Leaflet: information for the user

Voriconazole Accord 50 mg film-coated tablets

Voriconazole Accord 200 mg film-coated tablets

Voriconazole

Read 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. Do not give it to others, even if they have the same symptoms, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

Voriconazol Accord contains the active ingredient voriconazol. Voriconazol Accord is an antifungal medication. It acts by eliminating or preventing the growth of fungi that cause infections.

It is used for the treatment of patients (adults and children aged 2 years or older) with:

• invasive aspergillosis (a type of fungal infection produced byAspergillus sp),
• candidemia (another type of fungal infection produced byCandida sp) in non-neutropenic patients (patients who do not have an abnormally low count of white blood cells),
• severe invasive infections produced byCandida sp, when the fungus is resistant to fluconazol (another antifungal medication),
• severe fungal infections produced byScedosporium spor byFusarium sp(two different species of fungi).

Voriconazol Accord is used in patients with severe fungal infections that can put their lives at risk.

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

This medication must be used only under medical supervision.

Do not take Voriconazol Accord

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

It is very important to inform your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription, or herbal remedies.

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

continuation:

• Terfenadine (used for allergies).
• Astemizol (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 for tuberculosis treatment).
• Efavirenz (used for HIV treatment) at doses of 400 mg and above once a day.
• Carbamazepine (used to treat seizures).
• Phenobarbital (used for severe insomnia and seizures).
• Ergot alkaloids (e.g., ergotamine, dihydroergotamine; used for migraines).
• Sirolimus (used in patients who have received a transplant).
• Ritonavir (used for HIV treatment) at doses of 400 mg and above twice a day.

• St. John's Wort (hypericum, herbal remedy).
• Naloxegol (used to treat constipation caused specifically by analgesics, called opioids [e.g., morphine, oxycodone, fentanyl, tramadol, codeine]).
• Tolvaptan (used to treat hyponatremia (low sodium levels in the blood) or to slow the deterioration of kidney function in patients with polycystic kidney disease).

• Lurasidone (used to treat depression).
• Venetoclax (used for the treatment of patients with chronic lymphocytic leukemia [CLL]).

Warnings and precautions

Consult 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 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 while you are taking Voriconazol Accord by performing blood tests.
• you know you have heart failure, irregular heartbeats, slow heart rate, or an electrocardiogram (ECG) anomaly called "prolonged QTc syndrome."

You should avoid any exposure to the sun and sunlight during treatment. It is essential to cover exposed areas and use a high-factor sunscreen, as you may experience increased skin sensitivity to UV rays from the sun. These precautions also apply to children.

While taking Voriconazol Accord:

• inform your doctor if you experience

• 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 may consider regular examinations. There is a small chance that you may develop skin cancer with long-term use of Voriconazol Accord.

If you develop signs of "adrenal insufficiency" where your adrenal glands do not produce sufficient amounts of certain steroid hormones, such as cortisol, which may cause symptoms like:

chronic or prolonged fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, inform your doctor.

If you experience signs of the "Cushing's syndrome" where your body produces too much cortisol hormone, which may cause symptoms like:

weight gain, hump of fat between the shoulders, rounded face, darkening of the skin on the abdomen, thighs, breasts, and arms, thin skin, easy bruising, high blood sugar, excessive hair growth, excessive sweating, inform your doctor.

Your doctor should monitor your liver and kidney function by performing blood tests.

Children and adolescents

Voriconazol Accord should not be administered to children under 2 years old.

Taking Voriconazol Accord with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take 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 using the following medicines, as simultaneous treatment with Voriconazol Accord should be avoided if possible:

• Ritonavir (used for HIV treatment) at doses of 100 mg twice a day.

• Glasdegib (used for cancer treatment); if you need to use both medicines, your doctor will monitor your heart rate frequently.

Inform your doctor if you are using any of the following medicines, as simultaneous treatment with Voriconazol Accord should be avoided as much as possible, and you may need to adjust your voriconazole dose:

• Rifabutin (used for tuberculosis treatment). If you are already takingrifabutin, you will need to monitor your blood count and rifabutin side effects.Fenitoin (used to treat epilepsy). If you are already taking fenitoin, you will need to monitor the concentration of fenitoin in your blood during your treatment with Voriconazol Accord and may need to adjust your dose.

Inform your doctor if you are taking any of the following medicines, as you may need to adjust your dose or monitor to ensure that these medicines and/or Voriconazol Accord continue to produce the desired effect:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to reduce blood clotting).
• Ciclosporin (used in patients who have received a transplant).
• Tacrolimus (used in patients who have received a transplant).
• Sulfonilureas (e.g., tolbutamide, glipizide, and glibenclamide) (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 for stomach ulcer treatment).
• Oral contraceptives (if you take Voriconazol Accord while using oral contraceptives, you may experience side effects such as nausea and menstrual disorders).

• Vincristine and vinblastine alkaloids (used to treat cancer).
• Inhibitors of tyrosine kinase (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).
• Nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, and nevirapine) (used to treat HIV infection) (some doses of efavirenz CANNOT be taken at the same time as Voriconazol Accord).
• Methadone (used to treat heroin addiction).
• Alfentanil, fentanyl, and other short-acting opioids (e.g., sufentanil) (used for analgesia during surgery).
• Oxycodone and other long-acting opioids (e.g., hydrocodone) (used to treat moderate to severe pain).
• Nonsteroidal 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 patients who have received a transplant).
• Letermovir (used to prevent cytomegalovirus (CMV) infection after a bone marrow transplant).
• Ivacaftor: used to treat cystic fibrosis.

• Flucloxacillin (antibiotic used to treat bacterial infections)

Pregnancy and breastfeeding

You should not take Voriconazol Accord during pregnancy unless your doctor indicates it. Women of childbearing age taking Voriconazol Accord should use effective contraception.

Immediately contact your doctor if you become pregnant during treatment with Voriconazol Accord.

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

Driving and operating machinery

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

Voriconazol Accord contains lactose

If your doctor has told you that you have an intolerance to some 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."

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Your doctor will determine the dose based on your 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 a day.

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

Use in children and adolescents

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

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

Take the tablets at least one hour before or after a meal. Swallow the tablet whole with a little water.

If you or your child are taking Voriconazol Accord for the prevention of fungal infections, your doctor may discontinue Voriconazol Accord if you or your child experience adverse effects related to treatment.

If you take more Voriconazol Accord than you should

If you take more tablets than prescribed (or if someone else takes your tablets), immediately seek medical assistance or go to the nearest emergency hospital. Bring the box of Voriconazol Accord tablets with you. You may notice an abnormal sensitivity to light as a result of taking more Voriconazol Accord than you should.

If you forget to take Voriconazol Accord

It is essential to take Voriconazol Accord tablets regularly at the same time of day. If you forget to take a dose, take the next one when it is due. Do not take a double dose to compensate for the missed dose.

If you interrupt treatment with Voriconazol Accord

It has been demonstrated that correctly following the indicated dosage, administering each dose at the right time, can significantly increase the effectiveness of this medication. Therefore, unless your doctor indicates that you should discontinue treatment, it is essential to continue taking Voriconazol Accord correctly, as previously indicated.

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

When your doctor suspends treatment with Voriconazol Accord, you should not experience any effects resulting from the interruption.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

Severe side effects - Stop taking Voriconazol Accord and see a doctor immediately

immediately

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

Other side effects

Very common: may affect more than 1 in 10 people

Visual disturbances (change in vision, such as blurred vision, visual color disturbances, abnormal light perception intolerance, color blindness, eye disorder, visual field loss, night blindness, oscillating vision, spark vision, visual aura, decreased visual acuity, visual clarity, partial loss of the usual visual field, visual field spots).

• Fever.
• Skin rash.
• Nausea, vomiting, and diarrhea.
• Headache.
• Swelling of the extremities.
• Abdominal pain.
• Difficulty breathing.
• Elevated liver enzymes.

Common: may affect up to 1 in 10 people

• Sinusitis, gum inflammation, chills, weakness.
• Low count, including severe, of some types of red blood cells (occasionally of an immunological type) and/or white blood cells (occasionally accompanied by fever) in the blood, low platelet count that helps blood to clot.
• Low blood sugar levels, low potassium levels in the blood, low sodium levels in the blood.
• 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.
• Cardiac rhythm problems that include very fast heart rate, very slow heart rate, fainting, hypotension, vein inflammation (which may be associated with blood clot formation).
• Acute difficulty breathing, chest pain, facial swelling (mouth, lips, and around the eyes), pulmonary fluid retention.
• Constipation, indigestion, lip inflammation.
• Jaundice (yellow skin discoloration), liver inflammation, and liver damage.
• Skin eruptions, which can be severe, with blisters and peeling, characterized by a flat, red area covered with small protuberances that converge, skin redness.
• Itching.
• Alopecia.
• Back pain.
• Renal failure, blood in urine, renal function test abnormalities.

Uncommon: may affect up to 1 in 100 people

• Flu-like symptoms, gastrointestinal tract irritation and inflammation, antibiotic-associated diarrhea, lymphatic tract inflammation.
• Abdominal wall inflammation.
• Swollen (sometimes painful) lymph nodes, bone marrow insufficiency, eosinophil increase.

• Adrenal gland dysfunction, hypothyroidism.
• Abnormal brain function, Parkinson's disease-like symptoms, nerve damage causing numbness, pain, tingling, or burning in the hands or feet.
• Balance or coordination problems.
• Brain swelling.
• Dual vision, severe eye diseases, such as: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage causing vision disturbances, papillary optic inflammation.

• Reduced sensitivity to touch.
• Altered sense of taste.
• Difficulty hearing, tinnitus, 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 or extrasystolic heart rate, occasionally with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• Elevated blood cholesterol, elevated blood urea.

Skin allergic reactions (occasionally severe), such as skin disease, potentially fatal that causes painful blisters and sores on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, sunburn or severe skin reaction after exposure to light or the sun, skin redness and irritation, skin discoloration or purpura that may be caused by low platelet count, eczema.

• Reaction at the infusion site.
• Allergic reaction or excessive immune response.

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

• Hyperactive thyroid gland.
• Cerebral activity deterioration as a severe complication of liver disease.

• Optic nerve fiber loss, corneal opacity, involuntary eye movement.
• Blister formation due to photosensitivity.
• Disease in which the immune system attacks part of the peripheral nervous system.
• Cardiac rhythm problems or conduction problems (occasionally potentially fatal).
• Potentially fatal allergic reaction.
• Blood coagulation abnormalities.
• Skin allergic reactions (occasionally severe), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, pruritic and painful skin plaques with thickened and scaly skin, skin and mucous membrane irritation, potentially fatal skin disease that causes large areas of the epidermis, the skin's outermost layer, to peel off from the layers of skin beneath it.
• Small, scaly, and dry skin plaques, sometimes thick and with points or "horns".

Side effects with unknown frequency:

• Moles and pigmented spots.

Other important side effects whose frequency is unknown, but which should be reported to the doctor immediately:

• Skin cancer.
• Periosteal inflammation.
• Red, scaly, or ring-shaped skin lesions that may be a symptom of an autoimmune disease called lupus erythematosus.

Since Voriconazol Accord has been observed to affect the liver and kidneys, your doctor should monitor liver and renal function through blood tests. Inform your doctor if you have abdominal pain or if your stools have a different consistency.

Cases of skin cancer have been reported in patients treated with Voriconazol Accord for long periods of time.

The frequency of sunburns or severe skin reactions after exposure to light or the sun was higher in children. If you or your child experience skin problems, your doctor may refer you to a dermatologist, who, after consultation, may decide that it is necessary for you or your child to undergo regular follow-up. Elevated liver enzymes were also observed more frequently in children.

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

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

Voriconazole Accord Composition

• The active ingredient 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 lactose monohydrate, pregelatinized starch, sodium croscarmellose, povidone, and magnesium stearate, which constitute the tablet core, and hypromellose, titanium dioxide (E171), lactose monohydrate, and triacetin, which constitute the film coating (see section 2, Voriconazole Accord 50 mg film-coated tablets or Voriconazole Accord 200 mg film-coated tablets contain lactose and sodium).

Appearance of the Product and Contents of the Package

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

Voriconazole Accord 200 mg tablets are presented as film-coated tablets, white to off-white in color, oval in shape, approximately 15.6 mm in length and 7.8 mm in width, with “V200” engraved on one face and smooth on the other.

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

Only some package 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

Manufacturing

Responsible for Manufacturing:

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,

Netherlands

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

The detailed information on this medicine is available on the European Medicines Agency website

at http://www.ema.europa.eu.