VFEND 50 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

VFEND50mg film-coated tablets

VFEND200mg film-coated tablets

voriconazole

Read all of this leaflet carefully before you start taking 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, pharmacist 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, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is VFEND and what is it used for
2. What you need to know before you take VFEND
3. How to take VFEND
4. Possible side effects
5. Storage of VFEND
6. Contents of the pack and other information

1. What is VFEND and what is it used for

VFEND contains the active substance voriconazole. VFEND is an antifungal medicine. It works by killing or preventing the growth of fungi that cause infections.

It is used for the treatment of patients (adults and children aged 2 years or older) with:

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

VFEND is used in patients with serious fungal infections that may be life-threatening.

Prevention of fungal infections in patients undergoing bone marrow transplantation who are at high risk.

This medicine should only be used under medical supervision.

2. What you need to know before you take VFEND

Do not take VFEND

if you are allergic to voriconazole or any of the other ingredients of this medicine (listed in section 6).

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

During treatment with VFEND, you must not take the following medicines:

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

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting treatment with 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 with blood tests while you are taking VFEND.
• you know that you have cardiomyopathy, irregular heartbeats, slow heart rate or an abnormality in your electrocardiogram (ECG) called "QTc prolonged syndrome".

You should avoid any exposure to the sun and sunlight during treatment. It is important that you cover exposed areas and use a sunscreen with a high sun protection factor (SPF), as you may be more sensitive to the UV rays of the sun. This sensitivity can be increased by the use of other medicines that make your skin more sensitive to sunlight, such as methotrexate. These precautions also apply to children.

While taking VFEND:

• tell your doctor if you get

• 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 it important to examine you regularly. There is a small chance that you may develop skin cancer with long-term use of VFEND.

If you develop signs of "adrenal insufficiency" where the adrenal glands do not produce enough of certain steroid hormones, such as cortisol, which can cause symptoms such as: chronic or prolonged fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, tell your doctor.

If you develop signs of "Cushing's syndrome" where the body produces too much cortisol hormone which can 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 levels, excessive hair growth or excessive sweating, tell your doctor.

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

Children and adolescents

VFEND should not be given to children under 2 years of age.

Other medicines and VFEND

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

• Some medicines, when used at the same time as VFEND, can affect the action of VFEND or VFEND may affect the action of other medicines.

Tell your doctor if you are using the following medicines, as concurrent treatment with VFEND should be avoided if possible:

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

Tell your doctor if you are using any of the following medicines, as concurrent treatment with VFEND should be avoided as much as possible, and a dose adjustment of voriconazole may be required:

• Rifabutin (used for the treatment of tuberculosis). If you are already being treated with rifabutin, your blood count and the side effects of rifabutin will need to be monitored.
• Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin, the concentration of phenytoin in your blood will need to be monitored during your treatment with VFEND and your dose may need to be adjusted.

Tell your doctor if you are taking any of the following medicines, as you may need a dose adjustment or monitoring to check that these medicines and/or VFEND are still working as they should:

• 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).
• Sulphonylureas (e.g. tolbutamide, glipizide and gliburide) (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 the treatment of stomach ulcers).
• Oral contraceptives (if you take VFEND while using oral contraceptives, you may experience side effects such as nausea and menstrual disorders).
• Vinca alkaloids (e.g. vincristine and vinblastine) (used to treat cancer).
• Tyrosine kinase inhibitors (e.g. axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (used to treat cancer).
• Tretinoin (used to treat leukaemia).
• Indinavir and other HIV protease inhibitors (used to treat HIV infection).
• Non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz, delavirdine and nevirapine) (used to treat HIV infection) (some doses of efavirenz MUST NOT be taken at the same time as VFEND).
• Methadone (used to treat heroin addiction).
• Alfentanil, fentanyl and other short-acting opioids such as sufentanil (painkillers used for operations).
• Oxycodone and other long-acting opioids such as hydrocodone (used to treat moderate to severe pain).
• Non-steroidal anti-inflammatory medicines (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 bone marrow transplantation).
• Ivacaftor: used to treat cystic fibrosis.
• Flucloxacillin (antibiotic used against bacterial infections).

Pregnancy and breast-feeding

Do not take VFEND during pregnancy unless your doctor has told you to. Women of childbearing age taking VFEND must use effective contraception. Contact your doctor immediately if you become pregnant while taking VFEND.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

VFEND may cause blurred vision or sensitivity to light. If this happens, do not drive or use tools or machines and tell your doctor.

VFEND contains lactose

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

VFEND contains sodium

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

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

3. How to take VFEND

Always take this medicine exactly as your doctor has told you. If you are not sure, check with your doctor or pharmacist.

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

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

Depending on your response to treatment, your doctor may increase the daily dose to 300 mg twice daily.

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

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.

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

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 to prevent fungal infections, your doctor may stop the administration of VFEND if you or your child experience side effects related to treatment.

If you take more VFEND than you should

If you take more tablets than you have been told to take (or if someone else takes your tablets), you must contact a doctor or go to the nearest hospital emergency department immediately. Take the VFEND pack 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 important that you take your VFEND tablets regularly at the same time each day. If you forget to take a dose, take the next dose when it is due. Do not take a double dose to make up for a forgotten dose.

If you stop taking VFEND

It has been shown that strictly following the prescribed dosage, taking each dose at the right time, can significantly increase the effectiveness of this medicine. Therefore, unless your doctor tells you to stop treatment, it is important that you continue to take VFEND as prescribed above.

Continue to take VFEND until your doctor tells you to stop. Do not stop treatment early, as the infection may not be fully cured. Patients with a weakened immune system or with complicated infections may need longer treatment to prevent the infection from coming back.

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

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

If any appear, it is most likely to be mild and transient. However, some can be serious and require medical attention.

Severe Adverse Effects - Stop taking VFEND and consult your doctor immediately

• Skin rash.
• Jaundice, alterations in blood tests to control liver function.
• Pancreatitis.

Other Adverse Effects

Very frequent: may affect more than 1 in 10 people

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

Frequent: may affect up to 1 in 10 people

• Sinusitis, gum inflammation, chills, weakness.
• Low count, including severe, of some types of red blood cells (sometimes of an immune nature) or white blood cells (sometimes accompanied by fever) in the blood, low platelet count that helps blood clot.
• Low blood sugar levels, low blood potassium levels, low blood sodium levels.
• Anxiety, depression, confusion, agitation, insomnia, hallucinations.
• Seizures, tremors, or uncontrolled muscle movements, tingling, or abnormal sensations in the skin, increased muscle tone, somnolence, dizziness.
• Eye hemorrhage.
• Heart rhythm problems, including very fast heartbeat, very slow heartbeat, fainting.
• Hypotension, inflammation of the veins (which may be associated with the formation of blood clots).
• Acute difficulty breathing, chest pain, swelling of the face (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 can be severe, with blisters and peeling, characterized by a flat, red area covered with small bumps that merge, skin redness.
• Itching.
• Alopecia.
• Back pain.
• Kidney failure, presence of blood in urine, alterations in kidney function tests.
• Sunburn or severe skin reaction after exposure to light or sun.
• Skin cancer.

Infrequent: may affect up to 1 in 100 people

• Flu-like symptoms, irritation, and inflammation of the gastrointestinal tract, gastrointestinal tract inflammation that causes antibiotic-associated diarrhea, inflammation of the lymphatic vessels.
• Inflammation of the thin tissue that lines the inner wall of the abdomen and covers the abdominal organs.
• Enlargement (sometimes painful) of the lymph nodes, bone marrow failure, increased eosinophils.
• Decreased adrenal gland function, underactive thyroid gland.
• Abnormal brain function, symptoms similar to Parkinson's disease, nerve damage causing numbness, pain, tingling, or burning in the hands or feet.
• Problems with balance or coordination.
• Brain swelling.
• Double vision, severe eye diseases, such as: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage that causes vision changes, inflammation of the optic papilla.
• Decreased sensitivity to touch.
• Alteration of the sense of taste.
• Difficulty hearing, ringing in the ears, vertigo.
• Inflammation of certain internal organs, pancreas, and duodenum, swelling, and inflammation of the tongue.
• Liver enlargement, liver failure, gallbladder disease, gallstones.
• Joint inflammation, inflammation of the veins under the skin (which may be associated with the formation of a blood clot).
• Kidney inflammation, protein in the urine, kidney damage.
• Very high heart rate or extrasystoles, sometimes with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• High blood cholesterol, high blood urea.
• Skin allergic reactions (sometimes severe), such as a potentially fatal skin disease that causes painful blisters and ulcers on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, skin redness, and irritation, reddish or purplish skin color that may be caused by low platelet count, eczema.
• Infusion site reaction.
• Allergic reaction or exaggerated immune response.
• Inflammation of the tissue surrounding the bone.

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

• Overactive thyroid gland.
• Worsening of brain activity as a severe complication of liver disease.
• Loss of most of the optic nerve fibers, corneal opacity, involuntary eye movement.
• Blister formation due to photosensitivity.
• Disorder in which the immune system attacks part of the peripheral nervous system.
• Heart rhythm or conduction problems (sometimes potentially fatal).
• Potentially fatal allergic reaction.
• Alterations in blood coagulation.
• Skin allergic reactions (sometimes severe), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, itchy, and painful thickened skin plaques with silvery scales, skin irritation, and mucous membrane irritation, potentially fatal skin disease that causes large portions of the epidermis to peel off from the underlying skin layers.
• Small, scaly, dry patches on the skin, sometimes thick and with tips or "horns".

Adverse effects with unknown frequency:

• Pigmented spots and patches.

Other important adverse effects whose frequency is not known but should be reported to the doctor immediately:

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

Since it has been observed that VFEND affects the liver and kidneys, your doctor should monitor liver and kidney function through blood tests. Inform your doctor if you have stomach pain or if your stools have a different consistency.

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

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

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

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of VFEND

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date stated on the label. The expiration date is the last day of the month indicated.

This medicine does not require special storage 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. Package Contents and Additional Information

Composition of VFEND

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

• The other ingredients are lactose monohydrate, pregelatinized starch, sodium croscarmellose, povidone, and magnesium stearate, which make up the tablet core, and hypromellose, titanium dioxide (E171), lactose monohydrate, and triacetin, which make up the film coating (see section 2, VFEND 50 mg film-coated tablets or VFEND 200 mg film-coated tablets contain lactose and sodium).

Appearance and Package Contents

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

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

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

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

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

Manufacturers

Pfizer Italia S.r.l.

Località Marino del Tronto

63100 Ascoli Piceno (AP)

Italy

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

Date of Last Approval of this Prospectus:09/2023.

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.