FOSCAVIR 24 mg/ml SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Foscavir 24 mg/ml Solution for Infusion

Foscarnet Sodium Hexahydrate

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Foscavir 24 mg/ml Solution for Infusion and what is it used for
2. What you need to know before you use Foscavir 24 mg/ml Solution for Infusion
3. How to use Foscavir 24 mg/ml Solution for Infusion
4. Possible side effects
5. Storage of Foscavir 24 mg/ml Solution for Infusion
6. Contents of the pack and further information

1. What is Foscavir 24 mg/ml Solution for Infusion and what is it used for

The active substance foscarnet is an antiviral agent that works by inhibiting the multiplication of certain viruses.

Foscavir is used to treat the following infections caused by viruses:

• An eye infection (retinitis) or gastrointestinal infection caused by CMV virus in patients with HIV infection.

Foscavir is indicated for the treatment of induction and maintenance of the disease, although it cannot repair the damage caused.

• Skin or mucous membrane infections caused by the herpes simplex virus (HSV) that have not improved with acyclovir, in immunosuppressed patients (the immune system does not function properly).

• Viral infection caused by a virus, cytomegalovirus (CMV), after receiving a bone marrow transplant when other treatments have not been suitable.

2. What you need to know before you use Foscavir 24 mg/ml Solution for Infusion

Do not use Foscavir 24 mg/ml Solution for Infusion

• If you are allergic to foscarnet or any of the other ingredients of this medicine listed in section 6.

Warnings and Precautions

Consult your doctor or nurse before starting treatment with Foscavir 24 mg/ml Solution for Infusion

• If you have kidney problems, as analytical controls must be performed during treatment. Adequate hydration should be maintained in all patients.
• If you have heart problems.

Foscavir is eliminated in high concentrations in the urine and can cause significant genital irritation and/or ulcers. To avoid irritation and ulcers, it is recommended to maintain good personal hygiene and cleanliness of the genital area after urination.

Foscavir is deposited in teeth, bones, and cartilage. Animal data show that the deposit is greater in young animals. The safety of Foscavir and its effect on skeletal development have not been investigated in children.

The administration of the drug may be associated with a sudden reduction in calcium. For this reason, calcium and magnesium levels should be monitored before and during treatment with Foscavir to correct any deficiencies. Electrolyte and mineral concentrations in the blood should also be monitored periodically, especially calcium and magnesium.

Children and Adolescents

The safety and efficacy of Foscavir in children have not been established.

Other Medicines and Foscavir

Tell your doctor or pharmacist if you are using, have recently used, or might use other medicines, including those obtained without a prescription. Especially if you are taking aminoglycosides (a group of antibiotics); amphotericin B (for fungal infections); cyclosporin A, methotrexate, tacrolimus (immunosuppressants); acyclovir (antiviral); pentamidine (injections); quinidine, amiodarone, sotalol, or other medicines that may affect your heart rate and rhythm; tranquilizers (neuroleptics); as well as some protease inhibitors such as ritonavir and saquinavir.

Pregnancy and Breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

• Foscavir is not recommended during pregnancy.
• It is not recommended to try to become pregnant during therapy with Foscavir, and effective contraceptive methods should be used.
• Men being treated with Foscavir should not father a child during or up to 6 months after therapy.
• Do not take Foscavir if you are breastfeeding.

Driving and Using Machines

Foscavir may affect your ability to drive or use machines. Consult your doctor before performing any of these activities.

Foscavir Contains Sodium

The maximum daily recommended dose of this medicine contains 2.75 g of sodium (found in table salt). This is equivalent to 138% of the maximum daily recommended dietary intake of sodium in adults.

Consult your doctor or pharmacist if you need Foscavir daily for a prolonged period, especially if you have been advised to follow a low-salt diet (sodium).

3. How to Use Foscavir 24 mg/ml Solution for Infusion

Foscavir should be administered by a healthcare professional, intravenously.

Your doctor will calculate the correct amount of Foscavir for you, based on your body weight and blood test results.

Your doctor will follow the guidelines indicated below, depending on the infection, for the time deemed necessary.

If you are being treated for CMV retinitis, treatment will be carried out in two stages: induction and maintenance. Induction is the initial stage in which you will receive infusions lasting more than one hour, at intervals of 8 or 12 hours a day, for two or three weeks. Depending on how the virus responds, you may or may not proceed to the maintenance stage, in which you will receive infusions once a day. If the viral infection worsens at any time, induction treatment may be reinstated. Your doctor will indicate any necessary changes in infusion times, modifying the dose as needed, to increase the antiviral effect or reduce the risk of kidney damage.

If you are being treated for a CMV gastrointestinal infection, this treatment will be carried out in a single stage. The infusion will be administered at intervals of 12 hours for 2-4 weeks.

If you are being treated for skin or mucous membrane infections caused by the herpes simplex virus (HSV), this treatment will also be carried out in a single stage. The infusion will be administered at intervals of 8 hours for 2-3 weeks, or until cure.

If you are being treated after receiving a bone marrow transplant for a viral infection caused by CMV, treatment will be carried out in two stages: induction and maintenance. Induction is the initial stage in which you will receive infusions lasting more than one hour, at intervals of 12 hours a day, for two weeks. Depending on how the virus responds, you may or may not proceed to the maintenance stage, in which you will receive infusions 5 days a week for two weeks. If the viral infection worsens at any time, induction treatment may be reinstated. Your doctor will indicate any necessary changes in infusion times, modifying the dose as needed, to increase the antiviral effect or reduce the risk of kidney damage.

Hydration

The renal toxicity of this medicine can be reduced by adequate hydration. Your doctor will follow the most suitable guidelines for you.

Patients with Renal Impairment

Your doctor will take into account the degree of renal impairment to adjust the dose according to the table above. It is not recommended to use this medicine in patients undergoing hemodialysis.

Patients with Hepatic Impairment

No dose reduction is necessary for patients with hepatic insufficiency.

Elderly Patients

No dose adjustment is required.

If You Are Given Too Much Foscavir

Relative overdoses have occurred in some patients with kidney problems due to inadequate dose adjustment; however, note that in some cases, no clinical sequelae have occurred after this overdose.

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 medicine and the amount ingested.

Information for the Healthcare Professional

Hemodialysis increases the elimination of the medicine and may be beneficial in some cases.

4. Possible Side Effects

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

The side effects observed with Foscavir are:

Note: In these clinical trials, hydration or attention to electrolyte balance was not provided systematically, so the frequency of some adverse reactions may be lower when current recommendations are followed (see section 3).

Reporting of Side Effects

If you experience any side effects, talk to your doctor or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Foscavir 24 mg/ml Solution for Infusion

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

Before opening: Store at a temperature below 25°C. Do not store in the refrigerator.

If stored in the refrigerator or exposed to temperatures below the freezing point, it may precipitate. This precipitate can be redissolved by keeping the vial at room temperature and shaking repeatedly.

Before opening: Do not use this medicine after the expiry date stated on the vial. The expiry date is the last day of the month indicated.

After first opening: The solution must be used within 24 hours (does not contain preservatives).

From a microbiological point of view, the product should be used immediately. If not used immediately, the storage conditions and the time before use are the responsibility of the professional and should not exceed 24 hours, stored between 2 and 8°C, unless the reconstitution has taken place in controlled and validated aseptic conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Contents of the Pack and Further Information

Composition of Foscavir 24 mg/ml Solution for Infusion

• The active substance is foscarnet sodium hexahydrate. 1 ml of solution contains 24 mg of foscarnet sodium hexahydrate. See section 2 ‘Foscavir contains sodium’.
• The other ingredients are: hydrochloric acid (E507) and water for injections.

Appearance of the Product and Contents of the Pack

This medicine is a solution for infusion, which comes in a 250 ml vial.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Clinigen Healthcare B.V.

Schiphol Boulevard 359

WTC Schiphol Airport, D Tower 11th floor

1118BJ Schiphol

Netherlands

Manufacturer Responsible

Fresenius Kabi Austria GmbHHafnerstraße 36A-8055 GrazAustria

Date of the last revision of this prospectus:May 2023

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)

This information is intended solely for healthcare professionals:

INSTRUCTIONS FOR CORRECT ADMINISTRATION

Foscavir does not contain preservatives, and once the sterility seal is broken, the solution must be used within 24 hours.

From a microbiological point of view, the product must be used immediately. If it is not used immediately, the storage conditions and time before use are the responsibility of the professional and should not exceed 24 hours, stored between 2 and 8 ºC, unless the reconstitution has taken place in controlled and validated aseptic conditions. The individual doses of Foscavir to be dispensed can be transferred aseptically to infusion bags by hospital pharmacy services. The physical-chemical stability of Foscavir and its dilutions in equal parts with 9% sodium chloride (9 mg/ml) or 50 mg/ml glucose, in PVC bags, is 7 days.

Dosage

Adults

CMV retinitis in HIV patients

Induction treatment:Foscavir will be administered for 2-3 weeks, depending on the clinical response, in the form of intermittent infusions every 8 hours at a dose of 60 mg/kg or every 12 hours at a dose of 90 mg/kg in patients with normal renal function. The dose must be adjusted individually according to renal function (see Table of doses below). The duration of each infusion should not be less than 2 hours for the 90 mg/kg dose or 1 hour for the 60 mg/kg dose.

Maintenance treatment:In maintenance treatment, once the induction treatment of CMV retinitis is completed, Foscavir is administered 7 days a week for as long as considered appropriate. In patients with normal renal function, the dose is between 90 and 120 mg/kg, in the form of a single daily infusion of 2 hours duration. The dosage should be individualized according to the patient's renal function (see Table of doses below). It is recommended to start treatment with 90 mg/kg. The dose can be gradually increased up to 120 mg/kg in those patients who show good tolerance to the previous dose.

Patients who experience progression of retinitis during maintenance treatment may switch back to induction treatment or to a combined treatment of Foscavir and ganciclovir. Once stabilized, maintenance treatment with Foscavir or a combination of Foscavir and ganciclovir should be established.

Due to physical incompatibility, Foscavir and ganciclovir SHOULD NOT be mixed.

CMV infections in the upper and lower gastrointestinal tract in HIV patients

Treatment with Foscavir will be administered as intermittent infusions every 12 hours at a dose of 90 mg/kg in patients with normal renal function. Most patients will experience remission of their symptoms within 2 to 4 weeks. The dose should be individualized according to the patient's renal function (see Table of doses below). The infusion time should not be less than 2 hours.

Mucocutaneous HSV infections that do not respond to acyclovir

For induction treatment, Foscavir will be administered in the form of intermittent infusions for 1 hour at a dose of 40 mg/kg, every 8 hours, in patients with normal renal function. The dose must be adjusted individually according to renal function (see Table of doses below). The duration of each infusion should not be less than 1 hour.

The time to healing depends on the size of the initial lesion, and treatment with Foscavir should continue until complete re-epithelialization, usually 2-3 weeks. The clinical response to Foscavir should be evident after one week of treatment; treatment should be reconsidered in patients who do not respond within this time period.

The efficacy of maintenance therapy with Foscavir after induction treatment in HSV infections that do not respond to acyclovir has not been established. In the event of a relapse, the lack of response to acyclovir should be confirmed.

Preemptive treatment in high-risk patients and treatment of CMV infection in patients with TCMH

Induction treatment:a dose of 60 mg/kg is administered for 14 days in the form of intermittent infusion every 12 hours, in patients with normal renal function.

The dose must be adjusted individually according to renal function (see Table of doses below).

The duration of each infusion should not be less than 1 hour.

Maintenance treatment:once the induction treatment of CMV disease is completed, 90 mg/kg is administered, 5 days a week for 14 days in patients with normal renal function, in the form of a single daily infusion of 2 hours duration.

The dosage should be individualized according to the patient's renal function (see Table of doses below).

Patients who experience progression of the infection during maintenance therapy may switch back to induction treatment.

Table1Foscavir Dose Table

Induction treatment

Maintenance treatment

Hydration

Clinically dehydrated patients must correct their condition before starting treatment with Foscavir.

The renal toxicity of Foscavir can be reduced by adequate patient hydration. To achieve this, it is recommended to promote diuresis by hydrating with 0.5 - 1.0 liters of physiological serum before the first Foscavir infusion and subsequently adding 0.5 - 1.0 liters of physiological serum to each infusion. In collaborative patients, a similar hydration schedule can be used orally.

Patient with altered renal function

The dose should be reduced for patients with renal insufficiency according to the creatinine clearance rates described in the table above. The use of Foscavir is not recommended in patients undergoing hemodialysis, as dosage guidelines have not been established.

Patient with altered hepatic function

No dose reduction is necessary for patients with hepatic insufficiency.

Elderly patients

No dose adjustment is required.

Pediatric population

The safety and efficacy of foscarnet in children have not been established.

Administration method

Foscavir should be administered exclusively by the intravenous route, either through a central venous catheter or in a peripheral vein.

DO NOT administer this medication by rapid intravenous injection.

For administration in a peripheral vein, the solution must be diluted immediately before administration in 5% glucose or physiological serum to a concentration of 12 mg/ml.

The Foscavir solution can be administered undiluted via central venous route.

Accidental contact of the Foscavir solution with the skin or eyes can cause local irritation and a burning sensation. In case of accidental contact, the exposed area should be washed with water.