Vfend 50 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

VFEND 50 mg film-coated tablets

VFEND 200 mg film-coated tablets

voriconazole

Read the 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 and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, including any possible side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What VFEND is and what it is used for

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

It is used to treat patients (adults and children aged 2 years and 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 white blood cell count),
• serious invasive infections caused by Candida sp, when the fungus is resistant to fluconazole (another antifungal medicine),
• serious fungal infections caused by Scedosporium sp or by 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 high-risk bone marrow transplant recipients.

This medicine should only be used under medical supervision.

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

Do not take VFEND

if you are allergic to voriconazole or to 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 taking or have recently taken any 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 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 to treat tuberculosis).
• Efavirenz (used to treat 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 transplant patients).
• Ritonavir (used to treat HIV) at doses of 400 mg or higher twice daily.
• St. John’s wort (hypericum, herbal remedy).
• Naloxegol (used to treat constipation specifically caused by painkillers called opioids [e.g., morphine, oxycodone, fentanyl, tramadol, codeine]).
• Tolvaptan (used to treat hyponatremia [low sodium levels in blood] or to slow down the decline in kidney function in patients with polycystic kidney disease).
• Lurasidone (used to treat depression).
• Venetoclax (used to treat patients with chronic lymphocytic leukemia [CLL]).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to take VFEND if:

• you have had an allergic reaction to other azoles.
• you have or have ever 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 during treatment with VFEND by performing blood tests.
• you know you have cardiomyopathy, irregular heartbeat, slow heart rate, or an abnormality on the electrocardiogram (ECG) known as “prolonged QTc syndrome.”

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

While being treated with VFEND:

• inform your doctor if you develop
• 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 have you examined regularly. There is a small possibility that long-term use of VFEND may lead to skin cancer.

If you experience signs of “adrenal insufficiency,” in which the adrenal glands do not produce enough 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 “Cushing’s syndrome,” in which the body produces too much cortisol hormone, which may cause symptoms such as: weight gain, fatty hump 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, or excessive sweating, inform your doctor.

Your doctor should monitor the function of your liver and kidneys by performing blood tests.

Children and adolescents

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

Other medicines and VFEND

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

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

Inform your doctor if you are taking the following medicines, as concomitant treatment with VFEND should be avoided if possible:

• Ritonavir (used to treat HIV) at a dose of 100 mg twice daily.
• Glasdegib (used to treat cancer); if you need to take both medicines, your doctor will frequently monitor your heart rhythm.

Inform your doctor if you are taking any of the following medicines, as concomitant treatment with VFEND should be avoided if possible, and a dose adjustment of voriconazole may be needed:

• Rifabutin (used to treat tuberculosis). If you are already being treated with rifabutin, your blood count and adverse effects of rifabutin should be monitored.
• Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin, the concentration of phenytoin in your blood should be monitored during 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 ensure these medicines and/or VFEND are still having the desired effect:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to reduce blood clotting).
• Cyclosporine (used in transplant patients).
• Tacrolimus (used in transplant patients).
• Sulfonylureas (e.g., tolbutamide, glipizide, glyburide) (used for diabetes).
• Statins (e.g., atorvastatin, simvastatin) (used to lower 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 adverse effects such as nausea and menstrual disorders).
• Vinca alkaloids (e.g., vincristine, 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 leukemia).
• Indinavir and other HIV protease inhibitors (used to treat HIV infection).
• Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, 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 (analgesics used during surgery).
• Oxycodone and other long-acting opioids such as 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 transplant).
• Ivacaftor: used to treat cystic fibrosis.

Flucloxacillin (an antibiotic used to treat bacterial infections).

Pregnancy and breastfeeding

You must not take VFEND during pregnancy unless specifically instructed by your doctor. Women of childbearing potential being treated with VFEND should use effective contraception. Contact your doctor immediately if you become pregnant during treatment with VFEND.

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

Driving and using machines

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 lactose

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

VFEND contains sodium

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

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

3. How to take VFEND

Follow exactly the instructions for use of this medicine given by your doctor. If you are unsure, consult your doctor or pharmacist again.

Your doctor will determine the dose based on your body 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 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.

• The tablets should only be administered 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 some water.

If you or your child are taking VFEND for the prevention of fungal infections, your doctor may stop treatment if you or your child experience adverse effects related to the 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 attention or go to the nearest hospital emergency department. Take the VFEND tablet pack with you. You may experience abnormal sensitivity to light as a result of taking more VFEND than you should.

If you forget to take VFEND

It is important to take VFEND tablets regularly at the same time each day. If you forget to take a dose, take the next dose at the usual time. Do not take a double dose to make up for the missed dose.

If you stop taking VFEND

It has been shown that correctly following the prescribed dosing schedule, taking each dose at the appropriate time, can significantly increase the effectiveness of this medicine. Therefore, unless your doctor tells you otherwise, it is important to continue taking VFEND correctly as indicated above.

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

When your doctor stops treatment with VFEND, you should not experience any effects due to discontinuation.

If you have any further questions about 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 everyone experiences them.

If any occur, they are most likely to be mild and transient. However, some may be serious and require immediate medical attention.

Serious adverse effects – Stop taking VFEND and contact your doctor immediately

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

Other adverse effects

Very common: may affect more than 1 in 10 people

• Visual disturbance (changes in vision such as blurred vision, color vision disturbances, abnormal intolerance to visual perception of light, color blindness, eye disorder, visual halos, night blindness, oscillating vision, perception of sparks, visual aura, decreased visual acuity, visual clarity, partial loss of normal visual field, spots in the visual field).

• Fever.

• Skin rash.

• Nausea, vomiting, and diarrhea.

• Headache.

• Swelling of the limbs.

• Stomach pain.

• Difficulty breathing.

• Elevated liver enzymes.

Common: may affect up to 1 in 10 people

• Sinusitis, gum inflammation, chills, weakness.

• Low blood counts, including severe cases, of certain types of red blood cells (sometimes immune-mediated) or white blood cells (sometimes accompanied by fever), low platelet count affecting blood clotting.

• 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, drowsiness, dizziness.

• Ocular hemorrhage.

• Heart rhythm problems including very fast heartbeat, very slow heartbeat, fainting.

• Hypotension, inflammation of veins (which may be associated with blood clot formation).

• Acute breathing difficulty, chest pain, facial swelling (mouth, lips, and around the eyes), fluid accumulation in the lungs.

• Constipation, indigestion, inflammation of the lips.

• Jaundice (yellowing of the skin), liver inflammation, and liver damage.

• Skin rashes, which may become severe, with blisters and peeling, characterized by flat, red areas covered with small merging bumps, skin redness.

• Itching.

• Alopecia.

• Back pain.

• Kidney failure, presence of blood in urine, abnormalities in kidney function tests.

• Sunburn or severe skin reaction following exposure to light or sunlight.

• Skin cancer.

Uncommon: may affect up to 1 in 100 people

• Flu-like symptoms, irritation and inflammation of the gastrointestinal tract, gastrointestinal inflammation causing antibiotic-associated diarrhea, inflammation of lymphatic vessels.

• Inflammation of the thin tissue lining the abdominal wall and covering abdominal organs (peritonitis).

• Enlargement (sometimes painful) of lymph nodes, bone marrow failure, increased eosinophils.

• Decreased adrenal gland function, underactive thyroid gland.

• Abnormal brain function, Parkinson-like symptoms, nerve damage causing numbness, pain, tingling, or burning sensations in hands or feet.

• Problems with balance or coordination.

• Brain swelling.

• Double vision, serious eye disorders such as: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage causing vision disturbances, optic disc inflammation.

• Decreased sensitivity to touch.

• Altered sense of taste.

• Hearing difficulty, tinnitus, 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 veins under the skin (which may be associated with blood clot formation).

• Kidney inflammation, protein in urine, kidney damage.

• Very high heart rate or extrasystoles, sometimes with erratic electrical impulses.

• Abnormal electrocardiogram (ECG).

• Elevated blood cholesterol, elevated blood urea.

• Skin allergic reactions (sometimes severe), such as skin disorders, potentially life-threatening conditions causing blisters and painful sores on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, skin redness and irritation, reddish or purplish skin discoloration possibly due to 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.

• Deterioration of brain function as a serious complication of liver disease.

• Loss of most of the optic nerve fibers, corneal opacity, involuntary eye movements.

• 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 life-threatening allergic reaction.

• Blood clotting disorders.

• Skin allergic reactions (sometimes severe), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, itchy and painful thickened red skin plaques with silvery scales, skin and mucous membrane irritation, potentially life-threatening skin disorders causing large areas of the epidermis, the outermost skin layer, to detach from underlying skin layers.

• Small scaly, dry skin patches, sometimes thick with tips or "horns".

Adverse effects with unknown frequency:

• Freckles and pigmented spots.

Other important adverse effects with unknown frequency that must be reported to your doctor immediately:

• Scaly red patches or ring-shaped skin lesions which may be a sign of an autoimmune disease called cutaneous lupus erythematosus.

Since VFEND has been observed to affect the liver and kidneys, your doctor should monitor liver and kidney function through blood tests. Inform your doctor if you experience stomach pain or if your stools have an unusual consistency.

Cases of skin cancer have been reported in patients treated with VFEND over long periods.

The frequency of sunburn or severe skin reactions following exposure to light or sunlight was higher in children. If you or your child develop skin disorders, your doctor may refer you to a dermatologist who, after evaluation, may determine that regular follow-up is necessary. Elevated liver enzymes were also observed more frequently in children.

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of VFEND

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

Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of VFEND

• The active substance 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 components are monohydrate lactose, pregelatinized starch, sodium croscarmellose, povidone and magnesium stearate, which constitute the tablet core, and hypromellose, titanium dioxide (E171), monohydrate lactose and glyceryl triacetate, which constitute the film coating (see section 2, VFEND 50 mg film-coated tablets or VFEND 200 mg film-coated tablets contain lactose and sodium).

Nature of the product and contents of the pack

VFEND 50 mg tablets are presented as film-coated tablets, white to off-white in colour and rounded 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 colour 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 tablets.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer Responsible

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

Manufacturers Responsible

Pfizer Italia S.r.l.

Località Marino del Tronto

63100 Ascoli Piceno (AP)

Italy

For more information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent approval of this package leaflet: 09/2023.

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