Patient leaflet - Doxorubicin Accord Pegylated liposomal 2 mg/ml concentrate for solution for infusion

1. What Doxorubicin Accord pegylated liposomal is and what it is used for

Doxorubicin Accord pegylated liposomal is an antitumour agent.

Doxorubicin Accord pegylated liposomal is used to treat cancer of the breast in patients at risk for heart problems. Doxorubicin Accord pegylated liposomal is also used to treat cancer of the ovary. It is used to kill cancer cells, shrink the size of the tumour, delay the growth of the tumour, and extend your survival.

Doxorubicin Accord pegylated liposomal is also used in combination with another medicine, bortezomib, to treat multiple myeloma (a cancer of the blood) in patients who have received at least 1 prior therapy.

Doxorubicin Accord pegylated liposomal is also used to produce an improvement in your Kaposi’s sarcoma including flattening, lightening and even shrinkage of the cancer. Other symptoms of Kaposi’s sarcoma, such as swelling around the tumour, may also improve or disappear.

Doxorubicin Accord pegylated liposomal contains a medicine which is able to interact with cells in such a way as to selectively kill cancer cells. The doxorubicin hydrochloride in Doxorubicin Accord pegylated liposomal is enclosed in tiny spheres called pegylated liposomes which help to deliver the medicinal product from the blood stream to the cancerous tissue rather than healthy normal tissue.

2. What you need to know before you use Doxorubicin Accord pegylated liposomal

Do not use Doxorubicin Accord pegylated liposomal

if you are allergic to doxorubicin hydrochloride, peanut or soya or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

You should tell your doctor about any of the following:

if you are receiving any treatment for heart disease or liver disease
if you are diabetic, because Doxorubicin Accord pegylated liposomal contains sugar which may require an adjustment to the treatment of your diabetes
if you have Kaposi’s sarcoma and have had your spleen removed
if you notice sores, discolouration or any discomfort in your mouth.

The cases of Interstitial lung diseases have been observed in patients receiving pegylated liposomal doxorubicin including fatal cases. The symptoms of Interstitial lung disease are cough and shortness of breath sometimes with fever which are not caused by physical activity. Seek immediate medical attention, if you experience symptoms that may be signs of Interstitial lung disease.

Children and adolescents

Doxorubicin Accord pegylated liposomal should not be used in children and adolescents, because it is not known how the medicine will affect them.

Other medicines and Doxorubicin Accord pegylated liposomal

Tell your doctor or pharmacist:

if you are taking or have recently taken any other medicines, including medicines obtained without a prescription
about any other cancer treatments you are on or have been taking, as particular care needs to be taken with treatments which reduce the number of white blood cells, as this may cause further reduction in the number of white blood cells. If you are unsure about what treatments you have received or any illnesses you have had, discuss these with your doctor.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking this medicine.

Because the active ingredient doxorubicin hydrochloride in Doxorubicin Accord pegylated liposomal may cause birth defects, it is important to tell your doctor if you think you are pregnant. Women must avoid becoming pregnant and use contraception while taking Doxorubicin pegylated liposomal and in the eight months following discontinuation of Doxorubicin pegylated liposomal treatment. Men must use contraception while taking Doxorubicin Accord pegylated liposomal and in the six months following discontinuation of Doxorubicin Accord pegylated liposomal, so that their partner does not become pregnant.

Because doxorubicin hydrochloride may be harmful to nursing infants, women must discontinue breast-feeding before starting treatment with Doxorubicin Accord pegylated liposomal. Health experts recommend that HIV-infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.

Driving and using machines

Do not drive or use any tools or machines if you feel tired or sleepy from treatment with Doxorubicin Accord pegylated liposomal.

Doxorubicin Accord pegylated liposomal contains soya oil and sodium

Doxorubicin Accord pegylated liposomal contains soya oil. If you are allergic to peanut or soya, do not use this medicine. Doxorubicin Accord pegylated liposomal contains less than 1 mmol sodium (23 mg) per dose, that is to say ‘essentially sodium-free’.

3. How to use Doxorubicin Accord pegylated liposomal

Doxorubicin Accord pegylated liposomal is a unique formulation. It must not be used interchangeably with other formulations of doxorubicin hydrochloride.

How much Doxorubicin Accord pegylated liposomal is given

If you are being treated for breast cancer or ovarian cancer, Doxorubicin Accord pegylated liposomal will be administered at a dose of 50 mg per square metre of your body surface area (based on your height and weight). The dose is repeated every 4 weeks for as long as the disease does not progress and you are able to tolerate the treatment.

If you are being treated for multiple myeloma, and have already received at least 1 prior therapy, Doxorubicin Accord pegylated liposomal will be administered at a dose of 30 mg per square metre of your body surface area (based on your height and weight) as a 1 hour intravenous infusion on day 4 of the bortezomib 3 week regimen immediately after the bortezomib infusion. The dose is repeated as long as you respond satisfactorily and tolerate treatment.

If you are being treated for Kaposi’ sarcoma, Doxorubicin Accord pegylated liposomal will be administered at a dose of 20 mg per square metre of your body surface area (based on your height and weight). The dose is repeated every 2 to 3 weeks for 2-3 months, then as often as necessary to maintain an improvement in your condition.

How Doxorubicin Accord pegylated liposomal is given

Doxorubicin Accord pegylated liposomal will be given to you by your doctor in a drip (infusion) into a vein. Depending on the dose and indication, this may take from 30 minutes to more than one hour (i.e., 90 minutes).

If you use more Doxorubicin Accord pegylated liposomal than you should

Acute overdosing worsens side effects like sores in the mouth or decreases the number of white blood cells and platelets in the blood. Treatment will include administration of antibiotics, platelet cell transfusions, use of factors which stimulate production of white blood cells and symptomatic treatment of mouth sores.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

During the infusion of Doxorubicin Accord pegylated liposomal, the following reactions may occur:

severe allergic reaction that may include a swollen face, lips, mouth, tongue or throat; difficulty swallowing or breathing; itchy rash (hives)
inflamed and narrowed airways in the lungs, causing coughing, wheezing and shortness of breath (asthma)
flushing, sweating, chills or a fever
chest pain or discomfort
back pain
high or low blood pressure
fast heart beat
fits (seizures)

Leaking of the injection fluid from the veins into the tissues under the skin may occur. If the drip stings or hurts while you are receiving a dose of Doxorubicin Accord pegylated liposomal, tell your doctor immediately.

Your doctor should be contacted immediately if any of the following serious side effects are noticed:

you develop fever, feel tired, or if you have signs of bruising or bleeding (very common)
redness, swelling, peeling or tenderness, mainly on the hands or feet (‘hand-foot’ syndrome). These effects have been seen very commonly and are sometimes severe. In severe cases, these effects may interfere with certain daily activities, and may last for 4 weeks or longer before resolving completely. The doctor may wish to delay the start and/or reduce the dose of the next treatment (see Strategies to prevent and treat hand-foot syndrome, below)
sores in mouth, severe diarrhoea or vomiting or nausea (very common)
infections (common), including lung infections (pneumonia) or infections that may affect your vision
being short of breath (common)
severe stomach pain (common)
severe weakness (common)
severe allergic reaction that may include a swollen face, lips, mouth, tongue or throat; difficulty swallowing or breathing; itchy rash (hives) (uncommon)
cardiac arrest (heart stops beating); heart failure, in which the heart does not pump enough blood to the rest of the body, which makes you short of breath and may lead to swollen legs (uncommon)
blood clot that moves to the lungs, causes chest pain and makes you short of breath (uncommon)
swelling, warmth, or tenderness in the soft tissues of your leg, sometimes with pain which gets worse when you stand or walk (rare)
severe or life-threatening rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome) or over most of the body (toxic epidermal necrolysis) (rare)

Other side effects

Between infusions, the following may occur:

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

decrease in the number of white blood cells, which can increase the chances of infections. In rare cases, having low white blood cells may lead to severe infection. Anaemia (reduction in red blood cells) may cause tiredness, and decreased platelets in the blood may increase the risk of bleeding. It is because of the potential changes in your blood cells that you will have regular blood tests.
decreased appetite;
constipation;
skin rashes, including redness of the skin, allergic skin rash, red or raised rash on the skin
hair loss
pain including in the muscles and chest muscle, joint, arm, or leg
feeling very tired

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

infections, including severe infection throughout the body (sepsis), lung infections, herpes zoster virus infections (shingles), a type of bacterial infection (mycobacterium avium complex infection), urinary tract infection, fungal infection (including thrush and oral thrush in the mouth) infection of the hair roots, infected or irritated throat, infected nose, sinuses or throat (cold)
low number of a type of white blood cell (neutrophils), with a fever
severe weight loss and muscle wasting, not enough water in the body (dehydration), low level of potassium, sodium or calcium in the blood
feeling confused, feeling anxious, depression, difficulty sleeping
nerve damage that may cause tingling, numbness, pain or loss of pain sensation, nerve pain, unusual feeling in the skin (such as tingling or a crawling feeling), decreased feeling or sensitivity, especially in the skin
change in sense of taste, headache, feeling very sleepy with low energy, feeling dizzy;
inflamed eyes (conjunctivitis)
fast heart beat
high or low blood pressure, flushing
shortness of breath that may be brought on by physical activity, nose bleeds, cough
inflamed stomach lining or foodpipe, ulcers (sores) in the mouth, indigestion, difficulty swallowing, mouth pain, dry mouth
skin problems, including flaky or dry skin, redness of the skin, blister or ulcer (sore) on the skin, itching, dark skin patches
excessive sweating
muscle spasms or aches
pain including in the muscles, bone, or back
pain when passing urine
allergic reaction to infusion of the medicine, flu-like illness, chills, inflamed lining of the cavities and passages in the body, such as the nose, mouth or windpipe, feeling weak, generally feeling unwell, swelling caused by fluid build up in the body, swollen hands, ankles or feet
weight loss

When Doxorubicin Accord pegylated liposomal is used alone, some of these effects are less likely to occur, and some have not occurred at all.

Uncommon side effects (may affect up to 1 in 100 people)

herpes simplex virus infections (cold sores or genital herpes), fungal infection
low number of all types of blood cells, increased number of ‘platelets’ (cells that help blood to clot)
allergic reaction
high level of potassium in the blood, low level of magnesium in the blood
nerve damage affecting more than one area of the body

The following information is intended for medical or healthcare professionals only (see section 3):

Caution must be exercised in handling Doxorubicin Accord pegylated liposomal solution. The use of gloves is required. If Doxorubicin Accord pegylated liposomal comes into contact with skin or mucosa, wash immediately and thoroughly with soap and water. Doxorubicin Accord pegylated liposomal must be handled and disposed of in a manner consistent with that of other anticancer medicinal products.

Determine the dose of Doxorubicin Accord pegylated liposomal to be administered (based upon the recommended dose and the patient's body surface area). Take the appropriate volume of Doxorubicin Accord pegylated liposomal up into a sterile syringe. Aseptic technique must be strictly observed since no preservative or bacteriostatic agent is present Doxorubicin Accord pegylated liposomal. The appropriate dose of Doxorubicin Accord pegylated liposomal must be diluted in glucose 50 mg/mL (5%) solution for infusion prior to administration. For doses < 90 mg, dilute Doxorubicin Accord pegylated liposomal in 250 mL, and for doses ≥ 90 mg, dilute Doxorubicin Accord pegylated liposomal in 500 mL.

To minimise the risk of infusion reactions, the initial dose is administered at a rate no greater than 1 mg/minute. If no infusion reaction is observed, subsequent Doxorubicin Accord pegylated liposomal infusions may be administered over a 60-minute period.

In the breast cancer trial program, modification of the infusion was permitted for those patients experiencing an infusion reaction as follows: 5% of the total dose was infused 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 over the next hour for a total infusion time of 90 minutes.

If the patient experiences early symptoms or signs of infusion reaction, immediately discontinue the infusion, give appropriate premedications (antihistamine and/or short acting corticosteroid) and restart at a slower rate.

The use of any diluent other than 5% (50 mg/ml) glucose solution for infusion, or the presence of any bacteriostatic agent such as benzyl alcohol may cause precipitation of Doxorubicin Accord pegylated liposomal.

			-
		Customer	Accord
		Description	Doxorubicin 2 mg/ml (Liposomal)
		Market	UK
		Language	English
			450 x 450 mm (Final Folded size 80x45 mm )(PIL)
			9
		Version No.	8 (Page 2 of 2)
		Date	13_04_22 (Doxorubicin 2 mg-ml (ACC-UK) PIL)

INP125 51 5923 4 740148

fits (seizures), fainting
unpleasant or painful sensation, especially to touch, feeling sleepy
blurred vision, watery eyes
heart beat feels fast or uneven (palpitations), heart muscle disease, heart damage
tissue damage (necrosis) where the injection is given, inflamed veins that cause swelling and pain, feeling dizzy upon sitting up or standing up
chest discomfort
passing wind, inflamed gums (gingivitis)
skin problems or rashes, including flaky or peeling skin, allergic skin rash, ulcer (sore) or hives on the skin, discoloured skin, change in the natural colour (pigment) of the skin, small red or purple spots caused by bleeding under the skin, nail problems, acne
muscle weakness
breast pain
irritation or pain where the injection is given
swollen face, high body temperature
symptoms (such as inflammation, redness or pain) come back at a part of the body that previously received radiation therapy or was previously damaged by a chemotherapy injection into a vein

Rare side effects (may affect up to 1 in 10000 people)

infection that occurs in people with a weak immune system
low number of blood cells made in the bone marrow
inflamed retina, which may cause changes in vision or blindness
abnormal heart rhythm, abnormal heart tracing on an ECG (electrocardiogram) and may be with a slow heart beat, problem with the heart that affects the heart beat and rhythm, blue colour to the skin and mucosa caused by low oxygen in the blood
widening of blood vessels
tight feeling in the throat
sore and swollen tongue, ulcer (sore) on the lip
skin rash with fluid-filled blisters
vaginal infection, redness of the scrotum
problems with the lining of the cavities and passages in the body, such as the nose, mouth or windpipe
abnormal liver blood test results, increased level of ‘creatinine’ in the blood

Not known (frequency cannot be estimated from the available data)

cancer of the blood that develops quickly and affects the blood cells (acute myeloid leukaemia), bone marrow disease that affects the blood cells (myelodysplastic syndrome), cancer of the mouth or lip
coughing and shortness of breath, possibly accompanied by fever, that is not brought on by physical activity (Interstitial lung disease)
clogging of very small blood vessels in the kidneys (renal-limited thrombotic microangiopathy).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.

Strategies to prevent and treat hand-foot syndrome include:

soaking hands and/or feet in basins of cold water when possible (e.g., while watching television, reading, or listening to
the radio)
keeping hands and feet uncovered (no gloves, socks, etc.)
staying in cool places
taking cool baths during hot weather
avoiding vigorous exercise that might cause trauma to the feet (e.g., jogging)
avoiding exposure of skin to very hot water (e.g., jacuzzis, saunas)
avoiding tight fitting footwear or high-heeled shoes.

Pyridoxine (Vitamin B6):

vitamin B6 is available without prescription
take 50-150 mg daily beginning at the first signs of redness or tingling.

5. How to store Doxorubicin Accord pegylated liposomal

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

Store in a refrigerator (2ºC – 8ºC). Do not freeze.

After dilution:

Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 24 hours at 2°C to 8°C. Partially used vials must be discarded.

Do not use this medicine after the expiry date which is stated on the label and carton.

Do not use this medicine if you notice that it shows evidence of precipitation or any other particulate matter.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Doxorubicin Accord pegylated liposomal contains

The active substance is doxorubicin hydrochloride. One ml of Doxorubicin Accord pegylated liposomal contains 2 mg of doxorubicin hydrochloride in a pegylated liposomal formulation.
The other ingredients are hydrogenated soy phosphatidylcholine, N- (carbonylmethoxypolyethylene glycol-2000)-1,2- distearoyl- sn-glycero-3- phosphoethanolamine, sodium salt (MPEG 2000-DSPE), cholesterol, ammonium sulphate, histidine, sucrose, water for injections, hydrochloric acid concentrated (for pH-adjustment), sodium hydroxide (for pH-adjustment). See section 2.

Doxorubicin Accord pegylated liposomal: vials which provide 10 ml (20 mg) or 25 ml (50 mg).

What Doxorubicin Accord pegylated liposomal looks like and contents of the pack

This medicine is a translucent red coloured dispersion filled in a clear glass vial. Doxorubicin Accord pegylated liposomal is available in glass vials as a single pack or packs of ten vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Accord Healthcare Limited

Sage House, 319 Pinner Road

North Harrow, Middlesex

HA1 4HF

United Kingdom

Manufacturers

Accord Healthcare Polska Sp. z o.o.

ul. Lutomierska 50, Pabianice, 95-200

Poland