Citovirax

Package leaflet: Information for the user

Citovirax 500 mg powder for concentrate for solution for infusion

ganciclovir
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Citovirax is and what it is used for

What Citovirax is
Citovirax contains the active substance ganciclovir, which belongs to a group of medicines called
antivirals.
What Citovirax is used for
Citovirax is used to treat diseases caused by a virus called cytomegalovirus (CMV) in adult and adolescent patients aged 12 years and older who have a weakened immune system, as well as to prevent CMV infections following organ transplantation or during chemotherapy in adults and children from birth.

• The virus can affect any part of the body, including the retina, a layer that lines the back of the eye – this means the virus can cause vision problems.
• The virus can affect anyone, but it poses a particular risk for individuals with a weakened immune system. In these people, CMV can cause serious disease. Immune system weakness may be due to other medical conditions (such as AIDS) or to medications (such as chemotherapy or immunosuppressants).

2. What you need to know before using Citovirax

Do not use Citovirax:

• if you are allergic to ganciclovir, valganciclovir, or any of the other ingredients of this medicine (listed in section 6);
• if you are breastfeeding (see subsection “Breastfeeding”). Do not use Citovirax if any of the above apply to you. If you have any doubts, consult your doctor, pharmacist, or nurse before using Citovirax.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Citovirax:

• if you are allergic to aciclovir, valaciclovir, penciclovir, or famciclovir – these are other medicines used to treat viral infections;
• if you have low levels of white blood cells, red blood cells, or platelets – your doctor will perform blood tests before and during treatment;
• if you have previously experienced blood cell problems due to medications;
• if you have kidney problems – your doctor will prescribe a lower dose and monitor your blood cell counts more frequently during treatment;
• if you are undergoing radiotherapy.

If any of the above apply to you (or if you have any doubts), consult your doctor, pharmacist, or nurse before using Citovirax.
Be aware of side effects
Citovirax may cause serious side effects that must be reported immediately to your doctor. Pay attention to the serious side effects listed in section 4 and inform your doctor if you experience any of them during treatment with Citovirax – your doctor may instruct you to stop taking Citovirax, and urgent medical intervention may be required.
Tests and monitoring
During treatment with Citovirax, your doctor will perform regular blood tests to ensure the dose you are taking is appropriate for you. During the first 2 weeks, these blood tests will be performed more frequently than after this initial period.
Children and adolescents
Information on the safety and efficacy of Citovirax for the treatment of CMV disease in children under 12 years of age is limited. Newborns and infants treated with Citovirax for prevention of CMV disease will undergo regular blood tests.
Other medicines and Citovirax
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor or pharmacist if you are taking any of the following medicines:

• imipenem/cilastatin – used to treat bacterial infections;
• pentamidine – used to treat parasitic or lung infections;
• flucytosine, amphotericin B – used to treat fungal infections;
• trimethoprim, trimethoprim/sulfamethoxazole, dapsone – used to treat bacterial infections;
• probenecid – used to treat gout;
• mycophenolate mofetil, ciclosporin, tacrolimus – used after organ transplantation;
• vincristine, vinblastine, doxorubicin – used to treat cancer;
• hydroxyurea – used to treat a condition called polycythaemia, sickle cell anaemia, and cancer;
• didanosine, stavudine, zidovudine, tenofovir, or other medicines used to treat HIV;
• adefovir or any other medicine used to treat hepatitis B.

If any of the above apply to you (or if you have any doubts), consult your doctor or pharmacist before using Citovirax.
Pregnancy, breastfeeding and fertility
Pregnancy
Citovirax must not be used in pregnant women unless the benefits to the mother outweigh the potential risks to the fetus.
If you are pregnant or suspect you may be pregnant, do not use this medicine unless specifically instructed by your doctor, as Citovirax could be harmful to the fetus.
Contraception
You must not become pregnant during treatment with this medicine, as it could be harmful to the fetus.
Women
If you are a woman of childbearing potential, you must use an effective method of contraception during treatment with Citovirax and for at least 30 days after stopping Citovirax.
Men
If you are a man whose partner is of childbearing potential, you must use a barrier method of contraception (e.g. condom) during treatment with Citovirax and for at least 90 days after stopping Citovirax.
If you or your partner become pregnant during treatment with Citovirax, inform your doctor immediately.
Breastfeeding
Do not use Citovirax if you are breastfeeding. If your doctor prescribes Citovirax, you must stop breastfeeding before starting this medicine, as Citovirax may pass into breast milk.
Fertility
Citovirax may affect fertility. In men, Citovirax may temporarily or permanently impair sperm production. If you are planning a pregnancy, consult your doctor or pharmacist before using Citovirax.
Driving and using machines
During treatment with Citovirax, you may experience drowsiness, dizziness, confusion, tremors, loss of balance, or seizures. If this occurs, do not drive or operate tools or machinery.
Citovirax contains sodium
This medicine contains 43 mg of sodium (a component of table salt) per 500 mg vial. This is equivalent to 2% of the maximum recommended daily dietary intake of sodium for an adult.

3. How to use Citovirax

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
How to use this medicine
Citovirax will be administered to you by a doctor or nurse through a small tube inserted into a
vein. This method of administration is called intravenous infusion and usually takes
about one hour.
The required amount of Citovirax varies from patient to patient. Your doctor will calculate the dose to
be administered. This will depend on:

• body weight (in children, height may also be considered)
• age
• kidney function
• blood cell count
• the reason for which you are using this medicine

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

• Normally, treatment starts with one or two infusions per day.
• In the case of two infusions per day, this regimen will continue for up to 21 days.
• Afterwards, your doctor may prescribe one infusion per day.

Patients with kidney or blood problems
If you have kidney or blood problems, your doctor may advise you to receive a lower
dose of Citovirax and monitor your blood cell count more frequently during
treatment.
If you use more Citovirax than you should
If you suspect that the dose of Citovirax you received exceeds the recommended amount, speak to your
doctor or go to hospital immediately. If you have been given an excessive dose, you may experience the following symptoms:

• stomach pain, diarrhoea or vomiting
• tremors or seizures
• blood in the urine
• kidney or liver problems
• changes in blood cell count

If you stop treatment with Citovirax
Do not stop treatment with Citovirax without first talking to your doctor.
If you have any questions about how to use this medicine, consult your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. With this medicine, you may experience the following side effects:

Serious side effects
Tell your doctor immediately if you notice any of the following serious side effects – your doctor may advise you to stop taking Citovirax and urgent medical treatment may be required:

Very common: may affect more than 1 in 10 people:

• low white blood cell count, with signs of infection such as sore throat, mouth ulcers or fever
• low red blood cell count, signs of which include breathlessness, feeling tired, palpitations or paleness

Common: may affect up to 1 in 10 people:

• blood infection (sepsis), signs of which include fever, chills, palpitations, confusion and difficulty speaking
• low platelet count, signs of which include increased tendency to bleed or bruise, blood in urine or stools, or bleeding gums. Bleeding may be severe
• markedly low blood cell count
• pancreatitis, signs of which include severe stomach pain spreading to the back
• seizures

Uncommon: may affect up to 1 in 100 people:

• inability of the bone marrow to produce blood cells
• hallucinations, i.e. hearing or seeing things that are not real
• abnormal thoughts or feelings, loss of contact with reality
• impaired kidney function

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

• severe allergic reaction, signs of which may include skin redness and itching, swelling of the throat, face, lips or mouth, difficulty swallowing or breathing

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

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

Very common: may affect more than 1 in 10 people:

• fungal infections (candidiasis) and oral thrush
• upper respiratory tract infection (e.g. sinusitis, tonsillitis)
• loss of appetite
• headache
• cough
• breathlessness
• diarrhoea
• nausea and vomiting
• abdominal pain
• eczema
• feeling tired
• fever

Common: may affect up to 1 in 10 people:

• influenza
• urinary tract infection, signs of which include fever, more frequent urination, pain when passing urine
• skin and subcutaneous tissue infection
• mild allergic reaction, signs of which may include red, itchy skin
• weight loss
• feeling depressed, anxious or confused
• sleep disorders
• feeling of weakness and numbness in hands or feet which may affect balance
• altered sense of touch, tingling, tickling, pricking or burning sensation
• altered sense of taste
• chills
• eye inflammation (conjunctivitis), eye pain or vision problems
• ear pain
• low blood pressure, which may cause dizziness or fainting
• difficulty swallowing
• constipation, flatulence, indigestion, stomach ache, abdominal bloating
• mouth ulcers
• abnormal laboratory tests for liver and kidney function
• night sweats
• itching, skin rash
• hair loss
• back pain, muscle or joint pain, muscle spasms
• dizziness, weakness or general malaise
• skin reaction at the injection site, such as inflammation, pain and swelling

Uncommon: may affect up to 1 in 100 people:

• feeling restless
• tremors, shaking
• deafness
• irregular heartbeat
• hives, dry skin
• blood in urine
• infertility in men; see section "Fertility"
• chest pain

Side effects in children and adolescents
Low blood cell counts are observed more frequently in children, especially in neonates and infants.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Citovirax

Keep this medicine out of the sight and reach of children.
Powder: no special storage precautions are required. Do not use this medicine
after the expiry date stated on the label and the outer carton. The expiry date refers to the last
day of that month.
After reconstitution:
The chemical and physical in-use stability of the reconstituted product has been demonstrated for 12 hours at 25 °C after dissolution with water for injections. Do not refrigerate or freeze.
From a microbiological standpoint, the reconstituted solution should be used immediately. Otherwise, the duration and conditions of in-use storage prior to use are the responsibility of the user.
After dilution in infusion solution (0.9% sodium chloride injectable solutions, 5% dextrose, Ringer’s solution or Ringer’s lactate):
In-use chemical and physical stability has been demonstrated for 24 hours at a temperature between 2 °C and 8 °C (do not freeze).
From a microbiological standpoint, the Citovirax infusion solution should be used immediately. Otherwise, the duration and conditions of in-use storage prior to use are the responsibility of the user and must not exceed 24 hours at a temperature between 2 °C and 8 °C, unless reconstitution and dilution were carried out under validated controlled and aseptic conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Citovirax contains

• The active substance 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.

Description of the appearance of Citovirax and contents of the pack
Citovirax is a white to off-white powder for concentrate for solution for infusion,
supplied in a single-dose glass vial with a rubber stopper and an aluminium seal with a flip-off cap. The colour of reconstituted Citovirax solutions varies from colourless to pale yellow.
Citovirax vials are available in packs of 1 or 5. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation 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 authorised in the European Economic Area member states under the
following names:
Cymevene: Austria, Belgium, Croatia, Czech Republic, Denmark, Finland, Hungary, Ireland,
Luxembourg, Netherlands, Norway, Poland, Portugal, Slovak Republic, Spain, Sweden
Cymeven i.v.: Germany
Cymevan: France
Citovirax: Italy

Other sources of information
More detailed information on this medicinal product is available on the website of the Italian Medicines Agency (AIFA) https://www.aifa.gov.it/.
The following information is intended for healthcare professionals only.

INSTRUCTIONS FOR USE AND HANDLING

For complete prescribing information, refer to the Summary of Product Characteristics.
Route of administration
Warning:
Ganciclovir must be administered by intravenous infusion over 1 hour at a maximum concentration of 10 mg/mL. Rapid intravenous injection or bolus administration must be avoided due to the potential increase in ganciclovir toxicity resulting from excessively high plasma levels.
Intramuscular or subcutaneous injection must be avoided, as it may cause severe tissue irritation due to the high pH (~11) of ganciclovir solutions.
Do not exceed the recommended dosage, frequency, or infusion rate.
Citovirax is a powder for solution for infusion. After reconstitution, Citovirax is a colourless or slightly yellowish solution, practically free from visible particles.
The infusion should be administered into a vein with adequate blood flow, preferably using a plastic cannula.
Care must be taken when handling Citovirax.
Since Citovirax is considered potentially teratogenic and carcinogenic in humans, caution must be exercised during handling. Avoid inhaling or coming into direct contact with the powder contained in the vials, as well as direct contact between the reconstituted solution and skin or mucous membranes. Citovirax solutions are alkaline (pH ~11). In case of contact, wash the affected area thoroughly with soap and water and rinse eyes abundantly with running water.

Preparation of the reconstituted concentrate
Reconstitution of lyophilized Citovirax requires the use of aseptic techniques.

1. Remove the flip-off cap to expose the central portion of the rubber stopper. Withdraw 10 mL of water for injections using a syringe, then slowly inject it into the vial by inserting the needle through the center of the rubber stopper and directing it toward the vial wall. Do not use bacteriostatic water for injections containing parabens (para-hydroxybenzoates), as they are incompatible with Citovirax.
2. Gently swirl the vial to ensure complete dissolution of the medicinal product.
3. Gently rotate/swirl the vial for several minutes until a clear reconstituted solution is obtained.
4. Before dilution with a compatible diluent, carefully inspect the reconstituted solution to ensure the medicinal product is completely dissolved and practically free from visible particles. The colour of reconstituted Citovirax solutions ranges from colourless to pale yellow.

Preparation of the final diluted infusion solution
Withdraw from the vial the volume of concentrate required according to the patient's body weight using a syringe, and further dilute it in a suitable infusion solution. Add 100 mL of diluent to the reconstituted solution. Infusion concentrations exceeding 10 mg/mL are not recommended.
Sodium chloride solutions, 5% dextrose, Ringer's solution, or Ringer's lactate are considered chemically and physically compatible with Citovirax.
Citovirax must not be mixed with other intravenous products.
The diluted solution should then be administered intravenously over 1 hour.
Intramuscular or subcutaneous injection must be avoided, as it may cause severe tissue irritation due to the high pH (~11) of the ganciclovir solution.

Disposal
For single use only. Unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.