CYMEVENE POWDER FOR INFUSION

Patient Information Leaet

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Cymevene powder for infusion 500 mg
Ganciclovir

Please read all of this leaet carefully before you start having this medicine.

Taking other medicines

Keep this leaet. You may need to read it again. If you have any further questions, ask your doctor or nurse. If any of the side effects become serious or troublesome, or if you notice any side effects not listed in this leaet, please tell your doctor or nurse. In this leaet: 1. What Cymevene is and what it is used for 2. Before you are given Cymevene 3. How Cymevene will be given 4. Possible side effects 5. How Cymevene is stored 6. Further information

Please tell your doctor or nurse if you are taking or have recently taken any other medicines. This includes medicines that you buy without a prescription and herbal medicines. This is because Cymevene can affect the way some medicines work. Also some medicines can affect the way Cymevene works. In particular, tell your doctor or nurse if you are taking any of the following medicines: Probenecid (used to treat gout). Mycophenolate mofetil (used after an organ transplant). Zidovudine, didanosine, cidofovir or foscarnet (used to treat HIV). Imipenem-cilastatin, trimethoprim, pentamidine, ucytosine, amphotericin B or dapsone (antibiotics used to treat infections). Doxorubicin, vincristine, vinblastine or hydroxyurea (used to treat cancer).

1. What Cymevene is and what it is used for
Cymevene contains a medicine called ganciclovir. This belongs to a group of medicines called anti-virals. Cymevene is used to treat infections caused by a virus called cytomegalovirus (CMV). The virus can infect any part of the body. This includes the retina of the eye where it causes problems with eye sight. The virus can infect anyone. However, in people who have a poor immune system because of other diseases or medicines (people who are immunocompromised), it can lead to serious infections. Cymevene is also used to prevent cytomegalovirus (CMV) infection after an organ transplant.

Pregnancy and breast-feeding

You must not have Cymevene if you are pregnant or breast-feeding. Cymevene will damage an unborn baby. If you are a man and your partner is at an age where she could get pregnant, you must use condoms during your treatment with Cymevene and for 90 days after the end of treatment. If you are a woman at an age where you could get pregnant, you must use contraception (birth control) during your treatment. If you are not sure if you are protected (have adequate contraception), talk to your doctor or nurse before having Cymevene.

Driving and using machines

2. Before you are given Cymevene You must not be given Cymevene if:
You are allergic (hypersensitive) to ganciclovir (the only ingredient in Cymevene). You are allergic to similar medicines called anti-virals. These include valganciclovir, aciclovir and valaciclovir. You are pregnant or breast-feeding a baby. See the section on Pregnancy and breast-feeding. You must not be given Cymevene if any of the above apply to you. If you are not sure, talk to your doctor or nurse before having Cymevene.

Ganciclovir can make you feel dizzy, sleepy or confused. It can also cause ts and loss of co-ordination. If any of these happen to you, do not drive or use any tools or machines.

3. How Cymevene will be given
Cymevene will be given to you by a doctor or nurse. It will be given to you through a small tube into one of your veins (called an intravenous infusion). It usually takes one hour for the medicine to be given. The dose of Cymevene varies from one patient to another. It depends on your age, weight, how well your kidneys are working and what you need the medicine for. The doctor will work out how much to give you. How often you have Cymevene and how long you keep having it for also varies from one patient to another. You will usually start by having one infusion every 12 hours for up to 21 days. After that you may have one infusion a day. Your doctor will see how you respond to this medicine, you may need to have regular blood tests. If necessary your dose might be changed or your treatment stopped.

Take special care with Cymevene

Check with your doctor or nurse before having Cymevene if: You have low numbers of white blood cells, red blood cells or platelets in your blood. You have had blood problems in the past that have been caused by medicines. You are having radiotherapy, or have recently had it. You have kidney problems. You or your partner might become pregnant during treatment. See the section on Pregnancy and breast-feeding. If any of the above apply to you, or if you are not sure, talk to your doctor or nurse before you have Cymevene.
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If you are given more Cymevene than you should If you are given too much Cymevene you may get changes to your blood, problems with your liver or kidneys, stomach pain, being sick, diarrhoea, ts and shaking.
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This information is intended for medical or healthcare professionals only: INFORMATION FOR HEALTHCARE PROFESSIONALS
Cymevene powder for infusion 500 mg

Ganciclovir Please refer to the Summary of Product Characteristics for full prescribing information.

Posology and method of administration
For intravenous infusion following reconstitution with 10ml Water for Injections BP. Based on patient weight the appropriate calculated dose volume should be removed from the vial (ganciclovir concentration 50mg/ml) and added to an acceptable infusion uid (typically 100ml) for delivery over the course of 1 hour. Infusion concentrations greater than 10mg/ml are not recommended. (For further information see Instructions for use/handling and disposal). Adults Treatment of CMV infection Initial (induction) treatment: 5mg/kg infused at a constant rate over 1 hour every 12 hours (10mg/kg/day) for 14 to 21 days. Long-term (maintenance) treatment: For immunocompromised patients at risk of relapse of CMV retinitis a course of maintenance therapy may be given. Intravenous infusion of 6mg/kg once daily 5 days per week, or 5mg/kg once daily 7 days per week is recommended. Treatment of disease progression: Indenite treatment may be required in patients with AIDS, but even with continued maintenance treatment, patients may have progression of retinitis. Any patient in whom the retinitis progresses, either while on maintenance treatment or because treatment with Cymevene has been withdrawn, may be re-treated using the induction treatment regimen. Prevention of CMV disease Induction regimen: 5mg/kg infused every 12 hours (10mg/kg/day) for 7 to 14 days. Maintenance regimen: Intravenous infusion of 6mg/kg once daily 5 days per week, or 5mg/kg once daily 7 days per week is recommended.

No studies on the efcacy or safety of Cymevene in elderly patients have been conducted. Since elderly individuals often have reduced renal function, Cymevene should be administered to elderly patients with special consideration for their renal status (see above).

Elderly patients

Paediatric patients

There has been limited clinical experience in treating patients under the age of 12 years. Reported adverse events were similar to those seen in adults.

However, the use of Cymevene in children warrants extreme caution due to the potential for long-term carcinogenicity and reproductive toxicity. The benets of treatment should outweigh the risks. Cymevene is not indicated for the treatment of congenital or neonatal CMV infections.
For less severe neutropenia or other cytopenias a reduction in the total daily dose should be considered. Cell counts usually normalise within 3 to 7 days after discontinuing the drug or decreasing the dose. As evidence of marrow recovery becomes apparent gradual increases in dose, with careful monitoring of white blood cell counts, may be appropriate.

Dosage reductions

Patients with severe leucopenia, neutropenia, anaemia, thrombocytopenia and pancytopenia

Severe leucopenia, neutropenia, anaemia, thrombocytopenia, pancytopenia, bone marrow depression and aplastic anaemia have been observed in patients treated with Cymevene. Therapy should not be initiated if the absolute neutrophil count is less than 500 cells/L, or the platelet count is less than 25000/L, or the haemoglobin level is less than 8g/dL. Cymevene should be used with caution in patients with pre-existing haematological cytopenia or a history of drug-related haematological cytopenia and in patients receiving radiotherapy. If there is a signicant deterioration of blood cell counts during therapy with Cymevene, treatment with haematopoetic growth factors and/or dose interruption should be considered.

Special dosage instructions Patients with renal impairment:
Serum creatinine levels or creatinine clearance should be monitored carefully. Dosage adjustment is required according to creatinine clearance as shown in the table below. An estimated creatinine clearance (ml/min) can be related to serum creatinine by the following formulae: (140 age [years]) For males = x (body weight [kg]) (72) x (0.011 x serum creatinine [micromol/L]) For females = 0.85 x male value

Method of administration

Cymevene is a powder for solution for intravenous infusion. For directions on the preparation of the infusion solution, see Instructions for use/handling, and disposal. Cymevene must only be given by intravenous infusion, preferably via a plastic cannula, into a vein with adequate blood ow. Caution - do not administer by rapid or bolus i.v. injection! The toxicity of Cymevene may be increased as a result of excessive plasma levels. Caution - i.m. or s.c. injection may result in severe tissue irritation due to the high pH (~11) of ganciclovir solutions. The recommended dosage, frequency, or infusion rates should not be exceeded.

CrCl
70 ml/min 50 69 ml/min 25 49 ml/min 10 24 ml/min < 10 ml/min

Induction dose of ganciclovir
5.0mg/kg every 12 hours 2.5mg/kg every 12 hours 2.5mg/kg/day 1.25mg/kg/day 1.25mg/kg/day after haemodialysis
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If you think you have been given too much Cymevene, tell your doctor or nurse. If you have any further questions on the use of this medicine, ask your doctor or nurse.

Feeling tired, unwell or weak, high temperature (fever), shivering, weight loss. A reaction where Cymevene was given into your vein.

Uncommon (affect less than 1 in 100 people)

4. Possible side effects
Like all medicines, Cymevene can cause side effects, although not everyone will get them. Allergic reactions (uncommon, affect less than 1 in 100 people) If you have an allergic reaction, tell a doctor straight away. The signs may include: A raised itchy skin rash (hives). Difculty breathing or swallowing caused by sudden swelling of the throat, face, lips and mouth. Sudden swelling of the hands, feet and ankles.

Other possible side effects: Very common (affect more than 1 in 10 people)

Low numbers of one type of white blood cell (called neutrophils). The signs include infections of the mouth, gums, throat and lungs. Your doctor may want you to have blood tests. Low numbers of red blood cells (anaemia). The signs include feeling tired, pale skin, palpitations (a uttering sensation in the heart) and being short of breath. Difculty breathing. Diarrhoea.

Changes to your bone marrow (which may affect how your body produces some blood cells). Disturbances of the mind, including feeling agitated and losing contact with reality. Shaking or trembling that you cannot control. Infection of the eye (conjunctivitis). Deafness. Uneven heart beat. Low blood pressure. The signs include feeling dizzy or light-headed. Mouth ulcers, swelling of the abdomen (tummy) and pancreatitis. The signs of pancreatitis include severe pain in the stomach which spreads to your back. Loss of hair and dry skin. Serious kidney disease. Blood in your urine (water). Infertility in men. Cymevene may stop men from producing sperm. This can be temporary or permanent. If any of the side effects become serious or troublesome, or if you notice any side effects not listed in this leaet, please tell your doctor or nurse.

5. How Cymevene is stored
Your doctor or pharmacist are responsible for storing Cymevene. They are also responsible for disposing of any unused Cymevene correctly. Keep out of the reach and sight of children. Do not store Cymevene above 30C. Do not use Cymevene after the expiry date printed on the pack.

Common (affect less than 1 in 10 people)





Infections of the blood, skin, urinary tract and mouth. The signs include high temperature (fever), chills, feeling tired, redness and swelling of the skin, pain on passing water and creamy white spots in the mouth. Low numbers of all types of white blood cells. The signs include infections of the mouth, gums, throat and lungs. Low numbers of platelets in your blood. The signs include bruising easily and nose bleeds. Low numbers of all the types of cells in your blood. The signs include feeling tired, bruising easily, being short of breath and nose bleeds. Loss of appetite. Depression, anxiety, feelings of confusion and abnormal thinking. Headache. Difculty in sleeping. Changes to the way things taste. Dizziness. Fits (convulsions). Changes in your skin sensitivity (such as numbness, pins and needles, burning sensations). Changes to your eye-sight (vision), loss of vision or eye pain. Pain in your ears. A cough. Feeling or being sick, pain in your stomach, constipation, wind and difculty swallowing. Problems with your liver, shown in a blood test. Skin rashes (including inammation, redness and blistering), itchiness and sweating at night. Pain in your back, joints, muscles or chest or muscle cramps. Problems with your kidneys. This may affect the amount of water (urine) that you pass.

6. Further information What Cymevene contains
The active substance in Cymevene powder for infusion is ganciclovir. Each glass vial contains 500 mg (milligrams) ganciclovir as ganciclovir sodium 543 mg. Sodium content per vial is 43 mg. There are no other ingredients in Cymevene.

What Cymevene looks like and contents of the pack

Cymevene is a powder, supplied in a glass vial. Before it is given, Cymevene is made into a solution by adding sterile water to the vial. The correct dose is then taken out of the vial and added to the bag of infusion solution to be given to the patient. Vials of Cymevene are supplied in packs of 5 or 25. Not all packs may be marketed.

Marketing Authorisation Holder and Manufacturer:
Roche Products Limited 6 Falcon Way Shire Park Welwyn Garden City, AL7 1TW United Kingdom.

This leaet was last approved in 09/2010

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Instructions for use/handling and disposal Caution should be exercised in the handling of Cymevene.

Since Cymevene is considered a potential teratogen and carcinogen in humans, caution should be exercised in its handling. Avoid inhalation or direct contact of the powder contained in the vials or direct contact of the reconstituted solution with the skin or mucous membranes. Cymevene solutions are alkaline (pH approximately 11). If such contact occurs, wash thoroughly with soap and water, rinse eyes thoroughly with sterile water, or plain water if sterile water is unavailable.

Method of Preparation of Cymevene solution
1. Lyophilized Cymevene should be reconstituted by injecting 10ml of sterile Water for Injections into the vial. Do not use bacteriostatic water for injection containing parabens (para-hydroxybenzoates), since these are incompatible with Cymevene sterile powder and may cause precipitation. 2. The vial should be shaken to dissolve the drug. 3. Reconstituted solution should be inspected for particulate matter prior to proceeding with the admixture preparation. 4. Reconstituted solution in the vial is stable at room temperature for 12 hours. It should not be refrigerated.

Based on patient weight the appropriate calculated dose volume should be removed from the Cymevene vial (concentration 50mg/ml) and added to an acceptable infusion uid. Normal saline, dextrose 5% in water, Ringers or lactated Ringers solution are determined chemically or physically compatible with Cymevene. Infusion concentrations greater than 10mg/ml are not recommended. Cymevene should not be mixed with other iv products. Because Cymevene is reconstituted with nonbacteriostatic sterile water, the infusion solution should be used as soon as possible and within 24 hours of dilution in order to reduce the risk of bacterial contamination. The infusion solution should be refrigerated. Freezing is not recommended. Any unused product or waste material should be disposed of in accordance with local requirements.

Preparation and administration of infusion solution

This leaet was last approved in 09/2010

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10120155 GB 1004.1077