Voriconazole Accord

Patient Information Leaflet: Information for the User

Voriconazole Accord 50 mg film-coated tablets, 200 mg film-coated tablets

voriconazole
Please read all of this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Voriconazolo Accord is and what it is used for

Voriconazolo Accord contains the active substance voriconazole. Voriconazolo Accord is an antifungal medicine. It works by stopping the growth of, or killing, the fungi that cause infections.
It is used to treat patients (adults and children over 2 years of age) who have:

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

Voriconazolo Accord is indicated for patients with worsening fungal infections that are potentially life-threatening.
Prevention of fungal infections in high-risk patients undergoing bone marrow transplantation.
This medicine should only be used under medical supervision.

2. What you should know before taking Voriconazole Accord

Do not take Voriconazole Accord
if you are allergic to voriconazole or to any of the other ingredients of this medicine (listed
in section 6).
It is very important that you inform your doctor or pharmacist if you are taking or have recently taken other
medicines, including those without a prescription, or herbal medicines.
The medicines listed below must not be used during treatment with Voriconazole Accord:

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

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

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

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

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

If you develop any of the skin conditions described above, your doctor may refer you to a
dermatologist, who after consultation may decide that regular check-ups are necessary. With long-term use of Voriconazole Accord, there is a small risk of developing
skin carcinoma.
If you develop signs of "adrenal insufficiency", in which the adrenal glands do not produce
adequate amounts of certain steroid hormones such as cortisol, which may cause symptoms such as:
persistent or chronic fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, inform your doctor.
Inform your doctor if you develop signs of “Cushing's syndrome”, in which the body produces excessive amounts of the hormone cortisol, which may cause symptoms such as weight gain, fat accumulation between the shoulders, rounded face, darkening of the skin on the abdomen, thinning of legs, breasts and arms, thinning of the skin, easy bruising, increased blood sugar, excessive body hair growth, excessive sweating.
Your doctor will need to monitor liver and kidney function through blood tests.
Children and adolescents
Voriconazole Accord must not be administered to children under 2 years of age.
Other medicines and Voriconazole Accord:
Inform your doctor or pharmacist if you are taking, have recently taken, or might take
any other medicine, including those without a prescription.
Some medicines, when taken together with Voriconazole Accord, may alter
the activity of Voriconazole Accord or Voriconazole Accord may alter the activity of these
medicines.
Inform your doctor if you are taking the following medicine because, if possible, concomitant treatment
with Voriconazole Accord should be avoided:

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

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

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

Inform your doctor if you are taking any of the following medicines because dose adjustments or monitoring may be necessary to ensure these medicines and/or Voriconazole Accord continue to have the desired effect:

• Warfarin and other anticoagulants (e.g. fenprocoumon, acenocoumarol; to slow down the blood clotting process)
• Cyclosporine (for transplant patients)
• Tacrolimus (for transplant patients)
• Sulfonylureas (e.g. tolbutamide, glipizide, glyburide) (for diabetes)
• Statins (e.g. atorvastatin, simvastatin) (to reduce cholesterol)
• Benzodiazepines (e.g. midazolam, triazolam) (for severe insomnia and stress)
• Omeprazole (for the treatment of ulcers)
• Oral contraceptives (if you take Voriconazole Accord while using oral contraceptives, side effects such as nausea and menstrual disorders may occur)
• Vinca alkaloids (e.g. vincristine and vinblastine) (for cancer treatment)
• Tyrosine kinase inhibitors (e.g. axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (for cancer treatment)

Tretinoin (for the treatment of leukemia)

• Indinavir and other protease inhibitors for AIDS (for the treatment of AIDS)
• Non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz, delavirdine, nevirapine) (for the treatment of AIDS) (some doses of efavirenz cannot be taken together with Voriconazole Accord)
• Methadone (for the treatment of heroin addiction)
• Alfentanil and fentanyl and other short-acting opioids such as sufentanil (analgesics used in surgical procedures)
• Oxycodone and other long-acting opioids such as hydrocodone (used for the treatment of moderate to severe pain)
• Non-steroidal anti-inflammatory drugs (e.g. ibuprofen, diclofenac) (used for the treatment of pain and inflammation)
• Fluconazole (used to treat fungal infections)
• Everolimus (used for the treatment of advanced renal cell carcinoma and in transplant patients)
• Letermovir (used to prevent cytomegalovirus (CMV) disease following bone marrow transplantation)
• Ivacaftor: used for the treatment of cystic fibrosis
• Flucloxacillin (an antibiotic indicated for bacterial infections)

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

3. How to take Voriconazole Accord

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

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

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

• The tablets should only be administered if the child is able to swallow tablets. Take the tablets at least one hour before or one hour after meals. Swallow the tablet whole with some water.

If you or your child are taking Voriconazole Accord to prevent fungal infections, your doctor may decide to discontinue treatment with Voriconazole Accord if you or your child develop treatment-related adverse effects.

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

If you forget to take Voriconazole Accord
It is important to take Voriconazole Accord tablets regularly every day at the same time. If you forget to take a dose, take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose.

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
If side effects occur, most will probably be mild and temporary. However, some may be serious and require immediate medical attention.
Serious side effects – Stop taking Voriconazole Accord and consult a doctor immediately

• Rash
• Jaundice; abnormal liver function tests
• Pancreatitis

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

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

Common: may affect up to 1 in 10 people

• Sinus inflammation, gum inflammation, chills, fatigue
• Reduction, sometimes severe, in the number of certain types of red blood cells (sometimes immune-mediated) and/or white blood cells (sometimes with fever), reduction in the number of blood cells (called platelets) responsible for blood clotting
• Low blood sugar levels, low blood potassium levels, low blood sodium levels
• Anxiety, depression, confusion, agitation, sleep disorders, hallucinations
• Seizures, tremor or uncontrolled muscle movements, tingling or abnormal skin sensations, increased muscle tone, drowsiness, dizziness
• Bleeding in the eye
• Heart rhythm problems including very fast heartbeat, very slow heartbeat, fainting
• Low blood pressure, inflammation of a vein (which may be associated with blood clot formation)
• Acute breathing difficulty, chest pain, facial swelling (mouth, lips and around the eyes), fluid accumulation in the lungs
• Constipation, indigestion, inflammation of the lips, jaundice, liver inflammation and liver injury
• Skin rash which may lead to severe blistering and peeling of the skin, characterised by a flat red area of skin with small merging bumps, skin redness
• Itching
• Hair loss
• Back pain
• Kidney failure, blood in the urine, altered kidney function tests
• Sunburn or severe skin reactions 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, gastrointestinal inflammation which may cause antibiotic-associated diarrhoea, inflammation of lymphatic vessels

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

• Enlarged lymph nodes (sometimes painful), bone marrow failure (with increased eosinophils)

• Reduced adrenal gland function, reduced thyroid gland activity

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

• Problems with balance and coordination

• Brain swelling

• Double vision, serious eye conditions including: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage with visual impairment, swelling of the optic disc

• Reduced sensitivity to touch

• Altered taste

• Hearing disorders, ringing in the ears, vertigo

• Inflammation of certain internal organs – pancreas and duodenum, swelling and inflammation of the tongue

• Enlarged liver, liver failure, gallbladder diseases, gallstones

• Joint inflammation, inflammation of subcutaneous veins (which may be associated with blood clot formation)

• Kidney inflammation, presence of protein in the urine, kidney damage

• Increased heart rate or irregular heartbeat, sometimes with electrical impulses

• Abnormal electrocardiogram (ECG)

• Increased cholesterol, increased blood urea

• Allergic skin reactions (sometimes severe), including potentially life-threatening skin condition causing blisters and painful sores of the skin and mucous membranes, especially in the mouth,
  skin inflammation, urticaria, redness and irritation of the skin, skin discolouration (red or purplish) which may be due to low platelet count, eczema

• Infusion site reaction

• Allergic reactions or exaggerated immune response

• Inflammation of the tissue surrounding the bone

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

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

Side effects with unknown frequency:

• Freckles and pigmented spots

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

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

Since Voriconazole Accord has been observed to affect the liver and kidneys, your doctor will monitor liver and kidney function through blood tests. Inform your doctor if you experience stomach pain or if your stools have an unusual consistency.
If any of these side effects persist or are bothersome, inform your doctor.
Sunburn or severe skin reactions following exposure to light or sun have been reported more frequently in children. If you or your child develops skin problems, your doctor may refer you to a dermatologist who may decide whether regular follow-up visits with a dermatologist are necessary for you or your child. Elevated liver enzymes have also been observed more frequently in children.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
Reporting of suspected adverse reactions
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Voriconazole Accord

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Voriconazolo Accord contains

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

Description of the appearance of Voriconazolo Accord and pack contents
Voriconazolo Accord 50 mg film-coated tablets are white to off-white, round, film-coated tablets, approximately 7.00 mm in diameter, marked with 'V50' on one side and smooth on the other side.
Voriconazolo Accord 200 mg film-coated tablets are white to off-white, oval, film-coated tablets, approximately 15.6 mm long and 7.8 mm wide, marked with 'V200' on one side and smooth on the other side.
Voriconazolo Accord 50 mg film-coated tablets and Voriconazolo Accord 200 mg film-coated tablets are available in packs of 2, 10, 14, 20, 28, 30, 50, 56 and 100 tablets, or in unit-dose divisible blisters (PVC/Aluminum) containing 10x1, 14x1, 28x1, 30x1, 56x1 or 100x1 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n,
Edifici Est, 6th floor,
08039 Barcelona,
Spain

Manufacturer:
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park,
Paola, PLA 3000
Malta
Accord Healthcare Polska Sp.z o.o.,
ul. Lutomierska 50, 95-200 Pabianice, Poland
Accord Healthcare B.V.,
Winthontlaan 200,
3526 KV Utrecht,
The Netherlands
Accord Healthcare single member S.A.
64th Km National Road Athens, Lamia,
Schimatari, 32009, Greece

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

AT / BE / BG / CY / CZ / DE / DK / EE / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT / NL / NO / PT / PL / RO / SE / SI / SK / ES
Accord Healthcare S.L.U.
Tel: +34 93 301 00 64

EL
Win Medica A.E.
Tel: +30 210 7488 821

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