2 mg/ml concentrate for infusion solution, dispersion
doxorubicin hydrochloride (doxorubicin. hydrochloride.)
What ZOLSKETIL pegylated liposomal is and what it is used for
ZOLSKETIL pegylated liposomal is an antitumor agent.
ZOLSKETIL pegylated liposomal is used to treat breast cancer in patients at risk of heart problems. ZOLSKETIL pegylated liposomal is also used to treat ovarian cancer. It is used to kill cancer cells, reduce the size of a tumor, delay the growth of a tumor, and prolong the patient’s survival.
ZOLSKETIL pegylated liposomal is also used in combination with another medicine, bortezomib, to treat multiple myeloma, a type of blood cancer in patients who have received at least one previous treatment regimen.
ZOLSKETIL pegylated liposomal is also used to bring about an improvement in Kaposi’s sarcoma so that cancer flattens, lightens, and even shrinks. Other symptoms of Kaposi’s sarcoma, such as swelling around the tumor, may also improve or disappear.
ZOLSKETIL pegylated liposomal contains a drug that can interact with cells in such a way that it selectively kills cancer cells. The doxorubicin hydrochloride in ZOLSKETIL pegylated liposomal is encapsulated in small spheres called pegylated liposomes, which help deliver the drug from the bloodstream to the cancer tissue to a greater extent than to normal healthy tissue.
What you need to know before you use ZOLSKETIL pegylated liposomal
Do not use ZOLSKETIL pegylated liposomal
- if you are allergic to doxorubicin hydrochloride, peanuts or soya, or any of the ingredients of this medicine (listed in section 6).
Warnings and precautions
Talk to a doctor:
- if you are being treated for heart disease or liver disease
- if you have diabetes because ZOLSKETIL pegylated liposomal contains sugar, which means that your diabetes treatment may need to be adjusted
- if you have Kaposi’s sarcoma and have had your spleen removed
- if you get sores, discoloration, or any discomfort in your mouth
- if your bone marrow does not make enough blood cells
- if you have cancer and your bone marrow makes abnormal blood cells
- if you get a painful, red-spotted rash
- if you have leakage of irritating fluids or medicines from the vein into the surrounding tissue
- if you get hand-foot syndrome ( redness, swelling, and blistering [a pocket of fluid between the top layers of the skin] on the palm or sole).
Strategies to prevent and treat hand-foot syndrome include:
- keeping your hands and/or feet in a tub of cold water whenever possible (eg when watching TV, reading, or listening to the radio)
- to keep hands and feet bare (no gloves, socks, etc.)
- to stay in cool places
- to take cool baths in hot weather
- to avoid vigorous exertion that may cause foot discomfort (e.g. jogging)
- to avoid exposing the skin to very hot water (e.g. jacuzzi, sauna)
- to avoid tight and/or high-heeled shoes.
Pyridoxine (vitamin B6):
- vitamin B6 is available without a prescription.
- take 50-150 mg daily at the first symptoms of redness or tingling.
Children and young people
Other medicines and ZOLSKETIL pegylated liposomal
Tell your doctor or pharmacist
- if you are taking, have recently taken, or may be taking other medicines, including over-the-counter medicines
- if you are receiving or have received other cancer treatments, as special consideration needs to be given to treatments that reduce the number of white blood cells, as they may cause a further decrease in the number of white blood cells. If you are unsure about the treatments you have received or the diseases you have had, you should discuss these with your doctor.
Pregnancy and breastfeeding
Consult your doctor or pharmacist before taking this medicine.
Because the active ingredient doxorubicin hydrochloride in ZOLSKETIL pegylated liposomal can cause birth defects, you must tell your doctor if you think you are pregnant. You must avoid becoming pregnant while you or your partner are being treated with ZOLSKETIL pegylated liposomal and for six months after finishing treatment with ZOLSKETIL pegylated liposomal.
Because doxorubicin hydrochloride may be harmful to breastfed infants, women must discontinue breastfeeding before starting treatment with ZOLSKETIL pegylated liposomal. Experts recommend that HIV -infected women do not under any circumstances breastfeed their infants to avoid transmission of HIV.
Driving ability and use of machinery
ZOLSKETIL pegylated liposomal contains soybean oil and sodium
ZOLSKETIL pegylated liposomal contains soybean oil. If you are allergic to peanuts or soya, you should not use this medicine.
ZOLSKETIL pegylated liposomal contains less than 1 mmol (23 mg) of sodium per dose, i.e. is almost “sodium-free”.
How to use ZOLSKETIL pegylated liposomal
ZOLSKETIL pegylated liposomal is a unique pharmaceutical form. It must not be exchanged for other preparations of doxorubicin hydrochloride.
How much ZOLSKETIL pegylated liposomal is given
If you are being treated for breast or ovarian cancer, ZOLSKETIL pegylated liposomal will be given at a dose of 50 mg per square meter of your body surface area (based on your height and weight). Infusion one is repeated every 4 weeks as long as the disease does not worsen and you tolerate the treatment.
If you are being treated for multiple myeloma and have already received at least one previous treatment regimen, ZOLSKETIL pegylated liposomal will be given at a dose of 30 mg per square meter of your body surface area (based on your height and weight). ZOLSKETIL pegylated liposomal will be given as a one-hour intravenous infusion on Day 4 of the bortezomib 3-week regimen, immediately following the bortezomib infusion. Dose one is repeated as long as you respond satisfactorily and tolerate treatment.
If you are being treated for Kaposi’s sarcoma, ZOLSKETIL pegylated liposomal will be given at a dose of 20 mg per square meter of your body surface area (based on your height and weight). Infusion one is repeated every two to three weeks for two to three months, then as often as needed to maintain an improvement in your condition.
How ZOLSKETIL pegylated liposomal is given
ZOLSKETIL pegylated liposomal will be given by your doctor as a drip ( infusion ) into a vein. Depending on the dose and what the medicine is used for, the infusion can take from 30 minutes to more than an hour (ie 90 minutes).
If you have used too much ZOLSKETIL pegylated liposomal
Acute overdose worsens side effects such as ulcers in the mouth or reduced numbers of white blood cells and platelets in the blood. Treatment will include the administration of antibiotics, transfusion of platelets, use of factors that stimulate the production of white blood cells, and symptomatic treatment of mouth ulcers.
If you have further questions about this medicine, contact your doctor or pharmacist.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
During the infusion of ZOLSKETIL pegylated liposomal, you should immediately contact a doctor if the following reactions occur:
- the severe allergic reaction which may include swelling of the face, lips, mouth, tongue, or throat; difficulty swallowing or breathing; itchy rash ( hives )
- inflamed and narrow airways in the lungs causing coughing, wheezing, and shortness of breath ( asthma )
- hot flushes, sweating, chills, or fever
- chest pain or discomfort
- back pain
- high or low blood pressure
- rapid heartbeat
- convulsions (seizures)
Leakage of the injection fluid from the veins into the tissue under the skin may occur. If the drop stings or hurts when you receive a dose of ZOLSKETIL pegylated liposomal, tell your doctor immediately.
Your doctor should be contacted immediately if any of the following serious side effects are detected
- you develop a fever, feel tired or see signs of bruising or bleeding (very common)
- skin redness, swelling, scaling, or tenderness, mainly on the hands or feet (“hand-foot syndrome”). These side effects have been seen very often and are sometimes serious. In severe cases, these side effects may affect some daily activities and may persist for 4 weeks or longer before complete healing. The doctor may want to delay and/or reduce the dose for the next treatment (see below, Strategies for preventing and treating hand-foot syndrome)
- mouth ulcers, severe diarrhea or vomiting, or nausea (very common)
- infection (common), including pneumonia or infection affecting your vision
- shortness of breath (common)
- severe abdominal pain (common)
- the severe feeling of weakness (common)
- the severe allergic reaction which may include swelling of the face, lips, mouth, tongue, or throat; difficulty swallowing or breathing; itchy rash ( hives ) (uncommon)
- cardiac arrest (the heart stops beating); heart failure, when the heart does not pump enough blood to the rest of the body, giving you shortness of breath and can leading to swollen legs (uncommon)
- a blood clot that travels to the lung, causing chest pain and giving you shortness of breath (uncommon)
- swelling, warmth, or tenderness in the soft parts of the legs, sometimes with pain that gets worse when standing or walking (rare)
- severe or life-threatening rash with blisters and peeling skin, mainly around the mouth, nose, eyes, and genitals ( Stevens-Johnson syndrome ) or over most of the body ( toxic epidermal necrolysis ) (rare)
Other side effects ar
Between infusions, the following may occur:
Very common side effects ( may affect more than 1 in 10 users)
- decrease in the number of white blood cells, which can increase the risk of infection. In rare cases, a low white blood cell count can lead to severe infection. Anemia (a decrease in red blood cells ) can cause fatigue. Decreased number of platelets can increase the risk of bleeding. Because the blood can be affected, you must take blood samples regularly.
- decreased appetite
- skin rash, including redness of the skin, allergic skin rash, red or raised rash on the skin
- hair loss
- pain, including pain in muscles and chest muscles, joints, arms, or legs
- great feeling of fatigue
Common side effects ( may affect up to 1 in 10 users):
- infection, including serious infection of the whole body ( sepsis ), lung infections, viral infection with herpes zoster ( shingles ), a type of bacterial infection ( mycobacterium avium complex infection), urinary tract infection, fungal infections (including thrush and oral thrush), infection in hair roots, infection or irritation of the throat, infection of the nose, sinuses or throat (cold)
- the low number of a type of white blood cell ( neutrophils ) with fever
- severe weight loss and muscle wasting, dehydration ( dehydration ), low levels of potassium, sodium, or calcium in the blood
- feeling confused, feeling anxious, depressed, difficulty sleeping
- nerve damage that may cause tingling, numbness, pain or lack of pain sensation, nerve pain, unusual sensation in the skin (such as tingling or crawling), decreased sensation or sensitivity, especially in the skin
- altered sense of taste, headache, feeling very tired and low energy levels, dizziness
- inflammation of the eyes ( conjunctivitis )
- high or low blood pressure, cramps
- shortness of breath that can occur during physical activity, nosebleeds, coughing
- inflammation of the lining of the stomach or esophagus, mouth ulcers, indigestion, difficulty swallowing, pain in the mouth, dry mouth
- skin problems, including flaky and dry skin, redness of the skin, blisters or sores on the skin, itching, dark spots on the skin
- abnormally heavy sweating
- muscle cramps or muscle pain
- pain in the muscles, bones, or back
- pain when urinating
- allergic reaction to the drug infusion, flu-like illness, chills, inflamed mucous membranes in body cavities or passages such as the nose, mouth, or windpipe, feeling weak, feeling generally unwell, swelling caused by fluid retention in the body, swollen hands, ankles or feet
- weight loss
When ZOLSKETIL pegylated liposomal alone is used, some of these side effects are less likely to occur and some have not occurred at all.
Uncommon side effects ( may affect up to 1 in 100 users):
- viral infection with herpes simplex (cold sores or genital herpes ), fungal infection
- the low number of all types of blood cells, increased number of platelets (cells that help the blood to clot)
- allergic reaction
- high levels of potassium in the blood, low levels of magnesium in the blood
- nerve damage that affects more than one area of the body
- convulsions, fainting
- unpleasant or painful sensation, especially when touched, sleepiness
- blurred vision, watery eyes
- heartbeats that feel fast or irregular ( palpitations ), disease of the heart muscle, damage to the heart
- tissue damage ( necrosis ) where the injection is given, inflamed veins causing swelling and pain, dizziness when sitting or standing
- chest discomfort
- emission of gases, inflamed gums ( gingivitis )
- skin problems or rashes, including flaky or scaly skin, allergic skin rash, sores or hives on the skin, skin discoloration, change in skin color (pigmentation), small red or purple spots caused by bleeding under the skin, nail problems, acne
- muscle weakness
- pain in the chest
- irritation or pain at the injection site
- swelling of the face, high body temperature
- symptoms (such as inflammation, redness, or pain) come back in places that were previously treated with radiation or that were previously damaged by an injection of chemotherapy into a vein
Rare side effects ( may affect up to 1 in 1,000 users)
- infection that occurs in people with weak immune systems
- the low number of blood cells are produced in the bone marrow
- inflammation of the retina that can cause vision changes or blindness
- abnormal heart rhythm, abnormal EKG ( electrocardiogram ) which can be caused by a slow heart rhythm, problems with the heart that affect the heartbeat and heart rhythm, blue skin and mucous membranes caused by a lack of oxygen in the blood
- dilation of blood vessels
- tightness in the throat
- sore and swollen tongue, sores on the lips (cold sores)
- skin rash with fluid-filled blisters
- vaginal infection, redness of the scrotum
- problems with the mucous membranes in body cavities or passages, such as the nose, mouth, or trachea
- abnormal liver blood test results increased blood levels of ‘creatinine’
Frequency not known (cannot be estimated from available data)
- cancer of the blood that develops rapidly and affects the blood cells ( acute myeloid leukemia ), bone marrow disease that affects the blood cells ( myelodysplastic syndrome ), cancer of the mouth or lips
How to store ZOLSKETIL pegylated liposomal
Keep this medicine out of the sight and reach of children.
Use before the expiry date stated on the vial label and carton.
Store in a refrigerator (2 °C‑8 °C). Do not freeze.
Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C-8°C.
For microbiological reasons, the product must be used immediately. If not used immediately, in-use storage times and conditions before use are the responsibility of the user and would not be longer than 24 hours at 2°C-8°C. Partially used vials must be destroyed.
Do not use this medicine if you see any signs of precipitation or other particle formation.
Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.
Contents of the packaging and other information
- The active substance is doxorubicin hydrochloride. One ml of ZOLSKETIL pegylated liposomal contains 2 mg of doxorubicin hydrochloride in a pegylated liposomal preparation.
- Other ingredients are hydrogenated soy phosphatidylcholine, N‑(carbonyl‑methoxypolyeyltenglycol‑2000)‑1,2‑stearoyl‑sn‑glycerol‑3‑phosphoethanolamine, sodium salt (MPEG‑2000‑DSPE), cholesterol, ammonium sulfate, histidine, sucrose, water for injections, concentrated hydrochloric acid (for pH adjustment), and sodium hydroxide (for pH adjustment). See section 2.
ZOLSKETIL pegylated liposomal concentrate for infusion, solution: vials of 10 ml (20 mg) or 25 ml (50 mg).
Appearance and package sizes of the medicine
ZOLSKETIL pegylated liposomal is a transparent and red-colored dispersion filled in a clear glass vial.
ZOLSKETIL pegylated liposomal is supplied in packs of one vial or ten vials.
Marketing Authorisation Holder
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