Voriconazole Accord 200 mg film-coated tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Voriconazole Accord 50 mg film-coated tablets

Voriconazole Accord 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, as 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 and must not be given to other people, even if they have the same symptoms, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are adverse effects not listed in this leaflet. 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 Voriconazol Accord is and what it is used for

Voriconazol Accord contains the active substance voriconazole. Voriconazol Accord is an antifungal medicine. It works by killing or preventing the growth of fungi that cause infections.

It is used to treat patients (adults and children aged 2 years and older) with:

• invasive aspergillosis (a type of fungal infection caused by Aspergillus sp),
• candidaemia (another type of fungal infection caused by Candida sp) in non-neutropenic patients (patients who do not have an abnormally low white blood cell count),
• serious invasive infections caused by Candida sp, 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).

Voriconazol Accord is used in patients with serious fungal infections that may be life-threatening.

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

This medicine should only be used under medical supervision.

2. What you need to know before starting to take Voriconazol Accord

Do not take Voriconazol 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 any other medicines, including those obtained without a prescription, or herbal remedies.

During treatment with Voriconazol Accord, you must not take the following medicines:

• Terfenadine (used for allergies).
• Astemizole (used for allergies).
• Cisapride (used for digestive problems).
• Pimozide (used for mental disorders).
• Quinidine (used for heart arrhythmias).
• Ivabradine (used for symptoms of chronic heart failure).
• Rifampicin (used to treat tuberculosis).
• Efavirenz (used to treat HIV) at doses of 400 mg or higher 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 to treat HIV) at doses of 400 mg or higher twice daily.
• St. John’s wort (hypericum, herbal remedy).
• Naloxegol (used to treat constipation specifically caused by painkillers called opioids [e.g., morphine, oxycodone, fentanyl, tramadol, codeine]).
• Tolvaptan (used to treat hyponatremia (low sodium levels in blood) or to slow down the decline in kidney function in patients with polycystic kidney disease).
• Lurasidone (used to treat depression).
• Finerenone (used to treat chronic kidney disease).
• Venetoclax (used for the treatment of patients with chronic lymphocytic leukemia [CLL]).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to take Voriconazol Accord if:

• you have had an allergic reaction to other azoles.
• you have or have previously had liver disease. If you have liver disease, your doctor may prescribe a lower dose of Voriconazol Accord. Your doctor should also monitor your liver function during treatment with Voriconazol Accord by performing blood tests.
• you know you have cardiomyopathy, irregular heartbeat, slow heart rate, or an abnormality on the electrocardiogram (ECG) known as “prolonged QTc syndrome”.

You must avoid any exposure to sunlight and UV light during treatment. It is important to cover exposed areas and use sunscreen with a high sun protection factor (SPF), as increased sensitivity of the skin to UV rays from the sun may occur. These precautions also apply to children.

While you are being treated with Voriconazol Accord:

• inform your doctor if you experience

• sunburn

• severe skin rash or blistering

• bone pain

If you develop skin disorders such as those described above, your doctor may refer you to a dermatologist, who may consider it important for you to have regular check-ups. There is a small possibility that you may develop skin cancer with long-term use of Voriconazol Accord.

If you develop signs of “adrenal insufficiency”, in which the adrenal glands do not produce enough steroid hormones such as cortisol, which may cause symptoms such as: prolonged or chronic fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, inform your doctor.

If you experience signs of “Cushing's syndrome”, in which the body produces too much cortisol hormone, which may cause symptoms such as: weight gain, fatty hump between the shoulders, rounded face, darkening of the skin on the abdomen, thighs, breasts and arms, thin skin, easy bruising, high blood sugar levels, excessive hair growth or excessive sweating, inform your doctor.

Your doctor should monitor the function of your liver and kidneys by performing blood tests.

Children and adolescents

Voriconazol Accord must not be given to children under 2 years of age.

Taking Voriconazol Accord with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription.

Some medicines, when used at the same time as Voriconazol Accord, may affect the action of Voriconazol Accord or Voriconazol Accord may affect the action of other medicines.

Inform your doctor if you are taking the following medicines, as concomitant treatment with Voriconazol Accord should be avoided if possible:

• Ritonavir (used to treat HIV) at a dose of 100 mg twice daily.
• Glasdegib (used to treat cancer); if you need to take both medicines, your doctor will frequently monitor your heart rhythm.

Inform your doctor if you are taking any of the following medicines, as concomitant treatment with Voriconazol Accord should be avoided as much as possible, and a dose adjustment of voriconazole may be required:

• Rifabutin (used to treat tuberculosis). If you are already being treated with rifabutin, your blood count and adverse effects of rifabutin should be monitored.
• Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin, the concentration of phenytoin in your blood should be monitored during treatment with Voriconazol Accord, and your dose may need to be adjusted.

Tell your doctor if you are taking any of the following medicines, as you may need a dose adjustment or monitoring to ensure these medicines and/or Voriconazol Accord are still producing the desired effect:

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

Pregnancy and breastfeeding

You must not take Voriconazol Accord during pregnancy unless instructed by your doctor. Women of childbearing age receiving Voriconazol Accord should use effective contraception.

Contact your doctor immediately if you become pregnant while taking Voriconazol Accord.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

Voriconazol Accord may cause blurred vision or discomfort due to increased sensitivity to light. If this occurs, do not drive or operate tools or machinery and inform your doctor.

Voriconazol Accord contains lactose

If your doctor has informed you that you have an intolerance to certain sugars, speak with your doctor before taking Voriconazol Accord.

Voriconazol Accord contains sodium

This medicine contains less than 23 mg (1 mmol of sodium) per 50 mg tablet; this is essentially “sodium-free”.

This medicine contains less than 23 mg (1 mmol of sodium) per 200 mg tablet; this is essentially “sodium-free”.

3. How to take Voriconazol Accord

Follow exactly the instructions for use of this medicine as provided by your doctor. If in doubt, consult your doctor or pharmacist again.

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

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

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

Your doctor may decide to reduce the dose if you have mild to moderate cirrhosis.

Use in children and adolescents

The recommended dose in children and adolescents is as follows:

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

• Tablets should only be administered if the child is able to swallow whole tablets.

Take the tablets 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 Voriconazole Accord for the prevention of fungal infections, your doctor may stop the administration of Voriconazole Accord if you or your child develop adverse reactions related to treatment.

If you take more Voriconazole Accord than you should

If you take more tablets than prescribed (or if someone else takes your tablets), you must immediately seek medical assistance or go to the nearest hospital emergency department. Take the pack of Voriconazole Accord tablets with you. You may experience abnormal sensitivity to light as a result of taking more Voriconazole Accord than you should.

If you forget to take Voriconazole Accord

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

If you stop taking Voriconazole Accord

It has been shown that correctly following the prescribed dosing schedule, by taking each dose at the correct time, can significantly increase the effectiveness of this medicine. Therefore, unless your doctor tells you otherwise, it is important that you continue taking Voriconazole Accord correctly as previously indicated.

Continue taking Voriconazole Accord until your doctor tells you otherwise. Do not stop treatment prematurely, as the infection may not be cured. Patients with weakened immune systems or with complicated infections may require longer treatment courses to prevent the infection from recurring.

When your doctor discontinues treatment with Voriconazole Accord, you should not experience any effects due to stopping the medication.

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

4. Possible adverse effects

Like all medicines, this medicine can have adverse effects, although not everyone will experience them.

If any occur, they are most likely to be mild and temporary. However, some may be serious and require immediate medical attention.

Serious adverse effects – Stop taking Voriconazole Accord and see a doctor immediately

• Skin rash.
• Jaundice; changes in liver function detected in blood tests.
• Pancreatitis.

Other adverse effects

Very common: may affect more than 1 in 10 people

• Visual disturbance (changes in vision, such as blurred vision, color vision disturbances, abnormal intolerance to visual perception of light, color blindness, eye disorder, visual halos, night blindness, oscillating vision, perception of sparks, visual aura, decreased visual acuity, reduced visual clarity, partial loss of normal visual field, spots in the visual field).
• Fever.
• Skin rash.
• Nausea, vomiting, and diarrhea.
• Headache.
• Swelling of the limbs.
• Stomach pain.
• Difficulty breathing.
• Elevated liver enzymes.

Common: may affect up to 1 in 10 people

• Sinusitis, gum inflammation, chills, weakness.
• Low blood counts, including severe cases, of certain types of red blood cells (sometimes immune-mediated) and/or white blood cells (sometimes accompanied by fever), low platelet count affecting blood clotting.
• Low blood sugar levels, low blood potassium levels, low blood sodium levels.
• Anxiety, depression, confusion, agitation, insomnia, hallucinations.
• Seizures, tremors or uncontrolled muscle movements, tingling or abnormal sensations in the skin, increased muscle tone, drowsiness, dizziness.
• Eye hemorrhage.
• Heart rhythm problems including very fast or very slow heartbeat, fainting, hypotension, vein inflammation (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, lip swelling.
• Jaundice (yellowing of the skin), liver inflammation, and liver damage.
• Skin rashes, which may become severe, with blisters and peeling, characterized by flat, red areas covered with small merging bumps, skin redness.
• Itching.
• Alopecia.
• Back pain.
• Kidney failure, presence of blood in urine, abnormalities in blood tests monitoring kidney function.
• 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, gastrointestinal inflammation causing antibiotic-associated diarrhea, inflammation of lymphatic vessels.
• Inflammation of the thin tissue lining the abdominal wall and covering abdominal organs.
• Enlargement (sometimes painful) of lymph nodes, bone marrow failure, increased eosinophils.
• Decreased adrenal gland function, underactive thyroid gland.
• Abnormal brain function, symptoms resembling Parkinson's disease, nerve damage causing numbness, pain, tingling, or burning in hands or feet.
• Problems with balance or coordination.
• Brain swelling.
• Double vision, serious eye disorders such as eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage causing vision changes, optic disc inflammation.
• Decreased sensitivity to touch.
• Disturbance of taste sensation.
• Hearing difficulty, tinnitus (ringing in the ears), vertigo.
• Inflammation of certain internal organs, pancreas and duodenum, swelling and inflammation of the tongue.
• Enlarged liver, hepatitis, liver failure, gallbladder disease, gallstones.
• Joint inflammation, vein inflammation under the skin (which may be associated with blood clot formation).
• Kidney inflammation, protein in urine, kidney damage.
• Very high heart rate or extrasystoles, sometimes with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• Elevated blood cholesterol, elevated blood urea.
• Skin allergic reactions (sometimes severe), such as skin disease, potentially life-threatening causing blisters and painful sores on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, skin redness and irritation, reddish or purplish skin discoloration possibly due to low platelet count, eczema.
• Reaction at the infusion site.
• Allergic reaction 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 fibers of the optic nerve, corneal opacity, involuntary eye movements.
• Blister formation due to photosensitivity.
• Disorder in which the immune system attacks part of the peripheral nervous system.
• Heart rhythm or conduction problems (sometimes potentially fatal).
• Potentially life-threatening allergic reaction.
• Blood clotting disorders.
• Skin allergic reactions (sometimes severe), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, itchy and painful plaques of thickened, red, scaly skin with silvery scales, skin and mucous membrane irritation, potentially life-threatening skin disease causing large areas of the epidermis (the outermost skin layer) to detach from underlying skin layers.
• Small scaly, dry skin patches, sometimes thick with tips or "horns".

Adverse effects with unknown frequency:

• Freckles and pigmented spots.

Other important adverse effects whose frequency is unknown, but which must be reported to a doctor immediately:

• Red, scaly plaques or ring-shaped skin lesions, which may be a symptom of an autoimmune disease called cutaneous lupus erythematosus.

Since Voriconazole Accord has been observed to affect the liver and kidneys, your doctor should monitor liver and kidney function through blood tests. Inform your doctor if you have stomach pain or if your stools have an unusual consistency.

Cases of skin cancer have been reported in patients treated with Voriconazole Accord over long periods.

The frequency of sunburn or severe skin reactions following exposure to light or sun was higher in children. If you or your child develop skin disorders, your doctor may refer you to a dermatologist who, after consultation, may decide that regular monitoring is necessary. Elevated liver enzymes were also observed more frequently in children.

If any of these adverse effects persist or are bothersome, inform your doctor.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 the month indicated.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Voriconazole Accord

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

Nature of the product and pack contents

Voriconazole Accord 50 mg tablets are presented as film-coated tablets, white to off-white, round, approximately 7.0 mm in diameter, with "V50" engraved on one side and smooth on the other.

Voriconazole Accord 200 mg tablets are presented as film-coated tablets, white to off-white, oval-shaped, approximately 15.6 mm long and 7.8 mm wide, with "V200" engraved on one side and smooth on the other.

Voriconazole Accord 50 mg film-coated tablets and Voriconazole Accord 200 mg film-coated tablets are available in packs of 2, 10, 14, 20, 28, 30, 50, 56 and 100, or unit-dose blister packs (PVC/aluminum) containing 10x1, 14x1, 28x1, 30x1, 56x1 or 100x1 film-coated tablets.

Only certain 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

Further information on this medicine is available upon request by contacting the local representative of the Marketing Authorization Holder:

AT / BE / BG / CY / CZ / DE / DK / EE / ES / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT / NL / NO / PL / PT / RO / SE / SI / SK

Accord Healthcare S.L.U.

Tel: +34 93 301 00 64

EL

Win Medica A.E.

Tel: +30 210 74 88 821

This leaflet has been approved on {MM/YYYY}.

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu.