Package leaflet: Information for the user

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

Keep this leaflet for future reference.
If you have any questions, 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 someone else, even if their symptoms are the same.
If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

What Cymevene is and what it is used for
Important information before using Cymevene
How to use Cymevene
Possible side effects
How to store Cymevene
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 used to treat diseases caused by cytomegalovirus (CMV) in adult patients and adolescents aged 12 years and older with weakened immune systems. Cymevene is also used to prevent CMV infection after organ transplantation or during chemotherapy in adults and children from birth.

CMV infection can affect any part of the body, including the retina of the eye – this means the virus may cause vision problems.
The virus can cause disease in anyone, but it is particularly problematic in people with weakened immune systems. In individuals with weakened immunity, CMV can cause serious diseases. Immune system weakness may result from other illnesses (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 section "Breast-feeding").

Do not use Cymevene if any of the above apply to the patient. If in doubt, talk to 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 a low number of white blood cells, red blood cells, or platelets – your doctor will perform blood tests before and during treatment;
the patient has previously had problems with blood cell counts due to taking medicines;
the patient has impaired kidney function – the dose of the medicine may need to be reduced and blood cell counts monitored more frequently during treatment;
the patient is receiving radiotherapy.

If any of the above apply (or if in doubt), talk to your doctor, pharmacist, or nurse before taking Cymevene.

Be aware of adverse reactions
Cymevene may cause certain serious adverse reactions, which should be reported immediately to your doctor. Be alert for the serious adverse reactions 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 carry out regular blood tests. These are to ensure that the dose of medicine is appropriate for you. During the first 2 weeks, blood tests will be performed frequently. After that, blood tests will be performed less often.

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 tests.

Cymevene with other medicines
Tell your doctor or pharmacist if the patient is currently taking, has recently taken, or might take any other medicines.

In particular, inform your doctor or pharmacist if the patient is taking any of the following medicines:

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 in doubt), talk to your doctor or pharmacist before taking Cymevene.

Pregnancy, breastfeeding, and fertility

Pregnancy
Women who are pregnant should not take Cymevene unless the therapeutic benefits to the mother outweigh the potential risks to the unborn child.
If the patient is pregnant or suspects she may be pregnant, she should not take this medicine unless advised otherwise by her doctor. 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 should use contraception during treatment with Cymevene. Contraception should also be used 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 used 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 considers treatment with Cymevene 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
Cymevene contains 43 mg of sodium (the main component of table salt) per 500 mg vial. This corresponds to 2% of the maximum daily recommended sodium intake in the adult diet.

3. How to use Cymevene

This medicine should always be used exactly as instructed by the doctor or pharmacist. If in doubt,
consult the 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 lasts one hour.
The dose of Cymevene varies depending on the patient. The doctor will determine the appropriate dose.
The dose depends on:

the patient's body weight (in children, height may also be considered),
age,
kidney function,
blood counts,
the indication for which the medicine is being 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 are given daily, treatment will last up to 21 days at most.
Afterwards, the 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 recommend 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 an overdose of Cymevene is suspected, contact a doctor immediately or go to hospital without delay.
The following symptoms may occur after administration of a higher than recommended dose:

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

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, consult your doctor, pharmacist or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The following adverse reactions may occur during treatment with this medicine:
Serious adverse reactions
Contact your doctor immediately if any of the following serious adverse reactions occur – your doctor may advise you to stop taking Cymevene and you may require urgent medical treatment:
Very common: may occur in more than 1 in 10 patients

low white blood cell count – symptoms of infection such as sore throat, mouth ulcers or fever,
low red blood cell count – symptoms include shortness of breath or fatigue, palpitations or pale skin.

Common: may occur in up to 1 in 10 patients

blood infection (septicaemia) – symptoms include fever, chills, palpitations, confusion and slurred speech,
low platelet count – symptoms include bleeding or bruising more easily than usual, 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 occur in 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 occur in up to 1 in 1000 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 adverse reactions occur.
Other adverse reactions
Tell your doctor, pharmacist or nurse if you experience any of the following adverse reactions:
Very common: may occur in more than 1 in 10 patients

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

Common: may occur in up to 1 in 10 patients

influenza,
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 of depression, anxiety or confusion,
difficulty falling asleep,
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, abdominal bloating,
mouth ulcers,
abnormal liver and kidney laboratory test results,
night sweats,
itching, 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 occur in up to 1 in 100 patients

feeling of restlessness,
tremor, shaking,
deafness,
irregular heartbeat,
urticaria, dry skin,
blood in urine,
infertility in males – see section "Effect on fertility",
chest pain.

Adverse reactions in children and adolescents
Low blood cell counts are more likely to occur in children, especially newborns and infants.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel: +48 (22) 49 21 301
Fax: +48 (22) 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions 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 requirements.
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 or freeze.
From a microbiological point of view, the prepared solution should be used immediately. If the medicine is not used immediately, the responsibility for storage conditions and duration prior to use lies with the user.
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 temperatures from 2°C to 8°C (do not freeze).
From a microbiological point of view, the prepared infusion solution of Cymevene should be used immediately. If not used immediately, the determination of storage time and conditions prior to 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. These measures will help protect the environment.

6. Contents of the Package 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.
Other ingredients: sodium hydroxide and hydrochloric acid.

What Cymevene Looks Like and Contents of the Package
Cymevene is a white or almost white powder for solution for infusion concentrate, supplied in a
clear glass vial with a capacity of 10 ml, containing one dose, closed with a fluoro-rubber laminated/siliconized rubber stopper and an aluminium flip-off cap, packed in a cardboard box.
The prepared solution of Cymevene is colourless to pale yellow.
Vials of Cymevene are available in packs containing 1 vial.
For more detailed 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
Parallel Importer:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Repackaged in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Marketing Authorisation Number in the Czech Republic, country of export: 42/138/91-C
Parallel Import Authorisation Number: 59/14
This medicinal product is authorised for marketing in the following European Economic Area
countries under the following trade names:
Cymevene: Austria, Belgium, Croatia, Czech Republic, 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, ADMINISTRATION AND HANDLING OF THE MEDICINAL PRODUCT
Before prescribing the medicinal product, please refer to the Summary of Product Characteristics.

Route of Administration
Warning:
Ganciclovir must be administered by intravenous infusion over 1 hour at a concentration not exceeding 10 mg/ml. The medicinal product must not be given as a rapid intravenous injection or 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 rates must not be used.
Cymevene is a powder for preparing an infusion solution. After reconstitution, Cymevene is a colourless or slightly yellow solution, practically free from visible particles.
Intravenous infusions should be administered into a vein with adequate blood flow, preferably through a plastic cannula.
Cymevene must be handled with care.
Due to the potential teratogenic and carcinogenic effects of Cymevene in humans, precautions must be taken during the preparation and administration of Cymevene solutions. Avoid inhalation and direct contact of the powder contained in vials or direct contact of the solution with skin or mucous membranes. Cymevene solutions are alkaline (pH ~11). In case of direct contact, the affected area should be thoroughly washed with soap and water; in case of eye contact, rinse thoroughly with running water.

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

Remove the flip-off cap and expose the central part of the rubber stopper. Using a syringe, draw up 10 ml of Water for Injections and insert the needle through the centre of the rubber stopper, slowly injecting the water into the vial while directing the needle towards the vial wall. Do not use Water for Injections containing bacteriostatic agents with parabens (parahydroxybenzoates), as these are incompatible with Cymevene.
Gently shake the vial to ensure complete wetting of the powder.
Gently rotate/shake the vial for several minutes until a clear concentrate solution is obtained.
Before dilution with a compatible diluent, inspect the prepared concentrate solution visually to confirm complete dissolution and absence of particulate matter. The prepared solution of Cymevene is colourless to pale yellow.

Preparation of the Diluted Infusion Solution
Withdraw the appropriate dose based on the patient's body weight from the concentrate vial of Cymevene using a syringe and add it to the appropriate infusion solution. Add 100 ml of diluent to the prepared solution. Infusion solutions with a concentration exceeding 10 mg/ml are not recommended.
Sodium chloride solution, 5% glucose solution, Ringer's solution, or Ringer's solution with lactates have been shown to be chemically and physically compatible with Cymevene.
Cymevene must not be mixed with other medicinal products intended for intravenous administration.
The diluted solution should then be administered by 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 medicinal product is intended for single use only. Any unused portions or waste material must be disposed of in accordance with local regulations.