Product Information for the User

VFEND200mg Powder for Solution for Infusion

voriconazole

Read this entire product information carefully before starting to use the medicine, as it contains important information for you.

-Keep this product information, as you may need to read it again.

-If you have any questions, consult your doctor, pharmacist, or nurse.

-This medicine has been prescribed only for you and should not be given to others, even if they have the same symptoms as you, as it may harm them.

-If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this product information. See section4.

1.What is VFEND and what it is used for

2.What you need to know before starting to use VFEND

3.How to use VFEND

4.Possible side effects

5.Storage of VFEND

6.Contents of the pack and additional information

VFEND contains the active ingredient voriconazole. VFEND is an antifungal medication. It acts by eliminating or preventing the growth of fungi that cause infections.

It is used to treat patients (adults and children 2 years of age or older) with:

• invasive aspergillosis (a type of fungal infection produced by Aspergillus sp),
• candidemia (another type of fungal infection produced by Candida sp) in non-neutropenic patients (patients who do not have an abnormally low count of white blood cells),
• serious invasive infections produced by Candida sp, when the fungus is resistant to fluconazole (another antifungal medication),
• serious fungal infections produced by Scedosporium sp or by Fusarium sp (two different species of fungi).

VFEND is used in patients with serious fungal infections that can put their lives at risk.

Prevention of fungal infections in bone marrow transplant recipients with a high risk.

This medication must be used only under medical supervision.

No use VFEND

If you are allergic to voriconazole or to sodium sulfobutylether beta-cyclodextrin (included in section 6).

It is very important to inform your doctor or pharmacist if you are using or have recently used other medications, including those obtained without a prescription, or herbal remedies.

Do not take the following medications during treatment with VFEND:

• Terfenadine (used for allergies).
• Astemizole (used for allergies).
• Cisapride (used for digestive problems).
• Pimozide (used for mental disorders).
• Quinidine (used for arrhythmias).
• Ivabradine (used for symptoms of chronic heart failure).
• Rifampicin (used for tuberculosis treatment).
• Efavirenz (used for HIV treatment) at doses of 400 mg and above once a day.
• Carbamazepine (used to treat seizures).
• Phenobarbital (used for severe insomnia and seizures).
• Ergot alkaloids (e.g., ergotamine, dihydroergotamine; used for migraines).
• Sirolimus (used in patients who have received a transplant).
• Ritonavir (used for HIV treatment) at doses of 400 mg and above twice a day.
• St. John's Wort (hypericum, herbal remedy).
• Naloxegol (used to treat constipation caused specifically by opioids [e.g., morphine, oxycodone, fentanyl, tramadol, codeine]).
• Tolvaptan (used to treat hyponatremia [low sodium levels in the blood] or to slow the deterioration of renal function in patients with polycystic kidney disease).
• Lurasidone (used to treat depression).
• Venetoclax (used for the treatment of patients with chronic lymphocytic leukemia [CLL]).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use VFEND if:

• You have had an allergic reaction to other azoles.
• You have or have had liver disease. If you have liver disease, your doctor may prescribe a lower dose of VFEND. Your doctor should also monitor your liver function while you are taking VFEND by performing blood tests.
• You know you have heart disease, irregular heartbeats, slow heart rate, or an electrocardiogram (ECG) anomaly called "prolonged QTc syndrome."

Avoid any exposure to the sun and sunlight during treatment. It is essential to cover exposed areas and use a high-factor sunscreen, as you may experience increased skin sensitivity to UV rays from the sun. This may be exacerbated by the use of other medications that sensitize the skin to sunlight, such as methotrexate. These precautions also apply to children.

While taking VFEND:

• Inform your doctor if you experience:
• sunburn
• severe skin rash or blisters
• bone pain

If you develop skin disorders as described above, your doctor may refer you to a dermatologist, who may consider regular examinations. There is a small probability of developing skin cancer with long-term use of VFEND.

If you develop signs of "adrenal insufficiency" in which the adrenal glands do not produce sufficient amounts of certain steroid hormones, such as cortisol, which may cause symptoms such as:

chronic or prolonged fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, inform your doctor.

If you experience signs of the "Cushing syndrome" in which the body produces too much cortisol hormone, which may cause symptoms such as:

weight gain, hump of fat between the shoulders, rounded face, darkening of the skin on the abdomen, thighs, breasts, and arms, thin skin, easy bruising, high blood sugar levels, excessive hair growth, excessive sweating, inform your doctor.

Your doctor should monitor your liver and kidney function by performing blood tests.

Children and adolescents

VFEND should not be administered to children under 2 years old.

Other medications and VFEND

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication.

• Some medications, when used at the same time as VFEND, may affect the action of VFEND or vice versa.

Inform your doctor if you are using the following medications, as simultaneous treatment with VFEND should be avoided if possible:

• Ritonavir (used for HIV treatment) at doses of 100 mg twice a day.
• Glasdegib (used for cancer treatment); if you need to use both medications, your doctor will monitor your heart rate frequently.

Inform your doctor if you are using any of the following medications, as simultaneous treatment with VFEND should be avoided as much as possible, and you may need to adjust the dose of voriconazole:

• Rifabutin (used for tuberculosis treatment). If you are already taking rifabutin, your doctor will need to monitor your blood count and the side effects of rifabutin.
• Phenitoin (used to treat epilepsy). If you are already taking phenitoin, your doctor will need to monitor the concentration of phenitoin in your blood during your treatment with VFEND and may need to adjust your dose.

Inform your doctor if you are taking any of the following medications, as you may need to adjust your dose or have your medication monitored to ensure it continues to produce the desired effect:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to reduce blood clotting).
• Ciclosporin (used in patients who have received a transplant).
• Tacrolimus (used in patients who have received a transplant).
• Sulfonilureas (e.g., tolbutamide, glipizide, and glibenclamide) (used for diabetes).
• Statins (e.g., atorvastatin, simvastatin) (used to reduce cholesterol levels).
• Benzodiazepines (e.g., midazolam, triazolam) (used for severe insomnia and stress).
• Omeprazole (used for stomach ulcer treatment).
• Oral contraceptives (if you use VFEND while taking oral contraceptives, you may experience side effects such as nausea and menstrual disorders).
• Vincristine and vinblastine alkaloids (used to treat cancer).
• Indinavir and other HIV protease inhibitors (used to treat HIV infection).
• Tyrosine kinase inhibitors (e.g., axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (used to treat cancer).
• Tretinoin (used to treat leukemia).
• Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, and nevirapina) (used to treat HIV infection) (some doses of efavirenz cannot be taken at the same time as VFEND).
• Methadone (used to treat heroin addiction).
• Alfentanil, fentanyl, and other short-acting opioids (e.g., sufentanil) (used for surgical procedures).
• Oxycodone and other long-acting opioids (e.g., hydrocodone) (used to treat moderate to severe pain).
• Nonsteroidal anti-inflammatory drugs (e.g., ibuprofen, diclofenac) (used to treat pain and inflammation).
• Fluconazole (used to treat fungal infections).
• Everolimus (used to treat advanced kidney cancer and in patients who have received a transplant).
• Letermovir (used to prevent cytomegalovirus (CMV) infection after a bone marrow transplant).
• Ivacaftor (used to treat cystic fibrosis).
• Flucloxacillin (antibiotic used to treat bacterial infections).

Pregnancy and breastfeeding

You should not use VFEND during pregnancy unless your doctor indicates it. Women of childbearing age taking VFEND should use effective contraception. Contact your doctor immediately if you become pregnant during treatment with VFEND.

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

Driving and operating machinery

VFEND may cause blurred vision or increased sensitivity to light. If this occurs, do not drive or operate tools or machines and inform your doctor.

VFEND contains sodium

This medication contains 221 mg of sodium (main component of table salt/for cooking) per vial. This is equivalent to 11% of the recommended daily maximum sodium intake for an adult.

VFEND contains cyclodextrin

This medication contains 3,200 mg of cyclodextrin in each vial, equivalent to 160 mg/ml when reconstituted in 20 ml. If you have kidney disease, consult your doctor before taking this medication.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Your doctor will determine the dose based on your weight and the type of infection you have.

Your doctor may change your dose based on your situation.

The recommended dose in adults (including elderly patients) is as follows:

Depending on your response to treatment, your doctor may reduce the dose to 3 mg/kg twice a day.

Your doctor may decide to reduce the dose if you have mild to moderate cirrhosis.

Use in children and adolescents

The recommended dose in children and adolescents is as follows:

Depending on your response to treatment, your doctor may increase or decrease the daily dose.

VFEND powder for solution for infusion must be reconstituted and diluted to the correct concentration by hospital pharmacy or nursing staff (for more information, see the end of this leaflet).

It will be administered through intravenous infusion (in vein) at a maximum rate of 3 mg/kg per hour for 1 to 3 hours.

If you or your child are taking VFEND for the prevention of fungal infections, your doctor may stop administering VFEND if you or your child experience adverse effects related to treatment.

If you forgot a dose of VFEND

Given that you will receive this medication under close medical supervision, it is unlikely that you will forget a dose. However, inform your doctor or pharmacist if you think you have forgotten a dose.

If you interrupt treatment with VFEND

Treatment with VFEND should be continued for as long as your doctor considers necessary, however, the duration of treatment with VFEND powder for solution for infusion should not exceed 6 months.

Patients with compromised immune systems or those with complicated infections may require longer treatments to prevent the infection from recurring. Once your condition improves, you may switch from intravenous infusion to taking tablets.

When your doctor stops treatment with VFEND, you should not experience any effects resulting from the interruption.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them. If any occur, they are likely to be mild and temporary. However, some may be serious and require medical attention.

Serious side effects - Stop using VFEND and seek medical attention immediately

• Skin rash.
• Jaundice, changes in liver function tests.
• Pancreatitis.

Other side effects

Very common: may affect more than 1 in 10 peoplepeople

• Visual disturbances (change in vision, blurred vision, visual color disturbances, abnormal light perception intolerance, color blindness, eye disorders, halo vision, night blindness, oscillating vision, spark vision, visual aura, decreased visual acuity, visual clarity, partial loss of the usual visual field, visual field spots).
• Fever.
• Skin rash.
• Nausea, vomiting, and diarrhea.
• Headache.
• Swelling of the extremities.
• Abdominal pain.
• Difficulty breathing.
• Elevated liver enzymes.

Common: may affect up to 1 in 10 people

• Sinusitis, gum inflammation, chills, weakness.
• Low count, including severe, of some types of red or white blood cells in the blood, low platelet count that helps blood to clot.
• Low blood sugar, low potassium levels in the blood, low sodium levels in the blood.
• Anxiety, depression, confusion, agitation, insomnia, hallucinations.
• Seizures, tremors, or uncontrolled muscle movements, tingling or abnormal sensations in the skin, increased muscle tone, drowsiness, dizziness.
• Eye hemorrhage.
• Cardiac rhythm problems that include very fast or very slow heart rate, fainting.
• Hypotension, inflammation of the veins (which may be associated with blood clot formation).
• Acute difficulty breathing, chest pain, facial swelling (mouth, lips, and around the eyes), fluid retention in the lungs.
• Constipation, indigestion, lip inflammation.
• Jaundice (yellow skin discoloration), liver inflammation, and liver damage.
• Skin eruptions, which may be severe, with blisters and peeling, characterized by a flat, red area covered with small protuberances that converge, skin redness.
• Itching.
• Alopecia.
• Back pain.
• Renal failure, blood in the urine, changes in renal function tests.
• Sunburn or severe skin reaction after exposure to light or the sun.
• Skin cancer.

Uncommon: may affect up to 1 in 100 peoplepeople

• Flu-like symptoms, gastrointestinal tract irritation, gastrointestinal tract inflammation that causes diarrhea associated with antibiotics, lymphatic vessel inflammation.
• Peritoneal inflammation, which is the thin tissue that lines the abdominal wall and covers the abdominal organs.
• Enlargement (sometimes painful) of the lymph nodes, bone marrow insufficiency, eosinophil increase.
• Adrenal gland dysfunction, hypothyroidism.
• Abnormal brain function, Parkinson's disease-like symptoms, nerve damage causing numbness, pain, tingling, or burning in the hands or feet.
• Balance or coordination problems.
• Brain swelling.
• Dual vision, severe eye diseases, such as: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage that causes vision changes, papillary optic inflammation.
• Decreased sensitivity to touch.
• Altered sense of taste.
• Difficulty hearing, tinnitus, vertigo.
• Inflammation of certain internal organs, pancreas and duodenum, tongue swelling and inflammation.
• Enlarged liver, liver failure, gallbladder disease, gallstones.
• Joint inflammation, inflammation of the veins under the skin (which may be associated with blood clot formation).
• Kidney inflammation, protein in the urine, kidney damage.
• Very high or irregular heart rate, sometimes with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• Elevated blood cholesterol, elevated blood urea.
• Severe skin reactions, such as skin disease, potentially fatal that causes blisters and painful sores on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, redness, and irritation, skin discoloration or purpura that may be caused by low platelet count, eczema.
• Reaction in the perfusion area.
• Severe allergic reaction or excessive immune response.
• Inflammation of the tissue surrounding the bone.

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

• Hyperactive thyroid gland.
• Severe brain activity deterioration as a complication of liver disease.
• Loss of most of the optic nerve fibers, corneal opacity, involuntary eye movements.
• Blister formation due to photosensitivity.
• Disease in which the immune system attacks part of the peripheral nervous system.
• Cardiac rhythm problems or conduction problems (sometimes potentially fatal).
• Potentially fatal allergic reaction.
• Blood clotting disorders.
• Severe skin reactions, such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, pruritic and painful skin plaques with scaly skin, skin irritation and mucous membranes, potentially fatal skin disease that causes large areas of the epidermis, the skin's outermost layer, to peel off from the layers of skin beneath it.
• Small, scaly, and dry skin patches, sometimes thick and with points or "horns".

Side effects of unknown frequency:

• Moles and pigmented spots.

Other important side effects whose frequency is unknown, but which should be reported to your doctor immediately:

• Red, scaly, or ring-shaped skin lesions that may be a symptom of a skin autoimmune disease called lupus erythematosus.

During perfusion, infrequently, there have been reactions with VFEND (including facial redness, fever, sweating, increased heart rate, and difficulty breathing). Your doctor may stop the perfusion if this happens.

Since VFEND has been observed to affect the liver and kidneys, your doctor should monitor liver and renal function through blood tests. Inform your doctor if you have abdominal pain or if your stools have a different consistency.

Cases of skin cancer have been reported in patients treated with Vfend for long periods of time.

The frequency of sunburns or severe skin reactions after exposure to light or the sun was higher in children. If you or your child experience skin problems, your doctor may refer you to a dermatologist who, after consultation, may decide that it is necessary for you or your child to undergo regular follow-up. Elevated liver enzymes were also observed more frequently in children.

If any of these side effects persist or are bothersome, inform your doctor.

Reporting side effects

If you experienceany type of side effect, consult your doctor, pharmacist, or nurse, even if it is apossibleside effect that does not appear in this prospectus.You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products 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 label. The expiration date is the last day of the month indicated.

Once reconstituted, VFEND must be used immediately, although, if necessary, it can be stored for up to 24 hours between 2°C - 8°C (in a refrigerator). Reconstituted VFEND must be diluted first with a compatible infusion diluent before being infused. (For more information, see the end of this prospectus).

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you do not need. This will help protect the environment.

VFEND Composition

• The active ingredient is voriconazole.
• The other component is sodium sulfobutyl ether beta-cyclodextrin (see section 2, VFEND 200 mg powder for solution for infusion contains cyclodextrin and sodium).

Each vial contains 200 mg of voriconazole, which is equivalent to a concentrated solution of 10 mg/ml once reconstituted following the instructions indicated by the pharmacy or nursing staff of the hospital (see the information at the end of this leaflet).

Appearance of the product and contents of the pack

VFEND is presented in the form of a powder for solution for infusion in single-use glass vials.

Marketing authorization holder and responsible person for manufacturing

Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Brussels, Belgium.

Responsible person for manufacturing

Fareva Amboise, Zone Industrielle, 29 route des Industries, 37530 Pocé-sur-Cisse, France.

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last approval date of this leaflet:09/2023.

Further information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

-----------------------------------------------------------------------------------------------------------------------

The following information is intended only for healthcare professionals:

Information on reconstitution and dilution

• VFEND powder for solution for infusion must be reconstituted with 19 ml of water for injections or 19 ml of sodium chloride 9 mg/ml (0.9%) for infusion to obtain a usable volume of 20 ml of a clear concentrate containing 10 mg/ml of voriconazole.
• Discard the VFEND vial if the vacuum does not allow the solvent to be introduced into the vial.
• It is recommended to use a standard 20 ml syringe (not automatic) to ensure that the exact amount (19.0 ml) of water for injections or sodium chloride 9 mg/ml (0.9%) is dispensed.
• The required volume of reconstituted concentrate is then added to one of the following compatible infusion solutions to obtain a final VFEND solution containing 0.5 to 5 mg/ml of voriconazole.
• This product is for single use only and any unused solution must be discarded and only clear, particle-free solutions should be used.
• It should not be administered as a bolus.
• For information on storage, see section 5 “Storage of VFEND”.

Volumes of VFEND concentrate 10 mg/ml required

VFEND is a sterile, preservative-free, single-dose lyophilisate. From a microbiological point of view, the solution must be used immediately after reconstitution. If not used immediately, the time and conditions of storage before use are the responsibility of the user, and it should be maintained between 2°C and 8°C for a maximum period of 24 hours unless the reconstitution has been performed in controlled and validated aseptic conditions.

Compatible infusion solutions:

The reconstituted solution can be diluted with:

Sodium chloride 9 mg/ml (0.9%) for injection

Intravenous Perfusion Solution of sodium lactate compound

Glucose 5% solution for infusion

Ringer lactate solution for intravenous infusion

Glucose 5% solution and sodium chloride 0.45% for intravenous infusion

Glucose 5% solution for intravenous infusion

Glucose 5% solution with 20 mEq of potassium chloride for intravenous infusion

Sodium chloride 0.45% solution for intravenous infusion

Glucose 5% solution and sodium chloride 0.9% for intravenous infusion

The compatibility of voriconazole with other diluents other than those specifically mentioned above (or mentioned below in “Incompatibilities”) is unknown.

Incompatibilities:

VFEND should not be infused through the same vein or cannula simultaneously with other infusions of drugs, including parenteral nutrition (e.g. Aminofusin 10% Plus).

Simultaneous infusion of blood derivatives should not be performed with the administration of VFEND.

Parenteral nutrition can be administered simultaneously with VFEND, but not through the same vein or cannula.

VFEND should not be diluted with sodium bicarbonate 4.2% solution.