Vfend

Informazzjoni prinċipali

  • Isem kummerċjali:
  • Vfend
  • Dominju tal-mediċina:
  • Bnedmin
  • Tip ta 'mediċina:
  • Droga allopatika

Dokumenti

Lokalizzazzjoni

  • Disponibbli fi:
  • Vfend
    Unjoni Ewropea
  • Lingwa:
  • Ingliż

Informazzjoni terapewtika

  • Grupp terapewtiku:
  • ANTIMYCOTICS FOR SYSTEMIC USE
  • Żona terapewtika:
  • Candidiasis, Mycoses, Aspergillosis
  • Indikazzjonijiet terapewtiċi:
  • Voriconazole, is a broad spectrum, triazole antifungal agent and is indicated in adults and children aged 2 years and above as follows: treatment of invasive aspergillosis;, treatment of in candidaemianon-neutropenic patients;, treatment of fluconazole-resistant serious invasive Candida infections (including C. krusei);, Treatment of serious fungal infections caused by Scedosporium spp. and Fusarium spp., Vfend should be administered primarily to patients with progressive, possibly life-threatening infections. Prophylaxis of invasive fungal infections in high risk allogeneic hematopoietic stem cell transplant (HSCT) recipients.,
  • Sommarju tal-prodott:
  • Revision: 45

Status

  • Sors:
  • EMA - European Medicines Agency
  • L-istatus ta 'awtorizzazzjoni:
  • Authorised
  • Numru ta 'awtorizzazzjoni:
  • EMEA/H/C/000387
  • Data ta 'l-awtorizzazzjoni:
  • 18-03-2002
  • Kodiċi EMEA:
  • EMEA/H/C/000387
  • L-aħħar aġġornament:
  • 23-05-2019

Rapport ta 'Valutazzjoni Pubblika

7 Westferry Circus

Canary Wharf

London E14 4HB

United Kingdom

An agency of the European Union

Telephone

+44 (0)20 7418 8400

Facsimile

+44 (0)20 7418 8416

E-mail

info@ema.europa.eu

Website

www.ema.europa.eu

© European Medicines Agency, 2014. Reproduction is authorised provided the source is acknowledged.

EMA/359520/2014

EMEA/H/C/000387

EPAR summary for the public

Vfend

voriconazole

This is a summary of the European public assessment report (EPAR) for Vfend. It explains how the

Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in

favour of granting a marketing authorisation and its recommendations on the conditions of use for

Vfend.

What is Vfend?

Vfend is an antifungal medicine that contains the active substance voriconazole. It is available as

tablets (50 mg or 200 mg), as an oral suspension (40 mg/ml) and as a powder to be made up into a

solution for infusion (drip into a vein).

What is Vfend used for?

Vfend is used for the treatment of adults and children over the age of two years who have the

following fungal infections:

invasive aspergillosis (a type of fungal infection due to Aspergillus);

candidaemia (another type of fungal infection due to Candida) in patients with a normal white

blood cell count;

serious invasive Candida infections when the fungus is resistant to fluconazole (another antifungal

medicine);

serious fungal infections caused by Scedosporium or Fusarium (two different types of fungus).

When used for treatment of fungal infections, Vfend is intended mainly for patients with worsening and

possibly life-threatening infections.

Vfend

Page 2/4

Vfend is also used to prevent invasive fungal infections in patients who have had undergone

haematopoietic (blood) stem-cell transplant (a transplant of a type of stem cells that can develop into

blood cells) and are at high risk of infection.

The medicine can only be obtained with a prescription.

How is Vfend used?

Vfend is given twice a day at least one hour before or one hour after a meal. The dose of Vfend to use

depends on the weight of the patient and on which formulation of the medicine is used.

When used to treat fungal infections, patients need to receive an initial higher dose (loading dose) on

the first day. The aim of the loading dose is to reach stable blood levels. The loading dose is then

followed by a maintenance dose that can be adjusted according to the patient’s response. The dose

may be increased or decreased according to how the patient responds and the side effects experienced

respectively. Treatment duration should be as short as possible. Treatment beyond 180 days requires

careful assessment to ensure that the benefits continue to outweigh the risk for the patient.

In adults, both the loading and the maintenance doses can be given by infusion or by mouth using

either the tablets or the suspension, but in children it is recommended to start treatment with the

infusion and to consider switching to the suspension if an improvement is seen. The tablets and

suspension are to be taken at least one hour before or after a meal.

When used to prevent infections in patients who have had blood stem-cell transplantation, Vfend is

given on the day of the transplantation and for up to 100 days after. Preventive treatment should last

for as short a time as possible. It may be continued for a further 80 days but only if the patient’s

immune system is still suppressed or if they develop graft-versus-host disease (when the transplanted

cells start attacking the body’s own cells). Treatment should be stopped if patients experience

treatment-related side effects.

For further information, see the package leaflet.

How does Vfend work?

The active substance in Vfend, voriconazole, belongs to the ‘triazole’ class of antifungal medicines. It

works by disrupting the formation of ergosterol, which is an important component of fungal cell

membranes. Without a functional cell membrane, the fungus is killed or prevented from spreading. The

list of fungi against which Vfend is active can be found in the summary of product characteristics (also

part of the EPAR).

How has Vfend been studied?

The study of Vfend in the treatment of invasive aspergillosis involved 277 immunocompromised

patients (patients whose immune system was not working properly). Vfend was compared with

amphotericin B (another antifungal medicine).

The study of Vfend in the treatment of candidaemia compared Vfend with a treatment of

amphotericin B followed by fluconazole in 370 patients.

Vfend has also been studied in the treatment of serious refractory Candida infections in 55 patients, in

scedosporiosis in 38 patients, and in fusariosis in 21 patients. ‘Refractory’ means that the infections

were not responding to treatment. Most patients receiving Vfend treatment for these rare infections did

not tolerate or did not respond to prior treatment with other antifungal medicines.

Vfend

Page 3/4

Vfend has also been studied in 285 children.

The main measure of effectiveness in all these studies was the number of patients who had a complete

or partial response to treatment.

Vfend has also been studied as a preventative treatment in patients who have had blood stem-cell

transplantation. In a study involving 465 patients, Vfend was compared with another antifungal

medicine, itraconazole. Treatment was considered to be successful if a patient was able to continue

treatment for 100 days after the transplantation and had not developed a fungal infection by day 180.

What benefit has Vfend shown during the studies?

In the treatment of invasive aspergillosis, the proportion of patients responding to treatment was

higher with Vfend than with amphotericin B (53% versus 31%). The survival for voriconazole was

significantly greater than that for amphotericin B.

For candidaemia, the percentage of responders to Vfend treatment at the end of therapy was the same

as for the comparator (72%).

A successful outcome was seen in 44% of the patients with serious refractory Candida infections (24

out of 55). In most of these (15 out of 24), the response was complete.

In the treatment of scedosporiosis and fusariosis, 28 out of 59 patients had a complete or partial

response to treatment.

In the study on prevention in patients who had blood stem-cell transplantation, around 49% of

patients who were given Vfend (109 out of 224) had a successful treatment compared with around

33% of patients who received itraconazole (80 out of 241).

What is the risk associated with Vfend?

The most common side effects with Vfend (seen in more than 1 patient in 10) are peripheral oedema

(swelling of the arms and legs), headache, visual disturbances (including blurred vision, changes in

colour perception and excessive sensitivity to light), respiratory distress (difficulty breathing),

abdominal pain (stomach ache), nausea (feeling sick), vomiting, diarrhoea, rash and pyrexia (fever)

and abnormal liver function test results. For the full list of all side effects reported with Vfend, see the

package leaflet.

Vfend must not be used in patients who are taking any of the following medicines:

terfenadine, astemizole (commonly used for allergy – these medicines may be available without a

prescription);

cisapride (used for stomach problems);

pimozide (used to treat mental illnesses);

quinidine (used for irregular heart beat);

rifampicin (used to treat tuberculosis);

carbamazepine (used to treat seizures [fits]);

phenobarbital (used for severe insomnia and seizures);

ritonavir (used to treat HIV infection) at doses of 400 mg or more twice a day;

ergot alkaloids such as ergotamine and dihydroergotamine (used to treat migraine headache);

Vfend

Page 4/4

sirolimus (used in transplant patients);

St John’s wort (a herbal preparation used to treat depression);

high dose efavirenz (used to treat HIV infection).

Caution is also needed when Vfend is taken at the same time as other medicines. For the full list of

restrictions, see the package leaflet.

Why has Vfend been approved?

The CHMP decided that Vfend’s benefits are greater than its risks and recommended that it be given

marketing authorisation.

What measures are being taken to ensure the safe and effective use of

Vfend?

A risk management plan has been developed to ensure that Vfend is used as safely as possible. Based

on this plan, safety information has been included in the summary of product characteristics and the

package leaflet for Vfend, including the appropriate precautions to be followed by healthcare

professionals and patients.

Other information about Vfend

The European Commission granted a marketing authorisation valid throughout the European Union for

Vfend on 19 March 2002.

The full EPAR for Vfend can be found on the Agency’s website: ema.europa.eu/Find medicine/Human

medicines/European Public Assessment Reports. For more information about treatment with Vfend,

read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 06-2014.

Fuljett ta 'Informazzjoni għall-Pazjent: prodott - kompożizzjoni, indikazzjonijiet, effetti sekondarji, dożaġġ, interazzjonijiet, reazzjonijiet avversi, tqala, treddigħ

B. PACKAGE LEAFLET

Package Leaflet: Information for the user

VFEND 50 mg film-coated tablets

VFEND 200 mg film-coated tablets

Voriconazole

Read all of this leaflet carefully before you start taking this medicine because it contains important

information for you.

Keep this leaflet. You may need to read it again.

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

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if

their signs of illness are the same as yours.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

What VFEND is and what it is used for

What you need to know before you take VFEND

How to take VFEND

Possible side effects

How to store VFEND

Content 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 the fungi that cause infections.

It is used for the treatment of patients (adults and children over the age of 2) with:

invasive aspergillosis (a type of fungal infection due to Aspergillus sp),

candidaemia (another type of fungal infection due to Candida sp) in non-neutropenic patients

(patients without abnormally low white blood cells count),

serious invasive Candida sp. infections when the fungus is resistant to fluconazole (another

antifungal medicine),

serious fungal infections caused by Scedosporium sp. or Fusarium sp. (two different species of

fungi).

VFEND is intended for patients with worsening, possibly life-threatening, fungal infections.

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

This product should only be taken under the supervision of a doctor.

2. What you need to know before you take VFEND

Do not take VFEND:

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

It is very important that you inform your doctor or pharmacist if you are taking or have taken any other

medicines, even those that are obtained without a prescription, or herbal medicines.

The medicines in the following list must not be taken during your course of VFEND treatment:

Terfenadine (used for allergy)

Astemizole (used for allergy)

Cisapride (used for stomach problems)

Pimozide (used for treating mental illness)

Quinidine (used for irregular heart beat)

Rifampicin (used for treating tuberculosis)

Efavirenz (used for treating HIV) in doses of 400 mg and above 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 for treating HIV) in doses of 400mg and more twice daily

St. John’s Wort (herbal supplement)

Warnings and precautions

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

you have had an allergic reaction to other azoles.

you are suffering from, or have ever suffered from liver disease. If you have liver disease, your

doctor may prescribe a lower dose of VFEND. Your doctor should also monitor your liver function

while you are being treated with VFEND by doing blood tests.

you are known to have cardiomyopathy, irregular heart beat, slow heart rate or an abnormality of

electrocardiogram (ECG) called ‘long QTc syndrome’.

You should avoid any sunlight and sun exposure while being treated. It is important to cover sun exposed

areas of skin and use sunscreen with high sun protection factor (SPF), as an increased sensitivity of skin to

the sun’s UV rays can occur. These precautions are also applicable to children.

While being treated with VFEND:

tell your doctor immediately if you develop

sunburn

severe skin rash or blisters

bone pain

If you develop skin disorders as described above, your doctor may refer you to a dermatologist, who after

consultation may decide that it is important for you to be seen on a regular basis. There is a small chance that

skin cancer could develop with long-term use of VFEND.

Your doctor should monitor the function of your liver and kidney by doing blood tests.

Children and adolescents

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

Other medicines and VFEND

Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other

medicines, including those that are obtained without a prescription.

Some medicines, when taken at the same time as VFEND, may affect the way VFEND works or VFEND

may affect the way they work.

Tell your doctor if you are taking the following medicine, as treatment with VFEND at the same time should

be avoided if possible:

Ritonavir (used for treating HIV) in doses of 100 mg twice daily

Tell your doctor if you are taking either of the following medicines, as treatment with VFEND at the same

time should be avoided if possible, and a dose adjustment of voriconazole may be required:

Rifabutin (used for treating tuberculosis). If you are already being treated with rifabutin your blood

counts and side effects to rifabutin will need to be monitored.

Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin your blood

concentration of phenytoin will need to be monitored during your treatment with VFEND and your

dose may be adjusted.

Tell your doctor if you are taking any of the following medicines, as a dose adjustment or monitoring may be

required to check that the medicines and/ or VFEND are still having the desired effect:

Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to slow down clotting

of the blood)

Ciclosporin (used in transplant patients)

Tacrolimus (used in transplant patients)

Sulfonylureas (e.g., tolbutamide, glipizide, and glyburide) (used for diabetes)

Statins (e.g., atorvastatin, simvastatin) (used for lowering cholesterol)

Benzodiazepines (e.g midazolam, triazolam) (used for severe insomnia and stress)

Omeprazole (used for treating ulcers)

Oral contraceptives (if you take VFEND whilst using oral contraceptives, you may get side effects

such as nausea and menstrual disorders)

Vinca alkaloids (e.g., vincristine and vinblastine) (used in treating cancer)

Indinavir and other HIV protease inhibitors (used for treating HIV)

Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, nevirapine) (used for

treating HIV) (some doses of efavirenz can NOT be taken at the same time as VFEND)

Methadone (used to treat heroin addiction)

Alfentanil and fentanyl and other short-acting opiates such as sufentanil (painkillers used for surgical

procedures)

Oxycodone and other long-acting opiates such as hydrocodone (used for moderate to severe pain)

Non-steroidal anti-inflammatory drugs (e.g., ibuprofen, diclofenac) (used for treating pain and

inflammation)

Fluconazole (used for fungal infections)

Everolimus (used for treating advanced kidney cancer and in transplant patients)

Pregnancy and breast-feeding

VFEND must not be taken during pregnancy, unless indicated by your doctor. Effective contraception must

be used in women of childbearing potential. Contact your doctor immediately if you become pregnant while

taking VFEND.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your

doctor or pharmacist for advice before taking this medicine.

Driving and using machines

VFEND may cause blurring of vision or uncomfortable sensitivity to light. While affected, do not drive

or operate any tools or machines. Contact your doctor if you experience this.

VFEND contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, tell your doctor before

taking VFEND.

3.

How to take VFEND

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if

you are not sure.

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

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

Tablets

Patients 40 kg and above

Patients less than 40 kg

Dose for the first 24

hours

400 mg every 12 hours

200 mg every 12 hours

(Loading Dose)

the first 24 hours

the first 24 hours

Dose after the first 24

hours

200 mg twice a day

100 mg twice a day

(Maintenance Dose)

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

The doctor may decide to decrease the dose if you have mild to moderate cirrhosis.

Use in children and adolescents

The recommended dose for children and teenagers is as follows:

Tablets

Children aged 2 to less

than 12 years and

teenagers aged 12 to 14

years weighing less than

50 kg

Teenagers aged 12 to 14

years weighing 50 kg or

more; and all teenagers

older than 14

Dose for the first 24

hours

(Loading Dose)

Your treatment will be

started as an infusion

400 mg every 12 hours

for the first 24 hours

Dose after the first 24

hours

(Maintenance Dose)

9 mg/kg twice a day

(a maximum dose of

350 mg twice daily)

200 mg twice a day

Depending on your response to treatment, your doctor may increase or decrease the daily dose.

Tablets must only be given if the child is able to swallow tablets.

Take your tablet 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 prevention of fungal infections, your doctor may stop giving

VFEND if you or your child develop treatment related side effects.

If you take more VFEND than you should

If you take more tablets than prescribed (or if someone else takes your tablets) you must seek medical

advice or go to the nearest hospital casualty department immediately. Take your box of VFEND tablets with

you. You may experience abnormal intolerance to light as a result of taking more VFEND than you should.

If you forget to take VFEND

It is important to take your VFEND tablets regularly at the same time each day. If you forget to take one

dose, take your next dose when it is due. Do not take a double dose to make up for a forgotten dose.

If you stop taking VFEND

It has been shown that taking all doses at the appropriate times may greatly increase the effectiveness of

your medicine. Therefore unless your doctor instructs you to stop treatment, it is important to keep taking

VFEND correctly, as described above.

Continue taking VFEND until your doctor tells you to stop. Do not stop treatment early because your

infection may not be cured. Patients with a weakened immune system or those with difficult infections may

require long-term treatment to prevent the infection from returning.

When VFEND treatment is stopped by your doctor you should not experience any effects.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If any side effects occur, most are likely to be minor and temporary. However, some may be serious and

need medical attention.

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

-

Rash

-

Jaundice; Changes in blood tests of liver function

-

Pancreatitis

Other side effects

Very common: may affect more than 1 in 10 people

-

Visual impairment (change in vision including blurred vision, visual color alterations, abnormal

intolerance to visual perception of light, colour blindness, eye disorder, halo vision, night blindness,

swinging vision, seeing sparks, visual aura, visual acuity reduced, visual brightness, loss of part of

the usual field of vision, spots before the eyes)

-

Fever

-

Rash

-

Nausea, vomiting, diarrhoea

-

Headache

-

Swelling of the extremities

-

Stomach pains

-

Breathing difficulties

-

Elevated liver enzymes

Common: may affect up to 1 in 10 people

-

Inflammation of the sinuses, inflammation of the gums, chills, weakness

-

Low numbers of some types, including severe, of red (sometimes immune-related) and/or white

blood cells (sometimes with fever), low numbers of cells called platelets that help the blood to clot

-

Low blood sugar, low blood potassium, low sodium in the blood

-

Anxiety, depression, confusion, agitation, inability to sleep, hallucinations

-

Seizures, tremors or uncontrolled muscle movements, tingling or abnormal skin

sensations, increase in muscle tone, sleepiness, 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 the formation of a blood

clot)

-

Acute breathing difficulty, chest pain, swelling of the face (mouth, lips and around eyes), fluid

accumulation in the lungs

-

Constipation, indigestion, inflammation of the lips

-

Jaundice, inflammation of the liver and liver injury

-

Skin rashes which may lead to severe blistering and peeling of the skin characterized by a flat, red

area on the skin that is covered with small confluent bumps, redness of the skin

-

Itchiness

-

Hair loss

-

Back pain

-

Kidney failure, blood in the urine, changes in kidney function tests

Uncommon: may affect up to 1 in 100 people

-

Flu-like symptoms, irritation and inflammation of the gastrointestinal tract, inflammation of the

gastrointestinal tract causing antibiotic associated diarrhoea, inflammation of the lymphatic vessels

-

Inflammation of the thin tissue that lines the inner wall of the abdomen and covers the abdominal

organ

-

Enlarged lymph glands (sometimes painful), failure of blood marrow, increased eosinophil

-

Depressed function of the adrenal gland, underactive thyroid gland

-

Abnormal brain function, Parkinson-like symptoms, nerve injury resulting in numbness, pain,

tingling or burning in the hands or feet

-

Problems with balance or coordination

-

Swelling of the brain

-

Double vision, serious conditions of the eye including: pain and inflammation of the eyes and

eyelids, abnormal eye movement, damage to the optic nerve resulting in vision impairment, optic

disc swelling

-

Decreased sensitivity to touch

-

Abnormal sense of taste

-

Hearing difficulties, ringing in the ears, vertigo

-

Inflammation of certain internal organs- pancreas and duodenum, swelling and inflammation of the

tongue

-

Enlarged liver, liver failure, gallbladder disease, gallstones

-

Joint inflammation, inflammation of the veins under the skin (which may be associated with the

formation of a blood clot)

-

Inflammation of the kidney, proteins in the urine, damage to the kidney

-

Very fast heart rate or skipped heartbeats, sometimes with erratic electrical impulses

-

Abnormal electrocardiogram (ECG)

-

Blood cholesterol increased, blood urea increased

-

Allergic skin reactions (sometimes severe), including life-threatening skin condition that causes

painful blisters and sores of the skin and mucous membranes, especially in the mouth,

inflammation of the skin, hives, sunburn or severe skin reaction following exposure to light or sun,

skin redness and irritation, red or purple discoloration of the skin which may be caused by low

platelet count, eczema

-

Infusion site reaction

-

Allergic reaction or exaggerated immune response

Rare: may affect up to 1 in 1000 people

-

Overactive thyroid gland

-

Deterioration of brain function that is a serious complication of liver disease

-

Loss of most fibers in the optic nerve, clouding of the cornea, involuntary movement of the eye

-

Bullous photosensitivity

-

A disorder in which the body’s immune system attacks part of the peripheral nervous system

-

Heart rhythm or conduction problems (sometimes life threatening)

-

Life threatening allergic reaction

-

Disorder of blood clotting system

-

Allergic skin reactions (sometimes severe), including rapid swelling (oedema) of the dermis,

subcutaneous tissue, mucosa and submucosal tissues, itchy or sore patches of thick, red skin with

silvery scales of skin, irritation of the skin and mucous membranes, life-threatening skin condition

that causes large portions of the epidermis, the skin's outermost layer, to detach from the layers of

skin below

-

Small dry scaly skin patches, sometimes thick with spikes or ‘horns’

Side effects with frequency not known:

-

Freckles and pigmented spots

Other significant side effects whose frequency is not known, but should be reported to your doctor

immediately:

-

Skin cancer

-

Inflammation of the tissue surrounding the bone

-

Red, scaly patches or ring-shaped skin lesions that may be a symptom of an autoimmune disease

called cutaneous lupus erythematosus

As VFEND has been known to affect the liver and the kidney, your doctor should monitor the function

of your liver and kidney by doing blood tests. Please advise your doctor if you have any stomach pains

or if your stools have a different consistency.

There have been reports of skin cancer in patients treated with VFEND for long periods of time.

Sunburn or severe skin reaction following exposure to light or sun was experienced more frequently in

children. If you or your child develops skin disorders, your doctor may refer you to a dermatologist, who

after consultation may decide that it is important for you or your child to be seen on a regular basis. Elevated

liver enzymes were also observed more frequently in children.

If any of these side effects persist or are troublesome, please tell your doctor.

Reporting of side effects

If you get any side effects, talk to your doctor or, pharmacist or nurse. This includes any possible side effects

not listed in this leaflet. You can also report side effects directly via the national reporting system listed in

Appendix 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 which is 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 throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw

away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What VFEND contains

The active substance is voriconazole. Each tablet contains either 50 mg voriconazole (for VFEND 50

mg film-coated tablets) or 200 mg voriconazole (for VFEND 200 mg film-coated tablets).

other

ingredients

lactose

monohydrate,

pregelatinised

starch,

croscarmellose

sodium,

povidone and magnesium stearate which make up the tablet core and hypromellose, titanium dioxide

(E171), lactose monohydrate and glycerol triacetate which make up the film-coat.

What VFEND looks like and contents of the pack

VFEND 50 mg film-coated tablets are supplied as white to off-white round film-coated tablets with Pfizer

marked on one side and VOR50 on the reverse.

VFEND 200 mg film-coated tablets are supplied as white to off-white capsule shaped film-coated tablets

with Pfizer marked on one side and VOR200 on the reverse.

VFEND 50 mg film-coated tablets and 200 mg film-coated tablets are available as packs of 2, 10, 14, 20,

28, 30, 50, 56 and 100.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

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

Manufacturers

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 any information about this medicine, please contact the local representative of the

Marketing Authorisation Holder:

België /Belgique/Belgien

Pfizer S.A./N.V.

Tél/Tel: +32 (0)2 554 62 11

Lietuva

Pfizer Luxembourg SARL

Filialas Lietuvoje

Tel. +3705 2514000

България

Пфайзер Люксембург САРЛ, Клон България

Тел.: +359 2 970 4333

Luxembourg/Luxemburg

Pfizer S.A.

Tél: +32 (0)2 554 62 11

Česká republika

Pfizer s.r.o.

Tel: +420-283-004-111

Magyarország

Pfizer Kft.

Tel. + 36 1 488 37 00

Danmark

Pfizer ApS Tlf:

+45 44 20 11 00

Malta

V.J. Salomone Pharma Ltd.

Tel : +356 21 22 01 74

Deutschland

Pfizer Pharma PFE GmbH

Tel: +49 (0)800 8535555

Nederland

Pfizer bv

Tel: +31 (0)10 406 43 01

Eesti

Pfizer Luxembourg SARL Eesti filiaal

Tel: +372 666 7500

Norge

Pfizer AS

Tlf: +47 67 52 61 00

Ελλάδα

Pfizer ΕΛΛΑΣ A.E.

Τηλ.: +30 210 6785 800

Österreich

Pfizer Corporation Austria

Ges.m.b.H. Tel: +43 (0)1

521 15-0

España

Pfizer, S.L.

Tel: +34 91 490 99 00

Polska

Pfizer Polska Sp. z o.o.,

Tel.: +48 22 335 61 00

France

Pfizer

Tél: +33 (0)1 58 07 34 40

Portugal

Laboratórios Pfizer, Lda.

Tel: + 351 214 235 500

Hrvatska

Pfizer Croatia d.o.o.

Tel: + 385 1 3908 777

România

Pfizer România S.R.L

Tel: +40 (0)21 207 28 00

Ireland

Pfizer Healthcare Ireland

Tel: 1800 633 363 (toll free)

+44 (0)1304 616161

Slovenija

Pfizer Luxembourg SARL

Pfizer, podružnica za svetovanje s področja

farmacevtske dejavnosti, Ljubljana

Tel: + 386 (0)152 11 400

Ísland

Icepharma hf.,

Sími: + 354 540 8000

Slovenská republika

Pfizer Luxembourg SARL, organizačná zložka

Tel: +421-2-3355 5500

Italia

Pfizer Italia S.r.l.

Tel: +39 06 33 18 21

Suomi/Finland

Pfizer Oy

Puh/Tel: +358(0)9 43 00 40

Kύπρος

Pfizer ΕΛΛΑΣ Α.Ε. (Cyprus Branch)

Τηλ: +357 22 817690

Sverige

Pfizer AB

Tel: +46 (0)8 5505 2000

Latvija

Pfizer Luxembourg SARL

Filiāle Latvijā

Tel: +371 670 35 775

United Kingdom

Pfizer Limited

Tel: +44 (0)1304 616161

This leaflet was last approved in {MM/YYYY}.

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu

Package Leaflet: Information for the user

VFEND 200 mg powder for solution for infusion

Voriconazole

Read all of this leaflet carefully before you start taking this medicine because it contains important

information for you.

Keep this leaflet. You may need to read it again.

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

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if

their signs of illness are the same as yours.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

What VFEND is and what it is used for

What you need to know before you take VFEND

How to use VFEND

Possible side effects

How to store VFEND

Content 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 the fungi that cause infections.

It is used for the treatment of patients (adults and children over the age of 2) with:

invasive aspergillosis (a type of fungal infection due to Aspergillus sp),

candidaemia (another type of fungal infection due to Candida sp) in non-neutropenic patients

(patients without abnormally low white blood cells count),

serious invasive Candida sp. infections when the fungus is resistant to fluconazole (another

antifungal medicine),

serious fungal infections caused by Scedosporium sp. or Fusarium sp. (two different species of

fungi).

VFEND is intended for patients with worsening, possibly life-threatening, fungal infections.

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

This product should only be used under the supervision of a doctor.

2. What you need to know before you take VFEND

Do not take VFEND:

-

If you are allergic to the active ingredient voriconazole, or to sulfobutylether beta cyclodextrin sodium

(listed in section 6).

It is very important that you inform your doctor or pharmacist if you are taking or have taken any other

medicines, even those that are obtained without a prescription, or herbal medicines.

The medicines in the following list must not be taken during your course of VFEND treatment:

Terfenadine (used for allergy)

Astemizole (used for allergy)

Cisapride (used for stomach problems)

Pimozide (used for treating mental illness)

Quinidine (used for irregular heart beat)

Rifampicin (used for treating tuberculosis)

Efavirenz (used for treating HIV) in doses of 400 mg and above 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 for treating HIV) in doses of 400mg and more twice daily

St. John’s Wort (herbal supplement)

Warnings and precautions

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

you have had an allergic reaction to other azoles.

you are suffering from, or have ever suffered from liver disease. If you have liver disease, your

doctor may prescribe a lower dose of VFEND. Your doctor should also monitor your liver function

while you are being treated with VFEND by doing blood tests.

you are known to have cardiomyopathy, irregular heart beat, slow heart rate or an abnormality of

electrocardiogram (ECG) called ‘long QTc syndrome’.

You should avoid any sunlight and sun exposure while being treated. It is important to cover sun exposed

areas of skin and use sunscreen with high sun protection factor (SPF), as an increased sensitivity of skin to

the sun’s UV rays can occur. These precautions are also applicable to children.

While being treated with VFEND:

tell your doctor immediately if you develop

sunburn

severe skin rash or blisters

bone pain

If you develop skin disorders as described above, your doctor may refer you to a dermatologist, who after

consultation may decide that it is important for you to be seen on a regular basis. There is a small chance that

skin cancer could develop with long-term use of VFEND.

Your doctor should monitor the function of your liver and kidney by doing blood tests.

Children and adolescents

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

Other medicines and VFEND

Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other

medicines, including those that are obtained without a prescription.

Some medicines, when taken at the same time as VFEND, may affect the way VFEND works or VFEND

may affect the way they work.

Tell your doctor if you are taking the following medicine, as treatment with VFEND at the same time should

be avoided if possible:

Ritonavir (used for treating HIV) in doses of 100 mg twice daily

Tell your doctor if you are taking either of the following medicines, as treatment with VFEND at the same

time should be avoided if possible, and a dose adjustment of voriconazole may be required:

Rifabutin (used for treating tuberculosis). If you are already being treated with rifabutin your blood

counts and side effects to rifabutin will need to be monitored.

Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin your blood

concentration of phenytoin will need to be monitored during your treatment with VFEND and your

dose may be adjusted.

Tell your doctor if you are taking any of the following medicines, as a dose adjustment or monitoring may be

required to check that the medicines and/ or VFEND are still having the desired effect:

Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to slow down clotting

of the blood)

Ciclosporin (used in transplant patients)

Tacrolimus (used in transplant patients)

Sulfonylureas (e.g., tolbutamide, glipizide, and glyburide) (used for diabetes)

Statins (e.g., atorvastatin, simvastatin) (used for lowering cholesterol)

Benzodiazepines (e.g midazolam, triazolam) (used for severe insomnia and stress)

Omeprazole (used for treating ulcers)

Oral contraceptives (if you take VFEND whilst using oral contraceptives, you may get side effects

such as nausea and menstrual disorders)

Vinca alkaloids (e.g., vincristine and vinblastine) (used in treating cancer)

Indinavir and other HIV protease inhibitors (used for treating HIV)

Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, nevirapine) (used for

treating HIV) (some doses of efavirenz can NOT be taken at the same time as VFEND)

Methadone (used to treat heroin addiction)

Alfentanil and fentanyl and other short-acting opiates such as sufentanil (painkillers used for surgical

procedures)

Oxycodone and other long-acting opiates such as hydrocodone (used for moderate to severe pain)

Non-steroidal anti-inflammatory drugs (e.g., ibuprofen, diclofenac) (used for treating pain and

inflammation)

Fluconazole (used for fungal infections)

Everolimus (used for treating advanced kidney cancer and in transplant patients)

Pregnancy and breast-feeding

VFEND must not be used during pregnancy, unless indicated by your doctor. Effective contraception must

be used in women of childbearing potential. Contact your doctor immediately if you become pregnant

while being treated with VFEND.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your

doctor or pharmacist for advice before taking this medicine.

Driving and using machines

VFEND may cause blurring of vision or uncomfortable sensitivity to light. While affected, do not drive

or operate any tools or machines. Tell your doctor if you experience this.

VFEND contains sodium

Each vial of VFEND contains 217.6 mg of sodium per vial. This should be taken into consideration if you

are on a strictly controlled sodium diet.

3. How to use VFEND

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

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

Your doctor may change your dose depending on your condition.

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

Intravenous

Dose for the first 24 hours

6 mg/kg every 12 hours for

(Loading Dose)

first 24 hours

Dose after the first 24

hours

4 mg/kg twice a day

(Maintenance Dose)

Depending on your response to treatment, your doctor may decrease the dose to 3 mg/kg twice daily.

The doctor may decide to decrease the dose if you have mild to moderate cirrhosis.

Use in children and adolescents

The recommended dose for children and teenagers is as follows:

Intravenous

Children aged 2 to less

than 12 years and

teenagers aged 12 to 14

years weighing less than

50 kg

Teenagers aged 12 to 14

years weighing 50 kg or

more; and all teenagers

older than 14

Dose for the first 24

hours

(Loading Dose)

9 mg/kg every 12 hours

for the first 24 hours

6 mg/kg every 12 hours

for the first 24 hours

Dose after the first 24

hours

8 mg/kg twice a day

4 mg/kg twice a day

(Maintenance Dose)

Depending on your response to treatment, your doctor may increase or decrease the daily dose.

VFEND powder for solution for infusion will be reconstituted and diluted to the correct concentration by

your hospital pharmacist or nurse. (Please refer to the end of this leaflet for further information)

This will be given to you by intravenous infusion (into a vein) at a maximum rate of 3 mg/kg per hour over 1

to 3 hours.

If you or your child are taking VFEND for prevention of fungal infections, your doctor may stop giving

VFEND if you or your child develop treatment related side effects.

If a dose of VFEND has been forgotten

As you will be given this medicine under close medical supervision, it is unlikely that a dose would be

missed. However tell your doctor or pharmacist if you think that a dose has been forgotten.

If you stop taking VFEND

VFEND treatment will continue for as long as your doctor advises, however duration of treatment with

VFEND powder for solution for infusion should be no more than 6 months.

Patients with a weakened immune system or those with difficult infections may require long-term treatment

to prevent the infection from returning. You may be switched from the intravenous infusion to tablets once

your condition improves.

When VFEND treatment is stopped by your doctor you should not experience any effects.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If any side effects occur, most are likely to be minor and temporary. However, some may be serious and

need medical attention.

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

-

Rash

-

Jaundice; Changes in blood tests of liver function

-

Pancreatitis

Other side effects

Very common: may affect more than 1 in 10 people

-

Visual impairment (change in vision including blurred vision, visual color alterations, abnormal

intolerance to visual perception of light, colour blindness, eye disorder, halo vision, night blindness,

swinging vision, seeing sparks, visual aura, visual acuity reduced, visual brightness, loss of part of

the usual field of vision, spots before the eyes)

-

Fever

-

Rash

-

Nausea, vomiting, diarrhoea

-

Headache

-

Swelling of the extremities

-

Stomach pains

-

Breathing difficulties

-

Elevated liver enzymes

Common: may affect up to 1 in 10 people

-

Inflammation of the sinuses, inflammation of the gums, chills, weakness

-

Low numbers of some types, including severe, of red (sometimes immune-related) and/or white

blood cells (sometimes with fever), low numbers of cells called platelets that help the blood to clot

-

Low blood sugar, low blood potassium, low sodium in the blood

-

Anxiety, depression, confusion, agitation, inability to sleep, hallucinations

-

Seizures, tremors or uncontrolled muscle movements, tingling or abnormal skin

sensations, increase in muscle tone, sleepiness, 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 the formation of a blood

clot)

-

Acute breathing difficulty, chest pain, swelling of the face (mouth, lips and around eyes), fluid

accumulation in the lungs

-

Constipation, indigestion, inflammation of the lips

-

Jaundice, inflammation of the liver and liver injury

-

Skin rashes which may lead to severe blistering and peeling of the skin characterized by a flat, red

area on the skin that is covered with small confluent bumps, redness of the skin

-

Itchiness

-

Hair loss

-

Back pain

-

Kidney failure, blood in the urine, changes in kidney function tests

Uncommon: may affect up to 1 in 100 people

-

Flu-like symptoms, irritation and inflammation of the gastrointestinal tract, inflammation of the

gastrointestinal tract causing antibiotic associated diarrhoea, inflammation of the lymphatic vessels

-

Inflammation of the thin tissue that lines the inner wall of the abdomen and covers the abdominal

organ

-

Enlarged lymph glands (sometimes painful), failure of blood marrow, increased eosinophil

-

Depressed function of the adrenal gland, underactive thyroid gland

-

Abnormal brain function, Parkinson-like symptoms, nerve injury resulting in numbness, pain,

tingling or burning in the hands or feet

-

Problems with balance or coordination

-

Swelling of the brain

-

Double vision, serious conditions of the eye including: pain and inflammation of the eyes and

eyelids, abnormal eye movement, damage to the optic nerve resulting in vision impairment, optic

disc swelling

-

Decreased sensitivity to touch

-

Abnormal sense of taste

-

Hearing difficulties, ringing in the ears, vertigo

-

Inflammation of certain internal organs- pancreas and duodenum, swelling and inflammation of the

tongue

-

Enlarged liver, liver failure, gallbladder disease, gallstones

-

Joint inflammation, inflammation of the veins under the skin (which may be associated with the

formation of a blood clot)

-

Inflammation of the kidney, proteins in the urine, damage to the kidney

-

Very fast heart rate or skipped heartbeats, sometimes with erratic electrical impulses

-

Abnormal electrocardiogram (ECG)

-

Blood cholesterol increased, blood urea increased

-

Allergic skin reactions (sometimes severe), including life-threatening skin condition that causes

painful blisters and sores of the skin and mucous membranes, especially in the mouth,

inflammation of the skin, hives, sunburn or severe skin reaction following exposure to light or sun,

skin redness and irritation, red or purple discoloration of the skin which may be caused by low

platelet count, eczema

-

Infusion site reaction

-

Allergic reaction or exaggerated immune response

Rare: may affect up to 1 in 1000 people

-

Overactive thyroid gland

-

Deterioration of brain function that is a serious complication of liver disease

-

Loss of most fibers in the optic nerve, clouding of the cornea, involuntary movement of the eye

-

Bullous photosensitivity

-

A disorder in which the body’s immune system attacks part of the peripheral nervous system

-

Heart rhythm or conduction problems (sometimes life threatening)

-

Life threatening allergic reaction

-

Disorder of blood clotting system

-

Allergic skin reactions (sometimes severe), including rapid swelling (oedema) of the dermis,

subcutaneous tissue, mucosa and submucosal tissues, itchy or sore patches of thick, red skin with

silvery scales of skin, irritation of the skin and mucous membranes, life-threatening skin condition

that causes large portions of the epidermis, the skin's outermost layer, to detach from the layers of

skin below

-

Small dry scaly skin patches, sometimes thick with spikes or ‘horns’

Side effects with frequency not known:

-

Freckles and pigmented spots

Other significant side effects whose frequency is not known, but should be reported to your doctor

immediately:

-

Skin cancer

-

Inflammation of the tissue surrounding the bone

-

Red, scaly patches or ring-shaped skin lesions that may be a symptom of an autoimmune disease

called cutaneous lupus erythematosus

Reactions during the infusion have occurred uncommonly with VFEND (including flushing, fever,

sweating, increased heart rate and shortness of breath). Your doctor may stop the infusion if this occurs.

As VFEND has been known to affect the liver and the kidney, your doctor should monitor the function

of your liver and kidney by doing blood tests. Please advise your doctor if you have any stomach pains

or if your stools have a different consistency.

There have been reports of skin cancer in patients treated with VFEND for long periods of time.

Sunburn or severe skin reaction following exposure to light or sun was experienced more frequently in

children. If you or your child develops skin disorders, your doctor may refer you to a dermatologist, who

after consultation may decide that it is important for you or your child to be seen on a regular basis. Elevated

liver enzymes were also observed more frequently in children.

If any of these side effects persist or are troublesome, please tell your doctor.

Reporting of side effects

If you get any side effects, talk to your doctor or, pharmacist or nurse. This includes any possible side effects

not listed in this leaflet. You can also report side effects directly via the national reporting system listed in

Appendix 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 which is stated on the label. The expiry date refers to the last

day of that month.

Once reconstituted, VFEND should be used immediately, but if necessary may be stored for up to 24 hours

at 2°C - 8°C (in a refrigerator). Reconstituted VFEND needs to be diluted with a compatible infusion

solution first before it is infused. (Please refer to the end of this leaflet for further information).

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw

away medicines you no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What VFEND contains

-The active substance is voriconazole.

-The other ingredient is sulfobutylether beta cyclodextrin sodium.

Each vial contains 200 mg voriconazole, equivalent to a 10 mg/ml solution when reconstituted as

directed by your hospital pharmacist or nurse (see the information at the end of this leaflet).

What VFEND looks like and contents of the pack

VFEND is presented in single use glass vials as a powder for solution for infusion.

Marketing Authorisation Holder

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

Manufacturer

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

For any information about this medicinal product, please contact the local representative of the

Marketing Authorisation Holder:

België /Belgique/Belgien

Pfizer S.A./N.V.

Tél/Tel: +32 (0)2 554 62 11

Lietuva

Pfizer Luxembourg SARL

Filialas Lietuvoje

Tel. +3705 2514000

България

Пфайзер Люксембург САРЛ, Клон България

Тел.: +359 2 970 4333

Luxembourg/Luxemburg

Pfizer S.A.

Tél: +32 (0)2 554 62 11

Česká republika

Pfizer s.r.o.

Tel: +420-283-004-111

Magyarország

Pfizer Kft.

Tel. + 36 1 488 37 00

Danmark

Pfizer ApS Tlf:

+45 44 20 11 00

Malta

V.J. Salomone Pharma Ltd.

Tel : +356 21 22 01 74

Deutschland

Pfizer Pharma PFE GmbH

Tel: +49 (0)800 8535555

Nederland

Pfizer bv

Tel: +31 (0)10 406 43 01

Eesti

Pfizer Luxembourg SARL Eesti filiaal

Tel: +372 666 7500

Norge

Pfizer AS

Tlf: +47 67 52 61 00

Ελλάδα

Pfizer ΕΛΛΑΣ A.E.

Τηλ.: +30 210 6785 800

Österreich

Pfizer Corporation Austria

Ges.m.b.H. Tel: +43 (0)1

521 15-0

España

Pfizer, S.L.

Tel: +34 91 490 99 00

Polska

Pfizer Polska Sp. z o.o.,

Tel.: +48 22 335 61 00

France

Pfizer

Tél: +33 (0)1 58 07 34 40

Portugal

Laboratórios Pfizer, Lda.

Tel: + 351 214 235 500

Hrvatska

Pfizer Croatia d.o.o.

Tel: + 385 1 3908 777

România

Pfizer România S.R.L

Tel: +40 (0)21 207 28 00

Ireland

Pfizer Healthcare Ireland

Tel: 1800 633 363 (toll free)

+44 (0)1304 616161

Slovenija

Pfizer Luxembourg SARL

Pfizer, podružnica za svetovanje s področja

farmacevtske dejavnosti, Ljubljana

Tel: + 386 (0)152 11 400

Ísland

Icepharma hf.,

Sími: + 354 540 8000

Slovenská republika

Pfizer Luxembourg SARL, organizačná zložka

Tel: +421-2-3355 5500

Italia

Pfizer Italia S.r.l.

Tel: +39 06 33 18 21

Suomi/Finland

Pfizer Oy

Puh/Tel: +358(0)9 43 00 40

Kύπρος

Pfizer ΕΛΛΑΣ Α.Ε. (Cyprus Branch)

Τηλ: +357 22 817690

Sverige

Pfizer AB

Tel: +46 (0)8 5505 2000

Latvija

Pfizer Luxembourg SARL

Filiāle Latvijā

Tel: +371 670 35 775

United Kingdom

Pfizer Limited

Tel: +44 (0)1304 616161

This leaflet was last approved in {MM/YYYY}.

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu

<-----------------------------------------------------------------------------------------------------------------

The following information is intended for medical or healthcare professionals only:

Reconstitution and Dilution information

VFEND powder for solution for infusion needs to first be reconstituted with either 19 ml of Water for

Injections or 19 ml of 9 mg/ml (0.9%) Sodium Chloride for Infusion to obtain an extractable volume

of 20 ml of clear concentrate containing 10 mg/ml voriconazole.

Discard the VFEND vial if the vacuum does not pull the diluent into the vial.

It is recommended that a standard 20 ml (non-automated) syringe be used to ensure that the exact

amount (19.0 ml) of Water for Injections or of 9 mg/ml (0.9%) Sodium Chloride for Infusion is

dispensed.

The required volume of the reconstituted concentrate is then added to a recommended compatible

infusion solution listed below to obtain a final VFEND solution containing 0.5 to 5 mg/ml of

voriconazole.

This medicinal product is for single use only and any unused solution should be discarded and only

clear solutions without particles should be used.

Not for administration as a bolus injection.

For storage information, please refer to Section 5 ‘How to store VFEND’.

Required Volumes of 10 mg/ml VFEND Concentrate

Body

Weight

(kg)

Volume of VFEND Concentrate (10 mg/ml) required for:

3 mg/kg dose

(number of

vials)

4 mg/kg dose

(number of

vials)

6 mg/kg dose

(number of

vials)

8 mg/kg dose

(number of

vials)

9 mg/kg dose

(number of

vials)

4.0 ml (1)

8.0 ml (1)

9.0 ml (1)

6.0 ml (1)

12.0 ml (1)

13.5 ml (1)

8.0 ml (1)

16.0 ml (1)

18.0 ml (1)

10.0 ml (1)

20.0 ml (1)

22.5 ml (2)

9.0 ml (1)

12.0 ml (1)

18.0 ml (1)

24.0 ml (2)

27.0 ml (2)

10.5 ml (1)

14.0 ml (1)

21.0 ml (2)

28.0 ml (2)

31.5 ml (2)

12.0 ml (1)

16.0 ml (1)

24.0 ml (2)

32.0 ml (2)

36.0 ml (2)

13.5 ml (1)

18.0 ml (1)

27.0 ml (2)

36.0 ml (2)

40.5 ml (3)

15.0 ml (1)

20.0 ml (1)

30.0 ml (2)

40.0 ml (2)

45.0 ml (3)

16.5 ml (1)

22.0 ml (2)

33.0 ml (2)

44.0 ml (3)

49.5 ml (3)

18.0 ml (1)

24.0 ml (2)

36.0 ml (2)

48.0 ml (3)

54.0 ml (3)

19.5 ml (1)

26.0 ml (2)

39.0 ml (2)

52.0 ml (3)

58.5 ml (3)

21.0 ml (2)

28.0 ml (2)

42.0 ml (3)

22.5 ml (2)

30.0 ml (2)

45.0 ml (3)

24.0 ml (2)

32.0 ml (2)

48.0 ml (3)

25.5 ml (2)

34.0 ml (2)

51.0 ml (3)

27.0 ml (2)

36.0 ml (2)

54.0 ml (3)

28.5 ml (2)

38.0 ml (2)

57.0 ml (3)

30.0 ml (2)

40.0 ml (2)

60.0 ml (3)

VFEND is a single dose unpreserved sterile lyophile. Therefore, from a microbiological point of view, the

reconstituted solution must be used immediately. If not used immediately, in-use storage times and

conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2

to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.

Compatible Infusion Solutions:

The reconstituted solution can be diluted with:

Sodium Chloride 9 mg/ml (0.9%) Solution for Injection

Compound Sodium Lactate Intravenous Infusion

5% Glucose and Lactated Ringer’s Intravenous Infusion

5% Glucose and 0.45% Sodium Chloride Intravenous Infusion

5% Glucose Intravenous Infusion

5% Glucose in 20 mEq Potassium Chloride Intravenous Infusion

0.45% Sodium Chloride Intravenous Infusion

5% Glucose and 0.9% Sodium Chloride Intravenous Infusion

The compatibility of VFEND with diluents other than listed above (or listed below under

‘Incompatibilities’) is unknown.

Incompatibilities:

VFEND must not be infused into the same line or cannula concomitantly with other drug infusions,

including parenteral nutrition (e.g., Aminofusin 10% Plus).

Infusions of blood products must not occur simultaneously with VFEND.

Infusion of total parenteral nutrition can occur simultaneously with VFEND but not in the same line or

cannula.

VFEND must not be diluted with 4.2% Sodium Bicarbonate Infusion.

Package Leaflet: Information for the user

VFEND 200 mg powder and solvent for solution for infusion

Voriconazole

Read all of this leaflet carefully before you start taking this medicine because it contains important

information for you.

Keep this leaflet. You may need to read it again.

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

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if

their signs of illness are the same as yours.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

What VFEND is and what it is used for

What you need to know before you take VFEND

How to use VFEND

Possible side effects

How to store VFEND

Content 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 the fungi that cause infections.

It is used for the treatment of patients (adults and children over the age of 2) with:

invasive aspergillosis (a type of fungal infection due to Aspergillus sp),

candidaemia (another type of fungal infection due to Candida sp) in non-neutropenic patients

(patients without abnormally low white blood cells count),

serious invasive Candida sp. infections when the fungus is resistant to fluconazole (another

antifungal medicine),

serious fungal infections caused by Scedosporium sp. or Fusarium sp. (two different species of

fungi).

VFEND is intended for patients with worsening, possibly life-threatening, fungal infections.

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

This product should only be used under the supervision of a doctor.

2. What you need to know before you take VFEND

Do not take VFEND:

If you are allergic to the active ingredient voriconazole, or to sulfobutylether beta cyclodextrin sodium

(listed in section 6).

It is very important that you inform your doctor or pharmacist if you are taking or have taken any other

medicines, even those that are obtained without a prescription, or herbal medicines.

The medicines in the following list must not be taken during your VFEND treatment:

Terfenadine (used for allergy)

Astemizole (used for allergy)

Cisapride (used for stomach problems)

Pimozide (used for treating mental illness)

Quinidine (used for irregular heart beat)

Rifampicin (used for treating tuberculosis)

Efavirenz (used for treating HIV) in doses of 400 mg and above 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 for treating HIV) in doses of 400mg and more twice daily

St. John’s Wort (herbal supplement)

Warnings and precautions

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

you have had an allergic reaction to other azoles.

you are suffering from, or have ever suffered from liver disease. If you have liver disease, your

doctor may prescribe a lower dose of VFEND. Your doctor should also monitor your liver function

while you are being treated with VFEND by doing blood tests.

you are known to have cardiomyopathy, irregular heart beat, slow heart rate or an abnormality of

electrocardiogram (ECG) called ‘long QTc syndrome’.

You should avoid any sunlight and sun exposure while being treated. It is important to cover sun exposed

areas of skin and use sunscreen with high sun protection factor (SPF), as an increased sensitivity of skin to

the sun’s UV rays can occur. These precautions are also applicable to children.

While being treated with VFEND:

tell your doctor immediately if you develop

sunburn

severe skin rash or blisters

bone pain

If you develop skin disorders as described above, your doctor may refer you to a dermatologist, who after

consultation may decide that it is important for you to be seen on a regular basis. There is a small chance that

skin cancer could develop with long-term use of VFEND.

Your doctor should monitor the function of your liver and kidney by doing blood tests.

Children and adolescents

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

Other medicines and VFEND

Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other

medicines, including those that are obtained without a prescription.

Some medicines, when taken at the same time as VFEND, may affect the way VFEND works or

VFEND may affect the way they work.

Tell your doctor if you are taking the following medicine, as treatment with VFEND at the same time should

be avoided if possible:

Ritonavir (used for treating HIV) in doses of 100 mg twice daily

Tell your doctor if you are taking either of the following medicines, as treatment with VFEND at the same

time should be avoided if possible, and a dose adjustment of voriconazole may be required:

Rifabutin (used for treating tuberculosis). If you are already being treated with rifabutin your blood

counts and side effects to rifabutin will need to be monitored.

Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin your blood

concentration of phenytoin will need to be monitored during your treatment with VFEND and your

dose may be adjusted.

Tell your doctor if you are taking any of the following medicines, as a dose adjustment or monitoring may be

required to check that the medicines and/ or VFEND are still having the desired effect:

Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to slow down clotting

of the blood)

Ciclosporin (used in transplant patients)

Tacrolimus (used in transplant patients)

Sulfonylureas (e.g., tolbutamide, glipizide, and glyburide) (used for diabetes)

Statins (e.g., atorvastatin, simvastatin) (used for lowering cholesterol)

Benzodiazepines (e.g midazolam, triazolam) (used for severe insomnia and stress)

Omeprazole (used for treating ulcers)

Oral contraceptives (if you take VFEND whilst using oral contraceptives, you may get side effects

such as nausea and menstrual disorders)

Vinca alkaloids (e.g., vincristine and vinblastine) (used in treating cancer)

Indinavir and other HIV protease inhibitors (used for treating HIV)

Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, nevirapine) (used for

treating HIV) (some doses of efavirenz can NOT be taken at the same time as VFEND)

Methadone (used to treat heroin addiction)

Alfentanil and fentanyl and other short-acting opiates such as sufentanil (painkillers used for surgical

procedures)

Oxycodone and other long-acting opiates such as hydrocodone (used for moderate to severe pain)

Non-steroidal anti-inflammatory drugs (e.g., ibuprofen, diclofenac) (used for treating pain and

inflammation)

Fluconazole (used for fungal infections)

Everolimus (used for treating advanced kidney cancer and in transplant patients)

Pregnancy and breast-feeding

VFEND must not be used during pregnancy, unless indicated by your doctor. Effective contraception must

be used in women of childbearing potential. Contact your doctor immediately if you become pregnant

while being treated with VFEND.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your

doctor or pharmacist for advice before taking this medicine.

Driving and using machines

VFEND may cause blurring of vision or uncomfortable sensitivity to light. While affected, do not drive

or operate any tools or machines. Tell your doctor if you experience this.

VFEND contains sodium

Each vial of VFEND contains 217.6 mg of sodium per vial. This should be taken into consideration if you

are on a strictly controlled sodium diet.

3. How to use VFEND

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

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

Your doctor may change your dose depending on your condition.

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

Intravenous

Dose for the first 24 hours

6 mg/kg every 12 hours for

(Loading Dose)

first 24 hours

Dose after the first 24

hours

4 mg/kg twice a day

(Maintenance Dose)

Depending on your response to treatment, your doctor may decrease the dose to 3 mg/kg twice daily.

The doctor may decide to decrease the dose if you have mild to moderate cirrhosis.

Use in children and adolescents

The recommended dose for children and teenagers is as follows:

Intravenous

Children aged 2 to less

than 12 years and

teenagers aged 12 to 14

years weighing less than

50 kg

Teenagers aged 12 to 14

years weighing 50 kg or

more; and all teenagers

older than 14

Dose for the first 24

hours

(Loading Dose)

9 mg/kg every 12 hours

for the first 24 hours

6 mg/kg every 12 hours

for the first 24 hours

Dose after the first 24

hours

8 mg/kg twice a day

4 mg/kg twice a day

(Maintenance Dose)

Depending on your response to treatment, your doctor may increase or decrease the daily dose.

VFEND powder and solvent for solution for infusion will be reconstituted and diluted to the correct

concentration by your hospital pharmacist or nurse. (Please refer to the end of this leaflet for further

information)

This will be given to you by intravenous infusion (into a vein) at a maximum rate of 3 mg/kg per hour over 1

to 3 hours.

If you or your child are taking VFEND for prevention of fungal infections, your doctor may stop giving

VFEND if you or your child develop treatment related side effects.

If a dose of VFEND has been forgotten

As you will be given this medicine under close medical supervision, it is unlikely that a dose would be

missed. However tell your doctor or pharmacist if you think that a dose has been forgotten.

If you stop taking VFEND

VFEND treatment will continue for as long as your doctor advises, however duration of treatment with

VFEND powder for solution for infusion should be no more than 6 months.

Patients with a weakened immune system or those with difficult infections may require long-term treatment

to prevent the infection from returning. You may be switched from the intravenous infusion to tablets once

your condition improves.

When VFEND treatment is stopped by your doctor you should not experience any effects.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If any side effects occur, most are likely to be minor and temporary. However, some may be serious and

need medical attention.

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

-

Rash

-

Jaundice; Changes in blood tests of liver function

-

Pancreatitis

Other side effects

Very common: may affect more than 1 in 10 people

-

Visual impairment (change in vision including blurred vision, visual color alterations, abnormal

intolerance to visual perception of light, colour blindness, eye disorder, halo vision, night blindness,

swinging vision, seeing sparks, visual aura, visual acuity reduced, visual brightness, loss of part of

the usual field of vision, spots before the eyes)

-

Fever

-

Rash

-

Nausea, vomiting, diarrhoea

-

Headache

-

Swelling of the extremities

-

Stomach pains

-

Breathing difficulties

-

Elevated liver enzymes

Common: may affect up to 1 in 10 people

-

Inflammation of the sinuses, inflammation of the gums, chills, weakness

-

Low numbers of some types, including severe, of red (sometimes immune-related) and/or white

blood cells (sometimes with fever), low numbers of cells called platelets that help the blood to clot

-

Low blood sugar, low blood potassium, low sodium in the blood

-

Anxiety, depression, confusion, agitation, inability to sleep, hallucinations

-

Seizures, tremors or uncontrolled muscle movements, tingling or abnormal skin

sensations, increase in muscle tone, sleepiness, 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 the formation of a blood

clot)

-

Acute breathing difficulty, chest pain, swelling of the face (mouth, lips and around eyes), fluid

accumulation in the lungs

-

Constipation, indigestion, inflammation of the lips

-

Jaundice, inflammation of the liver and liver injury

-

Skin rashes which may lead to severe blistering and peeling of the skin characterized by a flat, red

area on the skin that is covered with small confluent bumps, redness of the skin

-

Itchiness

-

Hair loss

-

Back pain

-

Kidney failure, blood in the urine, changes in kidney function tests

Uncommon: may affect up to 1 in 100 people

-

Flu-like symptoms, irritation and inflammation of the gastrointestinal tract, inflammation of the

gastrointestinal tract causing antibiotic associated diarrhoea, inflammation of the lymphatic vessels

-

Inflammation of the thin tissue that lines the inner wall of the abdomen and covers the abdominal

organ

-

Enlarged lymph glands (sometimes painful), failure of blood marrow, increased eosinophil

-

Depressed function of the adrenal gland, underactive thyroid gland

-

Abnormal brain function, Parkinson-like symptoms, nerve injury resulting in numbness, pain,

tingling or burning in the hands or feet

-

Problems with balance or coordination

-

Swelling of the brain

-

Double vision, serious conditions of the eye including: pain and inflammation of the eyes and

eyelids, abnormal eye movement, damage to the optic nerve resulting in vision impairment, optic

disc swelling

-

Decreased sensitivity to touch

-

Abnormal sense of taste

-

Hearing difficulties, ringing in the ears, vertigo

-

Inflammation of certain internal organs- pancreas and duodenum, swelling and inflammation of the

tongue

-

Enlarged liver, liver failure, gallbladder disease, gallstones

-

Joint inflammation, inflammation of the veins under the skin (which may be associated with the

formation of a blood clot)

-

Inflammation of the kidney, proteins in the urine, damage to the kidney

-

Very fast heart rate or skipped heartbeats, sometimes with erratic electrical impulses

-

Abnormal electrocardiogram (ECG)

-

Blood cholesterol increased, blood urea increased

-

Allergic skin reactions (sometimes severe), including life-threatening skin condition that causes

painful blisters and sores of the skin and mucous membranes, especially in the mouth,

inflammation of the skin, hives, sunburn or severe skin reaction following exposure to light or sun,

skin redness and irritation, red or purple discoloration of the skin which may be caused by low

platelet count, eczema

-

Infusion site reaction

-

Allergic reaction or exaggerated immune response

Rare: may affect up to 1 in 1000 people

-

Overactive thyroid gland

-

Deterioration of brain function that is a serious complication of liver disease

-

Loss of most fibers in the optic nerve, clouding of the cornea, involuntary movement of the eye

-

Bullous photosensitivity

-

A disorder in which the body’s immune system attacks part of the peripheral nervous system

-

Heart rhythm or conduction problems (sometimes life threatening)

-

Life threatening allergic reaction

-

Disorder of blood clotting system

-

Allergic skin reactions (sometimes severe), including rapid swelling (oedema) of the dermis,

subcutaneous tissue, mucosa and submucosal tissues, itchy or sore patches of thick, red skin with

silvery scales of skin, irritation of the skin and mucous membranes, life-threatening skin condition

that causes large portions of the epidermis, the skin's outermost layer, to detach from the layers of

skin below

-

Small dry scaly skin patches, sometimes thick with spikes or ‘horns’

Side effects with frequency not known:

-

Freckles and pigmented spots

Other significant side effects whose frequency is not known, but should be reported to your doctor

immediately:

-

Skin cancer

-

Inflammation of the tissue surrounding the bone

-

Red, scaly patches or ring-shaped skin lesions that may be a symptom of an autoimmune disease

called cutaneous lupus erythematosus

Reactions during the infusion have occurred uncommonly with VFEND (including flushing, fever,

sweating, increased heart rate and shortness of breath). Your doctor may stop the infusion if this occurs.

As VFEND has been known to affect the liver and the kidney, your doctor should monitor the function

of your liver and kidney by doing blood tests. Please advise your doctor if you have any stomach pains

or if your stools have a different consistency.

There have been reports of skin cancer in patients treated with VFEND for long periods of time.

Sunburn or severe skin reaction following exposure to light or sun was experienced more frequently in

children. If you or your child develops skin disorders, your doctor may refer you to a dermatologist, who

after consultation may decide that it is important for you or your child to be seen on a regular basis. Elevated

liver enzymes were also observed more frequently in children.

If any of these side effects persist or are troublesome, please tell your doctor.

Reporting of side effects

If you get any side effects, talk to your doctor or, pharmacist or nurse. This includes any possible side effects

not listed in this leaflet. You can also report side effects directly via the national reporting system listed in

Appendix 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 which is stated on the label. The expiry date refers to the last

day of that month.

Once the powder in the vial has been reconstituted, VFEND should be used immediately, but if necessary

may be stored for up to 24 hours at 2°C - 8°C (in a refrigerator) with the infusion bag. Reconstituted VFEND

concentrate needs to be further diluted with sodium chloride (0.9%) infusion solution within the infusion bag

before it is infused. The bag containing the reconstituted and diluted VFEND should be used immediately,

but if necessary may be stored for up to a total of 24 hours at 2°C - 8°C (in a refrigerator) or at room

temperature. (Please refer to the end of this leaflet for further information).

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw

away medicines you no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What VFEND contains

-The active substance is voriconazole.

-The other ingredient is sulfobutylether beta cyclodextrin sodium.

Each vial contains 200 mg voriconazole, equivalent to a 10 mg/ml solution when reconstituted as

directed by your hospital pharmacist or nurse (see the information at the end of this leaflet).

Each bag contains 50 ml of sodium chloride 0.9% in Water for Injections.

What VFEND looks like and contents of the pack

VFEND powder and solvent for solution for infusion is presented as an administration kit containing:

VFEND powder for solution for infusion in single use glass vial.

VFEND solvent for solution for infusion in an overwrapped, sterile, single use, polypropylene

infusion bag.

A sterile, single use, syringe.

A sterile, single use vial adapter.

Marketing Authorisation Holder

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

Manufacturer

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

For any information about this medicinal product, please contact the local representative of the

Marketing Authorisation Holder:

België /Belgique/Belgien

Pfizer S.A./N.V.

Tél/Tel: +32 (0)2 554 62 11

Lietuva

Pfizer Luxembourg SARL

Filialas Lietuvoje

Tel. +3705 2514000

България

Пфайзер Люксембург САРЛ, Клон България

Тел.: +359 2 970 4333

Luxembourg/Luxemburg

Pfizer S.A.

Tél: +32 (0)2 554 62 11

Česká republika

Pfizer s.r.o.

Tel: +420-283-004-111

Magyarország

Pfizer Kft.

Tel. + 36 1 488 37 00

Danmark

Pfizer ApS Tlf:

+45 44 20 11 00

Malta

V.J. Salomone Pharma Ltd.

Tel : +356 21 22 01 74

Deutschland

Pfizer Pharma PFE GmbH

Tel: +49 (0)800 8535555

Nederland

Pfizer bv

Tel: +31 (0)10 406 43 01

Eesti

Pfizer Luxembourg SARL Eesti filiaal

Tel: +372 666 7500

Norge

Pfizer AS

Tlf: +47 67 52 61 00

Ελλάδα

Pfizer ΕΛΛΑΣ A.E.

Τηλ.: +30 210 6785 800

Österreich

Pfizer Corporation Austria

Ges.m.b.H. Tel: +43 (0)1

521 15-0

España

Pfizer, S.L.

Tel: +34 91 490 99 00

Polska

Pfizer Polska Sp. z o.o.,

Tel.: +48 22 335 61 00

France

Pfizer

Tél: +33 (0)1 58 07 34 40

Portugal

Laboratórios Pfizer, Lda.

Tel: + 351 214 235 500

Hrvatska

Pfizer Croatia d.o.o.

Tel: + 385 1 3908 777

România

Pfizer România S.R.L

Tel: +40 (0)21 207 28 00

Ireland

Pfizer Healthcare Ireland

Tel: 1800 633 363 (toll free)

+44 (0)1304 616161

Slovenija

Pfizer Luxembourg SARL

Pfizer, podružnica za svetovanje s področja

farmacevtske dejavnosti, Ljubljana

Tel: + 386 (0)152 11 400

Ísland

Icepharma hf.,

Sími: + 354 540 8000

Slovenská republika

Pfizer Luxembourg SARL, organizačná zložka

Tel: +421-2-3355 5500

Italia

Pfizer Italia S.r.l.

Tel: +39 06 33 18 21

Suomi/Finland

Pfizer Oy

Puh/Tel: +358(0)9 43 00 40

Kύπρος

Pfizer ΕΛΛΑΣ Α.Ε. (Cyprus Branch)

Τηλ: +357 22 817690

Sverige

Pfizer AB

Tel: +46 (0)8 5505 2000

Latvija

Pfizer Luxembourg SARL

Filiāle Latvijā

Tel: +371 670 35 775

United Kingdom

Pfizer Limited

Tel: +44 (0)1304 616161

This leaflet was last approved in {MM/YYYY}.

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu

<-----------------------------------------------------------------------------------------------------------------

The following information is intended for medical or healthcare professionals only:

Required Volumes of 10 mg/ml VFEND Concentrate

Body

Weight

(kg)

Volume of VFEND Concentrate (10 mg/ml) required for:

3 mg/kg dose

(number of

vials)

4 mg/kg dose

(number of

vials)

6 mg/kg dose

(number of

vials)

8 mg/kg dose

(number of

vials)

9 mg/kg dose

(number of

vials)

4.0 ml (1)

8.0 ml (1)

9.0 ml (1)

6.0 ml (1)

12.0 ml (1)

13.5 ml (1)

8.0 ml (1)

16.0 ml (1)

18.0 ml (1)

10.0 ml (1)

20.0 ml (1)

22.5 ml (2)

9.0 ml (1)

12.0 ml (1)

18.0 ml (1)

24.0 ml (2)

27.0 ml (2)

10.5 ml (1)

14.0 ml (1)

21.0 ml (2)

28.0 ml (2)

31.5 ml (2)

12.0 ml (1)

16.0 ml (1)

24.0 ml (2)

32.0 ml (2)

36.0 ml (2)

13.5 ml (1)

18.0 ml (1)

27.0 ml (2)

36.0 ml (2)

40.5 ml (3)

15.0 ml (1)

20.0 ml (1)

30.0 ml (2)

40.0 ml (2)

45.0 ml (3)

16.5 ml (1)

22.0 ml (2)

33.0 ml (2)

44.0 ml (3)

49.5 ml (3)

18.0 ml (1)

24.0 ml (2)

36.0 ml (2)

48.0 ml (3)

54.0 ml (3)

19.5 ml (1)

26.0 ml (2)

39.0 ml (2)

52.0 ml (3)

58.5 ml (3)

21.0 ml (2)

28.0 ml (2)

42.0 ml (3)

22.5 ml (2)

30.0 ml (2)

45.0 ml (3)

24.0 ml (2)

32.0 ml (2)

48.0 ml (3)

25.5 ml (2)

34.0 ml (2)

51.0 ml (3)

27.0 ml (2)

36.0 ml (2)

54.0 ml (3)

28.5 ml (2)

38.0 ml (2)

57.0 ml (3)

30.0 ml (2)

40.0 ml (2)

60.0 ml (3)

VFEND is a single dose unpreserved sterile lyophile. Therefore, from a microbiological point of view, the

reconstituted solution must be used immediately.

If not used immediately, in-use storage times and conditions of the reconstituted vial prior to use are the

responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution

has taken place in controlled and validated aseptic conditions.

Incompatibilities:

VFEND must not be infused into the same line or cannula concomitantly with other drug infusions,

including parenteral nutrition (e.g., Aminofusin 10% Plus).

Infusions of blood products must not occur simultaneously with VFEND.

Infusion of total parenteral nutrition can occur simultaneously with VFEND but not in the same line or

cannula.

VFEND must not be diluted with 4.2% Sodium Bicarbonate Infusion.

Kit Operating Instructions for Use:

VFEND Powder and Solvent for Solution for Infusion

Critical Instructions for safe and effective use of infusion kit

Aseptic procedures will be followed during kit preparation

Bag must be inverted when the reconstituted Voriconazole is added

Step 1

1a

Peel back the seal from the vial adaptor. Do not remove casing.

1b

To prepare the IV vial for reconstitution, remove the plastic cap from the vial and wipe the top with

an antiseptic swab. Place the vial on a flat surface. Ensure the internal spike of the vial adaptor is

placed at the centre of the vial septum and push the adaptor firmly onto the vial until it snaps into

place.

Step 2

2a

Snap open Blue port. Bend the outer tube by 90° each way to ensure it is fully broken.

2b

Push the syringe plunger down fully. Push and screw the syringe securely onto Blue port.

2c

Withdraw exactly 19 mL of the solution and unscrew the syringe.

Step 3

3a

Remove the adaptor casing from the vial adaptor and discard.

3b

Screw the syringe onto the vial adapter. Keeping the vial upright, empty contents of the syringe into

the vial.

3c

Swirl the vial gently until all the powder is dissolved. Inspect the vial. If particles are seen, swirl again

and re-inspect.

Step 4

4

Gently invert the vial. Slowly draw off the required volume of the solution. The potential to block the

venting action exists if large amounts of air or drug are injected when the vial is inverted. If this

occurs, turn the vial upright and pull the piston up the syringe barrel. When cleared, proceed as

directed. Unscrew the syringe and discard the vial adaptor and vial.

Step 5

5a

Invert the infusion bag and screw the syringe into Blue port.

5b

Empty the contents of the syringe into the bag. Remove the syringe. Gently mix the contents of the

infusion bag. If any particles are seen, discard the infusion bag.

Step 6

6a

Invert the infusion bag. Open the Twist-off port.

6b

Keeping the infusion bag inverted, connect the infusion line.

6c

Prime the IV line according to the manufacturer’s guidelines. Hang the infusion bag.

Step 7

7a

Attach the IV line to the patient injection site. Set the infusion rate accurately.

7b

Once the infusion delivery to the patient starts, do not manually squeeze the bag compartment as this

may interfere with the dose delivery to the patient and may cause air ingress into the IV line.

Package Leaflet: Information for the user

VFEND 40 mg/ml powder for oral suspension

Voriconazole

Read all of this leaflet carefully before you start taking this medicine because it contains important

information for you.

Keep this leaflet. You may need to read it again.

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

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if

their signs of illness are the same as yours.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

What VFEND is and what it is used for

What you need to know before you take VFEND

How to take VFEND

Possible side effects

How to store VFEND

Content 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 the fungi that cause infections.

It is used for the treatment of patients (adults and children over the age of 2) with:

invasive aspergillosis (a type of fungal infection due to Aspergillus sp),

candidaemia (another type of fungal infection due to Candida sp) in non-neutropenic patients

(patients without abnormally low white blood cells count),

serious invasive Candida sp. infections when the fungus is resistant to fluconazole (another

antifungal medicine),

serious fungal infections caused by Scedosporium sp. or Fusarium sp. (two different species of

fungi).

VFEND is intended for patients with worsening, possibly life-threatening, fungal infections.

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

This product should only be taken under the supervision of a doctor.

2. What you need to know before you take VFEND

Do not take VFEND:

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

It is very important that you inform your doctor or pharmacist if you are taking or have taken any other

medicines, even those that are obtained without a prescription, or herbal medicines.

The medicines in the following list must not be taken during your course of VFEND treatment:

Terfenadine (used for allergy)

Astemizole (used for allergy)

Cisapride (used for stomach problems)

Pimozide (used for treating mental illness)

Quinidine (used for irregular heart beat)

Rifampicin (used for treating tuberculosis)

Efavirenz (used for treating HIV) in doses of 400 mg and above 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 for treating HIV) in doses of 400mg and more twice daily

St. John’s Wort (herbal supplement)

Warnings and precautions

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

you have had an allergic reaction to other azoles.

you are suffering from, or have ever suffered from liver disease. If you have liver disease, your

doctor may prescribe a lower dose of VFEND. Your doctor should also monitor your liver function

while you are being treated with VFEND by doing blood tests.

you are known to have cardiomyopathy, irregular heart beat, slow heart rate or an abnormality of

electrocardiogram (ECG) called ‘long QTc syndrome’.

You should avoid any sunlight and sun exposure while being treated. It is important to cover sun exposed

areas of skin and use sunscreen with high sun protection factor (SPF), as an increased sensitivity of skin to

the sun’s UV rays can occur. These precautions are also applicable to children.

While being treated with VFEND:

tell your doctor immediately if you develop

sunburn

severe skin rash or blisters

bone pain

If you develop skin disorders as described above, your doctor may refer you to a dermatologist, who after

consultation may decide that it is important for you to be seen on a regular basis. There is a small chance that

skin cancer could develop with long-term use of VFEND.

Your doctor should monitor the function of your liver and kidney by doing blood tests.

Children and adolescents

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

Other medicines and VFEND

Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other

medicines, including those that are obtained without a prescription.

Some medicines, when taken at the same time as VFEND, may affect the way VFEND works or VFEND

may affect the way they work.

Tell your doctor if you are taking the following medicine, as treatment with VFEND at the same time should

be avoided if possible:

Ritonavir (used for treating HIV) in doses of 100 mg twice daily

Tell your doctor if you are taking either of the following medicines, as treatment with VFEND at the same

time should be avoided if possible, and a dose adjustment of voriconazole may be required:

Rifabutin (used for treating tuberculosis). If you are already being treated with rifabutin your blood

counts and side effects to rifabutin will need to be monitored.

Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin your blood

concentration of phenytoin will need to be monitored during your treatment with VFEND and your

dose may be adjusted.

Tell your doctor if you are taking any of the following medicines, as a dose adjustment or monitoring may be

required to check that the medicines and/ or VFEND are still having the desired effect:

Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to slow down clotting

of the blood)

Ciclosporin (used in transplant patients)

Tacrolimus (used in transplant patients)

Sulfonylureas (e.g., tolbutamide, glipizide, and glyburide) (used for diabetes)

Statins (e.g., atorvastatin, simvastatin) (used for lowering cholesterol)

Benzodiazepines (e.g midazolam, triazolam) (used for severe insomnia and stress)

Omeprazole (used for treating ulcers)

Oral contraceptives (if you take VFEND whilst using oral contraceptives, you may get side effects

such as nausea and menstrual disorders)

Vinca alkaloids (e.g., vincristine and vinblastine) (used in treating cancer)

Indinavir and other HIV protease inhibitors (used for treating HIV)

Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, nevirapine) (used for

treating HIV) (some doses of efavirenz can NOT be taken at the same time as VFEND)

Methadone (used to treat heroin addiction)

Alfentanil and fentanyl and other short-acting opiates such as sufentanil (painkillers used for surgical

procedures)

Oxycodone and other long-acting opiates such as hydrocodone (used for moderate to severe pain)

Non-steroidal anti-inflammatory drugs (e.g., ibuprofen, diclofenac) (used for treating pain and

inflammation)

Fluconazole (used for fungal infections)

Everolimus (used for treating advanced kidney cancer and in transplant patients)

Pregnancy and breast-feeding

VFEND must not be taken during pregnancy, unless indicated by your doctor. Effective contraception

must be used in women of childbearing potential. Contact your doctor immediately if you become

pregnant while taking VFEND.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your

doctor or pharmacist for advice before taking this medicine.

Driving and using machines

VFEND may cause blurring of vision or uncomfortable sensitivity to light. While affected, do not drive

or operate any tools or machines. Contact your doctor if you experience this.

VFEND contains sucrose

VFEND suspension contains 0.54g sucrose per ml of suspension. If you have been told by your doctor that

you have an intolerance to some sugars, contact your doctor before taking VFEND.

3.

How to take VFEND

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if

you are not sure.

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

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

Oral suspension

Patients 40 kg and above

Patients less than 40 kg

Dose for the first 24

hours

400 mg (10 ml) every 12

200 mg (5 ml) every 12

(Loading Dose)

hours for the first 24

hours

hours for the first 24

hours

Dose after the first 24

hours (Maintenance Dose)

200 mg (5 ml) twice a

100 mg (2.5 ml) twice a

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

The doctor may decide to decrease the dose if you have mild to moderate cirrhosis.

Use in children and adolescents

The recommended dose for children and teenagers is as follows:

Oral suspension

Children aged 2 to less

than 12 years and

teenagers aged 12 to 14

years weighing less than

50 kg

Teenagers aged 12 to 14

years weighing 50 kg or

more; and all teenagers

older than 14

Dose for the first 24

hours

(Loading Dose)

Your treatment will be

started as an infusion

400 mg every 12 hours

for the first 24 hours

Dose after the first 24

hours

(Maintenance Dose)

9 mg/kg twice a day

(a maximum dose of

350 mg twice daily)

200 mg twice a day

Depending on your response to treatment, your doctor may increase or decrease the daily dose.

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

If you or your child are taking VFEND for prevention of fungal infections, your doctor may stop giving

VFEND if you or your child develop treatment related side effects.

VFEND suspension should not be mixed with any other medicine. The suspension should not be further

diluted with water or any other liquids.

Instructions to constitute the suspension:

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

VFEND suspension is constituted if it is in a liquid form. If it appears to be a dry powder you should

constitute the oral suspension by following the instructions below.

Tap the bottle to release the powder.

Remove the cap.

Add 2 measuring cups (measure cup included in the carton) of water (total of 46 ml) to the bottle.

Fill the measuring cup to the top of the marked line then pour the water into the bottle. You should

always add a total of 46 ml of water irrespective of the dose you are taking.

Replace the cap and shake the bottle vigorously for about 1 minute. Following constitution, the total

volume of the suspension must be 75 ml.

Remove the cap. Press the bottle adaptor into the neck of the bottle (as shown on figure below). The

adaptor is provided so that you can fill the oral syringe with medicine from the bottle. Replace the

cap on the bottle.

Write the date of expiry of the constituted suspension on the bottle label (the shelf-life of the

constituted suspension is 14 days). Any unused suspension should be discarded after this date.

Instructions for use:

Your pharmacist should advise you how to measure the medicine using the multi-dosing oral syringe

provided in the pack. Please see instructions below before using VFEND suspension.

Shake the closed bottle of constituted suspension for approximately 10 seconds before use. Remove

the cap.

While the bottle is upright, on a flat surface, insert the tip of the oral syringe into the adaptor.

Turn the bottle upside down while holding the oral syringe in place. Slowly pull back the plunger of

the oral syringe to the graduation mark that marks the dose for you. To measure the dose accurately,

the top edge of the black ring should be lined up with the graduated mark on the oral syringe.

If large bubbles can be seen, slowly push the plunger back into the syringe. This will force the

medicine back into the bottle. Repeat step 3 again.

Turn the bottle back upright with the oral syringe still in place. Remove the oral syringe from the

bottle.

Put the tip of the oral syringe into the mouth. Point the tip of the oral syringe towards the inside of

the cheek. SLOWLY push down the plunger of the oral syringe. Do not squirt the medicine out

quickly. If the medicine is to be given to a child, make sure the child is sitting, or is held, upright

before giving the medicine.

Replace the cap on the bottle, leaving the bottle adaptor in place. Wash the oral syringe as instructed

below.

Cleaning and storing the syringe:

The syringe should be washed after each dose. Pull the plunger out of the syringe and wash both

parts in warm soapy water. Then rinse with water.

Dry the two parts. Push the plunger back in to the syringe. Keep it in a clean safe place with the

medicine.

If you take more VFEND than you should

If you take more suspension than prescribed (or if someone else takes your suspension) you must seek

medical advice or go to the nearest hospital casualty department immediately. Take your bottle of VFEND

suspension with you. You may experience abnormal intolerance to light as a result of taking more VFEND

than you should.

If you forget to take VFEND

It is important to take your VFEND suspension regularly at the same time each day. If you forget to take

one dose, take your next dose when it is due. Do not take a double dose to make up for the forgotten dose.

If you stop taking VFEND

It has been shown that taking all doses at the appropriate times may greatly increase the effectiveness of your

medicine. Therefore unless your doctor instructs you to stop treatment, it is important to keep taking VFEND

correctly, as described above.

Continue taking VFEND until your doctor tells you to stop. Do not stop treatment early because your

infection may not be cured. Patients with a weakened immune system or those with difficult infections may

require long-term treatment to prevent the infection from returning.

When VFEND treatment is stopped by your doctor you should not experience any effects.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If any side effects occur, most are likely to be minor and temporary. However, some may be serious and

need medical attention.

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

-

Rash

-

Jaundice; Changes in blood tests of liver function

-

Pancreatitis

Other side effects

Very common: may affect more than 1 in 10 people

-

Visual impairment (change in vision including blurred vision, visual color alterations, abnormal

intolerance to visual perception of light, colour blindness, eye disorder, halo vision, night blindness,

swinging vision, seeing sparks, visual aura, visual acuity reduced, visual brightness, loss of part of

the usual field of vision, spots before the eyes)

-

Fever

-

Rash

-

Nausea, vomiting, diarrhoea

-

Headache

-

Swelling of the extremities

-

Stomach pains

-

Breathing difficulties

-

Elevated liver enzymes

Common: may affect up to 1 in 10 people

-

Inflammation of the sinuses, inflammation of the gums, chills, weakness

-

Low numbers of some types, including severe, of red (sometimes immune-related) and/or white

blood cells (sometimes with fever), low numbers of cells called platelets that help the blood to clot

-

Low blood sugar, low blood potassium, low sodium in the blood

-

Anxiety, depression, confusion, agitation, inability to sleep, hallucinations

-

Seizures, tremors or uncontrolled muscle movements, tingling or abnormal skin

sensations, increase in muscle tone, sleepiness, 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 the formation of a blood

clot)

-

Acute breathing difficulty, chest pain, swelling of the face (mouth, lips and around eyes), fluid

accumulation in the lungs

-

Constipation, indigestion, inflammation of the lips

-

Jaundice, inflammation of the liver and liver injury

-

Skin rashes which may lead to severe blistering and peeling of the skin characterized by a flat, red

area on the skin that is covered with small confluent bumps, redness of the skin

-

Itchiness

-

Hair loss

-

Back pain

-

Kidney failure, blood in the urine, changes in kidney function tests

Uncommon: may affect up to 1 in 100 people

-

Flu-like symptoms, irritation and inflammation of the gastrointestinal tract, inflammation of the

gastrointestinal tract causing antibiotic associated diarrhoea, inflammation of the lymphatic vessels

-

Inflammation of the thin tissue that lines the inner wall of the abdomen and covers the abdominal

organ

-

Enlarged lymph glands (sometimes painful), failure of blood marrow, increased eosinophil

-

Depressed function of the adrenal gland, underactive thyroid gland

-

Abnormal brain function, Parkinson-like symptoms, nerve injury resulting in numbness, pain,

tingling or burning in the hands or feet

-

Problems with balance or coordination

-

Swelling of the brain

-

Double vision, serious conditions of the eye including: pain and inflammation of the eyes and

eyelids, abnormal eye movement, damage to the optic nerve resulting in vision impairment, optic

disc swelling

-

Decreased sensitivity to touch

-

Abnormal sense of taste

-

Hearing difficulties, ringing in the ears, vertigo

-

Inflammation of certain internal organs- pancreas and duodenum, swelling and inflammation of the

tongue

-

Enlarged liver, liver failure, gallbladder disease, gallstones

-

Joint inflammation, inflammation of the veins under the skin (which may be associated with the

formation of a blood clot)

-

Inflammation of the kidney, proteins in the urine, damage to the kidney

-

Very fast heart rate or skipped heartbeats, sometimes with erratic electrical impulses

-

Abnormal electrocardiogram (ECG)

-

Blood cholesterol increased, blood urea increased

-

Allergic skin reactions (sometimes severe), including life-threatening skin condition that causes

painful blisters and sores of the skin and mucous membranes, especially in the mouth,

inflammation of the skin, hives, sunburn or severe skin reaction following exposure to light or sun,

skin redness and irritation, red or purple discoloration of the skin which may be caused by low

platelet count, eczema

-

Infusion site reaction

-

Allergic reaction or exaggerated immune response

Rare: may affect up to 1 in 1000 people

-

Overactive thyroid gland

-

Deterioration of brain function that is a serious complication of liver disease

-

Loss of most fibers in the optic nerve, clouding of the cornea, involuntary movement of the eye

-

Bullous photosensitivity

-

A disorder in which the body’s immune system attacks part of the peripheral nervous system

-

Heart rhythm or conduction problems (sometimes life threatening)

-

Life threatening allergic reaction

-

Disorder of blood clotting system

-

Allergic skin reactions (sometimes severe), including rapid swelling (oedema) of the dermis,

subcutaneous tissue, mucosa and submucosal tissues, itchy or sore patches of thick, red skin with

silvery scales of skin, irritation of the skin and mucous membranes, life-threatening skin condition

that causes large portions of the epidermis, the skin's outermost layer, to detach from the layers of

skin below

-

Small dry scaly skin patches, sometimes thick with spikes or ‘horns’

Side effects with frequency not known:

-

Freckles and pigmented spots

Other significant side effects whose frequency is not known, but should be reported to your doctor

immediately:

-

Skin cancer

-

Inflammation of the tissue surrounding the bone

-

Red, scaly patches or ring-shaped skin lesions that may be a symptom of an autoimmune disease

called cutaneous lupus erythematosus

As VFEND has been known to affect the liver and the kidney, your doctor should monitor the function

of your liver and kidney by doing blood tests. Please advise your doctor if you have any stomach pains

or if your stools have a different consistency.

There have been reports of skin cancer in patients treated with VFEND for long periods of time.

Sunburn or severe skin reaction following exposure to light or sun was experienced more frequently in

children. If you or your child develops skin disorders, your doctor may refer you to a dermatologist, who

after consultation may decide that it is important for you or your child to be seen on a regular basis. Elevated

liver enzymes were also observed more frequently in children.

If any of these side effects persist or are troublesome, please tell your doctor.

Reporting of side effects

If you get any side effects, talk to your doctor or, pharmacist or nurse. This includes any possible side effects

not listed in this leaflet. You can also report side effects directly via the national reporting system listed in

Appendix 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 which is stated on the label. The expiry date refers to the last

day of that month.

Powder for oral suspension: store at 2°C - 8°C (in a refrigerator) before constitution.

For the constituted suspension:

Do not store above 30°C.

Do not refrigerate or freeze.

Store in the original container

Keep the container tightly closed.

Any remaining suspension should be discarded 14 days after constitution.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw

away medicines you no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What VFEND contains:

-

The active substance is voriconazole. Each bottle contains 45 g of powder providing 70 ml of suspension

when constituted with water as recommended. One ml of the constituted suspension contains 40 mg

voriconazole. (See section 3 ‘How to take VFEND’).

-

The other ingredients are sucrose; silica colloidal; titanium dioxide; xanthan gum; sodium citrate;

sodium benzoate; citric acid; natural orange flavour.

What VFEND looks like and contents of the pack

VFEND is supplied as a white to off-white powder for oral suspension providing a white to off-white, orange

flavoured suspension when constituted with water.

Marketing Authorisation Holder

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

Manufacturer

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

For any information about this medicine, please contact the local representative of the Marketing

Authorisation Holder:

België /Belgique/Belgien

Pfizer S.A./N.V.

Tél/Tel: +32 (0)2 554 62 11

Lietuva

Pfizer Luxembourg SARL

Filialas Lietuvoje

Tel. +3705 2514000

България

Пфайзер Люксембург САРЛ, Клон България

Тел.: +359 2 970 4333

Luxembourg/Luxemburg

Pfizer S.A.

Tél: +32 (0)2 554 62 11

Česká republika

Pfizer s.r.o.

Tel: +420-283-004-111

Magyarország

Pfizer Kft.

Tel. + 36 1 488 37 00

Danmark

Pfizer ApS Tlf:

+45 44 20 11 00

Malta

V.J. Salomone Pharma Ltd.

Tel : +356 21 22 01 74

Deutschland

Pfizer Pharma PFE GmbH

Tel: +49 (0)800 8535555

Nederland

Pfizer bv

Tel: +31 (0)10 406 43 01

Eesti

Pfizer Luxembourg SARL Eesti filiaal

Tel: +372 666 7500

Norge

Pfizer AS

Tlf: +47 67 52 61 00

Ελλάδα

Pfizer ΕΛΛΑΣ A.E.

Τηλ.: +30 210 6785 800

Österreich

Pfizer Corporation Austria

Ges.m.b.H. Tel: +43 (0)1

521 15-0

España

Pfizer, S.L.

Tel: +34 91 490 99 00

Polska

Pfizer Polska Sp. z o.o.,

Tel.: +48 22 335 61 00

France

Pfizer

Tél: +33 (0)1 58 07 34 40

Portugal

Laboratórios Pfizer, Lda.

Tel: + 351 214 235 500

Hrvatska

Pfizer Croatia d.o.o.

Tel: + 385 1 3908 777

România

Pfizer România S.R.L

Tel: +40 (0)21 207 28 00

Ireland

Pfizer Healthcare Ireland

Tel: 1800 633 363 (toll free)

+44 (0)1304 616161

Slovenija

Pfizer Luxembourg SARL

Pfizer, podružnica za svetovanje s področja

farmacevtske dejavnosti, Ljubljana

Tel: + 386(0)152 11 400

Ísland

Icepharm hf.,

Sími: + 354 540 8000

Slovenská republika

Pfizer Luxembourg SARL, organizačná zložka

Tel: +421-2-3355 5500

Italia

Pfizer Italia S.r.l.

Tel: +39 06 33 18 21

Suomi/Finland

Pfizer Oy

Puh/Tel: +358(0)9 43 00 40

Kύπρος

Pfizer ΕΛΛΑΣ Α.Ε. (Cyprus Branch)

Τηλ: +357 22 817690

Sverige

Pfizer AB

Tel: +46 (0)8 5505 2000

Latvija

Pfizer Luxembourg SARL

Filiāle Latvijā

Tel: +371 670 35 775

United Kingdom

Pfizer Limited

Tel: +44 (0)1304 616161

This leaflet was last approved in {MM/YYYY}.

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu