Product Information for the User

VFEND50Film-Coated Tablets

VFEND200Film-Coated Tablets

voriconazole

Read this entire leaflet carefully before you start taking 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, 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 who do not have an abnormally low 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 put their lives at risk.

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

This medication must be used only under medical supervision.

Do not take VFEND

If you are allergic to voriconazole or any of the other components of this medication (listed in section 6).

It is very important that you inform your doctor or pharmacist if you are using or have recently used other medications, including those purchased 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 heart 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 transplant patients).
• 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 opioid analgesics [e.g., morphine, oxycodone, fentanyl, tramadol, codeine]).
• Tolvaptan (used to treat hyponatremia [low sodium levels in the blood] or to slow the deterioration of kidney 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 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 risk of developing skin cancer with long-term use of VFEND.

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

• chronic or prolonged fatigue
• muscle weakness
• loss of appetite
• weight loss
• abdominal pain

Inform your doctor.

If you experience signs of "Cushing's syndrome" where the body produces too much cortisol hormone, which may cause symptoms like:

• weight gain
• hump of fat between the shoulders
• rounded face
• darkening of skin on the abdomen, thighs, breasts, and arms
• thin skin
• easily 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 rifabutin side effects.
• Phenobarbital (used for epilepsy treatment). If you are already taking phenobarbital, your doctor will need to monitor your phenobarbital blood levels 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).
• 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 take VFEND while using oral contraceptives, you may experience side effects such as nausea and menstrual disorders).
• Vincristine and vinblastine alkaloids (used for cancer treatment).
• Inhibitors of tyrosine kinase (e.g., axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (used for cancer treatment).
• Tretinoin (used for leukemia treatment).
• Indinavir and other HIV protease inhibitors (used for HIV treatment).
• Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, and nevirapine) (used for HIV treatment) (some doses of efavirenz cannot be taken at the same time as VFEND).
• Methadone (used for heroin addiction treatment).
• Alfentanil, fentanyl, and other short-acting opioids (e.g., sufentanil) (used for surgical procedures).
• Oxycodone and other long-acting opioids (e.g., hydrocodone) (used for moderate to severe pain).
• Nonsteroidal anti-inflammatory drugs (e.g., ibuprofen, diclofenac) (used for pain and inflammation).
• Fluconazole (used for fungal infections).
• Everolimus (used for advanced kidney cancer and in transplant patients).
• Letermovir (used to prevent cytomegalovirus (CMV) infection after bone marrow transplant).
• Ivacaftor (used for cystic fibrosis treatment).
• Flucloxacillin (antibiotic used for bacterial infections).

Pregnancy and breastfeeding

Do not take 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 machinery and inform your doctor.

VFEND contains lactose

If your doctor has informed you that you have an intolerance to some sugars, contact your doctor before taking VFEND.

VFEND contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per 50 mg tablet; it is essentially "sodium-free."

This medication contains less than 1 mmol of sodium (23 mg) per 200 mg tablet; it is essentially "sodium-free."

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 300 mg 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.

• Tablets should only be administered if the child is able to swallow whole tablets.

Take the tablets at least one hour before or one hour after a meal. Swallow the tablet whole with a little water.

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 take more VFEND than you should

If you take more tablets than prescribed (or if someone else takes your tablets), seek immediate medical assistance or go to the nearest emergency hospital. Bring the box of VFEND tablets with you. You may notice an abnormal sensitivity to light as a result of taking more VFEND than you should.

If you forget to take VFEND

It is essential to take VFEND tablets 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 the missed dose.

If you interrupt treatment with VFEND

It has been shown that following the recommended dosage and administering each dose at the correct time can significantly increase the effectiveness of this medication. 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 stop 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 suspends 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.

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 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 10people

• Sinusitis, gum inflammation, chills, weakness.
• Low white blood cell count, including severe cases, of certain 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 heart rate, 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 (yellowish skin color), 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 disturbances, 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 heart rate or extrasystoles, sometimes with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• Elevated cholesterol levels in the blood, elevated urea levels in the blood.
• Skin allergy reactions (sometimes severe), 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, skin redness and irritation, skin discoloration or purpura that may be caused by low platelet count, eczema.
• Reaction at the infusion site.
• Alergic reaction or excessive immune response.
• Periosteal inflammation.

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

• Hyperactive thyroid gland.
• Cerebral activity deterioration as a severe complication of liver disease.
• Optic nerve fiber loss, corneal opacity, involuntary eye movement.
• Photosensitivity blister formation.
• 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 coagulation abnormalities.
• Skin allergy reactions (sometimes severe), such as hives, rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, pruritic and painful skin plaques with scaly, plate-like skin, mucous membrane and skin 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 plaques, 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 ispossible side effects that do not appear in this prospectus. You can also report them directly through the Spanish System for the Vigilance of Medicinal Products for Human Use:www.notificaRAM.es.By reporting side effects, you can contribute to providing more informationon 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.

This medication does not require special storage conditions.

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

VFEND Composition

• The active ingredient is voriconazole. Each tablet contains 50mg of voriconazole (for VFEND 50mg film-coated tablets) or 200mg of voriconazole (for VFEND 200mg film-coated tablets).

• The other components are lactose monohydrate, pregelatinized starch, sodium croscarmellose, povidone, and magnesium stearate, which constitute the tablet core, and hypromellose, titanium dioxide (E171), lactose monohydrate, and triacetin, which constitute the film coating (see section2,VFEND 50mg film-coated tablets or VFEND 200mg film-coated tablets contain lactose and sodium).

Appearance of the product and contents of the pack

VFEND 50mg tablets are presented as film-coated tablets, white to off-white in color and round in shape, with “Pfizer” engraved on one face and “VOR50” on the other.

VFEND 200mg tablets are presented as film-coated tablets, white to off-white in color and capsule-shaped, with “Pfizer” engraved on one face and “VOR200” on the other.

VFEND 50mg film-coated tablets and VFEND 200mg film-coated tablets are available in packs of 2, 10, 14, 20, 28, 30, 50, 56, and 100.

Only some pack sizes may be marketed.

Marketing authorization holder and responsible person for manufacturing

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

Responsible persons for manufacturing

Pfizer Italia S.r.l.

Marino del Tronto

63100 Ascoli Piceno (AP)

Italy

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.

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