CYMEVENE 500 mg POWDER FOR CONCENTRATE FOR INFUSION SOLUTION

2. What you need to know before you use Cymevene

Do not use Cymevene:

? if you are allergic to ganciclovir, valganciclovir, or any of the other ingredients of this medicine (listed in section 6).

? if you are breast-feeding (see sub-section “Breast-feeding”).

Do not use Cymevene if any of the above applies to you. If you are not sure, consult your doctor, pharmacist, or nurse before using Cymevene.

Warnings and precautions

Tell your doctor, pharmacist, or nurse before you start using Cymevene if:

? you are allergic to aciclovir, valaciclovir, penciclovir, or famciclovir - these are other medicines used to treat viral infections

? you have a low number of white blood cells, red blood cells, or platelets in your blood - your doctor will do blood tests before you start and during your treatment

? you have had problems with your blood cell count in the past due to medicines

? you have kidney problems - your doctor may prescribe a lower dose and may need to do blood tests more frequently during your treatment

? you are having radiotherapy.

If any of the above applies to you (or if you are not sure), consult your doctor, pharmacist, or nurse before using Cymevene.

Monitor for side effects

Cymevene can cause serious side effects that you need to tell your doctor about immediately. Monitor the serious side effects listed in Section 4 and if you experience any while using Cymevene, tell your doctor - your doctor may tell you to stop taking Cymevene and may need urgent medical treatment.

Tests and checks

Your doctor will do regular blood tests during your treatment with Cymevene. This is to check that the dose you are taking is right for you. During the first two weeks, these blood tests will be done frequently. After that, the tests will be done less frequently.

Children and adolescents

There is limited information on the safety and efficacy of Cymevene in the treatment of CMV disease in children under 12 years of age. Blood tests will be done regularly in newborns and infants treated with Cymevene for the prevention of CMV disease.

Other medicines and Cymevene

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

In particular, tell your doctor or pharmacist if you are taking any of the following medicines:

? imipenem/cilastatin - used for bacterial infections

? pentamidine - used for infections caused by parasites or in the lungs

? flucytosine, amphotericin B - used for fungal infections

? trimethoprim, trimethoprim/sulfamethoxazole, dapsone - used for bacterial infections

? probenecid - used for gout

? mycophenolate mofetil, cyclosporin, tacrolimus - used after an organ transplant

? vincristine, vinblastine, doxorubicin - used for cancer

? hydroxyurea - used for a condition called ‘polycythemia’, sickle cell disease, and cancer

? didanosine, stavudine, zidovudine, tenofovir, or other medicines used for HIV

? adefovir or any other medicine used for the treatment of Hepatitis B.

If any of the above applies to you (or if you are not sure), consult your doctor or pharmacist before using Cymevene.

Pregnancy, breast-feeding, and fertility

Pregnancy

Cymevene should not be used by pregnant women unless the benefits to the mother outweigh the potential risks to the fetus.

If you are pregnant or think you may be pregnant, do not take this medicine unless your doctor tells you to. This is because Cymevene may harm the fetus.

Contraception

You must not become pregnant while using this medicine. This is because it may affect the fetus.

Women

If you are a woman of childbearing age, you must use a contraceptive method while using Cymevene. You must also use it for at least 30 days after finishing treatment with Cymevene.

Men

If you are a man whose partner could become pregnant, you must use a barrier contraceptive method (e.g., condoms) while taking Cymevene. Continue to use it for at least 90 days after finishing treatment with Cymevene.

If your partner becomes pregnant while you are taking Cymevene, consult your doctor immediately.

Breast-feeding

Do not use Cymevene if you are breast-feeding. If your doctor wants to start treating you with Cymevene, you must stop breast-feeding before starting to take this medicine. This is because Cymevene may pass into breast milk.

Fertility

Cymevene may affect fertility. Cymevene may temporarily or permanently stop sperm production in men. If you plan to have a child, consult your doctor or pharmacist before using Cymevene.

Driving and using machines

You may feel drowsy, dizzy, confused, or agitated, or you may lose your balance or have seizures while using Cymevene. If this happens, do not drive or use tools or machinery.

Cymevene contains sodium

This medicine contains 43 mg of sodium (the main component of cooking/table salt) in each 500 mg vial. This is equivalent to 2% of the maximum recommended daily intake of sodium for an adult.

3. How to use Cymevene

Follow the instructions for administration of this medicine exactly as told by your doctor or pharmacist. If you are not sure, consult your doctor or pharmacist again.

Use of this medicine

Your doctor or nurse will give you Cymevene. It will be given to you through a tube in your vein. This is called “intravenous infusion” and will take about an hour.

The dose of Cymevene varies from person to person. Your doctor will calculate the dose you need. This dose will depend on:

? your weight (in children, height must also be taken into account)

? your age

? how well your kidneys are working

? your blood cell count

? what you are using the medicine for

The frequency with which you will be given Cymevene and the time you will need to use it may also vary.

? You will usually start by receiving one or two infusions a day.

? If you receive two infusions a day, you will continue like this for 21 days.

? After that, your doctor may prescribe one infusion a day.

People with kidney or blood problems

If you have any kidney or blood problems, your doctor may recommend a lower dose of Cymevene and check your blood cell count more frequently during treatment.

If you use more Cymevene than you should

If you think you have been given too much Cymevene, consult your doctor or go to the hospital immediately. In case of overdose or accidental ingestion, you can also contact the Toxicology Information Service (Telephone: 91 5620420).

You may have the following symptoms:

? stomach pain, diarrhea, or nausea

? tremors or seizures

? blood in your urine

? liver or kidney problems

? changes in your blood cell count.

If you stop using Cymevene

Do not stop using Cymevene without consulting your doctor.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects may occur with this medicine:

Serious side effects

Tell your doctor immediately if you experience any of the following serious side effects – your doctor may tell you to stop taking Cymevene and may need urgent medical treatment:

Very common:may affect more than 1 in 10 people

? decrease in the number of white blood cells – with signs of infection such as sore throat, mouth ulcers, or fever

? decrease in the number of red blood cells – symptoms include feeling short of breath or tired, palpitations, or pale skin.

Common:may affect up to 1 in 10 people

? blood infection (sepsis) – with signs that include fever, chills, palpitations, confusion, and difficulty speaking

? decrease in the number of platelets – symptoms include bleeding and bruising more easily than normal, blood in urine or stools, or bleeding gums, these bleeds can be serious

? severe decrease in the number of blood cells

? pancreatitis with signs such as severe stomach pain that spreads to the back

? seizures.

Uncommon:may affect up to 1 in 100 people

? inability of the bone marrow to produce blood cells

? hallucinations - seeing or hearing things that are not real

? disturbed thinking or feelings, loss of contact with reality

? kidney failure.

Rare:may affect up to 1 in 1,000 people

? severe allergic reaction – symptoms can include redness and itching of the skin, swelling of the throat, face, lips, or mouth, difficulty swallowing or breathing.

Tell your doctor immediately if you notice any of the above side effects.

Other side effects

If you experience any of the following side effects, tell your doctor, pharmacist, or nurse:

Very common:may affect more than 1 in 10 people

? candidiasis and oral candidiasis

? upper respiratory tract infection (e.g., sinusitis, tonsillitis)

? loss of appetite

? headache

• cough

? shortness of breath

? diarrhea

? nausea and vomiting

? abdominal pain

? eczema

? fatigue

? fever.

Common:may affect up to 1 in 10 people

? flu

• urinary tract infection, with signs that include fever, frequent urination, pain when urinating
• skin and subcutaneous tissue infections
• mild allergic reactions, with signs that include redness and swelling of the skin
• weight loss
• feeling depressed, anxious, or confused

? difficulty sleeping

• numbness or weakness in hands and feet, which can affect your balance
• changes in sense of touch, tingling, prickling, or burning sensation
• changes in taste
• chills
• eye inflammation (conjunctivitis), eye pain, or vision problems
• ear pain
• low blood pressure, which can make you feel dizzy or have blurred vision
• difficulty swallowing
• constipation, gas, indigestion, stomach pain, abdominal distension
• mouth ulcers
• abnormal liver and kidney laboratory test results

? night sweats

• itching, rash
• hair loss
• back pain, muscle or joint pain, muscle spasms

? feeling dizzy, weak, or unwell

? skin reaction at the injection site – such as inflammation, pain, and swelling.

Uncommon:may affect up to 1 in 100 people

? agitation

• tremors

? deafness

• irregular heartbeat

? hives, dry skin

? blood in the urine

? infertility in men – see section “Fertility”

• chest pain

Other side effects in children and adolescents

A decrease in the number of blood cells is more likely in children, especially in babies and infants.

Reporting of side effects

If you experience 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 Spanish Medicines Monitoring System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Cymevene

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

Powder: No special storage conditions are required. Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date is the last day of the month shown.

After reconstitution:

The chemical and physical stability during handling has been demonstrated for the reconstituted product for 12 hours at 25°C after dissolving with water for injection. Do not refrigerate or freeze.

From a microbiological point of view, the reconstituted solution should be used immediately. If not used immediately, the time and storage conditions before use are the responsibility of the user.

After dilution in infusion solutions (sodium chloride 0.9%, dextrose 5%, Ringer’s solution, or lactated Ringer’s solution for injection):

The chemical and physical stability during use has been demonstrated for 24 hours at 2-8°C (do not freeze).

From a microbiological point of view, the Cymevene infusion solution should be used immediately. If not used immediately, the time and storage conditions before use are the responsibility of the user and should not exceed 24 hours at 2-8°C, unless the reconstitution and dilution are performed in a controlled and validated aseptic environment.

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 protect the environment.

6. Container contents and additional information

Composition ofCymevene

? The active ingredient is ganciclovir. Each glass vial contains 500 mg of ganciclovir as ganciclovir sodium. After reconstitution of the powder, 1 ml of solution contains 50 mg of ganciclovir.

? The other components are sodium hydroxide and hydrochloric acid.

Appearance of the product and container contents

Cymevene is a white to off-white powder for concentrate for solution for infusion, which comes in a single-dose glass vial with a rubber stopper and aluminum seal. The color of the reconstituted Cymevene solution ranges from colorless to light yellow.

The Cymevene vials are presented in packs of 1 or 5 vials.

Only some pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

CHEPLAPHARM Arzneimittel GmbH

Ziegelhof 24

17489 Greifswald

Germany

Manufacturer

CHEPLAPHARM Arzneimittel GmbH

Ziegelhof 23-24

17489 Greifswald

Germany

Prestige Promotion Verkaufsfoerderung & Werbeservice GmbH

Lindigstrasse 6

63801 Kleinostheim

Germany

Prestige Promotion Verkaufsfoerderung & Werbeservice GmbH

Borsigstrasse 2

63755 Alzenau

Germany

Further information on this medicinal product can be obtained from the local representative of the marketing authorization holder:

Laboratorios Rubió, S.A.

Industria, 29 - Pol. Ind. Comte de Sert

08755 Castellbisbal (Barcelona)

Spain

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Cymevene:Austria, Belgium, Croatia, Czech Republic, Denmark, Finland, Hungary, Ireland, Luxembourg, Netherlands, Norway, Poland, Portugal, Slovakia, Spain, Sweden, United Kingdom.

Cymevene i.v.:Germany

Cymevan:France

Citovirax:Italy

Date of last revision of thisleaflet: April 2020

Other sources of information

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

INSTRUCTIONS FOR USE AND HANDLING

Please consult the summary of product characteristics or package insert for complete prescribing information.

Method of administration

Warning:

Ganciclovir should be administered by intravenous infusion over 1 hour, with a concentration that should not exceed 10 mg/ml. It should not be administered by bolus or rapid intravenous injection because the resulting high plasma levels may increase the toxicity of ganciclovir.

Do not administer by intramuscular or subcutaneous injection as it may cause intense tissue irritation due to the high pH (~11) of the ganciclovir solution.

Do not exceed the recommended dose, frequency, and infusion rate.

Cymevene is a powder for solution for infusion. After reconstitution, Cymevene is a colorless to slightly yellowish solution, practically free from visible particles.

Infusion should be performed in veins with adequate blood flow, preferably through a plastic cannula.

Precautionsto be takenwhen handlingCymevene:

Since Cymevene is considered potentially teratogenic and carcinogenic in humans, caution should be exercised when handling it. Avoid inhalation or direct contact with the powder in the vials or direct contact with the reconstituted solution with skin or mucous membranes. Cymevene solutions are alkaline (pH ~11). If this occurs, wash the area carefully and thoroughly with soap and water and rinse the eyes thoroughly with plenty of water.

Preparation of the reconstituted concentrate

Aseptic technique should be used during the reconstitution of Cymevene lyophilized powder.

1. The aluminum seal should be removed to expose the central part of the rubber stopper. Withdraw 10 ml of water for injection with a syringe and then slowly inject it through the center of the rubber stopper into the vial with the needle directed towards the vial wall. Do not use bacteriostatic water for injection containing parabens (para-hydroxybenzoates), as they are incompatible with Cymevene.
2. Gently rotate the vial to ensure complete wetting of the product.

1. The vial should be rotated/gently shaken for a few minutes until a clear reconstituted solution is obtained.

1. The reconstituted solution should be carefully checked to ensure dissolution of the product and that it is practically free from visible particles before proceeding to dilution with a compatible solvent. The color of the reconstituted Cymevene solution ranges from colorless to light yellow.

Preparation of the final diluted solution for infusion

Based on the patient's body weight, withdraw the necessary volume from the vial with a syringe and then dilute it in a suitable infusion liquid. Add 100 ml of the solvent to the reconstituted solution. Concentrations of infusion greater than 10 mg/ml are not recommended.

Sodium chloride solutions, 5% dextrose, Ringer's injection, and Ringer's lactate injection have been shown to be chemically or physically compatible with Cymevene.

Cymevene should not be mixed with other intravenous products.

The diluted solution should be administered by intravenous infusion over 1 hour. Do not administer by intramuscular or subcutaneous injection as it may cause intense tissue irritation due to the high pH (~11) of the ganciclovir solution.

Disposal

It is for single use. Disposal of unused medicinal products and any waste material should be in accordance with local regulations.