Vfend

Package leaflet: Information for the user

VFEND 50 mg film-coated tablets, 200 mg film-coated tablets

voriconazole
Please 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 questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this 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 stopping the growth of, or killing, the fungi that cause infections.
It is used to treat patients (adults and children over 2 years of age) who have:

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

VFEND is indicated for patients with progressive fungal infections that may be life-threatening.
Prevention of fungal infections in high-risk bone marrow transplant patients.
This product should only be used under medical supervision.

2. What you should know before taking 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 other
medicines, including those without a prescription, or herbal medicines.
The following medicines must not be used during treatment with VFEND:

• Terfenadine (for allergies)
• Astemizole (for allergies)
• Cisapride (for stomach problems)
• Pimozide (for the treatment of mental illnesses)
• Quinidine (for irregular heartbeat)
• Ivabradine (for symptoms of chronic heart failure)
• Rifampicin (for the treatment of tuberculosis)
• Efavirenz (for the treatment of AIDS) at doses equal to or greater than 400 mg once daily
• Carbamazepine (for the treatment of seizures)
• Phenobarbital (for severe insomnia and seizures)
• Ergot alkaloids (e.g., ergotamine, dihydroergotamine; for migraine)
• Sirolimus (for transplant patients)
• Ritonavir (for the treatment of AIDS) at doses of 400 mg or more twice daily
• St. John’s wort (hypericum – a herbal supplement)
• Naloxegol (for the treatment of constipation specifically caused by opioid pain medicines [e.g., morphine, oxycodone, fentanyl, tramadol, codeine])
• Tolvaptan (for the treatment of hyponatremia, i.e., low sodium levels in the blood, or to slow the decline in kidney function in patients with polycystic kidney disease)
• Lurasidone (for the treatment of depression)
• Finerenone (for the treatment of chronic kidney disease)
• Eplerenone (for the treatment of heart and/or blood vessel problems)
• Voclosporin (for the treatment of immune system disorders)
• Venetoclax (for the treatment of patients with chronic lymphocytic leukemia - CLL)

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking VFEND if:

• you have had an allergic reaction to other azoles.
• you have or have had liver disease. If you have liver problems, your doctor may prescribe a lower dose of VFEND. Your doctor will need to monitor your liver function during treatment with VFEND through blood tests.
• you know you have heart disease, an irregular heartbeat, a slow heartbeat, or an abnormality on the electrocardiogram (ECG) called “long QTc syndrome”.

You must avoid any exposure to sunlight and solar radiation during treatment. It is important to cover
exposed skin areas and use sunscreens with high sun protection factor (SPF), as increased sensitivity of the skin to UV rays from sunlight may occur. This sensitivity may be further increased by other medicines that make the skin sensitive to sunlight, such as methotrexate. These precautions also apply to children.
During treatment with VFEND:

• inform your doctor immediately if you develop
• sunburn
• severe skin reaction or blistering
• bone pain

If you develop any of the skin conditions described above, your doctor may refer you to a dermatologist, who after consultation may decide that regular check-ups are necessary. With long-term use of VFEND, there is a small risk of developing cutaneous carcinoma.
If you develop signs of “adrenal insufficiency”, in which the adrenal glands do not produce adequate amounts of certain steroid hormones such as cortisol, which may cause symptoms such as chronic or persistent fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, inform your doctor.
Inform your doctor if you develop signs of “Cushing's syndrome”, in which the body produces excessive amounts of the hormone cortisol, which may cause symptoms such as weight gain, fat accumulation between the shoulders, rounded face, darkening of the skin on the abdomen, thinning of legs, breasts, and arms, thinning of the skin, easy bruising, increased blood sugar levels, excessive body hair growth, excessive sweating.
Your doctor will need to monitor your liver and kidney function through blood tests.
Children and adolescents
VFEND must not be administered 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 take any other medicines, including those without a prescription.
Some medicines, when taken together with VFEND, may alter the activity of VFEND or VFEND may alter the activity of these medicines.
Inform your doctor if you are taking the following medicine because, if possible, concomitant treatment with VFEND should be avoided:

• Ritonavir (for the treatment of AIDS) at doses of 100 mg twice daily
• Glasdegib (for cancer treatment): if you need to use both medicines, your doctor will frequently monitor your heart rhythm

Inform your doctor if you are taking either of these two medicines because, if possible, concomitant treatment with VFEND should be avoided and a dose adjustment of voriconazole may be necessary:

• Rifabutin (for the treatment of tuberculosis). If you are already being treated with rifabutin, blood cell counts and rifabutin-related side effects should be closely monitored.
• Phenytoin (for the treatment of epilepsy). If you are already being treated with phenytoin, blood levels of phenytoin should be monitored during treatment with VFEND and your dose may need to be adjusted.

Inform your doctor if you are taking any of the following medicines because dose adjustments or monitoring may be necessary to ensure these medicines and/or VFEND remain effective:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; to slow down the blood clotting process)
• Cyclosporine (for transplant patients)
• Tacrolimus (for transplant patients)
• Sulfonylureas (e.g., tolbutamide, glipizide, glyburide) (for diabetes)
• Statins (e.g., atorvastatin, simvastatin) (to reduce cholesterol)
• Benzodiazepines (e.g., midazolam, triazolam) (for severe insomnia and stress)
• Omeprazole (for the treatment of ulcers)
• Oral contraceptives (if you take VFEND while using oral contraceptives, side effects such as nausea and menstrual disturbances may occur)
• Vinca alkaloids (e.g., vincristine, vinblastine) (for cancer treatment)
• Tyrosine kinase inhibitors (e.g., axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (for cancer treatment)
• Tretinoin (for the treatment of leukemia)
• Indinavir and other protease inhibitors for AIDS (for the treatment of AIDS)
• Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, nevirapine) (for the treatment of AIDS) (some doses of efavirenz MUST NOT be taken together with VFEND)
• Methadone (for the treatment of heroin addiction)
• Alfentanil and fentanyl and other short-acting opioids such as sufentanil (analgesics used in surgical procedures)
• Oxycodone and other long-acting opioids such as hydrocodone (used for moderate to severe pain)
• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) (e.g., ibuprofen, diclofenac) (used for the treatment of pain and inflammation)
• Fluconazole (used to treat fungal infections)
• Everolimus (used for the treatment of advanced kidney cancer and in transplant patients)
• Letermovir (used to prevent cytomegalovirus (CMV) disease following bone marrow transplantation)
• Ivacaftor: used for the treatment of cystic fibrosis
• Flucloxacillin (an antibiotic indicated for bacterial infections)

Pregnancy and breastfeeding
VFEND must not be taken during pregnancy unless specifically decided by your doctor.
Women of childbearing potential must use an adequate method of contraception. Contact your doctor immediately if you become pregnant during treatment with VFEND.
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Driving and using machines
VFEND may cause blurred vision or increased sensitivity to light. In such cases, you should not drive and should not operate tools or machinery. In these cases, contact your doctor.
VFEND contains lactose
If your doctor has told you that you have an intolerance to certain sugars, contact your doctor before taking
VFEND.
VFEND contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 50 mg tablet, i.e.
essentially ‘sodium-free’.
This medicine contains less than 1 mmol (23 mg) of sodium per 200 mg tablet, i.e.
essentially ‘sodium-free’.

3. How to take VFEND

Take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Your doctor will determine the appropriate dose for you based on your body weight and the type of diagnosed infection.
The recommended dose for adults (including elderly patients) is as follows:

Depending on the response to treatment, your doctor may increase the daily dose to 300 mg twice a
day.
If you have mild to moderate cirrhosis, your doctor may decide to reduce the dose.
Use in children and adolescents
The recommended dose in children and adolescents is as follows:

Based on the 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.

Take the tablets at least one hour before or one hour after meals. Swallow the tablet whole with
some water.
If you or your child is taking VFEND for the prevention of fungal infections, your doctor may decide
to discontinue VFEND treatment if you or your child develops treatment-related adverse effects.

If you take more VFEND than you should
If you take more tablets than prescribed (or if someone else takes your tablets), contact your doctor or go to the nearest emergency room. Take the VFEND tablet pack with you. Abnormal sensitivity to light may occur if you take more VFEND than you should.

If you forget to take VFEND
It is important to take VFEND tablets regularly every day at the same time. 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 forgotten doses.

If you stop taking VFEND
It has been shown that taking doses at the correct time can significantly increase the effectiveness of your medicine. Therefore, unless your doctor has told you to stop treatment, it is important to continue taking VFEND correctly as described above.
Continue taking VFEND until your doctor tells you to stop. Do not stop treatment earlier than planned, as the infection may not be cured. Patients with a weakened immune system or those with difficult-to-treat infections may require long-term treatment to prevent the infection from returning.
When VFEND treatment is stopped at the doctor's instruction, no withdrawal effects should occur.

If you have any doubts about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
If side effects occur, most will probably be mild and temporary. However, some may be serious and require immediate medical attention.

Serious side effects – Stop taking VFEND and contact a doctor immediately

• Rash
• Jaundice, changes in liver function tests
• Pancreatitis

Other side effects
Very common: may occur in more than 1 out of 10 people

• Visual disturbances (including blurred vision, altered colour vision, abnormal sensitivity to light, colour blindness, eye disorders, seeing halos, night blindness, oscillating vision, seeing sparks, visual aura, reduced visual acuity, visual brightness, partial loss of visual field, spots in front of the eyes)
• Fever
• Skin rashes
• Nausea, vomiting, diarrhoea
• Headache
• Swelling of extremities
• Stomach pain
• Difficulty breathing
• Elevated liver enzymes

Common: may occur in up to 1 out of 10 people

• Sinus inflammation, gum inflammation, chills, fatigue
• Reduction, sometimes severe, in the number of certain types of red blood cells (sometimes immune-mediated) and/or white blood cells (sometimes with fever), reduction in the number of blood cells (called platelets) that help blood clotting
• Low blood sugar levels, low blood potassium levels, low blood sodium levels
• Anxiety, depression, confusion, agitation, sleep disturbances, hallucinations
• Seizures, tremor or uncontrolled muscle movements, tingling or abnormal skin sensations, increased muscle tone, drowsiness, dizziness
• Bleeding in the eye
• Heart rhythm problems including very fast heartbeat, very slow heartbeat, fainting
• Low blood pressure, inflammation of a vein (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, liver inflammation, liver damage
• Skin rash which may lead to severe blistering and peeling of the skin, characterized by flat red areas of skin with small merging bumps, skin redness
• Itching
• Hair loss
• Back pain
• Kidney failure, blood in urine, changes in kidney function tests
• Sunburn or severe skin reaction following exposure to light or sunlight
• Skin cancer

Uncommon: may occur in up to 1 out of 100 people

• Flu-like symptoms, irritation and inflammation of the gastrointestinal tract, gastrointestinal inflammation which may cause antibiotic-associated diarrhoea, inflammation of lymphatic vessels
• Inflammation of the thin tissue lining the abdominal wall and covering abdominal organs (peritonitis)
• Enlarged lymph nodes (sometimes painful), bone marrow failure, increased eosinophils
• Reduced adrenal gland function, reduced thyroid gland activity
• Changes in brain function, Parkinson-like symptoms, nerve damage leading to numbness, pain, tingling or burning in hands or feet
• Problems with balance and coordination
• Brain swelling (cerebral oedema)
• Double vision, serious eye conditions including: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage with visual impairment, optic disc swelling
• Reduced sensitivity to touch
• Altered taste
• Hearing disorders, ringing in the ears (tinnitus), vertigo
• Inflammation of internal organs – pancreas and duodenum, swelling and inflammation of the tongue
• Enlarged liver, liver failure, gallbladder diseases, gallstones
• Joint inflammation, inflammation of subcutaneous veins (which may be associated with blood clot formation)
• Kidney inflammation, presence of protein in urine, kidney damage
• Very rapid heartbeat or missed beats, sometimes with irregular electrical impulses
• Abnormal electrocardiogram (ECG)
• Increased cholesterol, increased blood urea
• Allergic skin reactions (sometimes severe), including a potentially life-threatening skin condition causing blisters and painful sores of the skin and mucous membranes, especially in the mouth, skin inflammation, hives, redness and irritation of the skin, skin discolouration (red or purplish) which may be due to low platelet count, eczema
• Infusion site reaction
• Allergic reactions or exaggerated immune response
• Inflammation of tissues surrounding bones

Rare: may occur in up to 1 out of 1000 people

• Overactive thyroid gland
• Deterioration of brain function as a serious complication of liver disease
• Loss of most of the optic nerve fibres, corneal opacity, involuntary eye movement
• Bullous photosensitivity
• Disorder in which the body's immune system attacks part of the peripheral nervous system
• Heart rhythm or conduction problems (sometimes fatal)
• Potentially life-threatening allergic reaction
• Disorders of the blood clotting system
• Allergic skin reactions (sometimes severe), including rapid swelling (oedema) of the dermis, subcutaneous tissue, mucosa, and submucosal tissues, itchy or painful patches of thickened, red, scaly skin with silvery scales, skin and mucous membrane irritation, potentially life-threatening skin condition causing detachment of large areas of the epidermis (the outer layer of skin) from underlying skin layers
• Small patches of dry, scaly skin, sometimes thickened, with tips or 'horns'

Side effects with unknown frequency:

• Freckles and pigmented spots

Other significant side effects, whose frequency is not known but which should be reported immediately to a doctor, include:

• Red, scaly or ring-shaped skin lesions which could be symptoms of an autoimmune disease called systemic lupus erythematosus

Since VFEND has been observed to affect the liver and kidneys, your doctor will monitor liver and kidney function through blood tests. Inform your doctor if you experience stomach pain or if your stools differ from normal in consistency.
Cases of skin carcinoma have been reported in patients treated with VFEND for prolonged periods.
Sunburn or a severe skin reaction following exposure to light or sunlight has been reported more frequently in children. If you or your child develops skin problems, your doctor may refer you to a dermatologist, who may decide whether it is important for you or your child to continue regular visits to the dermatologist. Elevated liver enzymes have also been observed more frequently in children.
If any of these side effects persist or are bothersome, inform your doctor.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What VFEND contains

• The active substance is voriconazole. Each tablet contains 50 mg of voriconazole (VFEND 50 mg film-coated tablets) or 200 mg of voriconazole (VFEND 200 mg film-coated tablets).
• The excipients are: monohydrate lactose, pregelatinized starch, sodium croscarmellose, povidone and magnesium stearate, which constitute the inner core of the tablet, and hypromellose, titanium dioxide (E171), monohydrate lactose and glycerol triacetate, which constitute the tablet's film coating (see section 2; VFEND 50 mg film-coated tablets or VFEND 200 mg film-coated tablets contain lactose and sodium).

Description of the appearance of VFEND and contents of the pack
VFEND 50 mg film-coated tablets are white to off-white, round, film-coated tablets, imprinted with "Pfizer" on one side and "VOR50" on the other.
VFEND 200 mg film-coated tablets are white to off-white, capsule-shaped, film-coated tablets, imprinted with "Pfizer" 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 containing 2, 10, 14, 20, 28, 30, 50, 56 and 100 tablets.
Not all pack sizes may be marketed.

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

Manufacturer:
R-Pharm Germany GmbH
Heinrich-Mack-Str. 35, 89257 Illertissen
Germany
Pfizer Italia S.r.l.
Località Marino del Tronto
63100 Ascoli Piceno (AP)
Italy

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

België/Belgique/Belgien/Luxembourg/Luxemburg
Pfizer Luxembourg SARL
Pfizer NV/SA Filialas Lietuvoje
Tél/Tel: +32 (0)2 554 62 11
Tel: +3705 2514000

България (Bulgaria)
Пфайзер Люксембург САРЛ, Клон България
Tel: +359 2 970 4333

Magyarország (Hungary)
Pfizer Kft.
Tel: +36 1 488 37 00

Česká republika (Czech Republic)
Pfizer, spol. s.r.o.
Tel: +420-283-004-111

Malta
Vivian Corporation Ltd.
Tel: +356 21344610

Danmark (Denmark)
Pfizer ApS
Tlf.: +45 44 20 11 00

Nederland (Netherlands)
Pfizer bv
Tel: +31 (0) 800 63 34 636

Deutschland (Germany)
PFIZER PHARMA GmbH
Tel: +49 (0)30 550055-51000

Norge (Norway)
Pfizer AS
Tlf: +47 67 52 61 00

Eesti (Estonia)
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

Österreich (Austria)
Pfizer Corporation Austria Ges.m.b.H.
Tel: +43 (0)1 521 15-0

Ελλάδα (Greece)
Pfizer ΕΛΛΑΣ A.E.
Tel: +30 210 6785 800

Polska (Poland)
Pfizer Polska Sp. z o.o.
Tel: +48 22 335 61 00

España (Spain)
Pfizer, S.L.
Tel: +34 91 490 99 00

Portugal
Laboratórios Pfizer, Lda.
Tel: +351 214 235 500

France
Pfizer
Tél: +33 (0)1 58 07 34 40

România (Romania)
Pfizer România S.R.L
Tel: +40 (0)21 207 28 00

Hrvatska (Croatia)
Pfizer Croatia d.o.o.
Tel: +385 1 3908 777

Slovenija (Slovenia)
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)152 11 400

Ireland
Pfizer Healthcare Ireland Unlimited Company
Tel: 1800 633 363 (toll free)
+44 (0)1304 616161

Slovenská republika (Slovakia)
Pfizer Luxembourg SARL, organizačná zložka
Tel: +421-2-3355 5500

Suomi/Finland
Pfizer Oy
Puh/Tel: +358(0)9 43 00 40

Ísland (Iceland)
Icepharma hf., Pfizer
Sími: +354 540 8000

Italia (Italy)
Pfizer S.r.l.
Tel: +39 06 33 18 21

Sverige (Sweden)
Pfizer AB
Tel: +46 (0)8 5505 2000

Kύπρος (Cyprus)
Pfizer ΕΛΛΑΣ Α.Ε. (Cyprus Branch)
Tel: +357 22 817690

Latvija (Latvia)
Pfizer Luxembourg SARL Filiāle Latvijā
Tel: +371 670 35 775

More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu .

Package leaflet: information for the user

VFEND 200 mg powder for solution for infusion

voriconazole
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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 other people, even if their symptoms are the same as yours, because it could be dangerous.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What VFEND is and what it is used for
2. What you need to know before taking VFEND
3. How to use 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 stopping the growth of, or killing, the fungi that cause infections.
It is used to treat patients (adults and children over 2 years of age) who have:

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

VFEND is indicated for patients with worsening fungal infections undergoing high-risk bone marrow transplantation.
Prevention of fungal infections in patients undergoing high-risk bone marrow transplantation.
This product should only be used under medical supervision.

2. What you should know before taking VFEND

Do not take VFEND
if you are allergic to the active substance voriconazole or to sodium sulfobutylether beta cyclodextrin (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 without a prescription, or herbal medicines.
The following medicines must not be used during treatment with VFEND:

• Terfenadine (for allergies)
• Astemizole (for allergies)
• Cisapride (for stomach problems)
• Pimozide (for the treatment of mental illnesses)
• Quinidine (for irregular heartbeat)
• Ivabradine (for symptoms of chronic heart failure)
• Rifampicin (for the treatment of tuberculosis)
• Efavirenz (for the treatment of AIDS) at doses equal to or greater than 400 mg once daily
• Carbamazepine (for the treatment of seizures)
• Phenobarbital (for severe insomnia and seizures)
• Ergot alkaloids (e.g., ergotamine, dihydroergotamine; for migraine)
• Sirolimus (for transplant patients)
• Ritonavir (for the treatment of AIDS) at doses of 400 mg or more, twice daily
• St. John’s Wort (Hypericum perforatum – a herbal supplement)
• Naloxegol (for the treatment of constipation specifically caused by pain medicines called opioids [e.g., morphine, oxycodone, fentanyl, tramadol, codeine])
• Tolvaptan (for the treatment of hyponatremia, i.e., low sodium levels in the blood, or to slow the decline in kidney function in patients with polycystic kidney disease)
• Lurasidone (for the treatment of depression)
• Finerenone (for the treatment of chronic kidney disease)
• Eplerenone (for the treatment of heart and/or blood vessel problems)
• Voclosporin (for the treatment of immune system disorders)
• Venetoclax (for the treatment of patients with chronic lymphocytic leukemia-CLL)

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking VFEND if:

• you have had an allergic reaction to other azole antifungals.
• you have or have had liver disease. If you have liver problems, your doctor may prescribe a lower dose of VFEND. Your doctor will need to monitor your liver function during treatment with VFEND through blood tests.
• you know you have heart disease, irregular heartbeat, slow heartbeat, or an abnormality on electrocardiogram (ECG) called "long QTc syndrome."

You must avoid any exposure to sunlight and UV light during treatment. It is important to cover sun-exposed skin areas and use sunscreens with high sun protection factor (SPF), as increased sensitivity of the skin to UV light may occur. This sensitivity may be further increased by other medicines that make the skin more sensitive to sunlight, such as methotrexate. These precautions also apply to children.
During treatment with VFEND:

• inform your doctor immediately if you develop
• sunburn
• severe skin reaction or blistering
• bone pain

If you develop any of the skin conditions described above, your doctor may refer you to a dermatologist, who after evaluation may decide that regular follow-up visits are necessary. With long-term use of VFEND, there is a small risk of developing skin carcinoma.
If you develop signs of "adrenal insufficiency", in which the adrenal glands do not produce adequate amounts of certain steroid hormones such as cortisol, which may cause symptoms such as chronic or persistent fatigue, muscle weakness, loss of appetite, weight loss, or abdominal pain, inform your doctor.
Inform your doctor if you develop signs of "Cushing's syndrome", in which the body produces excessive amounts of the hormone cortisol, which may cause symptoms such as weight gain, fat accumulation between the shoulders, rounded face, darkening of the skin on the abdomen, thinning of legs, breasts, and arms, thinning of the skin, easy bruising, increased blood sugar levels, excessive body hair growth, and excessive sweating.
Your doctor will need to monitor your liver and kidney function through blood tests.

Children and adolescents
VFEND must not be administered 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 take any other medicines, including those without a prescription.
Some medicines, when taken together with VFEND, may alter the effect of VFEND, or VFEND may alter the effect of these medicines.

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

• Ritonavir (for the treatment of AIDS) at doses of 100 mg twice daily
• Glasdegib (for cancer treatment): if you need to use both medicines, your doctor will frequently monitor your heart rhythm

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

• Rifabutin (for the treatment of tuberculosis). If you are already being treated with rifabutin, blood cell counts and rifabutin-related side effects should be closely monitored.
• Phenytoin (for the treatment of epilepsy). If you are already being treated with phenytoin, blood levels of phenytoin should be monitored during treatment with VFEND, and your dose may need to be adjusted.

Inform your doctor if you are taking any of the following medicines, as dose adjustment or monitoring may be needed to ensure these medicines and/or VFEND remain effective:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; to slow blood clotting)
• Cyclosporine (for transplant patients)
• Tacrolimus (for transplant patients)
• Sulfonylureas (e.g., tolbutamide, glipizide, glyburide) (for diabetes)
• Statins (e.g., atorvastatin, simvastatin) (to reduce cholesterol)
• Benzodiazepines (e.g., midazolam, triazolam) (for severe insomnia and stress)
• Omeprazole (for the treatment of ulcers)
• Oral contraceptives (if you take VFEND while using oral contraceptives, side effects such as nausea and menstrual disturbances may occur)
• Vinca alkaloids (e.g., vincristine, vinblastine) (for cancer treatment)
• Tyrosine kinase inhibitors (e.g., axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (for cancer treatment)
• Tretinoin (for the treatment of leukemia)
• Indinavir and other protease inhibitors for AIDS (for the treatment of AIDS)
• Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, nevirapine) (for the treatment of AIDS) (some doses of efavirenz cannot be taken with VFEND)
• Methadone (for the treatment of heroin addiction)
• Alfentanil and fentanyl and other short-acting opioids such as sufentanil (analgesics used in surgical procedures)
• Oxycodone and other long-acting opioids such as hydrocodone (used for moderate to severe pain)
• Non-steroidal anti-inflammatory drugs (e.g., ibuprofen, diclofenac) (used for pain and inflammation)
• Fluconazole (used to treat fungal infections)
• Everolimus (used to treat advanced renal cell carcinoma and in transplant patients)
• Letermovir (used to prevent cytomegalovirus (CMV) disease after bone marrow transplantation)
• Ivacaftor: used to treat cystic fibrosis
• Flucloxacillin (an antibiotic indicated for bacterial infections)

Pregnancy and breastfeeding
VFEND must not be used during pregnancy unless specifically advised by your doctor.
Women of childbearing potential must use an adequate method of contraception. Contact your doctor immediately if you become pregnant while taking VFEND.
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Driving and using machines
VFEND may cause blurred vision or increased sensitivity to light. If this occurs, you must not drive and must avoid using tools or machinery. In such cases, contact your doctor.

VFEND contains sodium
This medicine contains 221 mg of sodium (a main component of table salt) per vial. This corresponds to 11% of the maximum daily dietary intake recommended for an adult.

VFEND contains cyclodextrin
This medicine contains 3,200 mg of cyclodextrins per vial, equivalent to 160 mg/ml when reconstituted in 20 ml. If you have kidney problems, talk to your doctor before taking this medicine.

3. How to take VFEND

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor.
Your doctor will determine the appropriate dose for you based on your body weight and the type of infection diagnosed.
Your doctor may adjust the dose according to your condition.
The recommended dose for adults (including elderly patients) is as follows:

Depending on the response to treatment, your doctor may reduce the dose to 3 mg/kg twice daily.
If you have mild to moderate cirrhosis, your doctor may decide to reduce the dose.
Use in children and adolescents
The recommended dose in children and adolescents is as follows:

Based on the response to treatment, your doctor may increase or decrease the daily dose.
VFEND powder for solution for intravenous infusion will be reconstituted and diluted by a pharmacist or
hospital nurse to obtain the correct concentration. (For further information, see the final section of this leaflet.)
The medicine will be administered to you by intravenous infusion (into a vein) at a maximum infusion rate of
3 mg/kg/hr over 1–3 hours.
If you or your child is taking VFEND for the prevention of fungal infections, your doctor may decide to
discontinue VFEND administration if you or your child develops treatment-related adverse effects.
If you have forgotten a dose of VFEND
Since this medicine will be administered under medical supervision, it is unlikely that a dose will be missed.
However, if you think a dose has been missed, inform your doctor or pharmacist.
If you stop treatment with VFEND
Treatment with VFEND must continue for as long as your doctor decides; however, the duration of treatment with
VFEND powder for solution for intravenous infusion must not exceed 6 months.
Patients with a weakened immune system or those with difficult-to-treat infections may require long-term treatment to prevent the infection from recurring. When your condition has improved, treatment may be switched from the intravenous formulation to tablets.
When treatment with VFEND is discontinued at the doctor's discretion, no adverse effect should occur.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If side effects occur, most will probably be minor and temporary. However, some may be serious and require immediate medical attention.

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

• Rash
• Jaundice, changes in liver function tests
• Pancreatitis

Other side effects
Very common: may occur in more than 1 in 10 people

• Visual impairment (vision changes including blurred vision, altered colour vision, abnormal tolerance to light perception, colour blindness, eye disorder, seeing halos, night blindness, oscillating vision, seeing sparks, visual aura, reduced visual acuity, visual brightness, partial loss of visual field, spots in front of the eyes)
• Fever
• Skin rashes
• Nausea, vomiting, diarrhoea
• Headache
• Swelling of the extremities
• Stomach pain
• Difficulty breathing
• Elevated liver enzymes

Common: may occur in up to 1 in 10 people

• Sinus inflammation, gum inflammation, chills, fatigue
• Reduction, sometimes severe, in the number of certain types of red blood cells (sometimes immune-mediated) and/or white blood cells (sometimes with fever), reduction in the number of blood cells (called platelets) that help blood clotting
• Low blood sugar levels, low blood potassium levels, low blood sodium levels
• Anxiety, depression, confusion, agitation, sleep disorders, hallucinations
• Seizures, tremor or uncontrolled muscle movements, tingling or abnormal skin sensations, increased muscle tone, drowsiness, dizziness
• Bleeding in the eye
• Heart rhythm problems including very fast heartbeat, very slow heartbeat, fainting
• Low blood pressure, inflammation of a vein (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, liver inflammation, liver injury
• Skin rash which may lead to severe blistering and skin peeling, characterised by a flat, red area of skin with small raised bumps, confluent redness of the skin
• Itching
• Hair loss
• Back pain
• Kidney failure, blood in urine, changes in kidney function tests
• Sunburn or severe skin reaction following exposure to light or sun
• Skin cancer

Uncommon: may occur in up to 1 in 100 people

• Flu-like symptoms, irritation and inflammation of the gastrointestinal tract, gastrointestinal inflammation which may cause antibiotic-associated diarrhoea, inflammation of the lymphatic vessels
• Inflammation of the thin tissue lining the abdominal wall and covering abdominal organs
• Enlarged lymph nodes (sometimes painful), bone marrow failure, increased eosinophils
• Reduced adrenal gland function, reduced activity of the thyroid gland
• Changes in brain function, Parkinson-like symptoms, nerve damage leading to numbness, pain, tingling or burning in hands or feet
• Problems with balance and coordination
• Brain swelling
• Double vision, serious eye conditions including: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage with visual impairment, swelling of the optic disc
• Reduced sensitivity to touch
• Taste disturbances
• Hearing disorders, ringing in the ears, vertigo
• Inflammation of certain internal organs, pancreas and duodenum, swelling and inflammation of the tongue
• Liver enlargement, liver failure, gallbladder diseases, gallstones
• Joint inflammation, inflammation of subcutaneous veins (which may be associated with blood clot formation)
• Kidney inflammation, presence of protein in urine, kidney damage
• Very rapid heartbeat or missed beats, sometimes with irregular electrical impulses
• Abnormal electrocardiogram (ECG)
• Increased cholesterol, increased blood urea
• Allergic skin reactions (sometimes severe), including a potentially life-threatening skin condition causing blisters and painful sores of the skin and mucous membranes, especially in the mouth, skin inflammation, urticaria, redness and irritation of the skin, skin colour changes which may be due to low platelet count, eczema
• Infusion site reaction
• Allergic reactions or exaggerated immune response
• Inflammation of tissues surrounding the bones

Rare: may occur in up to 1 in 1000 people

• Overactive thyroid gland
• Worsening of brain function, severe complication of liver disease
• Loss of most of the fibres of the optic nerve, corneal opacity, involuntary eye movement
• Bullous photosensitivity
• Disorder in which the body's immune system attacks part of the peripheral nervous system
• Heart rhythm or conduction problems (sometimes fatal)
• Potentially life-threatening allergic reaction
• Coagulation disorders
• Allergic skin reactions (sometimes severe), including rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal tissues, itchy or painful thickened and red skin patches with silvery scales, skin and mucous membrane irritation, potentially life-threatening skin condition causing detachment of large portions of the epidermis (the outer layer of skin) from the underlying skin layers
• Small patches of dry, scaly skin, sometimes thick with tips or 'horns'

Side effects with unknown frequency:

• Freckles and pigmented spots

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

• Red, scaly patches or ring-shaped skin lesions which may be symptoms of an autoimmune disease called systemic lupus erythematosus

Reactions during VFEND infusion (including skin redness, fever, sweating, increased heart rate, and shortness of breath) are not common. If any of these reactions occur, your doctor may decide to stop the infusion.
Since VFEND has been observed to affect the liver and kidneys, your doctor will need to monitor liver and kidney function through blood tests. Inform your doctor if you have stomach pain or if your stools differ from normal.
Cases of skin carcinoma have been reported in patients treated with VFEND for prolonged periods. Sunburn or a severe skin reaction following exposure to light or sun has been reported more frequently in children. If you or your child develops skin problems, your doctor may refer you to a dermatologist who may decide whether regular follow-up visits with a dermatologist are necessary. Elevated liver enzymes have also been observed more frequently in children.
If any of these side effects persist or are bothersome, inform your doctor.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 that month.
Once reconstituted, VFEND must be used immediately; however, if necessary, it may be stored for up to 24 hours at 2°C to 8°C (in a refrigerator). The reconstituted VFEND solution must be diluted with a compatible diluent for intravenous infusion prior to administration. (For further information, see the final section of the package leaflet.)
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What VFEND Contains

• The active substance is voriconazole.
• The other component is sulfobutylether beta cyclodextrin sodium (see section 2; VFEND 200 mg powder for infusion solution contains cyclodextrin and sodium).

Each vial contains 200 mg of voriconazole, equivalent to a 10 mg/ml solution when reconstituted as recommended by the pharmacist or hospital nurse (see information provided at the end of this leaflet).
Description of the Appearance of VFEND and Contents of the Package
VFEND is supplied in single-use glass vials containing a powder for intravenous infusion solution.
Marketing Authorization Holder
Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Brussels, Belgium.
Manufacturer
Fareva Amboise, Zone Industrielle, 29 route des Industries, 37530 Pocé-sur-Cisse, France
For further information about this medicine, please contact the local representative of the marketing authorization holder:
België/Belgique/Belgien/Luxembourg/Luxemburg
Pfizer Luxembourg SARL
Pfizer NV/SA – Branch in Lithuania
Tél/Tel: +32 (0)2 554 62 11
Tel: +3705 2514000
България (Bulgaria)
Pfizer Luxembourg SARL, Branch Bulgaria
Tel: +359 2 970 4333
Magyarország (Hungary)
Pfizer Kft.
Tel: +36 1 488 37 00
Česká republika (Czech Republic)
Pfizer, spol. s.r.o.
Tel: +420-283-004-111
Malta
Vivian Corporation Ltd.
Tel: +356 21344610
Danmark (Denmark)
Pfizer ApS
Tlf.: +45 44 20 11 00
Nederland (Netherlands)
Pfizer bv
Tel: +31 (0) 800 63 34 636
Deutschland (Germany)
PFIZER PHARMA GmbH
Tel: +49 (0)30 550055-51000
Norge (Norway)
Pfizer AS
Tlf: +47 67 52 61 00
Eesti (Estonia)
Pfizer Luxembourg SARL, Estonian Branch
Tel: +372 666 7500
Österreich (Austria)
Pfizer Corporation Austria Ges.m.b.H.
Tel: +43 (0)1 521 15-0
Ελλάδα (Greece)
Pfizer ΕΛΛΑΣ A.E.
Tel: +30 210 6785 800
Polska (Poland)
Pfizer Polska Sp. z o.o.
Tel: +48 22 335 61 00
España (Spain)
Pfizer, S.L.
Tel: +34 91 490 99 00
Portugal
Laboratórios Pfizer, Lda.
Tel: +351 214 235 500
France
Pfizer
Tél: +33 (0)1 58 07 34 40
România (Romania)
Pfizer România S.R.L
Tel: +40 (0)21 207 28 00
Hrvatska (Croatia)
Pfizer Croatia d.o.o.
Tel: +385 1 3908 777
Slovenija (Slovenia)
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)152 11 400
Ireland
Pfizer Healthcare Ireland Unlimited Company
Tel: 1800 633 363 (toll free)
+44 (0)1304 616161
Ísland (Iceland)
Icepharma hf.
Sími: +354 540 8000
Suomi/Finland
Pfizer Oy
Puh/Tel: +358(0)9 43 00 40
Italia (Italy)
Pfizer S.r.l.
Tel: +39 06 33 18 21
Sverige (Sweden)
Pfizer AB
Tel: +46 (0)8 5505 2000
Kýpros (Cyprus)
Pfizer ΕΛΛΑΣ Α.Ε. (Cyprus Branch)
Tel: +357 22 817690
Latvija (Latvia)
Pfizer Luxembourg SARL
Filiale Latvijā
Tel: +371 670 35 775

More detailed information on this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu

---

The following information is intended exclusively for medical and healthcare professionals:
Information on Reconstitution and Dilution

• VFEND powder for intravenous infusion solution must first be reconstituted with 19 ml of Water for Injections or with 19 ml of 9 mg/ml (0.9%) Sodium Chloride infusion solution to obtain an extractable volume of 20 ml of a clear concentrate containing 10 mg/ml of voriconazole.
• Do not use the VFEND vial if the internal vacuum negative pressure fails to draw the diluent into the vial.
• It is recommended to use a standard 20 ml syringe (non-automatic) to ensure accurate delivery of the exact volume of Water for Injections (19.0 ml) or 9 mg/ml (0.9%) Sodium Chloride infusion solution.
• The required volume of reconstituted concentrate is then added to one of the compatible infusion solutions listed below to obtain a VFEND solution containing 0.5–5 mg/ml of voriconazole.
• This medicinal product is for single use only; any unused solution must be discarded, and only clear particle-free solutions should be used.
• The product must not be administered as an intravenous bolus.
• For information on storage of the product, refer to Section 5 “How to store VFEND”.

Required Volumes of Reconstituted VFEND Concentrate (10 mg/ml)

VFEND is a sterile, lyophilized, single-dose powder without preservatives. Therefore, from a microbiological standpoint, the reconstituted solution must be used immediately. If not used immediately, the storage conditions before and after opening are the responsibility of healthcare personnel, and the product must not be used more than 24 hours after opening, if stored at 2–8°C, unless reconstitution has been carried out under controlled and validated aseptic conditions.

Compatible diluents:
The reconstituted solution may be diluted with:
Sodium Chloride 9 mg/ml (0.9%) Injection
Sodium Lactate Compound for Intravenous Infusion
Glucose 5% and Lactated Ringer's for Intravenous Infusion
Glucose 5% and Sodium Chloride 0.45% for Intravenous Infusion
Glucose 5% for Intravenous Infusion
Glucose 5% with 20 mEq Potassium Chloride for Intravenous Infusion
Sodium Chloride 0.45% for Intravenous Infusion
Glucose 5% and Sodium Chloride 0.9% for Intravenous Infusion

The compatibility of VFEND with diluents other than those listed above (or listed in the section “Incompatibilities”) is unknown.

Incompatibilities:
VFEND must not be administered through the same intravenous line or cannula together with other intravenous infusion drugs, including parenteral nutrition (e.g., Aminofusin 10% Plus).
Concomitant administration of blood products via infusion must not be performed during VFEND administration.
Total parenteral nutrition may be administered simultaneously with VFEND, but not through the same infusion route.
VFEND must not be diluted with Sodium Bicarbonate 4.2% Infusion.

Package leaflet: information for the user

VFEND 40 mg/ml powder for oral suspension

voriconazole
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult 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, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse. See section 4.

Contents of this 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
stopping the growth of, or killing, the fungi that cause infections.
It is used to treat patients (adults and children over 2 years of age) who have:

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

VFEND is indicated for patients with progressive fungal infections that may be life-threatening.
Prevention of fungal infections in high-risk bone marrow transplant patients.
This product should only be used under medical supervision.

2. What you should know before taking 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 other
medicines, including those without a prescription, or herbal medicines.
The following medicines must not be used during treatment with VFEND:

• Terfenadine (for allergies)
• Astemizole (for allergies)
• Cisapride (for stomach problems)
• Pimozide (for the treatment of mental illnesses)
• Quinidine (for irregular heartbeat)
• Ivabradine (for symptoms of chronic heart failure)
• Rifampicin (for the treatment of tuberculosis)
• Efavirenz (for the treatment of AIDS) at doses equal to or greater than 400 mg once daily
• Carbamazepine (for the treatment of seizures)
• Phenobarbital (for severe insomnia and seizures)
• Ergot alkaloids (e.g., ergotamine, dihydroergotamine; for migraine)
• Sirolimus (for transplant patients)
• Ritonavir (for the treatment of AIDS) at doses of 400 mg or more, twice daily
• St. John’s Wort (hypericum – a herbal supplement)
• Naloxegol (for the treatment of constipation specifically caused by opioid pain medicines [e.g., morphine, oxycodone, fentanyl, tramadol, codeine])
• Tolvaptan (for the treatment of hyponatraemia, i.e. low sodium levels in the blood, or to slow the decline in kidney function in patients with polycystic kidney disease)
• Lurasidone (for the treatment of depression)
• Finerenone (for the treatment of chronic kidney disease)
• Eplerenone (for the treatment of heart and/or blood vessel problems)
• Voclosporin (for the treatment of immune system disorders)
• Venetoclax (for the treatment of patients with chronic lymphocytic leukaemia - CLL)

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking VFEND if:

• you have had an allergic reaction to other azoles.
• you have or have had liver disease. If you have liver problems, your doctor may prescribe a lower dose of VFEND. Your doctor will need to monitor your liver function during treatment with VFEND by performing blood tests.
• you know you have heart disease, irregular heartbeat, slow heartbeat, or an abnormality on the electrocardiogram (ECG) called “long QTc syndrome”.

You must avoid any exposure to sunlight and solar radiation during treatment. It is important to cover
exposed skin areas and use high-protection-factor (SPF) sunscreens, as increased sensitivity of the skin to UV rays from sunlight may occur. This sensitivity may be further increased by other medicines that make the skin more sensitive to sunlight, such as methotrexate. These precautions also apply to children.
During treatment with VFEND:

• inform your doctor immediately if you develop
• sunburn
• severe skin reaction or blistering
• bone pain.

If you develop any of the skin conditions described above, your doctor may refer you to a dermatologist, who after consultation may decide that regular check-ups are necessary. With long-term use of VFEND, there is a small risk of developing cutaneous carcinoma.
If you develop signs of “adrenal insufficiency”, in which the adrenal glands do not produce adequate amounts of certain steroid hormones such as cortisol, which may cause symptoms such as chronic or persistent fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, inform your doctor.
Inform your doctor if you develop signs of “Cushing's syndrome”, in which the body produces excessive amounts of the hormone cortisol, which may cause symptoms such as weight gain, fat accumulation between the shoulders, rounded face, darkening of the skin on the abdomen, thinning of legs, breasts and arms, thinning of the skin, easy bruising, increased blood sugar levels, excessive body hair growth, excessive sweating.
Your doctor will need to monitor your liver and kidney function through blood tests.
Children and adolescents
VFEND must not be administered 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 take any other medicines, including those without a prescription.
Some medicines, when taken together with VFEND, may alter the activity of VFEND or VFEND may alter the activity of these medicines.
Inform your doctor if you are taking the following medicine because, if possible, concomitant treatment with VFEND should be avoided:

• Ritonavir (for the treatment of AIDS) at doses of 100 mg twice daily
• Glasdegib (for the treatment of cancer): if you need to use both medicines, your doctor will frequently monitor your heart rhythm

Inform your doctor if you are taking either of these two medicines because, if possible, concomitant treatment with VFEND should be avoided and a dose adjustment of voriconazole may be necessary:

• Rifabutin (for the treatment of tuberculosis). If you are already being treated with rifabutin, blood cell counts and rifabutin-related side effects should be closely monitored.
• Phenytoin (for the treatment of epilepsy). If you are already being treated with phenytoin, blood levels of phenytoin should be monitored during treatment with VFEND and your dose may need to be adjusted.

Inform your doctor if you are taking any of these medicines because a dose adjustment or monitoring may be necessary to ensure that these medicines and/or VFEND continue to have the desired effect:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; to slow down the blood clotting process)
• Cyclosporine (for transplant patients)
• Tacrolimus (for transplant patients)
• Sulfonylureas (e.g., tolbutamide, glipizide, glyburide) (for diabetes)
• Statins (e.g., atorvastatin, simvastatin) (to reduce cholesterol)
• Benzodiazepines (e.g., midazolam, triazolam) (for severe insomnia and stress)
• Omeprazole (for the treatment of ulcers)
• Oral contraceptives (if you take VFEND during treatment with oral contraceptives, side effects such as nausea and menstrual disturbances may occur)
• Vinca alkaloids (e.g., vincristine and vinblastine) (for the treatment of cancer)
• Tyrosine kinase inhibitors (e.g., axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (for the treatment of cancer)
• Tretinoin (for the treatment of leukaemia)
• Indinavir and other protease inhibitors for AIDS (for the treatment of AIDS)
• Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, nevirapine) (for the treatment of AIDS) (some doses of efavirenz cannot be taken together with VFEND)
• Methadone (for the treatment of heroin addiction)
• Alfentanil and fentanyl and other short-acting opioids such as sufentanil (analgesics used in surgical procedures)
• Oxycodone and other long-acting opioids such as hydrocodone (used for the treatment of moderate to severe pain)
• Non-Steroidal Anti-Inflammatory Drugs (e.g., ibuprofen, diclofenac) (used for the treatment of pain and inflammation)
• Fluconazole (used to treat fungal infections)
• Everolimus (used for the treatment of advanced kidney cancer and in transplant patients)
• Letermovir (used to prevent cytomegalovirus (CMV) disease after bone marrow transplantation)
• Ivacaftor: used for the treatment of cystic fibrosis
• Flucloxacillin (an antibiotic indicated for bacterial infections)

Pregnancy and breastfeeding
VFEND must not be taken during pregnancy unless specifically decided by your doctor.
Women of childbearing potential must use an adequate contraceptive method. Contact your doctor immediately if you become pregnant during treatment with VFEND.
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Driving and using machines
VFEND may cause blurred vision or increased sensitivity to light. If this occurs, you must not drive and must not operate tools or machinery. In such cases, contact your doctor.
VFEND contains sucrose
This medicine contains 0.54 g of sucrose per ml of suspension. If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking VFEND. This should be considered in patients with diabetes mellitus. May be harmful to teeth.
VFEND contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 5 ml of suspension, i.e. essentially 'sodium-free'.
VFEND contains benzoate/sodium benzoate
This medicine contains 12 mg of benzoate (E211) in each 5 ml dose.

3. How to take VFEND

Take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Your doctor will determine the appropriate dose for you based on your body weight and the type of infection diagnosed.
The recommended dose for adults (including elderly patients) is as follows:

Depending on the response to treatment, the doctor may increase the daily dose to 7.5 ml (300 mg) twice daily.
If you have mild to moderate cirrhosis, the doctor may decide to reduce the dose.
Use in children and adolescents
The recommended dose in children and adolescents is as follows:

Based on the response to treatment, your doctor may increase or decrease the daily dose.
Take the suspension at least one hour before or two hours after meals.
If you or your child is taking VFEND for the prevention of fungal infections, your doctor may decide to discontinue VFEND if you or your child develops treatment-related adverse effects.
The VFEND suspension must not be mixed with other medicines. The suspension must not be further diluted with water or other liquids.

Instructions for reconstitution of the suspension:
It is recommended that the reconstitution of the VFEND suspension be performed by the pharmacist before dispensing the medicine.

The VFEND suspension is considered reconstituted when in liquid form. If it appears as dry powder, the oral suspension must be reconstituted according to the instructions below:

1. Shake the bottle to fully loosen the powder.
2. Remove the cap.
3. Add 2 dosing cups (the dosing cup is included in the package) of water (46 ml in total) into the bottle. Fill the dosing cup up to the mark and then pour the water into the bottle. Always add a total of 46 ml of water, regardless of the dose to be taken.
4. Replace the cap and shake the bottle vigorously for about 1 minute. After reconstitution, the total volume of the suspension should be 75 ml.
5. Remove the cap. Press the bottle adapter into the neck of the bottle (as shown in the figure below). The adapter is used to fill the syringe with the medication from the bottle. Replace the bottle cap.
6. Write the expiration date of the reconstituted suspension on the bottle label (the reconstituted suspension is valid for 14 days). Any unused suspension must be discarded 14 days after reconstitution.

Instructions for use:
Your pharmacist will advise you on how to measure the medication using the multi-dose syringe included in the package. Before using the VFEND suspension, read the instructions below:

1. Shake the closed bottle containing the reconstituted suspension for about 10 seconds each time before use. Remove the cap.
2. With the bottle in an upright position on a flat surface, insert the tip of the syringe into the adapter.
3. Invert the bottle, keeping the syringe in place. Slowly pull the plunger of the syringe to the mark indicating the dose to be taken.
4. If large bubbles are visible, slowly push the plunger back into the syringe. This will push the medication back into the bottle. Repeat step 3.
5. Return the bottle to an upright position, keeping the syringe in place. Remove the syringe from the bottle.
6. Insert the tip of the syringe into the mouth. Position the tip of the syringe toward the inside of the cheek. Push the plunger of the syringe SLOWLY. Do not expel the medication quickly. If administering to a child, ensure the child is sitting or held in an upright position before administration.
7. Replace the bottle cap, leaving the adapter in place. Rinse the syringe following the instructions below:

1 2 3 / 4 5 6

Washing and storage of the syringe:

1. The syringe must be rinsed after each use. Remove the plunger from the syringe and rinse both parts with warm soapy water. Then rinse with water.
2. Dry both parts. Reinsert the plunger into the syringe. Store in a dry and safe place together 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), contact your doctor or go to the nearest emergency room immediately. Bring the VFEND suspension packaging with you. Abnormal sensitivity to light may occur if you take more VFEND than prescribed.

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

If you stop taking VFEND
It has been shown that taking doses at the correct time significantly increases the effectiveness of your medicine. Therefore, unless your doctor has instructed you to stop treatment, it is important to continue taking VFEND correctly as described 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 a weakened immune system or those with difficult-to-treat infections may require long-term treatment to prevent the infection from returning.
When VFEND treatment is discontinued as directed by your doctor, no adverse effects should occur.

If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If side effects occur, most will probably be minor and temporary. However, some may be serious and require immediate medical attention.
Serious side effects – Stop taking VFEND and contact a doctor immediately

• Rash
• Jaundice, changes in liver function tests
• Pancreatitis

Other side effects
Very common: may occur in more than 1 in 10 people

• Visual impairment (visual disturbances including blurred vision, altered colour vision, abnormal tolerance to light perception, colour blindness, eye disorders, seeing halos, night blindness, oscillating vision, seeing sparks, visual aura, reduced visual acuity, visual brightness, partial loss of visual field, spots in front of the eyes)
• Fever
• Skin rashes
• Nausea, vomiting, diarrhoea
• Headache
• Swelling of the extremities
• Stomach pain
• Difficulty breathing
• Elevated liver enzymes

Common: may occur in up to 1 in 10 people

• Sinus inflammation, gum inflammation, chills, fatigue
• Reduction, sometimes severe, in the number of certain types of red blood cells (sometimes immune-mediated) and/or white blood cells (sometimes with fever), reduction in the number of blood cells (called platelets) that help blood clotting
• Low blood sugar levels, low blood potassium levels, low blood sodium levels
• Anxiety, depression, confusion, agitation, sleep disorders, hallucinations
• Seizures, tremor or uncontrolled muscle movements, tingling or abnormal skin sensations, increased muscle tone, drowsiness, dizziness
• Bleeding in the eye
• Heart rhythm problems including very fast heartbeat, very slow heartbeat, fainting
• Low blood pressure, inflammation of a vein (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, liver inflammation and liver injury
• Skin rash that may lead to severe blistering and peeling of the skin, characterised by a flat, red area of skin with small merging bumps, skin redness
• Itching
• Hair loss
• Back pain
• Kidney failure, blood in urine, changes in kidney function tests
• Sunburn or severe skin reaction following exposure to light or sun
• Skin cancer

Uncommon: may occur in up to 1 in 100 people

• Flu-like symptoms, irritation and inflammation of the gastrointestinal tract, gastrointestinal inflammation that may cause antibiotic-associated diarrhoea, inflammation of lymphatic vessels
• Inflammation of the thin tissue lining the abdominal wall and covering abdominal organs
• Enlarged lymph nodes (sometimes painful), bone marrow failure, increased eosinophils
• Reduced adrenal gland function, reduced thyroid gland activity
• Changes in brain function, Parkinson-like symptoms, nerve damage leading to numbness, pain, tingling or burning in hands or feet
• Problems with balance and coordination
• Brain oedema
• Double vision, serious eye conditions including: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage with visual impairment, swelling of the optic disc
• Reduced sensitivity to touch
• Taste disturbances
• Hearing disorders, ringing in the ears, dizziness
• Inflammation of certain internal organs, pancreas and duodenum, swelling and inflammation of the tongue
• Enlarged liver, liver failure, gallbladder diseases, gallstones
• Joint inflammation, inflammation of subcutaneous veins (which may be associated with blood clot formation)
• Kidney inflammation, presence of protein in urine, kidney damage
• Very rapid heartbeat or missed beats, sometimes with irregular electrical impulses
• Abnormal electrocardiogram (ECG)
• Increased cholesterol, increased blood urea
• Allergic skin reactions (sometimes severe), including a potentially life-threatening skin condition causing blisters and painful sores of the skin and mucous membranes, especially in the mouth, skin inflammation, urticaria, redness and irritation of the skin, skin colour changes that may be due to low platelet count, eczema
• Infusion site reaction
• Allergic reactions or exaggerated immune response
• Inflammation of tissues surrounding the bones

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

• Overactive thyroid gland
• Worsening of brain function, severe complication of liver disease
• Loss of most of the optic nerve fibres, corneal opacity, involuntary eye movement
• Bullous photosensitivity
• Disorder in which the body's immune system attacks part of the peripheral nervous system
• Heart rhythm or conduction problems (sometimes fatal)
• Potentially life-threatening allergic reaction
• Coagulation disorders
• Allergic skin reactions (sometimes severe), including rapid swelling (oedema) of the dermis, subcutaneous tissue, mucosa and submucosal tissues, itchy or painful patches of thickened and red skin with silvery scales, skin and mucous membrane irritation, potentially life-threatening skin condition causing detachment of large portions of the epidermis (the outer layer of skin) from underlying skin layers
• Small patches of dry, scaly skin, sometimes thick with tips or 'horns'

Side effects with unknown frequency:

• Freckles and pigmented spots

Other significant side effects, whose frequency is unknown but which should be reported immediately to a doctor, are:

• Red, scaly or ring-shaped skin lesions which could be symptoms of an autoimmune disease called systemic lupus erythematosus

Since VFEND has been observed to affect the liver and kidneys, your doctor will need to monitor liver and kidney function through blood tests. Inform your doctor if you have stomach pain or if your stools are different from normal.
Cases of skin carcinoma have been reported in patients treated with VFEND for prolonged periods.
Sunburn or severe skin reaction following exposure to light or sun has been reported more frequently in children. If you or your child develops skin disorders, your doctor may refer you to a dermatologist who may decide whether it is important for you or your child to continue regular visits with a dermatologist. Elevated liver enzymes have also been observed more frequently in children.
If any of these side effects persist or are bothersome, inform your doctor.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 that month.
Oral suspension powder: store between 2°C and 8°C (in the refrigerator) prior to reconstitution.
Reconstituted suspension:
Store at a temperature not exceeding 30°C.
Do not refrigerate or freeze.
Store in the original packaging.
Keep the container tightly closed.
Unused suspension must be discarded 14 days after reconstitution.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What VFEND contains

• The active substance is voriconazole. Each vial contains 45 g of powder, corresponding to 70 ml of suspension after reconstitution with water as recommended. Each ml of reconstituted suspension contains 40 mg of voriconazole (see Section 3, “How to take VFEND”).
• The other ingredients are: sucrose, colloidal silicon dioxide, titanium dioxide, xanthan gum, sodium citrate, sodium benzoate, citric acid, natural orange flavour (see section 2, VFEND 40 mg/ml oral suspension powder contains sucrose, benzoate salt (sodium benzoate) and sodium).

Description of the appearance of VFEND and contents of the pack
VFEND is a white to off-white powder for oral suspension, which, after reconstitution with water, forms a white to off-white suspension with an orange flavour.

Marketing Authorisation Holder:
Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Brussels, Belgium.

Manufacturer:
Fareva Amboise, Zone Industrielle, 29 route des Industries, 37530 Pouzolles-sur-Cisse, France.

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien / Luxembourg / Luxemburg
Pfizer Luxembourg SARL
Pfizer NV/SA Filialas Lietuvoje
Tél/Tel: +32 (0)2 554 62 11
Tel. +3705 2514000

България
Pfizer Luxembourg SARL, Branch Bulgaria
Тел.: +359 2 970 4333

Magyarország
Pfizer Kft.
Tel. +36 1 488 37 00

Česká republika
Pfizer, spol. s.r.o.
Tel: +420-283-004-111

Malta
Vivian Corporation Ltd.
Tel: +356 21344610

Danmark
Pfizer ApS
Tlf.: +45 44 20 11 00

Nederland
Pfizer bv
Tel: +31 (0) 800 63 34 636

Deutschland
PFIZER PHARMA GmbH
Tel: +49 (0)30 550055-51000

Norge
Pfizer AS
Tlf: +47 67 52 61 00

Eesti
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

Österreich
Pfizer Corporation Austria Ges.m.b.H.
Tel: +43 (0)1 521 15-0

Ελλάδα
Pfizer ΕΛΛΑΣ A.E.
Τηλ.: +30 210 6785 800

Polska
Pfizer Polska Sp. z o.o.
Tel.: +48 22 335 61 00

España
Pfizer, S.L.
Tel: +34 91 490 99 00

Portugal
Laboratórios Pfizer, Lda.
Tel: +351 214 235 500

France
Pfizer
Tél: +33 (0)1 58 07 34 40

România
Pfizer România S.R.L
Tel: +40 (0)21 207 28 00

Hrvatska
Pfizer Croatia d.o.o.
Tel: +385 1 3908 777

Slovenija
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)152 11 400

Ireland
Pfizer Healthcare Ireland Unlimited Company
Tel: 1800 633 363 (toll free)
+44 (0)1304 616161

Ísland
Icepharma hf.
Sími: +354 540 8000

Suomi/Finland
Pfizer Oy
Puh/Tel: +358 (0)9 43 00 40

Italia
Pfizer S.r.l.
Tel: +39 06 33 18 21

Sverige
Pfizer AB
Tel: +46 (0)8 5505 2000

Kύπρος
Pfizer ΕΛΛΑΣ Α.Ε. (Cyprus Branch)
Τηλ: +357 22 817690

Latvija
Pfizer Luxembourg SARL
Filiāle Latvijā
Tel: +371 670 35 775

More detailed information on this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu.