Onivyde pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

ONIVYDE pegylated liposomal 4.3 mg/ml concentrate for dispersion for infusion

irinotecan

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any adverse reactions, consult your doctor or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

1. What ONIVYDE pegylated liposomal is and what it is used for
2. What you need to know before using ONIVYDE pegylated liposomal
3. How to use ONIVYDE pegylated liposomal
4. Possible side effects
5. How to store 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 an anticancer medicine that contains the active substance irinotecan. This active substance has been incorporated into small lipid (fatty) particles called liposomes.

Irinotecan belongs to a group of anticancer medicines known as "topoisomerase inhibitors". It blocks an enzyme called topoisomerase I, which is involved in DNA replication. This prevents cancer cells from multiplying and growing, ultimately leading to the death of these cells.

The liposomes are expected to accumulate within the tumor and slowly release the medicine, allowing it to remain active for a longer period of 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 prior treatment for cancer included a medicine called gemcitabine.

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

For patients previously treated with gemcitabine, ONIVYDE pegylated liposomal is used in combination with other anticancer 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 starting ONIVYDE pegylated liposomal

Carefully follow all instructions given by your doctor. These may differ from the general information contained in this leaflet.

Do not use ONIVYDE pegylated liposomal:

• if you have a history of severe allergic reaction to irinotecan or to any of the other components of this medicine (listed in section 6).
• if you are breastfeeding

Warnings and precautions

Talk to your doctor or nurse before receiving ONIVYDE pegylated liposomal if:

• you have had liver problems or jaundice
• you have had lung disease or have previously received medications (colony-stimulating factors) to increase blood cell counts or radiotherapy
• you are taking other medicines (see section "Other medicines and ONIVYDE pegylated liposomal")
• you are considering vaccination, as many vaccines should not be administered during chemotherapy
• you are on a low-sodium diet, as this medicine contains sodium.

Contact your doctor or nurse immediately during treatment with ONIVYDE pegylated liposomal if you:

• suddenly experience difficulty breathing, flushing, headache, skin rash or urticaria (itchy rash with red, swollen lumps appearing suddenly on the skin), itching, swelling around the eyes, tightness in the chest or throat during or shortly after the infusion
• develop fever, chills, or other signs of infection
• develop diarrhea with frequent watery stools that does not improve within 12 to 24 hours of treatment (see below)
• have difficulty breathing or cough
• experience signs or symptoms of a blood clot, such as sudden pain and swelling in one arm or leg, sudden onset of cough, chest pain, or difficulty breathing.

What to do in case of diarrhea

As soon as the first watery stools occur, start drinking large amounts of rehydration fluids (e.g., water, soft drinks, carbonated beverages, soup) to prevent excessive loss of body fluids and salts. Contact your doctor immediately for appropriate treatment. Your doctor may give you loperamide-containing medication to start treatment at home, but you must not use it for more than 48 consecutive hours. If loose stools persist, contact 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 regular tests (blood tests or others) during treatment so your doctor can monitor your blood cells and assess your response to treatment. Your doctor may need to adjust your dose or 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

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

It is especially important to tell your doctor if you have previously received irinotecan in any form.

ONIVYDE pegylated liposomal must not be used interchangeably with other irinotecan-containing medicines, as it behaves differently when encapsulated in liposomes compared to its free formulation.

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

It is also especially important to inform your doctor if you are taking any of the following medicines, as they may decrease irinotecan levels in the body:

• phenytoin, phenobarbital, or carbamazepine (medicines used to treat seizures and fits)
• rifampicin and rifabutin (medicines used to treat tuberculosis)
• St John’s wort (a herbal medicine used to treat depression and low mood)

It is also especially important to inform your doctor if you are taking any of the following medicines, as they may increase irinotecan levels in the 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 low mood)
• gemfibrozil (a medicine used to treat high levels of fats in the blood)

Use of ONIVYDE pegylated liposomal with food and drink

Avoid eating grapefruit or drinking grapefruit juice while being treated with ONIVYDE pegylated liposomal, as these can increase irinotecan levels in your body.

Pregnancy, breastfeeding, and fertility

You must not be given ONIVYDE pegylated liposomal if you are pregnant, as it may harm the unborn baby. Inform your doctor if you are pregnant or think you might be. If you plan to become pregnant, consult your doctor. You must not breastfeed during treatment and for at least one month after the last dose.

Before starting this medicine, consult your doctor about the potential risk of this medicine and options that may preserve your ability to have children.

During treatment with ONIVYDE pegylated liposomal and for seven months afterwards, you must use an effective method of contraception suitable for you to avoid pregnancy during this period. Men must use condoms during treatment with ONIVYDE pegylated liposomal and for 4 months after stopping treatment.

Inform your doctor if you are breastfeeding. You must not be given ONIVYDE pegylated liposomal if you are breastfeeding, as it may harm the infant.

Driving and using machines

ONIVYDE pegylated liposomal may affect your ability to drive or use machines (as it may cause drowsiness, dizziness, or fatigue). If you feel drowsy, dizzy, or fatigued, you should avoid driving, operating machinery, or performing tasks requiring full attention.

ONIVYDE pegylated liposomal contains sodium

This medicine contains 33.1 mg of sodium (a key component of table/cooking salt) per vial. This corresponds to 1.65% of the maximum daily recommended sodium intake for an adult.

3. How ONIVYDE pegylated liposomal is used

ONIVYDE pegylated liposomal must only be administered by healthcare professionals experienced in the administration of anticancer medications.

Carefully follow all instructions provided by your doctor or nurse.

Your doctor will determine the doses to be administered.

ONIVYDE pegylated liposomal is administered as a single dose by intravenous infusion lasting at least 90 minutes.

If your cancer has not been previously treated, after administration of ONIVYDE pegylated liposomal you will receive three additional medicines: oxaliplatin, folinic acid, and 5-fluorouracil.

If your cancer has been previously treated with a medicine called gemcitabine, after administration of ONIVYDE pegylated liposomal you will receive two additional medicines: folinic acid and 5-fluorouracil.

Treatment will be repeated every two weeks.

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

You may receive premedication for nausea and vomiting. If you have previously experienced early-onset sweating, abdominal cramps, salivation, and frequent watery bowel movements during prior treatments with ONIVYDE pegylated liposomal, you may be given additional medications 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 everyone will experience them. It is important that you are aware of what these adverse effects may be.

Your doctor may also prescribe other medicines to help manage any adverse effects.

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

• if you develop swelling beneath the skin (angioedema) and/or symptoms of possible anaphylactic/anaphylactoid reactions such as sudden difficulty breathing, flushing, nausea, headache, skin rash or urticaria (itchy rash with sudden appearance of red, inflamed bumps on the skin), itching, swelling around the eyes, tightness in the chest or throat during or shortly after the infusion. Severe allergic reactions can be life-threatening. It may be necessary to stop the infusion and administer treatment or monitor adverse effects.
• if you have fever, chills, and signs of infection (as you may require immediate treatment)
• if you experience severe and persistent diarrhea (frequent liquid stools); see section 2

The following other adverse effects may also occur:

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

Laboratory test changes

• Low levels of white blood cells (neutropenia and leucopenia), low levels of red blood cells (anaemia)
• Low platelet count (thrombocytopenia)
• Low levels of salts in the body (e.g., potassium, magnesium)

Stomach and intestine

• Diarrhea (frequent soft or watery stools)
• Nausea and vomiting
• Stomach or intestinal area pain
• Mouth pain
• Pain and swelling of the digestive tract lining (mucosal inflammation)

General

• Weight loss
• Loss of appetite
• Loss of body fluids (dehydration)
• Tiredness and general weakness
• Abnormal retention of fluid in the body causing swelling in affected tissues (edema)
• Fever

Skin

• Unusual hair loss

Nervous system

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

Common (may affect up to 1 in 10 people)

Laboratory test changes

• Low levels of a subtype of white blood cells called lymphocytes, which play an important role in the immune system (lymphopenia)
• Low blood sugar levels (hypoglycemia)
• Abnormally low blood levels of albumin (an important body protein)
• Increased liver enzymes (alanine aminotransferase or aspartate aminotransferase or gamma-glutamyltransferase) in blood tests
• Elevated levels of alkaline phosphatase in blood, a protein involved in certain body chemical processes found in many body parts. Elevated blood levels of alkaline phosphatase may indicate liver or bone disorder.
• Increased bilirubin levels (a yellow-orange pigment, a waste product from normal red blood cell breakdown) in other liver function laboratory tests
• Increase in other laboratory tests (elevated international normalized ratio) related to blood coagulation system function
• Increased blood creatinine, a substance indicating impaired kidney function

Stomach and intestine

• Inflammation of the stomach and intestine (gastroenteritis)
• Intestinal inflammation (colitis), inflammation of the intestine causing diarrhea (enterocolitis), gas, abdominal bloating
• Indigestion
• Constipation
• Condition in which stomach acid rises into the esophagus (gastroesophageal reflux disease)
• Difficulty swallowing (dysphagia)
• Hemorrhoids (piles)
• Dry mouth

General

• Chills
• Sleeplessness
• Abnormal reaction to infusion causing symptoms such as difficulty breathing, flushing, headache, tightness in the chest or throat
• Rapid heartbeat
• Blurred vision
• Headache

Skin

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

Nervous system

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

Infections

• Infections, for example, fungal infections in the mouth (oral candidiasis), fever with low neutrophil counts in white blood cells (febrile neutropenia), infections related to intravenous administration of the medicine
• Potentially life-threatening complication of the body's systemic response to infection (septic shock)
• Lung infection (pneumonia)
• Urinary tract infection

Blood vessels

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

Lungs and airways

• Voice deterioration, hoarseness, or excessive wheezing
• Shortness of breath
• Inflammation of the nose and throat
• Hiccups
• Nosebleed

Kidney

• Sudden kidney function problems that may lead to impaired or loss of kidney function

Muscles

• Muscle weakness, muscle pain, abnormal muscle contractions

Uncommon (may affect up to 1 in 100 people)

Laboratory test changes

• Low levels of all types of blood cells (pancytopenia)
• Hemolytic anemia, excessive destruction of red blood cells
• Increased monocyte count, elevated blood levels of monocytes (a subtype of white blood cell)
• Elevated blood levels of troponin I, a protein indicating heart damage
• Decreased total proteins, reduced blood protein levels related to kidney or liver function or poor absorption
• Decreased creatinine clearance, reduced creatinine clearance indicating impaired kidney function
• Excess protein in urine
• Abnormal blood salt levels
• Low blood chloride levels (hypochloremia)
• Elevated blood levels of uric acid causing symptoms, especially painful joint inflammation (gout)
• High blood sugar levels (hyperglycemia)
• Iron deficiency in blood

Stomach and intestine

• Inflammation of the esophagus (the tube carrying food to the stomach)
• Inflammation of the rectal mucosa (end of the large intestine)
• Obstruction of the part of the intestine leaving the stomach (duodenal obstruction)
• Abnormal muscle contractions in the esophagus (the tube from mouth to stomach)
• Loss of intestinal muscle movement (paralytic ileus)
• Lack of control over defecation (anal incontinence), anal tear, difficulty defecating (pain, straining, or obstructed defecation)
• Passage of blood through the anal canal (hematochezia)
• Rectal bleeding
• Painful ulcer inside the mouth (aphthous ulcer), abnormal and unpleasant sensation in the mouth, tingling or numbness in the mouth, inflammation of the corners of the mouth (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 condition affecting the intestine)

General

• Allergic reaction to the active substance or excipients
• Eye irritation, reduced visual acuity, conjunctivitis, eye redness and discomfort
• Dizziness, spinning sensation
• General feeling of discomfort
• General deterioration in physical health
• Red, painful, and often swollen area on part of the body (inflammation)
• Failure of one or more organs simultaneously
• 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
• Inadequate nutrition
• Fluid retention around the tumor
• Excessive sweating
• Coldness in the extremities

Skin

• Urticaria (red, inflamed bumps)
• Toxicity causing nail disorders, discoloration of nail plates (nails)
• Skin lesion, skin redness (erythema), dry skin, sensitive skin
• Rash with pus-filled blisters (pustular rash)
• Skin inflammation with blisters (bullous dermatitis)
• Generalized exfoliative dermatitis, skin peeling or scaling
• Petechiae, small blood spots under the skin, and telangiectasia, small visible red linear blood vessels
• Inflammatory condition causing red, scaly patches on the skin (psoriasis)
• Vulvar and vaginal dryness

Nervous system

• Seizure
• Bleeding within the brain (cerebral hemorrhage), sudden interruption of blood flow to the brain due to blockage of blood supply to 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 function of the tongue (ageusia)
• Sensation of instability or dizziness (balance disorder)
• Excessive drowsiness
• Reduced sensitivity to touch, pain, and temperature
• Limitations in cognitive functioning and abilities (intellectual disability) and unusual lack of energy and mental sharpness (lethargy)
• Reduced ability to remember things
• Transient and imminent sensation of losing consciousness (presyncope) and fainting (syncope)
• Feeling of confusion
• Neurosis (a mental disorder with high levels of anxiety) and depression

Infections

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

Lungs and airways

• Decreased oxygen availability in body tissues or increased oxygen supply to body tissues and organs
• Cough
• Nasal inflammation
• Total or partial collapse of a lung (atelectasis)
• Lung inflammation (pneumonitis, interstitial lung disease)

Pain

• Pain, non-cardiac chest pain, axillary pain, joint pain, back pain, bone pain, limb pain, pain and inflammation in multiple joints (polyarthritis), pain in mouth and throat (oropharyngeal pain)
• Chest pain
• Mouth pain (oral paresthesia)
• Gum pain
• Pain during urination

Heart and blood vessels

• Angina pectoris – chest, jaw, and back pain caused by physical exertion due to problems with blood flow to the heart
• Heart attack
• Strong heartbeat that may be rapid or irregular
• Abnormal electrical activity of the heart affecting its rhythm (QT interval prolongation on electrocardiogram)
• High blood pressure (hypertension)
• Inflammation of a vein (phlebitis)
• Blood accumulation under the skin (hematoma)

Liver

• Inflammation of the bile duct, usually caused by bacteria (cholangitis)
• Liver inflammation as a reaction to certain substances
• Reduced bile flow from the liver due to obstruction (cholestasis)
• Hepatic cytolysis, liver inflammation with increased blood levels of transaminases, liver chemicals indicating liver function

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide 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 stated on the packaging and vial after EXP. The expiry date refers to 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 perfusion has been diluted with a 5% glucose injection solution or 9 mg/ml (0.9%) sodium chloride solution, the dispersion should be used as soon as possible, but may be stored at room temperature (between 15 °C and 25 °C) for up to 6 hours. Before use, the diluted perfusion dispersion may be stored in the refrigerator (2 °C–8 °C) for no longer than 24 hours. It must be protected from light and must not be frozen.

This medicine must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the container and additional information

Composition of ONIVYDE pegylated liposomal

• The active substance is irinotecan. A 10 ml vial of concentrate contains 43 mg of anhydrous free irinotecan base (as sucrosulfate 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 injections. ONIVYDE pegylated liposomal contains sodium; if you are on a low-sodium diet, see section 2.

Appearance of the product and contents of the container

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

Each pack contains one 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

For more information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Belgium/Belgium/Belgium S.A. Servier Benelux N.V. Tel/Tel: +32 (0)2 529 43 11	Lithuania UAB “SERVIER PHARMA” Tel: +370 (5) 2 63 86 28
	Luxembourg/Luxembourg S.A. Servier Benelux N.V. Tel/Tel: +32 (0)2 529 43 11
Czech Republic Servier s.r.o. Tel: +420 222 118 111	Hungary Servier Hungaria Kft. Tel.: +36 1 238 7799
Denmark Servier Danmark A/S Tlf.: +45 36 44 22 60	Malta V.J. Salomone Pharma Ltd Tel: + 356 21 22 01 74
Germany Servier Deutschland GmbH Tel: +49 (0)89 57095 01	Netherlands Servier Nederland Farma B.V. Tel: + 31 (0)71 5246700
Estonia Servier Laboratories OÜ Tel:+ 372 664 5040	Norway Servier Danmark A/S Tlf: +45 36 44 22 60
Greece ΣΕΡΒΙΕ ΕΛΛΑΣ ΦΑΡΜΑΚΕΥΤΙΚΗ ΕΠΕ Tel: +30 210 939 1000	Austria Servier Austria GmbH Tel: +43 (1) 524 39 99
Spain Laboratorios Servier S.L. Tel: + 34 91 748 96 30	Poland Servier Polska Sp. z o.o. Tel.: + 48 (0) 22 594 90 00
France Les Laboratoires Servier Tél: + 33 (0)1 55 72 60 00	Portugal Servier Portugal, Lda Tel: + 351 21 312 20 00
Croatia Servier Pharma, d. o. o. Tel: + 385 (0)1 3016 222	Romania Servier Pharma SRL Tel: + 4 021 528 52 80
Ireland Servier Laboratories (Ireland) Ltd. Tel: + 353 (0)1 663 8110	Slovenia Servier Pharma d. o. o. Tel: + 386 (0)1 563 48 11
Iceland Servier Laboratories c/o Icepharma hf Sími: + 354 540 8000	Slovakia Servier Slovensko spol. s r.o. Tel: + 421 2 5920 41 11
Italy Servier Italia S.p.A. Tel: + 39 (06) 669081	Finland/Finland Servier Finland Oy Puh /Tel: +358 (0)9 279 80 80
Cyprus CA Papaellinas Ltd. Tel: + 357 22 741 741	Sweden Servier Sverige AB Tel : +46 (0)8 522 508 00
Latvia SIA Servier Latvia Tel: + 371 67502039

Date of the most recent review of this summary: September 2024

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

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This information is intended for healthcare professionals only:

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 no larger than 21 gauge. Dilute with 5% glucose injection solution or 9 mg/mL (0.9%) sodium chloride injection solution to prepare a dispersion of the appropriate dose of diluted ONIVYDE pegylated liposomal to a final volume of 500 mL. Mix the diluted dispersion by gentle inversion.
• In first-line treatment of metastatic pancreatic adenocarcinoma, ONIVYDE pegylated liposomal should be administered before oxaliplatin, followed by folinic acid, then 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 folic acid, followed by 5-fluorouracil.
• ONIVYDE pegylated liposomal must not be administered as a rapid intravenous bolus injection or as an undiluted dispersion.
• Aseptic techniques must be used during the preparation of the infusion. ONIVYDE pegylated liposomal is for single use only.
• From a microbiological standpoint, the product should be used as soon as possible after dilution. Prior to use, the diluted infusion dispersion may be stored at room temperature (between 15 °C and 25 °C) for up to 6 hours or refrigerated (2 °C–8 °C) for no longer than 24 hours. It must be protected from light and must not be frozen.
• Care must be taken to avoid extravasation, and the infusion site should be monitored for signs of inflammation. In case of extravasation, the area should be irrigated with 9 mg/mL (0.9%) sodium chloride injection solution and/or sterile water and ice applied.

Handling and disposal of ONIVYDE pegylated liposomal

• ONIVYDE pegylated liposomal is a cytotoxic medicine and must 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 thoroughly washed immediately with soap and water. If contact occurs with mucous membranes, they should be thoroughly rinsed with water. Due to the cytotoxic nature of the medicine, pregnant personnel must not handle ONIVYDE pegylated liposomal.
• Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations.