9 mg/ml (0.9%) sodium chloride injectable solution and/or sterile water and apply ice.

Handling and Disposal of ONIVYDE pegylated liposomal

• ONIVYDE pegylated liposomal is a cytotoxic medicinal product and should be handled with caution. It is recommended to wear gloves, goggles, and protective clothing during handling or administration of ONIVYDE pegylated liposomal. If the dispersion comes into contact with the skin, it should be washed immediately with water and soap. If the dispersion comes into contact with mucous membranes, they should be washed immediately with water. Due to the cytotoxic nature of the medicinal product, pregnant employees should not handle ONIVYDE pegylated liposomal.
• Disposal of unused medicinal product and all materials that have come into contact with it should be carried out in accordance with local regulations.