Cymevene

Package leaflet: Information for the user

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
Cymevene, 500 mg, powder for solution for infusion concentrate
Ganciclovir
Please read this leaflet carefully before using the medicine, as it contains important
information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any doubts, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, inform the doctor, pharmacist, or nurse. See section 4.

Leaflet contents

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

1. What Cymevene is and what it is used for

What Cymevene is
The active substance in Cymevene is ganciclovir. It belongs to a group of antiviral medicines.
What Cymevene is used for
Cymevene is intended for the treatment of diseases caused by cytomegalovirus (CMV) in adult patients and adolescents aged 12 years and older with impaired immune function. Cymevene is also used for prevention of CMV infection following organ transplantation or during chemotherapy in adults and children from birth.

• CMV infection may affect any part of the body, including the retina of the eye – this means the virus may cause vision problems.
• The virus may cause disease in any person, but poses a particular risk in individuals with weakened immune systems. In such individuals, CMV may cause serious diseases. Immune system impairment may result from other diseases (e.g. AIDS) or from medications (e.g. chemotherapy or immunosuppressive drugs).

2. Important information before using Cymevene

When not to use Cymevene:

• if the patient is allergic to ganciclovir, valganciclovir, or to any of the other ingredients of this medicine (listed in section 6),
• during breastfeeding (see subsection "Breastfeeding").

Do not use Cymevene if any of the above apply to the patient.

If in doubt, speak with your doctor, pharmacist, or nurse before taking Cymevene.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting treatment with Cymevene if:

• the patient is allergic to acyclovir, valacyclovir, penciclovir, or famciclovir – medicines used to treat viral infections;
• the patient has low levels of white blood cells, red blood cells, or platelets – your doctor will perform blood tests before starting treatment and during treatment;
• the patient has previously had blood cell problems due to taking medicines;
• the patient has impaired kidney function – the dose of Cymevene may need to be reduced and blood counts monitored more frequently during treatment;
• the patient is undergoing radiotherapy.

If any of the above apply (or if you are unsure), speak with your doctor, pharmacist, or nurse before taking Cymevene.

Be aware of side effects

Cymevene may cause certain serious side effects that should be reported to your doctor immediately. Be alert for the serious side effects listed in section 4 and inform your doctor if you experience any of them while taking Cymevene – your doctor may advise stopping treatment and you may require urgent medical care.

Laboratory tests

While taking Cymevene, your doctor will perform regular blood tests to ensure the dose is appropriate for you. Blood tests will be frequent during the first 2 weeks, and less frequently thereafter.

Children and adolescents

There is limited information on the safety and efficacy of Cymevene in treating CMV disease in children under 12 years of age. Newborns and infants receiving Cymevene for prevention of CMV disease will undergo regular blood testing.

Cymevene with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or plan to take any other medicines.

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

• imipenem with cilastatin – used to treat bacterial infections;
• pentamidine – used to treat parasitic infections or lung infections;
• flucytosine, amphotericin B – used to treat fungal infections;
• trimethoprim, trimethoprim with sulfamethoxazole, dapsone – used to treat bacterial infections;
• probenecid – used to treat gout;
• mycophenolate mofetil, cyclosporine, tacrolimus – used after organ transplantation;
• vincristine, vinblastine, doxorubicin – used to treat cancers;
• hydroxyurea – used to treat excessive red blood cells (polycythaemia), sickle cell anaemia, and cancers;
• didanosine, stavudine, zidovudine, tenofovir, or other medicines used in HIV infection;
• adefovir or other medicines used to treat hepatitis B.

If any of the above apply (or if you are unsure), speak with your doctor or pharmacist before taking Cymevene.

Pregnancy, breastfeeding, and fertility

Pregnancy

Women who are pregnant should not take Cymevene unless the potential benefit to the mother outweighs the potential risk to the unborn child.

If you are pregnant or think you may be pregnant, do not take this medicine unless your doctor advises otherwise. Cymevene may harm the unborn child.

Contraception

Women must not become pregnant while taking this medicine. The medicine may harm the unborn child.

Women

Women of childbearing potential must use contraception during treatment with Cymevene. Contraception should also be continued for at least 30 days after stopping Cymevene.

Men

Men whose partners may become pregnant should use mechanical contraception (e.g. condoms) during treatment with Cymevene. Mechanical contraception should also be continued for at least 90 days after stopping Cymevene.

If a woman taking Cymevene becomes pregnant, or if a partner becomes pregnant while the patient is taking Cymevene, contact your doctor immediately.

Breastfeeding

Women who are breastfeeding should not take Cymevene. Breastfeeding should be discontinued if your doctor decides that Cymevene treatment is necessary. Cymevene may pass into breast milk.

Effect on fertility

Cymevene may have harmful effects on fertility. Cymevene may cause temporary or permanent suppression of sperm production. Patients planning to have children should discuss this with their doctor or pharmacist before starting treatment with Cymevene.

Driving and using machines

During treatment with Cymevene, drowsiness, dizziness, confusion, tremor, loss of balance, or seizures may occur. Patients experiencing these symptoms should refrain from driving vehicles or operating machinery.

Cymevene contains sodium

This medicine contains 43 mg of sodium (a main component of table salt) in the 500 mg vial. This is equivalent to 2% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use Cymevene

This medicine should always be used exactly as your doctor or pharmacist has told you. If you are not sure,
ask your doctor or pharmacist.
How to use Cymevene
Cymevene is administered by a doctor or nurse. The medicine is given through a tube inserted into a vein.
This method of administration is called an "intravenous infusion" and usually takes one hour.
The dose of Cymevene varies depending on the patient. Your doctor will determine the appropriate dose.
The dose of Cymevene depends on:

• the patient's body weight (in children, height may also be taken into account)
• age
• kidney function
• blood count
• the indication for which the medicine is used.

The frequency of Cymevene administration and the duration of treatment will also vary.

• Treatment usually starts with one or two infusions per day.
• If two infusions per day are given, treatment will last up to 21 days at most.
• Afterwards, your doctor may prescribe one infusion per day.

Patients with impaired kidney function or blood disorders
If the patient has impaired kidney function or blood disorders, the doctor may prescribe a lower dose of
Cymevene and more frequent monitoring of blood cell counts during treatment.
Use of a higher than recommended dose of Cymevene
If you suspect that a higher than recommended dose of Cymevene has been administered, contact your
doctor or go to hospital immediately. If a higher than recommended dose is given, the following symptoms
may occur:

• abdominal pain, diarrhoea or vomiting
• tremor or seizure
• blood in the urine
• impaired kidney or liver function
• changes in blood count.

Stopping treatment with Cymevene
Do not stop using Cymevene without first consulting your doctor.
If you have any further 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 will experience them.
The following side effects may occur during treatment with this medicine:
Serious side effects
Contact your doctor immediately if any of the following serious side effects occur – your doctor may advise you to stop taking Cymevene and you may require urgent medical treatment:
Very common: may affect more than 1 in 10 patients

• low number of white blood cells – symptoms include signs of infection such as sore throat, mouth ulcers or fever
• low number of red blood cells – symptoms include shortness of breath or fatigue, rapid heartbeat or pale skin.

Common: may affect up to 1 in 10 patients

• blood infection (sepsis) – symptoms include fever, chills, rapid heartbeat, confusion and slurred speech
• low number of platelets – symptoms include bleeding or bruising more easily than normal, blood in urine or stool, or bleeding gums; bleeding may be severe
• very low blood cell counts
• pancreatitis – symptoms include severe abdominal pain radiating to the back
• seizures.

Uncommon: may affect up to 1 in 100 patients

• failure of bone marrow to produce blood cells
• hallucinations – seeing or hearing things that are not there
• disturbances in thinking and perception, loss of contact with reality
• kidney function disorders.

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

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

Inform your doctor immediately if any of the above side effects occur.
Other side effects
Tell your doctor, pharmacist or nurse if you experience any of the following side effects:
Very common: may affect more than 1 in 10 patients

• fungal infections or oral thrush
• upper respiratory tract infections (e.g. sinusitis, tonsillitis)
• loss of appetite
• headache
• cough
• shortness of breath
• diarrhoea
• nausea or vomiting
• abdominal pain
• rash
• feeling tired
• fever.

Common: may affect up to 1 in 10 patients

• influenza-like illness
• urinary tract infection – symptoms include fever, more frequent urination, pain during urination
• skin and subcutaneous tissue infection
• mild allergic reaction – symptoms may include redness, itching of the skin
• weight loss
• feeling depressed, anxious or confused
• difficulty sleeping
• feeling of weakness or numbness in hands or feet, which may lead to loss of balance
• disturbances in sense of touch, tingling, itching, prickling or burning sensations
• changes in taste sensation
• chills
• eye inflammation (conjunctivitis), eye pain and vision problems
• ear pain
• low blood pressure, which may cause dizziness or fainting
• difficulty swallowing
• constipation, flatulence, indigestion, stomach pain, bloating
• mouth ulcers
• abnormal liver and kidney laboratory test results
• night sweats
• itching, skin rash
• hair loss
• back pain, muscle or joint pain, muscle cramps
• dizziness, weakness or general malaise
• skin reaction at the injection site – e.g. inflammation, pain and swelling.

Uncommon: may affect up to 1 in 100 patients

• feeling of restlessness
• tremor, shaking
• deafness
• irregular heartbeat
• urticaria, dry skin
• blood in urine
• infertility in men – see section “Effects on fertility”
• chest pain.

Side effects in children and adolescents
Low blood cell counts are more likely in children, especially newborns and infants.
Reporting of side effects
If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. Side effects can also be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website: https://smz.ezdrowie.gov.pl.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Cymevene

Keep this medicine out of the sight and reach of children.
Powder: no special storage conditions required.
Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the stated month.
After preparation:
Chemical and physical in-use stability has been demonstrated for 12 hours at 25°C after dissolution in Water for Injections.
Do not store in a refrigerator and do not freeze.
From a microbiological point of view, the prepared solution should be used immediately. If the product is not used immediately, the duration and conditions of storage prior to use are the responsibility of the user and must not exceed the established stability period.
After dilution in infusion solutions (0.9% sodium chloride solution, 5% glucose solution, Ringer's solution, or Ringer's lactate solution):
Chemical and physical stability of the solution has been demonstrated for 24 hours at a temperature of 2°C to 8°C (do not freeze).
From a microbiological point of view, the prepared Cymevene infusion solution should be used immediately. If not used immediately, the determination of storage duration and conditions before use is the responsibility of the person administering the medicine and must not exceed 24 hours at 2–8°C, unless the solution has been prepared and diluted under controlled and validated aseptic conditions.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Cymevene contains

• The active substance is ganciclovir. Each glass vial contains 500 mg of ganciclovir (as ganciclovir sodium). After reconstitution, 1 ml of solution contains 50 mg of ganciclovir.
• The other ingredients are: sodium hydroxide and hydrochloric acid.

What Cymevene looks like and contents of the pack
Cymevene is a white or almost white powder for concentrate for solution for infusion.
It is supplied in a glass vial containing one dose, closed with a rubber stopper and an aluminium flip-off cap.
The prepared solution of Cymevene is colourless to pale yellow.
Vials containing Cymevene are available in packs containing 1 vial.
For further information, please contact the Marketing Authorisation Holder or the parallel importer.
Marketing Authorisation Holder in the Czech Republic, country of export:
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
Parallel Importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Repackaged in:
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Pharma Innovations Sp. z o.o.
ul. Jagiellońska 76
03-301 Warsaw
Marketing Authorisation number in the Czech Republic, country of export: 42/138/91-C
Parallel Import Authorisation number: 343/19
This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Cymevene: Austria, Belgium, Croatia, Czech Republic, Cyprus, Denmark, Finland, Hungary, Ireland, Luxembourg, Netherlands, Norway, Poland, Portugal, Slovakia, Spain, Sweden, United Kingdom
Cymeven i.v.: Germany
Cymevan: France
Citovirax: Italy

The following information is intended exclusively for healthcare professionals.
INSTRUCTIONS FOR PREPARATION AND HANDLING OF THE MEDICINAL PRODUCT
Before prescribing, please refer to the Product Characteristics.

Method of administration
Warning:
Ganciclovir must be administered as an intravenous infusion over 1 hour at a concentration not exceeding 10 mg/ml. The medicinal product must not be given as a rapid intravenous infusion or by rapid intravenous injection (bolus), as excessively high serum concentrations resulting from such administration may increase the toxicity of ganciclovir.
The medicinal product must not be administered by intramuscular or subcutaneous injection, as the high pH (~11) of the ganciclovir solution may cause severe tissue irritation.
Doses higher than recommended, increased frequency of dosing, or increased infusion rate must not be used.
Cymevene is a powder for concentrate for solution for infusion. After reconstitution, Cymevene is a colourless or slightly yellow solution, practically free from visible particles.
Intravenous infusion should be administered into a vein with adequate blood flow, preferably through a plastic cannula.
Cymevene medicinal product must be handled with care.
Due to the potential teratogenic and carcinogenic effects of Cymevene in humans, caution must be exercised during preparation and administration of Cymevene solutions. Avoid inhalation and direct contact of the powder contained in vials or direct contact of the medicinal product solution with skin or mucous membranes. Solutions of Cymevene have an alkaline reaction (pH ~11). In case of direct contact, the affected area should be thoroughly washed with soap and water; in case of eye contact, rinse eyes with running water.

Preparation of the concentrate solution
Appropriate aseptic techniques must be used when preparing the lyophilised medicinal product Cymevene.

1. Remove the flip-off cap and expose the central part of the rubber stopper. Using a syringe, withdraw 10 ml of Water for Injections and insert the needle through the centre of the rubber stopper. Slowly inject the water into the vial, directing the needle towards the vial wall. Do not use Water for Injections containing bacteriostatic agents with parabens (parahydroxybenzoates), as they are incompatible with the medicinal product Cymevene.
2. Gently shake the vial to ensure complete wetting of the medicinal product.
3. Gently rotate/invert the vial for several minutes until a clear concentrate solution is obtained.
4. Before dilution with a compatible diluent, carefully inspect the prepared concentrate solution to ensure complete dissolution and absence of solid particles. The prepared solution of the medicinal product Cymevene is colourless to pale yellow.

Preparation of the diluted infusion solution
Withdraw from the vial containing the concentrate of Cymevene, using a syringe, the dose appropriate for the patient's body weight, and add it to the appropriate infusion solution. Add 100 ml of diluent to the prepared solution. Infusion of solutions with a concentration higher than 10 mg/ml is not recommended.
Sodium chloride solution, 5% glucose solution, Ringer's solution, or Ringer's lactate solution have been shown to be chemically or physically compatible with the medicinal product Cymevene.
Cymevene must not be mixed with other medicinal products intended for intravenous administration.
The diluted solution should then be administered as an intravenous infusion over 1 hour. The medicinal product must not be administered by intramuscular or subcutaneous injection, as the high pH (~11) of the ganciclovir solution may cause severe tissue irritation.

Disposal
The product is intended for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local regulations.