How does it work?

Vfend infusion, tablets and oral suspension contain the activeingredient voriconazole, which is a type of medicine called a triazoleantifungal. It is used to treat infections caused by fungi.

Voriconazole works by preventing fungi from producing asubstance called ergosterol, which is a component of fungal cell membranes.

The cell membranes of fungi are vital for their survival. Theykeep unwanted substances from entering the cells and stop the contents of thecells from leaking out. Without ergosterol as part of the cell membrane, themembrane is weakened and damaged and essential constituents of the fungalcells can leak out. This kills the fungi and hence clears up theinfection.

Voriconazole is used to treat serious fungal infections,including those caused by Candida, Aspergillus, Scedosporium and Fusariumspecies of fungi. To make sure the fungi causing an infection are susceptibleto voriconazole your doctor may take a tissue sample, for example a swab fromthe throat or skin, or a urine or blood sample.

Voriconazole is usually reserved as treatment for progressiveinfections in people whose immune systems are underactive, for example due tocancer treatment, AIDS, or following an organ transplant. Serious fungalinfections can sometimes be life-threatening in these groups ofpatients.

What is it used for?

• Serious fungal infections caused by Candida, Aspergillus, Scedosporium and Fusariumspecies of fungi, primarily in people with progressive and possibly life-threatening infections.

Warning!

• Vfend tablets should be taken at least an hour before, or an hour after a meal. Vfend suspension should be taken at least an hour before, or two hours after a meal.
• Before starting treatment with this medicine you should have a blood test to measure the levels of electrolytes (salts, such as potassium, calcium and magnesium) in your blood. If there are any problems your doctor will give you treatment to correct them before you start this medicine.
• This medicine may cause visual disturbances such as blurred vision and so may affect your ability to drive or operate machinary safely. Do not drive or operate machinary until you know how this medicine affects you.
• This medicine can make your skin more sensitive to sunlight. For this reason you should avoid exposing your skin to direct sunlight or sun lamps during treatment. When going out in the sun you should cover exposed areas of skin with clothing or use sunscreen with a high protection factor.
• This medicine can also cause some severe skin reactions. You should tell your doctor straight away if you get a skin rash or blisters while taking this medicine.
• This medicine can sometimes cause liver problems and for this reason your liver function will be monitored during treatment. Tell your doctor if you experience any of the following symptoms while taking this medicine, as they may suggest a problem with your liver: unexplained itching, loss of appetite, nausea and vomiting, abdominal pain, yellowing of the skin or whites of the eyes (jaundice), unusually dark urine or pale stools.
• Your kidney function should also be monitored during treatment with this medicine.
• Unless your doctor tells you otherwise, it is important that you finish the prescribed course of this antifungal medicine, even if you feel better or it seems the infection has cleared up. Stopping the course early increases the chance that the infection will come back and that the fungi will grow resistant to the medicine.
• This medicine should not normally be used for longer than six months.

Use with caution in

• People who are allergic to other azole antifungal medicines, eg fluconazole, itraconazole.
• Decreased liver function.
• Liver cirrhosis.
• Low level of potassium in the blood (hypokalaemia).
• People, particularly children, at risk of inflammation of the pancreas (acute pancreatitis).
• People who have recently received cancer chemotherapy, particularly that which could have side effects on the heart.
• Any long term disorder affecting the muscle of the heart (cardiomyopathy).
• Heart failure.
• Irregular heart beats (arrhythmias).
• Abnormal rhythm of the heart beat (prolonged QT interval on a heart monitor or ECG).
• People taking medicines that can cause prolonged QT interval on an ECG (see end of factsheet for examples).
• Slow heart rate caused by the pacemaker of the heart (sinus bradycardia).

Not to be used in

• Breastfeeding.
• People taking certain other medicines - see end of factsheet for more details.
• Vfend tablets contain lactose and are not suitable for people with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
• Vfend suspension contains sucrose and is not suitable for people with rare hereditary problems of fructose intolerance, sucrase-isomaltase deficiency or glucose-galactose malabsorption.
• This medicine is not recommended for children under two years of age, as its safety and effectiveness have not been studied in this age group.

This medicine should not be used if you are allergic to one orany of its ingredients. Please inform your doctor or pharmacist if you havepreviously experienced such an allergy.

If you feel you have experienced an allergic reaction, stopusing this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy orbreastfeeding. However, other medicines may be safely used in pregnancy orbreastfeeding providing the benefits to the mother outweigh the risks to theunborn baby. Always inform your doctor if you are pregnant or planning apregnancy, before using any medicine.

• The safety of this medicine in pregnancy has not been established. It should therefore not be used during pregnancy, unless the benefits to the mother outweigh any possible risks to the developing baby. Women who could get pregnant should use effective contraception to avoid getting pregnant while they are taking this medicine. Seek medical advice from your doctor.
• It is not known if this medicine passes into breast milk. Mothers who need to take this medicine should not breastfeed their infants during treatment. Seek medical advice from your doctor.

Label warnings

• Avoid exposure of skin to direct sunlight or sun lamps.

Side effects

Medicines and their possible side effects can affect individualpeople in different ways. The following are some of the side effects that areknown to be associated with this medicine. Just because a side effect is statedhere, it does not mean that all people using this medicine will experience thator any side effect.

Very common (affect more than 1 in 10 people)

• Headache.
• Visual disturbances.
• Swelling of the legs and ankles due to fluid retention (peripheral oedema).
• Disturbances of the gut such as diarrhoea, nausea, vomiting or abdominal pain.
• Fever.
• Rash.

Common (affect between 1 in 10 and 1 in 100 people)

• Gastroenteritis.
• Flu-like illness.
• Inflammation of the sinuses (sinusitis).
• Decreases in the numbers of white blood cells, red blood cells or platelets in the blood.
• Low levels of sugar or potassium in the blood.
• Depression.
• Hallucinations.
• Anxiety.
• Dizziness.
• Confusion.
• Tremor.
• Pins and needles sensations.
• Low blood pressure.
• Respiratory distress syndrome.
• Chest or back pain.
• Jaundice.
• Hair loss.
• Swelling of the face.
• Increased sensitivity of the skin to UV light (photosensitivity).
• Skin reactions such as rashes, redness or itching (see warning section above).
• Weakness.
• Acute kidney failure.

Uncommon (affect between 1 in 100 and 1 in 1000 people)

• Optic nerve disorder.
• Abnormal heart beats.
• Fainting.
• Inflammation of the pancreas (pancreatitis).
• Inflammation of the tongue or gums.
• Constipation.
• Indigestion.
• Liver problems such as hepatitis, liver failure or gallstones.
• Psoriasis.
• Severe skin reaction called Stevens-Johnson syndrome.
• Kidney inflammation (nephritis).

The side effects listed above may not include all of the sideeffects reported by the medicine's manufacturer.

For more information about any other possible risks associatedwith this medicine, please read the information provided with the medicine orconsult your doctor or pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicinesyou are already taking, including those bought without a prescription andherbal medicines, before you start treatment with this medicine. Similarly,check with your doctor or pharmacist before taking any new medicines whiletaking this one, to ensure that thecombination is safe.

This medicine must not be used in combination with any of thefollowing medicines:

• astemizole
• carbamazepine
• cisapride
• dihydroergotamine
• ergotamine
• phenobarbital
• pimozide
• quinidine
• rifampicin
• high doses of ritonavir (400 mg and above twice daily)
• sirolimus
• terfenadine
• the herbal remedy St John's wort (Hypericum perforatum).

This medicine should be avoided in people taking low doseritonavir (100 mg twice daily), unless your doctor considers the benefits tooutweigh the risks. This is because ritonavir decreases the blood level ofvoriconazole and could make it less effective at treatinginfection.

This medicine may increase the blood level of theimmunosuppressants ciclosporin and tacrolimus. If you are taking ciclosporin ortacrolimus when you start this medicine your doctor should decrease your doseto prevent side effects from the immunosuppressant. The level of ciclosporin ortacrolimus in your blood should be monitored after starting and stoppingtreatment with this medicine.

This medicine may increase the anti-blood-clotting effect ofanticoagulants such as warfarin. If you are taking an anticoagulant medicineyour blood clotting time (INR) should be monitored while taking thismedicine.

This medicine may increase the blood level of sulphonylureamedicines, such as tolbutamide and glipizide, that are used to treattype 2 diabetes. This could cause blood sugar to fall (hypoglycaemia). Peopletaking any of these medicines should therefore carefully monitor their bloodsugar during treatment with this medicine.

This medicine may increase the blood level of methadone. If youare taking methadone when you start this medicine your doctor may need toreduce your methadone dose in order to avoid side effects.

This medicine may increase the blood level of hormones from oralcontraceptives containing ethinylestradiol and norethisterone. It should notmake these contraceptives any less effective, but may increase the chance ofgetting side effects like nausea or changes in your bleeding.

This medicine may also increase the blood levels of thefollowing medicines. As this could increase the chance of their side effects,your doctor may need to reduce the dose of these medicines if you are takingany of them when you start treatment with voriconazole:

• alfentanil and other short acting opiates such as fentanyl and sufentanil (painkillers used for surgical procedures)
• benzodiazepines such as triazolam and midazolam
• non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or diclofenac
• omeprazole
• statins such as simvastatin
• vinblastine
• vincristine.

Phenytoin and rifabutin decrease the blood level ofvoriconazole. Conversely, voriconazole may increase the blood levels of thesemedicines. These combinations should be avoided where possible, but ifconsidered necessary your doctor will prescribe you a higher than normal doseof voriconazole and monitor you for side effects of the other medicine.

The anti-HIV medicine efavirenz also decreases the blood levelof voriconazole, while its blood level is increased by the voriconazole. As aresult, if you are taking efavirenz you will be prescribed a higher than normaldose of voriconazole. In addition, your dose of efavirenz will be decreasedduring the treatment and then increased again once your course of voriconazoleis finished.

If you are taking other anti-HIV medicines, such as proteaseinhibitors, your doctor will want to monitor you carefully for any new sideeffects if you are also prescribed this medicine.

There may be an increased risk of abnormal heart rhythms(prolonged QT interval on the heart monitoring trace or ECG) if this medicineis taken with the following:

• medicines to treat abnormal heart rhythms, eg amiodarone, procainamide, disopyramide, sotalol
• certain antidepressants, eg maprotiline, amitriptyline, imipramine
• certain antipsychotics, eg thioridazine, chlorpromazine, sertindole, haloperidol
• antimalarials, eg halofantrine, chloroquine, quinine, Riamet
• certain antimicrobials, eg erythromycin, moxifloxacin or pentamidine.

Other medicines containing the same active ingredient

There are currently no other medicines available in the UK thatcontain voriconazole as the active ingredient.