Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - vfend

Document Subject

Generated Narrative: MedicinalProductDefinition mp74e50e4505c090a88581d2832252680c

identifier: http://ema.europa.eu/identifier/EU/1/02/212/001-009

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: VFEND 50 mg film-coated tablets

type: Full name

part

part: nan

type: Invented name part

part

part: nan

type: Scientific name part

part

part: nan

type: Strength part

part

part: nan

type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-74e50e4505c090a88581d2832252680c

identifier: http://ema.europa.eu/identifier/EU/1/02/212/001-009

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - vfend

Attesters

What is in this leaflet

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

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.

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)
• Ivabradine (used for symptoms of chronic heart failure)
• 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)
• Naloxegol (used to treat constipation specifically caused by pain medicines, called opioids, (e.g., morphine, oxycodone, fentanyl, tramadol, codeine))
• Tolvaptan (used to treat hyponatremia (low levels of sodium in your blood) or to slow kidney function decline in patients with polycystic kidney disease)
• Lurasidone (used to treat depression)
• Venetoclax (used to treat patients with chronic lymphocytic leukaemia-CLL)

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

• you have had an allergic reaction to other azoles.
• you 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. This may be further increased by other medicines that sensitise the skin to sunlight, like methotrexate. 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.

If you develop signs of adrenal insufficiency where the adrenal glands do not produce adequate amounts of certain steroid hormones such as cortisol which may lead to symptoms such as: chronic, or long lasting fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, please tell your doctor.

If you develop signs of Cushing s syndrome where the body produces too much of the hormone cortisol
which may lead to symptoms such as: weight gain, fatty hump between the shoulders, a rounded face, darkening of the skin on the stomach, thighs breasts, and arms, thinning skin, bruising easily, high blood sugar, excessive hair growth, excessive sweating, please tell your doctor.

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
• Glasdegib (used for treating cancer) if you need to use both drugs your doctor will monitor your heart rhythm frequently

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)

• Tyrosine kinase inhibitors (e.g., axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (used for treating cancer)

• Tretinoin (used to treat leukaemia)

• 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)

• Letermovir (used for preventing cytomegalovirus (CMV) disease after bone marrow transplant)

• Ivacaftor: used to treat cystic fibrosis

• Flucloxacillin (antibiotic used against bacterial infections)

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.

VFEND contains sodium This medicine contains less than 1 mmol sodium (23 mg) per 50 mg tablet, that is to say essentially sodium-free .

This medicine contains less than 1 mmol sodium (23 mg) per 200 mg tablet, that is to say essentially sodium-free .

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 for 200 mg every 12 hours for (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 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.

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 colour 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
• Sunburn or severe skin reaction following exposure to light or sun
• Skin cancer

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, 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

• Inflammation of the tissue surrounding the bone

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:

• 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.

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.

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).
• The other ingredients are 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 (see section 2, VFEND 50 mg film-coated tablets or VFEND 200 mg film-coated tablets contains lactose and sodium).

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. Localit Marino del Tronto 63100 Ascoli Piceno (AP) Italy

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

Belgi /Belgique/Belgien / Luxembourg/Luxemburg Pfizer NV/SA
T l/Tel: +32 (0)2 554 62 Lietuva
Pfizer Luxembourg SARL
Filialas Lietuvoje
Tel. +3705 2514
,
.: +359 2 970 4Magyarorsz g
Pfizer Kft.
Tel. + 36 1 488 37 esk republika
Pfizer, spol. s.r.o. Tel: +420-283-004-Malta
Vivian Corporation Ltd.
Tel : +356 21344Danmark
Pfizer ApS Tlf:
+45 44 20 11 Nederland
Pfizer bv
Tel: +31 (0)800 63 34 Deutschland
PFIZER PHARMA GmbH
Tel: +49 (0)30 550055-51Norge
Pfizer AS
Tlf: +47 67 52 61 Eesti
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7 sterreich
Pfizer Corporation Austria Ges.m.b.H. Tel: +43 (0)1 521 15-0

Pfizer A.E. .: +30 210 6785 Polska
Pfizer Polska Sp. z o.o.,
Tel.: +48 22 335 61 Espa a
Pfizer, S.L. Tel: +34 91 490 99 Portugal
Laborat rios Pfizer, Lda.
Tel: + 351 214 235 France Pfizer T l: +33 (0)1 58 07 34 Rom nia
Pfizer Rom nia S.R.L
Tel: +40 (0)21 207 28 Hrvatska Pfizer Croatia d.o.o. Tel: + 385 1 3908 Slovenija
Pfizer Luxembourg SARL
Pfizer, podru nica za svetovanje s podro ja farmacevtske dejavnosti, Ljubljana
Tel: + 386 (0)152 11 Ireland
Pfizer Healthcare Ireland
Tel: 1800 633 363 (toll free) +44 (0)1304 616Slovensk republika
Pfizer Luxembourg SARL, organiza n zlo ka Tel: +421-2-3355 5 sland
Icepharma hf.,
S mi: + 354 540 8Suomi/Finland
Pfizer Oy
Puh/Tel: +358(0)9 43 00 Italia
Pfizer S.r.l.
Tel: +39 06 33 18 Sverige
Pfizer AB
Tel: +46 (0)8 5505 2K
Pfizer . . (Cyprus Branch)
: +357 22 817United Kingdom (Northern Ireland) Pfizer Limited
Tel: +44 (0)1304 616Latvija
Pfizer Luxembourg SARL
Fili le Latvij
Tel: +371 670 35 This leaflet was last approved in {MM/YYYY}. Detailed information on this medicine is available on the European Medicines Agency web site: