Cosmegen Lyovac 500 micrograms powder for solution for injection

• Keep this leaflet. You may need to read it again.
• If you have any further questions ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Cosmegen Lyovac Injection is and what it is used for
2. What do you need to know before you use Cosmegen Lyovac Injection
3. How to use Cosmegen Lyovac Injection
4. Possible side effects
5. How to store Cosmegen Lyovac Injection
6. Contents of the pack and other information

The name of your medicine is Cosmegen Lyovac injection and its active ingredient is dactinomycin.

Dactinomycin belongs to a group of medicines called antibiotics.

It works by preventing the reproduction of cells, especially abnormal cells which are associated with some types of cancer.

It also prevents reproduction of normal cells that multiply quickly.

Your doctor has prescribed Cosmegen for you because you may suffer from one of the following conditions which your doctor should have explained to you:

• Wilms’ tumour (a type of kidney cancer which usually occurs in children)
• Rhabdomyosarcoma (a rare cancer of the muscle)
• Ewing’s sarcoma (a type of bone cancer)
• cancer of the testis and uterus
• melanoma (a type of skin cancer).

Cosmegen may also be used in the treatment of other cancers.

Your doctor may prescribe radiotherapy as well as Cosmegen.

You should not be given Cosmegen injection if:

• you are allergic to dactinomycin or any of the other ingredients of this medicine (listed in section 6).
• you have chickenpox or shingles
• you are, or think you may be, pregnant
• you are planning to become pregnant
• you are breast feeding.

If you think any of these apply to you, tell your doctor.

There are other things regarding Cosmegen which you should know about. These are given below so that special care can be taken where needed.

Splashes or spills

Cosmegen is extremely harmful to soft tissue such as skin, and any leakage on to the skin will cause soft-tissue damage. Any spills or splashes of Cosmegen must be washed off immediately with lots of water or saline (salt water).

Medical attention should be sought immediately.

Radiation therapy

If you are receiving Cosmegen with radiation therapy your doctor will have to keep a close watch on you as there is an increased possibility of some other side effects.

Kidney, liver, bone marrow

Cosmegen may cause kidney, liver or bone marrow problems. This can result in a lower number of red and white blood cells and a lower number of platelets. Symptoms of lower red blood cells include tiredness, headaches, being short of breath when exercising, dizziness and looking pale. A lower number of white blood cells may make it harder for you to fight off infections. Symptoms of lower platelet counts include excessive bruising or a harder time to stop bleeding if you have a cut. Your doctor should assess these functions frequently.

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

• X-ray: You should tell your doctor if you received X-ray treatment at any time. There is some information that, rarely, other tumours may occur following treatment with X-rays and medicines like Cosmegen.
• Antibacterial medicines: Cosmegen may alter the results of tests that are done to measure the levels of antibacterial medicines.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

If you are breastfeeding, you should not be given Cosmegen injection.

It is recommended to use effective contraception during treatment with COSMEGEN, and for at least 6 months after the last dose for women, and 3 months for men. Please consult your doctor or pharmacist if you have any questions about the contraception methods to be used during this period.

Cosmegen can cause some people to feel less alert. Make sure you are not affected before you drive or operate machinery.

You will be given your Cosmegen injection by a doctor or nurse who is experienced in the use of cancer treatments.

The number of injections you need will depend upon your condition, your response to the medicine, any possible side effects, and whether you are having other treatments at the same time.

You may be given Cosmegen either as an injection (see below) or mixed with another solution as an infusion (a ‘drip’) into your vein.

It must not be taken by mouth.

There are two ways of giving Cosmegen injection:

• into a vein
• directly into the site of the cancer.

The dosage is different for each method.

In these cases your doctor will calculate the doses required and will tell you how long your treatment might take. Your doctor will determine the correct dose and duration of the treatment depending on your type of cancer.

Typical doses for injection into a vein:

• Not more than 15 micrograms per kg of body weight for 5 days in adults and children, or
• 400-600 micrograms per square metre of body surface daily, for 5 days.

Typical doses for giving Cosmegen directly into the site of the cancer:

• For the legs or pelvis, 50 micrograms per kg bodyweight.
• For the arms, 35 micrograms per kg bodyweight.

Your doctor will advise you of the method and number of injections and courses you require.

Your response to the medicine and your condition will be monitored by your doctor, who will determine if changes to your treatment are needed.

If you are confused or concerned about the number of doses you have received, or think you may have been given too much medicine, talk to your doctor immediately.

• serious bacterial infection in the bloodstream or body tissues (sepsis including neutropenic sepsis), which can lead to death. Symptoms include shivering, hot and cold, a sudden chill, diarrhoea. At the early stages the patient will be warm and alert and not look unwell. However, they can deteriorate rapidly and death can follow
• blisters and/or a rash that join together to cover a large portion of the body resulting in severe peeling of the skin, flu-like symptoms, followed by a painful red or purplish rash that spreads and blisters eventually causing the top layer of skin to die, peel, and shed
• facial or tongue swelling, hives, skin pain that may be accompanied by fever, chills, aching muscles and generally feeling unwell
• evenly distributed red patches and rash primarily on the arms and legs
• tumor lysis syndrome. Symptoms include irregular heart beat, tingling, muscle spasm, and decreased urine flow.
• severe bleeding or phlebitis caused by disseminated intravascular coagulation

• liver problems (such as liver failure, hepatitis (irritated liver caused by a virus), a painful enlarged liver, fluid retention, ascite, difficulty breathing with thoracic pain, confusion with musty or sweet breath odour and seizures)
• a lowering of the red blood cells which can cause tiredness (which may be severe)
• a lowering of white blood cells which can make you more prone to infections
• a lowering of platelets which can make you more prone to bleeding

Other side effects may include (especially in the first few hours after receiving Cosmegen):

• Vomiting
• Nausea (feeling ill)
• Generally feeling unwell

Apart from nausea and vomiting, side effects do not usually start until a few days after your treatment has stopped and may continue for one to two weeks afterwards.

Other possible side effects are listed below.

General side effects may include:

• infections
• kidney problems
• fever
• inflammation of the rectum
• muscle pain
• tiredness, feeling generally unwell
• slowing down of growth
• fertility problems

Side effects of the Eyes:

• decreased or blurry vision

Side effects of the Lungs:

• inflammation of the lungs
• difficulty breathing with thoracic pain

Side effects of the Mouth:

• difficulty swallowing, sore mouth or throat, mouth ulcers or sores, cracked lips
• spasm of the hands or feet and tingling around the mouth and vocal cords (due to low calcium levels in the blood)

Side effects on Nervous system:

• tingling in the hands and feet
• sharp, stabbing pains

Side effects on the stomach and intestine (gut):

• stomach ulcers, pains in stomach, diarrhoea
• loss of appetite
• inflammation of the rectum
• constipation

Side effects on the skin and soft tissues:

• any leakage on the skin will cause soft tissue damage
• blistering or reddening of the skin
• skin rashes
• acne
• flare up of rashes
• increased darkness in skin which has previously been exposed to radiation treatment
• hair loss

If you are receiving Cosmegen directly into the site of the cancer damage to the skin and soft tissues may occur from leaks. The side effects from leaks are:

• blood clots
• damage to soft tissue
• infections
• problems with wound healing
• blistering or reddening of the skin
• swelling of affected area
• in rare and severe cases, an affected arm can pull inwards and become stiff (contracture)

Any spills or splashes of Cosmegen must be washed off immediately with lots of water or saline (salt water).

There is some information that, rarely, other tumours may occur following treatment with X-rays and medicines like Cosmegen.

Your doctor will monitor you carefully and frequently for your response to treatment, but if you experience any of the above effects, especially fever or bleeding, or you have any other unusual symptoms or feelings or concerns, you should talk to your doctor.

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system : 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.

• Cosmegen should not be given after the expiry date, which is clearly marked on the pack
• Cosmegen is for YOU only. NEVER give it to anyone else
• It may harm others, even if their symptoms are the same as yours.

• The active ingredient is dactinomycin. Each vial contains 500 micrograms (0.5 mg) of dactinomycin as the active substance.
• The other ingredient is mannitol

Cosmegen is supplied as a yellow-orange powder in a glass vial. Each vial contains 500 micrograms of dactinomycin. It also contains mannitol E421. It is made up into a clear, gold-coloured liquid by adding sterile water to the powder in the vial.

The Marketing Authorisation is held by

Cosmegen is made by

Or

* Registered Trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA