Doxorubicin liposomal pegylated Dr. Reddy's: detailed information

Package leaflet: Information for the user

Doxorubicin liposomal pegylated Dr. Reddy’s 2 mg/mL concentrate for dispersion for

infusion
doxorubicin hydrochloride
Please read this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, as it may be harmful to them.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:
1. What Doxorubicin liposomal pegylated Dr. Reddy’s is and what it is used for
2. What you need to know before receiving Doxorubicin liposomal pegylated Dr. Reddy’s
3. How to receive Doxorubicin liposomal pegylated Dr. Reddy’s
4. Possible side effects
5. How to store Doxorubicin liposomal pegylated Dr. Reddy’s
6. Contents of the pack and other information

1. What Doxorubicin liposomal pegylated Dr. Reddy’s is and what it is used for
Doxorubicin liposomal pegylated Dr. Reddy’s is an antitumor agent.
Doxorubicin liposomal pegylated Dr. Reddy’s is used to treat breast cancer in patients at risk of cardiac problems. Doxorubicin liposomal pegylated Dr. Reddy’s is also used to treat ovarian cancer. It is used to kill cancer cells, reduce tumor size, slow tumor growth, and prolong survival.
Doxorubicin liposomal pegylated Dr. Reddy’s is also used in combination with another medicine, bortezomib, for the treatment of multiple myeloma (a blood cancer) in patients who have received at least one prior therapy.
Doxorubicin liposomal pegylated Dr. Reddy’s is also used to improve Kaposi's sarcoma, including flattening, pallor, and reduction in tumor size. Other symptoms of Kaposi's sarcoma, such as swelling around the tumor, may also improve or disappear.
Doxorubicin liposomal pegylated Dr. Reddy’s contains a substance capable of interacting with cells to selectively kill tumor cells. The doxorubicin hydrochloride contained in Doxorubicin liposomal pegylated Dr. Reddy’s is enclosed within tiny spheres called pegylated liposomes, which facilitate the delivery of the drug from the bloodstream to tumor tissue while minimizing its dispersion into healthy tissues.

2. What you should know before taking Doxorubicin Liposomal PEGylated Dr. Reddy’s

Do not take Doxorubicin Liposomal PEGylated Dr. Reddy’s

if you are allergic to doxorubicin hydrochloride, peanuts, or soy, or to any of the excipients of this medicine (listed in section 6).

Warnings and precautions
Inform your doctor if you have any of the following conditions:

if you are being treated for heart or liver disorders;
if you have diabetes, because Doxorubicin Liposomal PEGylated Dr. Reddy’s contains sugar and your diabetes treatment may need to be adjusted;
if you have Kaposi's sarcoma and your spleen has been removed;
if you notice mouth ulcers, color changes, or any other oral problems.

Interstitial lung disease, including fatal cases, has been observed in patients treated with pegylated liposomal doxorubicin. Symptoms of interstitial lung disease include cough and shortness of breath, sometimes accompanied by fever, not caused by physical exertion. Seek immediate medical attention if you develop symptoms that could indicate interstitial lung disease.

Children and adolescents
Doxorubicin Liposomal PEGylated Dr. Reddy’s must not be used in children and adolescents, as it is not known how the medicine affects them.

Other medicines and Doxorubicin Liposomal PEGylated Dr. Reddy’s
Inform your doctor or pharmacist

if you are taking or have recently taken any other medicines, including those not requiring a prescription;
about all cancer treatments you are currently receiving or have received in the past, as particular caution is required for therapies that reduce white blood cell counts, as this may lead to a further decrease in white blood cells. If you are unsure about previous treatments or medical conditions, discuss them with your doctor.

Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Since the active substance doxorubicin hydrochloride contained in Doxorubicin Liposomal PEGylated Dr. Reddy’s may cause birth defects, it is important that you inform your doctor if you think you may be pregnant.
Women must avoid pregnancy and use contraceptive measures during treatment with Doxorubicin Liposomal PEGylated Dr. Reddy’s and for eight months after stopping treatment with Doxorubicin Liposomal PEGylated Dr. Reddy’s.
Men must use contraceptive measures during treatment with Doxorubicin Liposomal PEGylated Dr. Reddy’s and for six months after stopping Doxorubicin Liposomal PEGylated Dr. Reddy’s to prevent their partner from becoming pregnant.
Because doxorubicin hydrochloride may be harmful to infants, women must stop breastfeeding before starting treatment with Doxorubicin Liposomal PEGylated Dr. Reddy’s. Healthcare professionals recommend that women with HIV infection should under no circumstances breastfeed their infants to prevent transmission of HIV.

Driving and using machines
Do not drive or operate tools or machinery if you feel tired or drowsy following treatment with Doxorubicin Liposomal PEGylated Dr. Reddy’s.

Doxorubicin Liposomal PEGylated Dr. Reddy’s contains soybean oil and sodium
Doxorubicin Liposomal PEGylated Dr. Reddy’s contains soybean oil. If you are allergic to peanuts or soy, do not use this medicine.
Doxorubicin Liposomal PEGylated Dr. Reddy’s contains less than 1 mmol of sodium (23 mg) per dose, i.e., "essentially sodium-free".

3. How to take Pegylated Liposomal Doxorubicin Dr. Reddy’s

Pegylated Liposomal Doxorubicin Dr. Reddy’s is a unique formulation. It must not be used interchangeably with other formulations containing doxorubicin hydrochloride.
What dose is given of Pegylated Liposomal Doxorubicin Dr. Reddy’s
For the treatment of breast or ovarian cancer, Pegylated Liposomal Doxorubicin Dr. Reddy’s will be administered to you at a dose of 50 mg per square meter of your body surface area (based on your height and weight). This dose will be repeated every 4 weeks for as long as the disease does not progress and you are able to tolerate the treatment.
For the treatment of multiple myeloma, if you have already received at least one prior therapy, Pegylated Liposomal Doxorubicin Dr. Reddy’s will be administered at a dose of 30 mg per square meter of body surface area (based on your height and weight) via a 1-hour intravenous infusion given immediately after bortezomib infusion on day 4 of the 3-week bortezomib treatment cycle. The dose will be repeated as long as you respond satisfactorily and tolerate the treatment.
For the treatment of Kaposi’s sarcoma, Pegylated Liposomal Doxorubicin Dr. Reddy’s will be administered at a dose of 20 mg per square meter of body surface area (based on height and weight). The dose is repeated every 2–3 weeks for 2–3 months, after which it will be repeated as needed to maintain improvement in your condition.
How Pegylated Liposomal Doxorubicin Dr. Reddy’s is administered
Pegylated Liposomal Doxorubicin Dr. Reddy’s will be administered to you by your doctor through an intravenous infusion (drip) into a vein. Depending on the dose and indication, the infusion will last from 30 minutes to more than one hour (i.e., 90 minutes).
If you take more Pegylated Liposomal Doxorubicin Dr. Reddy’s than you should
Acute overdose worsens side effects such as mouth sores or decreased numbers of white blood cells and platelets in the blood. Treatment will consist of administering antibiotics, platelet transfusions, use of factors that stimulate white blood cell production, and symptomatic treatment of mouth sores.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The following reactions may occur during infusion of Doxorubicin pegylated liposomal Dr. Reddy’s:

severe allergic reaction which may include swelling of the face, lips, mouth, tongue or throat; difficulty swallowing or breathing; itchy rash (urticaria)
inflammation and narrowing of the airways in the lungs, leading to cough, wheezing and shortness of breath (asthma)
flushing, sweating, chills or fever
chest pain or discomfort
back pain
high or low blood pressure
rapid heartbeat
seizures (convulsions)
Leakage of the infused liquid from the vein into surrounding tissues may occur. If the infusion causes discomfort or pain during administration of Doxorubicin pegylated liposomal Dr. Reddy’s, inform your doctor immediately.

Contact your doctor immediately if you experience any of the following serious side effects:

fever, fatigue, or signs of bruising or bleeding (very common)
redness, swelling, peeling or tenderness, especially on the hands or feet (hand-foot syndrome). These effects have been observed very commonly and can sometimes be severe. In severe cases, these effects may interfere with certain daily activities and may last up to 4 weeks or longer before resolving completely. Your doctor may delay and/or reduce the dose of your next treatment (see below: Strategies to prevent and treat hand-foot syndrome).
mouth sores, severe diarrhoea, vomiting or nausea (very common)
infections (common), including lung infections (pneumonia) or infections that may affect vision
shortness of breath (common)
severe stomach pain (common)
severe weakness (common)
severe allergic reaction which may include swelling of the face, lips, mouth, tongue or throat; difficulty swallowing or breathing; itchy rash (urticaria) (uncommon)
cardiac arrest (heart stops beating); heart failure, in which the heart does not pump enough blood to the rest of the body, causing shortness of breath and possibly swollen legs (uncommon)
blood clot travelling to the lungs, causing chest pain and shortness of breath (uncommon)
swelling, warmth or tenderness in the soft tissues of the legs, sometimes with pain that worsens when standing or walking (rare)
severe or potentially life-threatening skin rash, with blisters and peeling skin, particularly around the mouth, nose, eyes and genital organs (Stevens-Johnson syndrome) or over most of the body (toxic epidermal necrolysis) (rare)

Other side effects
The following side effects may occur between infusions:
Very common side effects (may affect more than 1 in 10 people)

reduced number of white blood cells, which may increase the risk of infections. In rare cases, low white blood cell count may lead to serious infections. Anaemia (reduction in red blood cells) may cause fatigue, and reduced platelet count may increase the risk of bleeding. Due to potential changes in blood cells, you will have regular blood tests.
reduced appetite
constipation, skin rashes, including skin redness, allergic skin rashes, red or raised rashes on the skin
hair loss
pain, including muscle pain, chest muscle pain, joint pain, arm or leg pain
extreme tiredness

Common side effects (may affect up to 1 in 10 people)

infections, including severe systemic infection (sepsis), lung infections, herpes zoster virus infections (shingles), a type of bacterial infection (Mycobacterium avium complex infection), urinary tract infections, fungal infections (including oral thrush and candidiasis), hair follicle infection, infection or irritation of the skin, infection of nose, sinuses or throat (cold)
low number of a type of white blood cells (neutrophils), with fever
severe weight loss and muscle wasting, insufficient body water (dehydration), low levels of potassium, sodium or calcium in the blood
confusion, anxiety, depression, difficulty sleeping
nerve damage which may cause tingling, numbness, pain or loss of sensation, nerve pain, unusual skin sensations (such as tingling or crawling sensations), reduced sensation and sensitivity, especially in the skin
altered taste, headache, drowsiness and lack of energy, dizziness
eye inflammation (conjunctivitis)
rapid heartbeat
high or low blood pressure, hot flushes
shortness of breath which may be triggered by physical activity, nosebleeds, cough
inflammation of the lining of the stomach and oesophagus, mouth ulcers (aphthae), indigestion, difficulty swallowing, mouth pain, dry mouth
skin problems, including dry or peeling skin, skin redness, blisters or ulcers (urticaria) on the skin, itching, dark spots on the skin
excessive sweating
muscle spasms or cramps
pain, including muscle, bone or back pain
pain during urination
allergic reaction to the medicine infusion, flu-like illness, chills, inflammation of the linings of cavities and passages inside the body, such as nose, mouth or trachea, weakness, general malaise, swelling due to fluid accumulation in the body, swollen hands, ankles or feet
decrease in body weight

When Doxorubicin pegylated liposomal Dr. Reddy’s is used alone, some of these side effects are less likely and some do not occur at all.
Uncommon side effects (may affect up to 1 in 100 people)

herpes simplex virus infections (cold sores or genital herpes), fungal infections
low number of all types of blood cells, increased number of "platelets" (cells that help blood to clot)
allergic reaction
high potassium levels in the blood, low magnesium levels in the blood
nerve damage affecting more than one part of the body
seizures (convulsions), fainting
unpleasant or painful sensation, especially on touch, drowsiness
blurred vision, watery eyes
sensation of rapid or irregular heartbeat (palpitations), heart muscle diseases, heart damage
tissue damage (necrosis) at the injection site, vein inflammation causing swelling and pain, dizziness when sitting or standing up, chest discomfort
flatulence, inflamed gums (gingivitis)
skin problems or rashes, including peeling or flaking skin, allergic skin rashes, skin ulcer (sore) or urticaria, discoloured skin, changes in natural skin colour (pigment), small red or purple spots caused by bleeding under the skin, nail problems, acne
muscle weakness
breast pain
irritation or pain at the injection site
facial swelling, high body temperature
symptoms (such as inflammation, redness or pain) reappear in an area of the body previously treated with radiotherapy or previously damaged by a chemotherapy injection into a vein

Rare side effects (may affect up to 1 in 1,000 people)

infection occurring in people with a weakened immune system
low number of blood cells produced in the bone marrow
inflamed retina, which may cause vision changes or blindness
abnormal heart rhythm, abnormal ECG (electrocardiogram) with possible slow heartbeat, heart condition affecting heartbeat and rhythm, bluish skin and mucous membranes due to low blood oxygen levels
dilation of blood vessels
sensation of tightness in the throat
swollen and painful tongue, ulcer (sore) on the lips
skin rash with fluid-filled blisters
vaginal infection, redness of the scrotum
problems affecting the lining of cavities and passages inside the body, such as nose, mouth or trachea
abnormal liver blood test results, increased blood levels of "creatinine"

Not known (frequency cannot be estimated from available data)

rapidly developing blood cancer affecting blood cells (acute myeloid leukaemia), bone marrow disease affecting blood cells (myelodysplastic syndrome), tumour of the mouth or lips
cough and shortness of breath, sometimes accompanied by fever, not caused by physical activity (interstitial lung disease)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse.
You can also report side effects directly via the national reporting system: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects can help provide more information on the safety of this medicine.

Strategies to prevent and treat hand-foot syndrome include:

when possible, immerse hands and/or feet in a basin of cold water (e.g., while watching television, reading or listening to the radio);
keep hands and feet uncovered (no gloves, socks, etc.);
stay in cool environments;
take cold baths during hot periods;
avoid vigorous exercise that may cause trauma to the feet (e.g., running);
avoid exposing skin to very hot water (e.g., hot tubs, saunas);
avoid tight or high-heeled shoes.

Pyridoxine (vitamin B6):

vitamin B6 can be purchased without a prescription;
take 50–150 mg daily at the first signs of redness or tingling.

5. How to store Doxorubicin Liposomal PEGylated Dr. Reddy’s

Keep this medicine out of the sight and reach of children.
Store in the refrigerator (2°C - 8°C). Do not freeze. Store in the original packaging to protect from light.

After dilution:
Chemical and physical in-use stability has been demonstrated for 24 hours at a temperature between 2°C and 8°C.
From a microbiological standpoint, unless the method of dilution excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the conditions and duration of in-use storage are the responsibility of the user. Partially used vials must be discarded.

Do not use this medicine after the expiry date stated on the label and carton.
Do not use this medicine if you notice any precipitate or other types of particles.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Doxorubicin liposomal pegylated Dr. Reddy’s contains

The active substance is doxorubicin hydrochloride. One mL contains 2 mg of doxorubicin hydrochloride in a pegylated liposomal formulation.
The excipients are α-(2-[1,2-distearoyl-sn-glycero(3)phospho]ethylcarbamoyl)-ω-methoxypoly(ethylene glycol)-40 sodium salt (MPEG-DSPE), fully hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, ammonium sulfate, histidine, sucrose and water for injections; for pH adjustment: hydrochloric acid and sodium hydroxide. See section 2.

Doxorubicin liposomal pegylated Dr. Reddy’s concentrate for dispersion for infusion: vials of
10 mL (20 mg) or 25 mL (50 mg).
Description of the appearance of Doxorubicin liposomal pegylated Dr. Reddy’s and contents of the
package
Doxorubicin liposomal pegylated Dr. Reddy’s is a sterile, translucent red solution. Doxorubicin liposomal
pegylated Dr. Reddy’s is available in glass vials sealed with a dark blue flip-off cap (10 mL) or red flip-off cap (25 mL), supplied in single packs or packs of ten vials.
Not all pack sizes may be marketed.
Marketing Authorization Holder
Dr. Reddy’s SRL
Piazza Santa Maria Beltrade 1
20123, Milan (MI)
Italy
Manufacturer
Betapharm Arzneimittel GmbH,
Kobelweg 95, 86156 Augsburg,
Germany
Rual Laboratories SRL,
313, Splaiul Unirii, Building H,
1st floor, sector 3, Bucharest, 030138,
Romania
DR. REDDY’S LABORATORIES ROMÂNIA S.R.L.,
Space 2 Sector 1 30-32 Strada Daniel
Danielopolu 5th Floor, Bucharest, 014134,
Romania
Pharmadox Healthcare Ltd.,
KW20A Kordin Industrial Park,
Paola PLA 3000,
Malta
This patient information leaflet was last revised on
This medicinal product is authorized in the European Economic Area Member States under the
following names:
Austria: Doxorubicin pegyliert liposomal Reddy 2 mg/ml Konzentrat zur Herstellung einer
Infusionsdispersion
Germany: Doxorubicin pegyliert liposomal beta 2 mg/ml Konzentrat zur Herstellung einer
Infusionsdispersion
Spain: Doxorubicina liposomal pegilado Dr. Reddys 2 mg/ml concentrado para dispersión para
perfusión
France: DOXORUBICINE PEGYLATED LIPOSOMAL REDDY PHARMA 2 mg/mL, dispersion à
diluer pour perfusion
Italy: Doxorubicina liposomiale pegilata Dr. Reddy’s
Romania: Doxlox 2 mg/ml concentrat pentru dispersie perfuzabilă
The following information is intended exclusively for physicians and healthcare professionals (see
section 3):
Doxorubicin liposomal pegylated Dr. Reddy’s dispersion must be handled with care. Gloves must be worn. If Doxorubicin liposomal pegylated Dr. Reddy’s comes into contact with skin or mucous membranes, wash immediately and thoroughly with water and soap. Doxorubicin liposomal pegylated Dr. Reddy’s must be handled and disposed of according to the precautions recommended for other antineoplastic drugs.
Determine the dose of Doxorubicin liposomal pegylated Dr. Reddy’s to be administered (based on the recommended dose and the patient's body surface area). Withdraw the correct volume of Doxorubicin liposomal pegylated Dr. Reddy’s using a sterile syringe. This must be done under strict aseptic conditions, as Doxorubicin liposomal pegylated Dr. Reddy’s contains neither preservatives nor bacteriostatic agents. Prior to administration, the correct dose of Doxorubicin liposomal pegylated Dr. Reddy’s must be diluted in 5% glucose solution for infusion (50 mg/mL). For doses < 90 mg, dilute Doxorubicin liposomal pegylated Dr. Reddy’s in 250 mL; for doses ≥ 90 mg, dilute Doxorubicin liposomal pegylated Dr. Reddy’s in 500 mL.
To minimize the risk of infusion reactions, the initial dose should be administered at a rate not exceeding 1 mg/minute. If no infusion reaction occurs, subsequent infusions of Doxorubicin liposomal pegylated Dr. Reddy’s may be administered over a 60-minute period.
In the clinical breast cancer study program, an alternative infusion schedule was permitted for patients who experienced an infusion reaction as follows:
5% of the total dose was administered slowly over the first 15 minutes. If tolerated without reaction, the infusion rate was doubled for the next 15 minutes. If tolerated, the infusion was completed within the following hour, for a total infusion time of 90 minutes.
If the patient shows early symptoms or signs of an infusion reaction, stop the infusion immediately, administer appropriate premedication (antihistamine and/or short-acting corticosteroid), and resume at a slower rate.
The use of a diluent other than 5% glucose solution for infusion (50 mg/mL), or the presence of any bacteriostatic agent such as benzyl alcohol, may cause precipitation of Doxorubicin liposomal pegylated Dr. Reddy’s.
It is recommended to connect the infusion line containing Doxorubicin liposomal pegylated Dr. Reddy’s to the side port of a 5% glucose (50 mg/mL) intravenous infusion. The infusion may be administered through a peripheral vein. Do not use in-line filters.