PACKAGE LEAFLET: INFORMATION FOR THE USER

Vistide 75 mg/ml concentrate for solution for infusion

Cidofovir

Read all of this leaflet carefully before you start using this medicine.

• Keep this leaflet. You may need to read it again.

• If you have any further questions, ask your doctor or pharmacist.

• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1. What Vistide is and what it is used for

2. Before you use Vistide

3. How to use Vistide

4. Possible side effects

5. How to store Vistide

6. Further information

1. What Vistide is and what it is used for

   
   

   Medicinal product no longer authorised

   Vistide is used to treat an eye infection called CMV retinitis in patients with AIDS (Acquired Immunodeficiency Syndrome). Vistide will not cure CMV retinitis but may improve your condition by delaying progression of the disease.

   
   

   The safety and efficacy of Vistide has not been demonstrated in diseases other than CMV retinitis in patients with AIDS.

   
   

   Vistide must be administered by a healthcare professional (doctor or nurse) in a hospital setting.

   
   

   What is CMV retinitis?

   
   

   CMV retinitis is an eye infection caused by a virus named cytomegalovirus (CMV). CMV attacks the retina of the eye and may cause loss of vision, and eventually lead to blindness. Patients with AIDS are at high risk of developing CMV retinitis or other forms of CMV disease such as colitis (an inflammatory bowel disease). Treatment for CMV retinitis is necessary to reduce the potential for blindness.

   
   

   Vistide is an antiviral medicine which blocks the replication of CMV by interfering with viral DNA production.

   
   

2. Before you use Vistide Do not use Vistide

   • If you are allergic (hypersensitive) to cidofovir or any of the other ingredients of Vistide.

   • If you have ever had kidney disease.

   • If you cannot take the medicine probenecid because of a serious allergy to probenecid or other sulfa-containing medicines (e.g. sulfamethoxazole).

     
     

     If any of these apply to you, talk to your doctor. You are not to be given Vistide.

     Take special care with Vistide

     
     

   • Kidney damage is the major side effect of Vistide treatment. To reduce the risk of kidney damage, you will receive intravenous fluids (normal saline) before each dose of Vistide and probenecid tablets before and after each dose of Vistide (see section 3 below for more information). Your doctor may also instruct you to drink plenty of fluids. Your doctor will monitor your kidney function before each dose of Vistide. Your treatment with Vistide may be stopped by your doctor if changes in kidney function occur.

     
     

   • Tell your doctor if you have diabetes mellitus. Vistide should be used with caution in diabetic patients due to the potential increased risk of developing low pressure in the eye (ocular hypotony).

     
     

   • During treatment with Vistide you should receive regular follow-up eye examinations for possible eye irritation, inflammation or swelling. If you get pain, redness or itching of the eye or changes in your vision, tell your doctor promptly.

     
     

   • Vistide caused reduced testes weight and low sperm count (hypospermia) in animals. Although not observed in human studies of Vistide, such changes may occur in humans and cause infertility. Men should practice barrier birth control methods during and for 3 months after treatment with Vistide.

     
     

   • Vistide is not used for the treatment of HIV infection. Vistide will not stop you passing HIV infection onto other people so you should continue to take precautions to avoid infecting others.

     
     

     Medicinal product no longer authorised

     Use in children

     
     

     Vistide has not been studied in children. Therefore, this medicine should not be used in children. Using other medicines

   • Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription, as these may interact with Vistide or probenecid.

     
     

     It is very important to tell your doctor if you are receiving other medicines that may damage your kidneys.

     
     

     These include:

   • tenofovir containing medicines, used to treat HIV-1 infection and/or chronic hepatitis B infection

   • aminoglycosides, pentamidine or vancomycin (for bacterial infections)

   • amphotericin B (for fungal infection)

   • foscarnet (for viral infection)

   • adefovir (for HBV infection)

     
     

     These medicines must be stopped at least 7 days before taking Vistide.

     
     

   • Probenecid may interact with other medicines commonly used in the treatment of AIDS and AIDS-related illnesses, such as zidovudine (AZT). If you are taking zidovudine, you should discuss with your doctor whether to temporarily stop taking zidovudine or decrease the dose of zidovudine by 50% on days when Vistide and probenecid are given.

     
     

   • The potential for interactions between Vistide and anti-HIV protease inhibitors has not been studied.

     Using Vistide with food and drink

     
     

     Food should be taken before you are given Vistide. Your doctor may instruct you to drink plenty of fluids before receiving Vistide.

     
     

     Pregnancy and breast-feeding

     
     

   • You should not be given Vistide if you are pregnant. If you become pregnant while receiving this medication, you must inform your doctor immediately. Vistide has been shown to cause damage in unborn animals and should not be used during pregnancy unless the potential benefits justify the risks to the foetus. If you could get pregnant, you must use an effective method of contraception to stop you getting pregnant during treatment with Vistide and for 1 month afterwards.

     
     

   • You should not be given Vistide if you are breast-feeding. It is not known whether Vistide is passed on to the baby in human milk. Because many medicines are passed through to human milk, nursing mothers should stop Vistide or stop breast-feeding if they continue to receive Vistide.

     
     

   • In general, women with HIV should not breast-feed in order to avoid passing HIV to their infant through the milk.

     
     

     Driving and using machines

     
     

     Medicinal product no longer authorised

     Vistide may cause short-term side effects such as fatigue or weakness. If you drive or operate machinery, discuss this with your doctor to get their advice about stopping these activities based upon your disease and your tolerance of the medicine.

     
     

     Important information about some of the ingredients of Vistide

     
     

     This medicine contains 2.5 mmol (or 57 mg) sodium per vial which should be taken into consideration if you are on a controlled sodium diet.

     
     

3. How to use Vistide

   
   

   Vistide is given by intravenous infusion (a drip into a vein). It must not be administered by other methods including intraocular injection (direct injection into the eye) or topically (on the skin). Vistide must be given by a doctor or nurse with appropriate experience in treating people with AIDS.

   
   

   The doctor or nurse will transfer the appropriate dose of Vistide from the vial to an infusion bag containing 100 ml 0.9% (normal) saline solution. The entire volume of the bag will be infused into your vein at a constant rate over a period of 1 hour using a standard infusion pump. The recommended dose, frequency of use, or rate of infusion must not be exceeded. At the end of this leaflet, there is further information for healthcare professionals on how to administer Vistide.

   
   

   To lower the risk of kidney damage, probenecid tablets and intravenous fluids (saline solution) must be given on the day of each Vistide infusion. (See sub-sections “How to take probenecid with Vistide” and “How IV fluids are given before Vistide” below.)

   Dose in adults

   
   

   The dose you will need is calculated based on your body weight.

   
   

   Starting (induction) treatment

   The recommended dose of Vistide in patients with normal kidney function is 5 mg per kg of body weight given once weekly for two consecutive weeks.

   
   

   Maintenance treatment

   Beginning two weeks after completion of induction treatment, the recommended maintenance dose of Vistide in patients with normal kidney function is 5 mg per kg of body weight given once every two weeks.

   
   

   Dose adjustment

   If you have kidney problems, Vistide may not be appropriate treatment for you. Samples of your urine and/or blood will be taken before each infusion of Vistide and used for testing kidney function. For patients with evidence of decreased kidney function, your Vistide dose may be interrupted or stopped depending on your individual case.

   
   

   If you have accidentally been given more Vistide than prescribed for you, tell your doctor immediately.

   
   

   How to take probenecid with Vistide

   
   

   Medicinal product no longer authorised

   Probenecid tablets are given to lower the risk of kidney damage. You must take 3 doses of probenecid tablets orally on the same day as Vistide as shown in the following table:

   
   

   Time	Dose
   3 hours before start of Vistide infusion	2 g probenecid
   2 hours after end of Vistide infusion	1 g probenecid
   8 hours after end of Vistide infusion	1 g probenecid
   Total	4 g probenecid

   
   

   Probenecid is only taken on the same day that Vistide is given.

   
   

   How IV fluids are given before Vistide

   
   

   Normal saline is given to lower the risk of kidney damage. You should receive a total of one litre of 0.9% (normal) saline solution intravenously (as a drip into a vein) before each Vistide dose. The saline solution should be infused over a 1 hour period immediately before the Vistide infusion. If you can tolerate the additional fluid load, your doctor may administer a second litre of fluid. If administered, the second litre of saline should be given either at the start of the Vistide infusion or immediately afterwards, and infused over a 1 to 3 hour period. Your doctor may also tell you to drink plenty of fluids.

   
   

   If you have any further questions on the use of this product, ask your doctor or pharmacist.

   
   

4. Possible side effects

   
   

   Like all medicines, Vistide can cause side effects, although not everybody gets them.

   
   

   These side effects usually disappear when treatment with Vistide is stopped. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist immediately.

   The most common side effect observed with Vistide is damage to the kidneys.

   
   

   Very common side effects

   (These can affect more than 1 user in 10)

   • low white blood cell counts, headache, nausea, vomiting, protein in the urine, increase in blood creatinine (a measure of kidney function), hair loss, rash, weakness/fatigue and fever.

     
     

     Common side effects

     (These can affect 1 to 10 users in 100)

   • inflammation of the eye, reduced pressure in the eyes, difficult or laboured breathing, shortness of breath, diarrhoea and chills.

     
     

     Any pain, redness or itching of the eye or changes in your vision should be promptly reported to your doctor so that your treatment can be reviewed.

     
     

     Additional reactions reported from post-marketing experience include kidney failure, damage to kidney tubule cells, inflammation of the pancreas and hearing impairment.

     
     

     Possible side effects of taking probenecid

     
     

     Very common side effects possibly related to probenecid

     (These can affect more than 1 user in 10)

   • nausea, vomiting, rash and fever.

     
     

     Common side effects possibly related to probenecid

     (These can affect 1 to 10 users in 100)

     Medicinal product no longer authorised

   • headache, weakness/fatigue, chills and allergic reactions.

     
     

     To reduce the risk of nausea and/or vomiting associated with taking probenecid, you should eat food before each dose. Your doctor might instruct you to take other medicines such as anti-emetics (anti sickness medicines), antihistamines and/or paracetamol to decrease the side effects of probenecid.

     
     

     Probenecid may also cause other side effects including loss of appetite, sore gums, flushing, hair loss, dizziness, reduced red blood cell count and increased frequency of passing water (urinating). Allergic reactions, with skin inflammation, itching, hives and, rarely, severe allergic reactions, and serious skin reaction have occurred. There have been reports of reduced white blood counts, liver toxicity, kidney toxicity and destruction of red blood cells. Reductions in blood cell and platelet counts have also occurred.

     
     

     Therefore before giving you probenecid your doctor should consult the current prescribing information regarding the safety of probenecid. You should also read the probenecid package leaflet.

     
     

5. How to store Vistide

   
   

   Keep out of the reach and sight of children.

   
   

   Do not use Vistide after the expiry date which is stated on the label. Do not store above 30°C. Do not refrigerate or freeze.

   Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Further information What Vistide contains

The active substance of Vistide 75 mg/ml is cidofovir. Each ml contains 75 mg cidofovir anhydrous. Each vial contains 375 mg/5 ml cidofovir anhydrous.

The other ingredients are

• Sodium hydroxide

• Hydrochloric acid

• Water for injections

What Vistide looks like and contents of the pack

Vistide is supplied as a sterile concentrate for solution for infusion in clear, glass vials containing 375 mg of the active ingredient, anhydrous cidofovir, formulated in 5 ml water for injections at a

concentration of 75 mg/ml. The formulation is pH-adjusted with sodium hydroxide (and hydrochloric acid if needed) and contains no preservatives.

Marketing Authorisation Holder Gilead Sciences International Limited Cambridge

CB21 6GT

United Kingdom

Manufacturer

Medicinal product no longer authorised

Gilead Sciences Limited

IDA Business & Technology Park Carrigtohill Co. Cork

Ireland

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien

Gilead Sciences Belgium BVBA Tél/Tel: + 32 (0) 24 01 35 79

Luxembourg/Luxemburg Gilead Sciences Belgium BVBA Tél/Tel: + 32 (0) 24 01 35 79

България

Gilead Sciences International Ltd

Тел.: + 44 (0) 20 7136 8820

Magyarország

Gilead Sciences International Ltd Tel: + 44 (0) 20 7136 8820

Česká republika

Gilead Sciences International Ltd Tel: + 44 (0) 20 7136 8820

Malta

Gilead Sciences International Ltd Tel: + 44 (0) 20 7136 8820

Danmark

Gilead Sciences Sweden AB Tlf: + 46 (0) 8 5057 1849

Nederland

Gilead Sciences Netherlands B.V. Tel: + 31 (0) 20 718 3698

Deutschland

Gilead Sciences GmbH Tel: + 49 (0) 89 899890-0

Norge

Gilead Sciences Sweden AB Tlf: + 46 (0) 8 5057 1849

Eesti

Gilead Sciences Sweden AB Tel: + 46 (0) 8 5057 1849

Österreich

Gilead Sciences GesmbH Tel: + 43 1 260 830

Ελλάδα

Gilead Sciences Ελλάς Μ.ΕΠΕ. Τηλ: + 30 210 8930 100

Polska

Gilead Sciences Poland Sp. z o. o. Tel: + 48 22 262 8702

España

Gilead Sciences, S.L. Tel: + 34 91 378 98 30

Portugal

Gilead Sciences, Lda. Tel: + 351 21 7928790

France

Gilead Sciences

Tél: + 33 (0) 1 46 09 41 00

România

Gilead Sciences International Ltd Tel: + 44 (0) 20 7136 8820

Ireland

Gilead Sciences Ltd

Tel: + 44 (0) 1223 897555

Slovenija

Gilead Sciences International Ltd Tel: + 44 (0) 20 7136 8820

Ísland

Gilead Sciences Sweden AB Sími: + 46 (0) 8 5057 1849

Slovenská republika

Gilead Sciences International Ltd Tel: + 44 (0) 20 7136 8820

Italia

Gilead Sciences S.r.l. Tel: + 39 02 439201

Suomi/Finland

Gilead Sciences Sweden AB Puh/Tel: + 46 (0) 8 5057 1849

Κύπρος

Medicinal product no longer authorised

Gilead Sciences Ελλάς Μ.ΕΠΕ. Τηλ: + 30 210 8930 100

Sverige

Gilead Sciences Sweden AB Tel: + 46 (0) 8 5057 1849

Latvija

Gilead Sciences Sweden AB Tel: + 46 (0) 8 5057 1849

United Kingdom

Gilead Sciences Ltd

Tel: + 44 (0) 1223 897555

Lietuva

Gilead Sciences Sweden AB Tel: + 46 (0) 8 5057 1849

This leaflet was last approved in

The following information is intended for medical or healthcare professionals only:

Vistide vials should be inspected visually prior to use. If visible particles or discolouration are observed, the vial should not be used.

Adequate precautions including the use of appropriate safety equipment are recommended for the preparation, administration and disposal of Vistide. The preparation of Vistide diluted solution should be done in a laminar flow biological safety cabinet. Personnel preparing the solution should wear

surgical gloves, safety glasses and a closed front surgical-type gown with knit cuffs. If Vistide contacts the skin, wash membranes and flush thoroughly with water.

The appropriate dose of Vistide should be transferred from the vial to an infusion bag containing 100 ml 0.9% (normal) saline solution. The entire volume of the bag should be infused into the patient’s vein at a constant rate over a period of 1 hour using a standard infusion pump. The recommended dose, frequency of use, or rate of infusion must not be exceeded.

The chemical stability of Vistide mixed in saline solution has been demonstrated in glass bottles, in infusion bags composed of either polyvinyl chloride (PVC) composition or ethylene/propylene copolymer, and in PVC based vented IV administration sets. Other types of IV set tubing and infusion bags have not been studied.

Compatibility of Vistide with Ringer’s Solution, Lactated Ringer’s Solution or bacteriostatic infusion fluids has not been evaluated.

From a microbiological point of view, the product must be used immediately.

Chemical and physical in-use stability has been demonstrated for up to 24 hours at 2 - 8ºC when dilution is performed under controlled and validated aseptic conditions. Storage beyond 24 hours or freezing is not recommended. Refrigerated infusion bags should be allowed to warm to room temperature prior to use.

Medicinal product no longer authorised

Vistide is supplied in single-use vials. Partially used vials must be discarded.