CYMEVENE 500 mg Powder

Contents of the leaflet

1. Leaflet accompanying the packaging: information for the user
2. Cymevene 500 mg powder for concentrate for solution for infusion
   1. Read the leaflet carefully before taking the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
3. What is Cymevene and what is it used for
   1. What is Cymevene
   2. What is Cymevene used for
4. Important information before taking Cymevene
   1. When not to take Cymevene:
   2. Warnings and precautions
   3. Pay attention to side effects
   4. Laboratory tests
   5. Children and adolescents
   6. Cymevene and other medicines
   7. Pregnancy, breastfeeding, and fertility
   8. Pregnancy
   9. Driving and using machines
   10. Cymevene contains sodium
5. How to take Cymevene
   1. Overdose of Cymevene
   2. Stopping treatment with Cymevene
6. Possible side effects
   1. Severe side effects
   2. Other side effects
   3. Side effects in children and adolescents
   4. Reporting side effects
7. How to store Cymevene
8. Contents of the packaging and other information
   1. What Cymevene contains
   2. What Cymevene looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. Marketing authorization holder
   5. Manufacturer
   6. This medicinal product is authorized in the Member States of the European Economic Area under the following names:
   7. Date of last revision of the leaflet: July 2021
   8. Handle the medicinal product Cymevene with care.

Leaflet accompanying the packaging: information for the user

Cymevene 500 mg powder for concentrate for solution for infusion

Ganciclovir

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Cymevene and what is it used for
• 2. Important information before taking Cymevene
• 3. How to take Cymevene
• 4. Possible side effects
• 5. How to store Cymevene
• 6. Contents of the packaging and other information

1. What is Cymevene and what is it used for

What is Cymevene

The active substance of Cymevene is ganciclovir. It belongs to a group of antiviral medicines.

What is Cymevene used for

Cymevene is used to treat diseases caused by cytomegalovirus (CMV) in adult patients and adolescents aged 12 years and older with impaired immune system function. The medicine is also used to prevent CMV infections 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 that the virus can cause vision problems.
• The virus can cause disease in anyone, but it is a particular problem for people with weakened immune systems. In people with weakened immune systems, CMV can cause serious diseases. Weakened immune system can be caused by other diseases (e.g. AIDS) or medications (e.g. chemotherapy or immunosuppressive drugs).

2. Important information before taking Cymevene

When not to take Cymevene:

• during breastfeeding (see "Breastfeeding"). Do not take Cymevene if any of the above points apply to you. In case of doubts, consult a doctor, pharmacist, or nurse before taking Cymevene.

Warnings and precautions

Before starting treatment with Cymevene, discuss it with your doctor, pharmacist, or nurse if:

• the patient has been found to be 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 - before starting treatment and during treatment, the doctor will perform blood tests;
• the patient has had problems with blood cell count in the past due to taking medicines;
• the patient has kidney function disorders - it will be necessary to reduce the dose of the medicine and more frequently monitor the blood cell count during treatment;
• the patient is undergoing radiation therapy. If any of the above points apply to you (or in case of doubts), consult a doctor, pharmacist, or nurse before taking Cymevene.

Pay attention to side effects

Cymevene can cause certain serious side effects, which should be reported to the doctor immediately. Pay attention to serious side effects listed in section 4 and inform the attending doctor if any of these side effects occur during treatment with Cymevene - the doctor may recommend stopping treatment with Cymevene and the patient may require emergency treatment.

Laboratory tests

During treatment with Cymevene, the doctor will perform regular blood tests. This is to check if the dose of the medicine is suitable for the patient. For the first 2 weeks, blood tests will be performed frequently. Then, blood tests will be performed 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. Newborns and infants receiving Cymevene for the prevention of CMV disease will undergo regular blood tests.

Cymevene and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or plan to take.
Particularly, inform your doctor or pharmacist if you are 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 and 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 cancer;
• hydroxyurea - used to treat excessive red blood cell count (polycythemia), sickle cell anemia, and cancer;
• didanosine, stavudine, zidovudine, tenofovir, or other medicines used to treat HIV infection;
• adefovir or other medicines used to treat hepatitis B. If any of the above points apply to you (or in case of doubts), consult a doctor or pharmacist before taking Cymevene.

Pregnancy, breastfeeding, and fertility

Pregnancy

Pregnant women 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 thinks she may be pregnant, she should not take this medicine unless the doctor recommends it. Cymevene may harm the unborn child.
Contraception
Women should not become pregnant while taking this medicine. The medicine may harm the unborn child.
Women
Women of childbearing age should use contraception while taking 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) while taking Cymevene. Mechanical contraception should also be used for at least 90 days after stopping Cymevene.
If a patient taking Cymevene becomes pregnant or the partner becomes pregnant while the patient is taking Cymevene, they should contact their doctor immediately.
Breastfeeding
Breastfeeding women should not take Cymevene. Breastfeeding should be stopped if the doctor decides that it is necessary to start taking Cymevene. Cymevene may pass into breast milk.
Fertility
Cymevene may have a harmful effect on fertility. Cymevene may cause temporary or permanent inhibition 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, or tremors may occur. Patients who experience such symptoms should refrain from driving vehicles and operating machines.

Cymevene contains sodium

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

3. How to take Cymevene

This medicine should always be taken as directed by your doctor or pharmacist. In case of doubts, consult a doctor or pharmacist.
How to take the medicine
Cymevene is administered by a doctor or nurse. The medicine is administered through a tube inserted into a vein. This method of administration is called "intravenous infusion" and usually lasts one hour.
The dose of Cymevene varies depending on the patient. The doctor will determine the dose to be used.
The dose of the medicine depends on:

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

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

• Treatment usually starts with one or two infusions per day.
• If two infusions are taken per day, the treatment duration will be up to 21 days.
• Then, the doctor may prescribe one infusion per day.

Patients with kidney function disorders or blood disorders
If the patient has kidney function disorders or blood disorders, the doctor may recommend using a lower dose of Cymevene and more frequent monitoring of the blood cell count during treatment.

Overdose of Cymevene

In case of suspected overdose of Cymevene, consult a doctor or go to the hospital immediately. In case of overdose, the following symptoms may occur:

• abdominal pain, diarrhea, or vomiting
• tremors or seizures
• blood in urine
• kidney or liver function disorders
• changes in blood morphology.

Stopping treatment with Cymevene

Do not stop taking Cymevene without consulting your doctor first.
In case of any further doubts about taking this medicine, consult a doctor, pharmacist, or nurse.

4. Possible side effects

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

Severe side effects

Consult a doctor immediately if any of the following severe side effects occur - the doctor may recommend stopping treatment with Cymevene and the patient may require emergency treatment:
Very common:may occur in more than 1 in 10 patients

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

Common:may occur in up to 1 in 10 patients

• blood infection (sepsis) - symptoms include fever, chills, palpitations, confusion, and slurred speech
• low platelet count - symptoms include bleeding or easier bruising, blood in urine or stool, or bleeding from the gums, bleeding may be severe.
• very low blood cell count
• pancreatitis - symptoms include severe abdominal pain radiating to the back
• seizures

Uncommon:may occur in up to 1 in 100 patients

• bone marrow failure
• hallucinations - seeing or hearing things that are not there
• thought and perception disorders, 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, swelling of the throat, face, lips, or mouth, difficulty swallowing or breathing.

Consult a doctor immediately if any of the above side effects occur.

Other side effects

Inform your doctor, pharmacist, or nurse if any of the following side effects occur:
Very common:may occur in more than 1 in 10 patients

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

Common:may occur in up to 1 in 10 patients

• flu
• urinary tract infection - symptoms include fever, 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 weak or numb in hands or feet, which may lead to balance disorders
• disorders of touch, tingling, itching, burning, or stinging
• changes in taste
• chills
• eye inflammation (conjunctivitis), eye pain, and vision problems
• ear pain
• low blood pressure, which may cause dizziness or fainting
• swallowing difficulties
• constipation, gas, indigestion, stomach pain, bloating
• mouth ulcers
• abnormal liver and kidney 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 - e.g. inflammation, pain, and swelling.

Uncommon:may occur in up to 1 in 100 patients

• feeling agitated
• tremors, shakiness
• deafness
• irregular heartbeat
• hives, dry skin
• blood in urine
• male infertility - see "Fertility" section
• chest pain.

Side effects in children and adolescents

Low blood cell count is more likely to occur in children, especially newborns and infants.

Reporting side effects

If any side effects occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring 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
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Cymevene

Keep the medicine out of sight and reach of children.
Powder: does not require special storage conditions. Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of the month stated.
After preparation:

• It has been shown that the chemical and physical stability of the prepared solution remains for 12 hours at 25°C after reconstitution in water for injection.
• Do not store in the 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 user is responsible for the storage period and conditions before use.
• After dilution in infusion solutions (0.9% sodium chloride solution, 5% glucose solution, Ringer's solution, or Ringer's solution with lactate):

It has been shown that the chemical and physical stability of the solution remains for 24 hours at a temperature of 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 it is not used immediately, the determination of the storage time and conditions of the prepared solution before use is the responsibility of the person administering the medicine and should not exceed 24 hours at a temperature of 2°C to 8°C, unless the solution has been prepared and diluted under controlled, validated aseptic conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Cymevene contains

• The active substance of Cymevene 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 ingredients are: sodium hydroxide and hydrochloric acid.

What Cymevene looks like and contents of the pack

Cymevene is a white or off-white powder for concentrate for solution for infusion, available in a glass vial containing one dose, with a rubber stopper and an aluminum flip-off cap.
The prepared solution of Cymevene has a color from colorless to light yellow.
The vials of Cymevene are available in packs containing 1 or 5 vials.
Not all 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

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 the leaflet: July 2021

The following information is intended for healthcare professionals only.
INSTRUCTIONS FOR PREPARATION AND HANDLING OF THE MEDICINAL PRODUCT
Before prescribing the medicine, read the Summary of Product Characteristics.
Method of administration
Note:
Ganciclovir must be administered by intravenous infusion over 1 hour at a concentration not exceeding 10 mg/ml. The medicinal product should not be administered by rapid intravenous injection (bolus) as the resulting high concentrations in the plasma may increase the toxicity of ganciclovir.
The medicinal product should not be administered by intramuscular or subcutaneous injection, as the high pH (~11) of the ganciclovir solution may cause severe tissue irritation.
Do not administer doses higher than recommended, increase the frequency of administration, or infusion rate.
Cymevene is a powder for solution for infusion. After preparation, Cymevene is a clear or slightly yellowish solution, practically free from visible particles.
Intravenous infusion should be administered into a vein with adequate blood flow, preferably through a plastic cannula.

Handle the medicinal product Cymevene with care.

Due to the potential teratogenic and carcinogenic effects of Cymevene in humans, caution is required when handling the medicinal product.
Avoid inhalation and direct contact of the powder in the vials or direct contact of the solution with the skin or mucous membranes. Solutions of Cymevene have an alkaline reaction (pH ~11). In case of direct contact, the exposed area should be thoroughly washed with soap and water, and in case of contact with the eyes, they should be rinsed with running water.
Preparation of the concentrate

• 1. Remove the flip-off cap and expose the central part of the rubber stopper. Draw up 10 ml of water for injection into a syringe, insert the needle through the center of the rubber stopper, and slowly inject the water into the vial, directing the needle towards the vial wall. Do not use water for injection with bacteriostatic additives containing parabens (parahydroxybenzoates), as they are incompatible with Cymevene.
• 2. Gently swirl the vial to completely wet the medicinal product.
• 3. Gently rotate/shake the vial for a few minutes to obtain a clear concentrate solution.
• 4. Before dilution using a compatible solvent, the prepared concentrate solution should be carefully inspected to ensure that the medicinal product has dissolved and that it does not contain visible particles. The prepared solution of Cymevene has a color from colorless to light yellow.

Preparation of the diluted solution for infusion
From the vial with the Cymevene concentrate, draw up the dose corresponding to the patient's body weight using a syringe and add it to the appropriate infusion solution. Add 100 ml of diluent to the prepared solution. It is not recommended to administer the solution at a concentration exceeding 10 mg/ml.
It has been shown that sodium chloride solution, 5% glucose solution, Ringer's solution, or Ringer's solution with lactate are compatible with Cymevene.
Cymevene should not be mixed with other products for intravenous administration.
The diluted solution should then be administered by intravenous infusion over 1 hour. The medicinal product should 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 requirements.