Summary of Product Characteristics: Information for the User

Cidofovir Zentiva 75 mg/ml Concentrate for Solution for Infusion EFG

This medicine is subject to additional monitoring, which will speed up the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this leaflet carefully before you start using this medicine,because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you must 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 leaflet. See section 4.

Cidofovir is used to treat an eye infection called cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS).Cidofovir will not cure your CMV retinitis, but it may improve your condition by delaying the progression of the disease.

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

Cidofovir 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 called cytomegalovirus (CMV). The CMV attacks the retina of the eye and may eventually lead to vision loss, and may ultimately result in blindness. Patients with AIDS are at a high risk of developing CMV retinitis or other forms of CMV disease, such as colitis (inflammatory intestinal disease). Treatment of CMV retinitis is necessary to reduce the risk of blindness.

Cidofovir is an antiviral medication that blocks CMV replication by interfering with viral DNA production.

No use Cidofovir Zentiva

If any of these things apply to you, talk to your doctor.You should not be given cidofovir.

Warnings and precautions

Consult your doctor,pharmacist or nurse before starting to use cidofovir.

• •The main side effect of treatment with cidofovir is kidney damage. Your doctor may need to keep a close eye on you, especially if you already have kidney problems or are on haemodialysis.
• • If you have diabetes mellitus.Cidofovir should be used with caution in diabetic patients due to the potential increased risk of developing low eye pressure(hypotony).

During treatment with cidofovir, you must have your eyes checked frequently,due to possible eye irritation, inflammation or swelling. Inform your doctor immediately if you notice eye pain, redness or itching, or changes in your vision.

Cidofovir caused a reduction in testicular weight and low sperm count(oligospermia)in animals. Although this has not been observed in human studies with cidofovir, it is possible that such changes may occur and cause infertility in humans.Males should use barrier contraceptive methods during and for 3 months after treatment with cidofovir.

Cidofovir is not used to treat HIV infection. Cidofovir will not prevent you from passing HIV to others, soyou should continue to take precautions to avoid infecting others.

Children

Cidofovir has not been studied in children. Therefore,it is not recommended for use in children.

Other medicines and Cidofovir Zentiva

Inform your doctor or pharmacist if you are using, have used recently or may need to use any other medicine, including those obtained without a prescription, as these may interact with cidofovir or probenecid.

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

This includes:

These medicines should be stoppedat least 7 daysbefore taking cidofovir.

Probenecid may interact with other medicines used frequently in the treatment of AIDS and related diseases, such as zidovudine (AZT). If you are taking zidovudine, you should talk to your doctor about stopping zidovudine or reducing your dose by 50% on the days when you are given cidofovir and probenecid.

The potential interactions between cidofovir and HIV protease inhibitors have not been studied.

Use of Cidofovir Zentiva with food and drinks

You should eat foodbefore you are given cidofovir. Your doctor may instruct you to drink plenty of fluids before receiving cidofovir.

Pregnancy and breastfeeding

You should not be given cidofovir if you are pregnant.If you become pregnant while receiving this medicine, you should inform your doctor immediately. Cidofovir has been shown to cause damage to unborn animals and should not be used during pregnancy unless the potential benefits justify the potential risks to the fetus.

Women of childbearing age should use effective contraceptive methodsduring treatment with cidofovir and for 6 months after treatment is completed.

Males should use effective contraceptive methods and not father a childwhile they are being treated with cidofovir and for 3 months after treatment is completed.

You should not be given cidofovir if you are breastfeeding.Cidofovir is not known to pass into breast milk. However, many medicines are excreted in breast milk, so mothers who are breastfeeding should stop cidofovir or stop breastfeeding if they continue to receive cidofovir.

Women with HIV should not breastfeedto avoid passing HIV to their baby through breast milk.

Driving and operating machinery

Cidofovir may cause short-term side effects, such as fatigue or weakness. If you drive or operate machinery, you should talk to your doctor about whether you should stop these activities based on your illness and your tolerance to the medicine.

Cidofovir 75 mg/ml concentrate for infusion solution EFG contains sodium

Patients on a low-sodium diet should note that this medicine contains 2.5 mmol (or 57 mg) of sodium per vial.

Cidofovir 75 mg/ml concentrated solution for infusion EFG is administered via intravenous infusion (drip in a vein). It should not be administered by other methods, including intraocular injection (direct injection into the eye), or topically (on the skin). Cidofovir should be given by a doctor or nurse with adequate experience in treating patients with AIDS.

The doctor or nurse will transfer the appropriate dose of cidofovir from the vial to an infusion bag containing 100 ml of sodium chloride 9 mg/ml (0.9%) infusion solution. The total volume of the bag will be pre-filled into your vein at a constant rate, over a period of 1 hour using a standard infusion pump. The recommended dose, frequency of use, and infusion rate should not be exceeded. Additional information for healthcare professionals on how to administer cidofovir is provided at the end of this leaflet.

To reduce the risk of renal damage, probenecid tablets and intravenous fluids (sodium chloride 9 mg/ml (0.9%) infusion solution) should be given on the day of each cidofovir infusion. (See below the subheadings “Taking probenecid with cidofovir” and “How IV fluids are given before cidofovir”).

Dosage in adults

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

Induction treatment (initiation)

The recommended dose of cidofovir in patients with normal renal function is 5 mg per kg of body weight given once a week for two consecutive weeks.

Maintenance treatment

Starting two weeks after completing the induction treatment, the recommended maintenance dose of cidofovir in patients with normal renal function is 5 mg per kg of body weight given once every two weeks.

Dose adjustment

If you have kidney problems, cidofovir may not be the appropriate treatment for you. Urine and/or blood samples will be taken before each administration of cidofovir, and used to monitor your renal function. In the case of patients with evidence of reduced renal function, your treatment with cidofovir may be interrupted or suspended, depending on your individual case.

If you take more cidofovir than you should

If you have been given accidentally more cidofovir than prescribed, inform your doctor immediately.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

How to take probenecid with cidofovir

Probenecid tablets are given to reduce the risk of renal damage.You should take 3 doses of probenecid tablets orally on the same day as cidofovir, as indicated in the following table:

Probenecid is taken only on the same day as cidofovir.

How IV fluids are given before cidofovir

Sodium chloride 9 mg/ml (0.9%) infusion solution is given to reduce the risk of renal damage.You should receive a total of 1 liter of sodium chloride 9 mg/ml (0.9%) infusion solution intravenously (drip in vein) before each dose of cidofovir. Sodium chloride 9 mg/ml (0.9%) infusion solution should be administered by infusion over a period of 1 hour, immediately before the infusion of cidofovir. If you can tolerate the additional fluid load, your doctor may administer a second liter of fluids. If administered, the second liter of sodium chloride 9 mg/ml (0.9%) infusion solution should be administered by infusion over a period of 1 to 3 hours, starting or at the beginning of the infusion of cidofovir, or immediately after. Your doctor will also instruct you to drink plenty of fluids.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

These side effects usually disappear when treatment with cidofovir is discontinued.If you consider any of the side effects you are experiencing to be severe or if you notice any side effect not mentioned in this leaflet, inform your doctor or pharmacist immediately.

The most frequently observed side effect with cidofovir is kidney damage.

Frequent side effects

(May affect more than 1 in 10 patients)

Low white blood cell count, headache, nausea, vomiting, protein in the urine, increased creatinine in the blood (a measure of renal function), hair loss, rash, weakness/fatigue, and fever.

Frequent side effects

(May affect between 1 and 10 in 100 patients)

Eye inflammation, reduced eye pressure, respiratory difficulty or labored breathing, shortness of breath, diarrhea, and chills.

Any eye pain, redness, itching, or changes in vision should be immediately reported to your doctor for review of treatment.

Additional adverse reactions have been observed during the post-marketing period, including renal insufficiency, renal tubular cell damage, pancreatitis, and auditory alterations.

Possible side effects of probenecid

Frequent side effects possibly related to probenecid

(May affect more than 1 in 10 patients)

Nausea, vomiting, rash, and fever.

Frequent side effects possibly related to probenecid

(May affect between 1 and 10 in 100 patients)

Headache, weakness/fatigue, chills, and allergic reactions.

You should take food before each dose to reduce the risk of nausea and/or vomiting associated with probenecid intake. Your doctor may advise the use of antiemetics (medicines to prevent vomiting), antihistamines, and/or paracetamol to reduce the side effects of probenecid.

Probenecid may cause other side effects, including loss of appetite, gum pain, redness, hair loss, dizziness, low red blood cell count, and increased frequency of urination. Allergic reactions are characterized by skin inflammation, itching, urticaria, and, rarely, severe allergic reactions and severe skin reactions. Cases of reduced white blood cell count, liver toxicity, renal toxicity, and red blood cell destruction have been reported. Additionally, a reduction in blood cells and platelets has been observed.

Therefore, before giving probenecid, your doctor should consult the available information on the safety of probenecid.You should also read the probenecid leaflet.

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 not mentioned in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: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.

Do not use this medication after the expiration date that appears on the packaging, after CAD.

Do not store at a temperature above 25°C. Do not refrigerate or freeze.

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Cidofovir Zentiva 75 mg/ml Concentrate for Solution for Infusion EFG

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

The other components are sodium hydroxide, hydrochloric acid, and water for injection.

Appearance of the product and contents of the pack

Cidofovir is supplied as a sterile concentrate for solution for infusion, in transparent glass vials containing 375 mg of the active substance, anhydrous cidofovir, formulated in 5 ml of water for injection at a concentration of 75 mg/ml. The pH of the formula has been adjusted with sodium hydroxide (and hydrochloric acid if necessary) and does not contain preservatives.

Marketing Authorization Holder and Responsible Person for Manufacturing

Marketing Authorization Holder:

Zentiva k.s.,

U kabelovny 130,

Dolní Mecholupy,

102 37 Prague 10

Czech Republic

Responsible Person for Manufacturing:

MIAS Pharma Limited

Suite 2, Stafford House, Strand Road

Portmarnock, Co. Dublin

Ireland

or

Tillomed Malta Limited,

Malta Life Sciences Park,

LS2.01.06 Industrial Estate,

San Gwann, SGN 3000, Malta

Further information on this medicinal product can be obtained by contacting the local representative of the Marketing Authorization Holder:

Zentiva Spain S.L.U.

Avenida de Europa, 19, Edificio 3, Planta 1.

28224 Pozuelo de Alarcón, Madrid

Spain

This medicinal product is authorized in the Member States of the European Economic Area with the following names:

Date of the last revision of this leaflet: March 2022.

This information is intended solely for healthcare professionals:

The vials of cidofovir should be visually examined before use. If visible particles or discoloration are observed, the vial should not be used.

It is recommended to adopt the necessary precautions, including the use of appropriate safety equipment, for the preparation, administration, and disposal of cidofovir. The preparation of the cidofovir diluted solution should be performed in a biological safety cabinet with laminar flow. The personnel responsible for preparing the solution should wear surgical gloves, safety glasses, and a closed-front surgical gown with cuffs. If cidofovir comes into contact with the skin, it should be washed and rinsed with abundant water.

The appropriate dose of cidofovir should be transferred from the vial to the infusion bag containing 100 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion. The total volume of the bag should be infused intravenously 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, and infusion rate should not be exceeded.

The chemical stability of cidofovir mixtures with sodium chloride 9 mg/ml (0.9%) solution for infusion has been demonstrated in glass bottles, in infusion bags made of chlorinated polyvinyl chloride (PVC) or copolymer propylene/ethylene, and in intravenous administration equipment made of PVC. Other types of IV tubes and infusion bags have not been studied.

The compatibility with Ringer's solution, lactated Ringer's solution, or bacteriostatic infusion liquids has not been evaluated.

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

The physical and chemical stability of the diluted solution has been demonstrated for 24 hours between 2 – 8°C when the dilution is performed in controlled and validated aseptic conditions.The diluted solution should not be stored for more than 24 hours or frozen. Refrigerated infusion bags should be allowed to come to room temperature before use.

Cidofovir is supplied in single-use vials. Partially used vials should be discarded.