Package Insert: Information for the User

Cymevene 500 mg Powder for Concentrate for Solution for Infusion

Ganciclovir

Read this package insert carefully before starting to use this medication, as it contains important information for you.

?Keep this package insert, as you may need to read it again.

?If you have any questions, consult your doctor, pharmacist, or nurse.

?This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.

?If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

1.What Cymevene is and for what it is used

2.What you need to know before starting to use Cymevene

3.How to use Cymevene

4.Possible adverse effects

5.Storage of Cymevene

6.Contents of the package and additional information

What is Cymevene

Cymevene contains ganciclovir as its active ingredient. It belongs to a group of medications called antivirals.

What is Cymevene used for

Cymevene is used to treat diseases caused by a virus called cytomegalovirus (CMV) in patientsadults and adolescents aged 12 years and older with a weakened immune system. It is also used to prevent CMV infection after an organ transplant or during chemotherapy in adults and in children from birth.

?The virus can affect any part of the body. Including the retina in the back of the eye – which means that the virus can cause vision problems.

?The virus can affect anyone, but it is a particular problem in people with a weakened immune system. In these people, the CMV virus can cause serious disease. A weakened immune system can be caused by other diseases (such as AIDS) or by medications (such as chemotherapy or immunosuppressants).

Do not use Cymevene:

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

?if you are breastfeeding (see subsection “Breastfeeding”).

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

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Cymevene if:

?you are allergic to aciclovir, valaciclovir, penciclovir, or famciclovir – these are other medications 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 perform blood tests before starting and during treatment

?you have had problems with blood cell counts due to medications in the past

?you have kidney problems – your doctor may prescribe a lower dose and you may need more frequent blood tests during treatment

?you are receiving radiation therapy.

If any of the above applies to you (or you are unsure), consult your doctor, pharmacist, or nurse before using Cymevene.

Monitor for adverse effects

Cymevene may cause severe adverse effects that you must report to your doctor immediately. Monitor for severe adverse effects listed in Section 4 and if you experience any while using Cymevene, tell your doctor – your doctor may instruct you to stop taking Cymevene and you may need urgent medical treatment.

Tests and controls

Your doctor will perform regular blood tests during treatment with Cymevene. This is to check that the dose you are taking is suitable for you. During the first two weeks, these blood tests will be performed frequently. After that, the 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 old.Regular blood tests will be performed on newborns and breastfeeding infants treated with Cymevene for the prevention of CMV disease.

Other medications and Cymevene

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Particularly, inform your doctor or pharmacist if you are taking any of the following medications:

?imipenem/cilastatina – used for bacterial infections,

?pentamidine – used for parasitic or lung infections,

?flucytosine, amphotericin B – used for fungal infections,

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

?probenecid – used for gout,

?mycophenolate mofetil, cyclosporine, tacrolimus – used after 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 medications used for HIV,

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

If any of the above applies to you (or you are unsure), consult your doctor or pharmacist before using Cymevene.

Pregnancy, breastfeeding, and fertility

Pregnancy

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

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

Contraception

You should not become pregnant while using this medication. 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 should also use it for at least 30 days after completing treatment with Cymevene.

Men

If you are a man, whose partner may become pregnant, you must use a barrier contraceptive method (such as condoms) while taking Cymevene. Continue using it for at least 90 days after completing treatment with Cymevene.

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

Breastfeeding

Do not use Cymevene if you are breastfeeding. If your doctor wants to start treating you with Cymevene, you must stop breastfeeding before starting to take this medication. 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 operating machinery

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

Cymevene contains sodium

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

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Use of this medication

Your doctor or nurse will administer Cymevene. You will receive it through a tube in your vein. This is called “intravenous infusion” and will last approximately one 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, your height will also be taken into account),

?your age,

?the correct functioning of your kidneys,

?the number of blood cells,

?why you are using the medication.

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

?Usually, you will start receiving one or two infusions per day.

?If you receive two infusions per day, you will continue this way for 21 days.

?Your doctor may then prescribe the infusion once a day.

People with kidney or blood problems

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

If you use more Cymevene than you should

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

You may experience the following symptoms:

?stomach pain, diarrhea, or nausea

?shaking or convulsions

?blood in your urine

?liver or kidney problems

?changes in your blood cell count.

If you interrupt treatment with Cymevene

Do not stop using Cymevene without consulting your doctor.

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

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

Severe side effects

Inform your doctor immediately if you experience any of the following severe side effects – your doctor may tell you to stop taking Cymevene and that you 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 includeshortness of breathorfatigue, 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 the appearance ofbruisesmore easily than normal, blood in urine or stool, or bleeding gums, these bleeding can be severe

?Intense decrease in the number of blood cells

?Pancreatitis with signs such as severe stomach pain that extends to the back

?Seizures.

Uncommon:may affect up to 1 in 100 people

?Bone marrow failure to produce blood cells

?Delusions – see or hear things that are not real

?Disturbed thinking or feelings, loss of contact with reality

?Renal function failure.

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

?Severe allergic reaction – symptoms may include, skin redness and itching, throat, face, lips, or mouth inflammation, difficulty swallowing or breathing.

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

Other side effects

If you experience any of the following side effects, inform 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

?Influenza

• Urinary tract infection, with signs that include fever, frequent urination, pain while urinating
• Skin and subcutaneous tissue infection
• Mild allergic reactions, with signs that include skin redness and swelling
• Weight loss
• Feeling of depression, anxiety, or confusion

?Difficulty sleeping

• Numbness or weakness in hands and feet, which may affect your balance
• Changes in the sense of touch, tingling, pins and needles, or burning sensation
• Changes in taste
• Chills
• Conjunctivitis, eye pain, or vision problems
• Ear pain
• Low blood pressure, which may make you feel dizzy or have blurred vision
• Difficulty swallowing
• Constipation, gas, indigestion, stomach pain, abdominal distension
• Mouth ulcers
• Abnormal results in liver and kidney laboratory tests

?Nocturnal sweating

• Itching, rash
• Hair loss
• Back, muscle, or joint pain, muscle spasms

?Feeling of dizziness, weakness, or general discomfort

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

Uncommon::may affect up to 1 in 100 people

?Agitation

• Tremors

?Deafness

• Irregular heart rhythm

?Urticaria, 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 side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Powder: No special storage conditions are required. Do not usethis medicationafter the expiration date that appears onthe packagingafter CAD. The expiration date is the last day of the month indicated.

After reconstitution:

Chemical and physical stability during handling has been demonstrated for the reconstituted product for 12 hours at 25°C after dissolving it with injectable water. 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 injection solution):

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 °C to 8 °C, unless reconstitution and dilution are made in a validated controlled and aseptic site.

Medicines should not be disposed of through the drains or in the trash.Deposit the containers and medicines that you no longer need at the SIGRE point of the pharmacyAsk your pharmacist how to dispose of the containers and medicines that you no longer need. This will help protect the environment.

Composition ofCymevene

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

?The other components are sodium hydroxide and hydrochloric acid.

Appearance of the product and contents of the package

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

Cymevene vials are presented in packages of 1 or 5 vials.

Only some sizes of packages may be commercially available.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

CHEPLAPHARM Arzneimittel GmbH

Ziegelhof 24

17489 Greifswald

Germany

Responsible 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 by contacting 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 with the following names:

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

Cymeven i.v.:Germany

Cymevan:France

Citovirax:Italy

Last update of thisleaflet: April 2020

Other sources of information

The detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

--------------------------------------------------------------------------------------------------------------------------

This information is intended solely for healthcare professionals:

INSTRUCTIONS FOR USE AND HANDLING

Please refer to the technical data sheet or product characteristics summary for complete prescribing information.

Administration form

Warning:

Ganciclovir must be administered by intravenous infusion over 1hour, with a concentration not exceeding 10mg/ml. It should not be administered as a bolus or rapid intravenous injection, as excessive plasma levels resulting from this 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 light yellow solution, practically free of visible particles.

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

Precautions to be takenin the handling ofCymevene:

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

Preparation of the reconstituted concentrate

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

1. Remove the aluminum cap seal to expose the central part of the rubber stopper. Extract 10 ml of water for injection with a syringe, then inject it slowly through the center of the rubber stopper into the vial with the needle pointing 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 humidification of the product.

3. Rotate/gently turn the vial for a few minutes to obtain a clear reconstituted solution.

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

Preparation of the final diluted solution for infusion

Depending on the patient's body weight, extract the necessary volume from the vial with a syringe and then dilute it in an appropriate infusion fluid. Add 100 ml of the solvent to the reconstituted solution. Concentrations of infusion exceeding 10 mg/ml are not recommended.

Solutions of sodium chloride, dextrose 5%, Ringer for injection, and Ringer with lactate for injection have been shown to be compatible chemically or physically 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.

Elimination

For single use only. The elimination of unused medication and any residue will be carried out in accordance with local regulations.