Leaflet: information for the user

VFEND40mg/ml powder for oral suspension

voriconazole

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

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

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

-This medicine has been prescribed for you only. Do not give it 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 leaflet. See section4.

1.What is VFEND and what it is used for.

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

3.How to take 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 with a normal white blood cell count),
• 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 be life-threatening.

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

This medication must be used only under medical supervision.

Do not take VFEND:

if you are allergic to voriconazole or any of the other ingredients of this medication (listed in section6).

It is very important that you inform your doctor or pharmacist if you are using, have used recently or may need to take any other medication or herbal remedies.

During treatment with VFEND, do not take the following medications:

• Terfenadine (used for allergies).
• Astemizol (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 400mg 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 transplant patients).
• Ritonavir (used for HIV treatment) at doses of 400mg and above twice a day.
• St. John's Wort (hypericum, medicinal plant).
• 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 take 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."

You should 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 be more sensitive to UV rays from the sun. This may be increased further 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 such as those described above, your doctor may refer you to a dermatologist, who may consider regular examinations. There is a small probability that you may develop 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's 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 of the abdomen, thighs, breasts, and arms, thin skin, easy bruising, high blood sugar, excessive hair growth, or 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 2years.

Other medications and VFEND

Inform your doctor or pharmacist if you are taking, have taken recentlyor may need totake 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 100mg 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.
• Phenobarbital (used to treat epilepsy). If you are already taking phenobarbital, your doctor will need to monitor the concentration of phenobarbital 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 monitor to ensure that these medications and/or VFEND continue to produce the desired effect:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to reduce blood clotting).
• Ciclosporin (used in transplant patients).
• Tacrolimus (used in transplant patients).
• Sulfonylureas (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 to treat stomach ulcers).
• Oral contraceptives (if you take VFEND while using oral contraceptives, you may experience side effects such as nausea and menstrual disorders).
• Vincristine and vinblastine alkaloids (used to treat cancer).
• Inhibitors of tyrosine kinase (e.g., axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (used to treat cancer).
• Tretinoin (used to treat leukemia).
• Indinavir and other HIV protease inhibitors (used to treat HIV infection).
• 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).
• Non-steroidal 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 transplant patients).
• Letermovir (used to prevent cytomegalovirus (CMV) infection after bone marrow transplantation).
• Ivacaftor (used to treat cystic fibrosis).
• Flucloxacillin (antibiotic used to treat bacterial infections).

Pregnancy and breastfeeding

You should not take VFEND during pregnancy unless your doctor indicates. 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 discomfort due to increased sensitivity to light. If this occurs, do not drive or operate tools or machinery and inform your doctor.

VFEND contains sucrose

This medication contains sucrose. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

Patients with diabetes mellitus should note that this medication contains 0.54g of sucrose per ml of suspension.

It may cause tooth decay.

VFEND contains sodium

This medication contains less than 1mmol of sodium (23mg) per 5ml of suspension; it is essentially “sodium-free.”

VFEND contains sodium benzoate/sodium

This medication contains 12mg of sodium benzoate (E211) per 5ml dose.

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

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

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

Your doctor may increase the daily dose to 7.5ml (300mg) twice a day depending on your response to treatment.

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:

Your doctor may increase or decrease the daily dose depending on your response to treatment.

Take the suspension at least one hour before or two hours after a meal.

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.

VFEND suspension should not be mixed with any other medication. The suspension should not be diluted with water or other liquids.

Instructions for preparing the suspension

It is recommended that your pharmacist prepare the VFEND suspension before giving it to you.

VFEND suspension is reconstituted if it has a liquid form. If it appears as a dry powder, the oral suspension should be reconstituted following the instructions below:

2.Remove the cap.

3.Add 2measuring cups (the measuring cup is included in the package) of water (up to a total of 46ml) to the bottle. Fill the measuring cup to the top of the marked line and then add the measured water to the bottle. Always add a total of 46ml of water, regardless of the dose you need to take.

4.Put the cap back on and shake the bottle vigorously for about 1minute. After reconstitution, the total volume of the suspension should be 75ml.

5.Remove the cap. Insert the adapter into the neck of the bottle (as shown in the diagram below). The adapter is supplied to fill the oral syringe with the medication from the bottle. Place the cap on the bottle.

6.Record the expiration date of the reconstituted suspension on the bottle label (the shelf life of the reconstituted suspension is 14days). Any remaining suspension should be discarded after this date.

Instructions for use:

Your pharmacist should explain how to measure the medication using the oral syringe multidose that is included in the package. Please read the following instructions before using VFEND suspension.

1.Shake the closed bottle with the reconstituted suspension for about 10seconds before use. Remove the cap.

2.With the bottle upside down, placed on a flat surface, insert the tip of the oral syringe into the adapter.

3.Hold the syringe in place, turn the bottle upside down. Pull the plunger of the syringe slowly to the marked graduation corresponding to your dose.

4.If large bubbles are seen, press the plunger of the syringe slowly. This will cause the medication to return to the bottle. Repeat step3.

5.Turn the bottle right side up with the syringe in place. Remove the syringe from the bottle.

6.Place the tip of the syringe in the mouth. Point the syringe towards the inner cheek. Press the plunger SLOWLY. Do not expel the medication quickly. If you are giving the medication to a child, make sure the child is sitting or held upright before giving the medication.

7.Put the cap back on the bottle, leaving the adapter in place. Wash the syringe following the instructions below.

Cleaning and storage of the syringe:

1.The syringe should be washed after each use. Remove the plunger and wash the two parts with warm soapy water. Then rinse it with water.

2.Dry the two parts. Put the plunger back in the syringe. Store it in a clean and safe place with the medication.

If you take more VFEND than you should

If you take more suspension than prescribed (or if someone else takes your suspension), seek medical help immediately or go to the nearest emergency hospital. Bring your VFEND suspension bottle with you. You may notice abnormal sensitivity to light as a result of taking too much VFEND.

If you forget to take VFEND

It is essential to take the VFEND suspension regularly at the same time of day. If you forget to take a dose, take the next one when it is due. Do not take a double dose to make up for missed doses.

If you interrupt treatment with VFEND

It has been shown that following the recommended dosage, administering each dose at the right time can significantly increase the effectiveness of this medication. Therefore, unless your doctor tells you to stop treatment, it is essential to continue taking VFEND as indicated above.

Continue taking VFEND until your doctor tells you to stop. Do not interrupt treatment prematurely, as the infection may not be cured. Patients with compromised immune systems or complicated infections may require longer treatments to prevent the infection from recurring.

When your doctor stops treatment with VFEND, you should not experience any effects related to 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, it is likely to be mild and temporary. However, some may be serious and require medical attention.

Severe side effects - Stop taking VFEND and seek medical attention immediately

• Skin rash.
• Jaundice, liver function test abnormalities.
• Pancreatitis.

Other side effects

Very common: may affect more than 1 in 10 peoplepeople

• Visual disturbance (change in vision, such as blurred vision, visual colour changes, abnormal light perception intolerance, colour blindness, eye disorder, 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 10people

• 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 levels, 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, renal function test abnormalities.
• Sunburn or severe skin reaction after exposure to light or the sun.
• Skin cancer.

Uncommon: may affect up to 1 in 100people

• 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 extrasystolic heart rate, sometimes with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• Elevated blood cholesterol, elevated blood urea.
• Severe skin reactions (sometimes life-threatening), such as skin disease, potentially fatal that causes painful blisters and sores on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, skin 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.
• Periosteal inflammation.

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

• 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 movement.
• 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 life-threatening).
• Life-threatening allergic reaction.
• Blood coagulation abnormalities.
• Severe skin reactions (sometimes life-threatening), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, pruritic and painful skin plaques with scaly, thickened, and red skin, skin and mucous membrane irritation, 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.

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 leaflet.You can also report them directly throughtheSpanish System for the 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.

Oral powder for suspension: store between 2°C - 8°C (in refrigerator) before reconstitution.

For the suspension, once reconstituted:

Do not store at a temperature above 30°C.

Do not store in refrigerator or freeze.

Store in its original container.

Keep the container tightly closed.

Any remaining suspension should be discarded 14days after reconstitution.

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

Composition of VFEND

• The active ingredient is voriconazole. Each bottle contains 45g of powder, which once reconstituted with water following the instructions, gives rise to 70ml of suspension. One ml of the reconstituted suspension contains 40mg of voriconazole. (see section3 ‘How to take VFEND’)
• The other components are sucrose; colloidal silica; titanium dioxide; xanthan gum, sodium citrate; sodium benzoate; citric acid; natural orange aroma (see section2, VFEND 40mg/ml powder for oral suspension contains sucrose, sodium benzoate (sodium benzoate) and sodium).

Appearance of the product and content of the container

VFEND is presented in the form of white to off-white powder for oral suspension that, once reconstituted with water, gives rise to a white to off-white suspension with orange flavor.

Holder of the marketing authorization and responsible for manufacturing

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

Responsible for manufacturing

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

You can request more information about this medication by contacting the local representative of the holder of the marketing authorization.

Last approval date of this leaflet:04/2024.

The detailed information about this medication is available on the website of the European Medicines Agency:http://www.ema.europa.eu.