Onivyde Pegylated Liposomal - Irinotecan uses, dose and side effects

ONIVYDE pegylated liposomal is a cancer drug that contains the active substance irinotecan. This active substance is found in small fat particles called liposomes.

Irinotecan belongs to a group of cancer drugs called topoisomerase inhibitors. It blocks an enzyme called topoisomerase I, which is involved in the division of DNA molecules. This prevents cancer cells from multiplying and growing, and they eventually die.

The liposomes are expected to accumulate in the tumor and slowly release the drug so that it can work 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 the body) who have previously undergone cancer treatment with a drug called gemcitabine. ONIVYDE pegylated liposomal is used in combination with other anticancer medicines called 5-fluorouracil and leucovorin.

If you have any further questions on the use of ONIVYDE pegylated liposomal or why you have been prescribed it, contact your doctor.

What you need to know before using ONIVYDE pegylated liposomal

Carefully follow all instructions from a doctor. They may differ from the general information in this leaflet.

Do not use ONIVYDE pegylated liposomal:

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

Warnings and cautions

Talk to your doctor or nurse before using ONIVYDE pegylated liposomal

if you have ever had liver problems or jaundice
if you have ever had a lung disease or have previously been given medicines (colony stimulating factors) to increase your blood count or radiation therapy
if you are taking other medicines (see section Other medicines and ONIVYDE pegylated liposomal)
if you are planning to be vaccinated then multiple vaccinations are inappropriate during chemotherapy
if you have been prescribed a low-sodium diet (low-salt) because this medicine contains sodium .

Talk to your doctor or nurse directly during treatment with ONIVYDE pegylated liposomal

if you suddenly have shortness of breath, redness , headache, rash or hives (rapidly itchy itchy rash with swollen red bumps on the skin), itching and swelling around the eyes, pressure over the chest or throat during or shortly after infusion a
if you experience fever, chills or other signs of infection
if you get diarrhea with frequent watery stools and can not control this after 12 to 24 hours of treatment (see below)
if you become short of breath or have a cough
if you get signs or symptoms of a blood clot, such as sudden pain or swelling in a leg or arm, sudden cough, chest pain or difficulty breathing.

What to do in case of diarrhea

As soon as the first watery stool arrives, start drinking large amounts of fluid against dehydration (eg water, soda, soda, soup) so as not to lose too much fluid and salt from the body. Contact a doctor immediately so that you receive appropriate treatment. Your doctor may give you a medicine that contains loperamide to start treatment at home, but you must not use it for more than 48 hours straight. If the stool is still loose, contact a doctor.

Blood tests and medical examinations

Before starting treatment with ONIVYDE pegylated liposomal, your doctor will take blood samples (or do other medical tests) to assess the best starting dose for you. You will need to undergo additional (blood‑ or other) tests during treatment so that your doctor can monitor your blood cells and assess how your body responds to treatment. The doctor may need to adjust the dose or discontinue treatment.

Children and young people

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

Other drugs and ONIVYDE pegylated liposomal

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

You must tell your doctor if you have previously received irinotecan in any form.

ONIVYDE pegylated liposomal must not be used instead of other medicines containing irinotecan as the substance behaves differently when present inside the liposome than when given in the free form.

It is also especially important that you tell your doctor if you are also taking the following medicines, as they reduce the availability 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 (an herbal medicine used to treat mild depression and mild anxiety)
as ONIVYDE pegylated liposomal should not be given to you along with those medicines.

It is also especially important that you tell your doctor if you are also taking the following medicines, as they increase the availability 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 depression)
gemfibrozil (medicines used to treat high blood fats)

ONIVYDE pegylated liposomal with food and drink

Avoid eating grapefruit and drinking grapefruit juice when receiving ONIVYDE pegylated liposomal as it may increase the availability of the active substance of ONIVYDE pegylated liposomal in your body.

Pregnancy and breastfeeding

You should not take ONIVYDE pegylated liposomal if you are pregnant as it may harm your baby. Tell your doctor if you are pregnant, or if you think you may be pregnant. Ask your doctor for advice if you are planning to have a baby. If you are receiving ONIVYDE pegylated liposomal, you should not breast-feed until one month after the last dose.

During the ONIVYDE pegylated liposomal treatment and one month later, you should choose an effective method of contraception that suits you to prevent pregnancy during this period. Men should use condoms during ONIVYDE pegylated liposomal treatment and four months after.

Tell your doctor if you are breast-feeding. You must not take ONIVYDE pegylated liposomal if you are breast-feeding as it may harm your baby.

Driving and using machines

ONIVYDE pegylated liposomal may affect your ability to drive and use machines (as you may become drowsy, dizzy, and exhausted when using ONIVYDE pegylated liposomal). You should avoid driving, using machines, or performing other tasks that require full attention if you feel sleepy, dizzy, or exhausted.

ONIVYDE pegylated liposomal contains sodium

One milliliter of this medicine contains 0.144 mmol (3.31 mg) sodium – remember if you have been prescribed a low-sodium (low-salt) diet.

How to use ONIVYDE pegylated liposomal

ONIVYDE pegylated liposomal should only be given by healthcare professionals who are trained to administer anti-cancer drugs.

Carefully follow all instructions given to you by your doctor or nurse.

Your doctor will decide what dose you should take.

ONIVYDE pegylated liposomal is given as a drip ( infusion fluid ) into a vein, which takes at least 90 minutes and should be given as a single dose.

Once you have received ONIVYDE pegylated liposomal, you will be given two other medicines, leucovorin and 5 ‑ fluorouracil.

The treatment is repeated every two weeks.

In some cases, lower doses or longer intervals between doses may be required.

You may be given premedication for nausea and vomiting. If you have experienced sweating, abdominal cramps, and salivation along with early frequent and watery bowel movements in previous treatments with ONIVYDE pegylated liposomal, you may be given additional medicines before ONIVYDE pegylated liposomal to prevent or reduce this in future treatment cycles.

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

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. You must be aware of what these side effects may be.

Your doctor may also prescribe other medicines to help you control your side effects.

Tell your doctor or nurse straight away if you experience any of the following side effects:

if you suddenly have shortness of breath, redness , nausea, headache, skin rash or hives (rapidly itchy itchy rash with swollen red bumps on the skin), itching and swelling around the eyes, pressure over the chest or throat during or shortly after infusion one (because infusion one may need to be stopped and you may need to be treated or admitted for side effects )
if you get a fever, chills and signs of infection (as it may require immediate treatment)
if you have severe persistent diarrhea (watery and frequent stools) – see section 2

The following side effects may occur:

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

Low levels of white blood cells ( neutropenia and leukopenia ), low levels of red blood cells ( anemia )
Low platelet count ( thrombocytopenia )
Diarrhea (loose or watery and frequent bowel movements)
Nausea and vomiting
Sore stomach or intestinal tract
Cold sores
Weight loss
Reduced appetite
Lost body fluid (dehydration)
Low salt levels ( electrolytes ) in the body (eg potassium , magnesium )
Abnormal hair loss
Fatigue
Dizziness
Swelling and fluid accumulation in soft tissues (peripheral edema )
Tenderness and swelling of the gastrointestinal tract (mucositis)
Fever
General weakness

Common (may affect up to 1 in 10 people)

Overindulge
Infection is, e.g. fungal infections of the mouth ( oral candidiasis), fever with low white blood cell count (febrile neutropenia ), infection are related to the administration of the product in a vein
Inflammation of the stomach and intestines ( gastroenteritis )
Systemic inflammation , caused by infection ( sepsis )
Potential life-threatening complication with whole-body inflammation ( septic shock )
Pneumonia _ _ _
Low levels of a subtype of white blood cells called lymphocytes with an important function of the immune system (lymphopenia)
Reduction of certain salts ( electrolytes ) in the body (eg phosphate , sodium )
Low blood sugar ( hypoglycaemia )
Insomnia
Bad taste in the mouth
A syndrome called cholinergic syndrome with sweating, salivation and abdominal cramps
Low blood pressure ( hypotension )
Formation of a blood clot in a deep vein (deep vein thrombosis ) or blockage of the main artery of the lungs or any of its branches ( pulmonary embolism ) or blockage due to a blood clot elsewhere in the bloodstream (embolism)
Voice impairment, hoarse or unusually hissing voice
Shortness of breath
Inflammation of the intestine
Hemorrhoids
Increase in liver enzyme ( alanine aminotransferase or aspartate aminotransferase ) in laboratory laboratory tests
Increased bilirubin levels (an orange ‑ yellow pigment, waste product in the normal breakdown of red blood cells ) in other laboratory values related to liver function
Increase in other laboratory values (increased internationally normalized ratio) related to the function of the blood clotting system
Abnormally low albumin levels in the blood (the main protein in the body)
Sudden problems with kidney function, which can lead to rapid deterioration or loss of kidney function
Abnormal reaction to infusion one that causes symptoms such as shortness of breath, redness , headache, pressure in the chest or throat
Abnormal fluid accumulation in the body that causes swelling in the affected tissues ( edema )

Uncommon (may affect up to 1 in 100 people)

Systemic inflammation , caused by infection of the gallbladder and bile ducts (biliary sepsis )
Allergic reaction to ONIVYDE pegylated liposomal (the active substance or excipient)
Reduced availability of oxygen to body tissues
Inflammation of the esophagus (esophagus)
Formation or presence of a blood clot inside a blood vessel, either vein or artery ( thrombosis )
Inflammation on the inside of the rectum (end of the colon)
Type of rash characterized by a flat, red area on the skin covered with bumps (maculopapular rash)
Changed color of the nail plates

How to store ONIVYDE pegylated liposomal

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

Do not use this medicine after the expiry date which is stated on the carton and vial after EXP. The expiration date is the last day of the specified month.

Store in a refrigerator (2 ° C – 8 ° C).

Do not freeze.

Keep the vial in the outer carton. Sensitive to light.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Contents of the package and other information

Content declaration

The active substance is irinotecan. A 10 ml concentrate vial contains 43 mg irinotecan as an anhydrous base (as sucrose salt in a pegylated liposomal mixture ).
The other ingredients are 1.2 ‑ distearoyl ‑ sn ‑ glycero ‑ 3 ‑ phosphocoline (DSPC), cholesterol , N‑ (carbonyl ‑ methoxypolyethylene glycol ‑ 2000) ‑1,2 ‑ distearoyl ‑ sn ‑ glycero ‑ 3 ‑ phosphoethanolamine (MPEG MP PEDSPE), sucrose octasulfate; 2‑ [4‑ (2‑ hydroxyethyl) piperazine ‑ 1‑yl] ethanesulfonic acid (HEPES‑ buffer ), sodium chloride and water for injections . ONIVYDE pegylated liposomal contains sodium – if you have been prescribed a low-sodium (low-salt) diet, see section 2.

What the medicine looks like and contents of the pack

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

Each pack contains a vial of 10 ml of concentrate.

Marketing Authorization Holder and Manufacturer

Marketing Authorisation Holder

Servier Laboratories Servier

50, rue Carnot

92284 Suresnes cedex

France

Manufacturer

The Laboratory Servier Industrie

905 Route de Saran

45520 Gidy