Voriconazole Accord 200 mg film-coated tablets

Introduction

Package Leaflet: Information for the User

Voriconazol Accord 50 mg film-coated tablets

Voriconazol Accord 200 mg film-coated tablets

Voriconazol

Read the entire package leaflet carefully before starting to take this medication, as it contains important information for you.

Keep this package leaflet, as you may need to read it again.

• Keep this package leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed to you only and should not be given to others, even if they have the same symptoms, as it may harm them.
• If you experience side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package leaflet. See section 4.

Contents of the package leaflet

1. What is Voriconazol Accord and what is it used for
2. What you need to know before taking Voriconazol Accord
3. How to take Voriconazol Accord
4. Possible side effects
5. Storage of Voriconazol Accord
6. Package contents and additional information

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

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

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

• invasive aspergillosis (a type of fungal infection caused by Aspergillus sp),
• candidemia (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),
• severe invasive infections caused by Candida sp, when the fungus is resistant to fluconazole (another antifungal medication),
• severe fungal infections caused by Scedosporium spor Fusarium sp(two different species of fungi).

Voriconazol Accord is used in patients with severe fungal infections that can be life-threatening.

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

This medication should only be used under medical supervision.

2. What you need to know before taking Voriconazol Accord

Do not take Voriconazol Accord

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

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

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

• Terfenadine (used for allergies).
• Astemizole (used for allergies).
• Cisapride (used for digestive problems).
• Pimozide (used for mental disorders).
• Quinidine (used for cardiac arrhythmias).
• Ivabradine (used for symptoms of chronic heart failure).
• Rifampicin (used for tuberculosis treatment).
• Efavirenz (used for HIV treatment) 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 migraines).
• Sirolimus (used in transplant patients).
• Ritonavir (used for HIV treatment) at doses of 400 mg or higher twice daily.

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

• Lurasidone (used to treat depression).
• Venetoclax (used to treat 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 with blood tests.
• you know you have cardiomyopathy, irregular heartbeats, slow heart rate, or an abnormal electrocardiogram (ECG) known as "QTc prolongation syndrome".

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

While taking Voriconazol Accord:

• tell your doctor if you experience

• sunburn
• severe skin rash or blisters
• bone pain

If you develop skin disorders such as those described above, your doctor may refer you to a dermatologist, who may consider it essential to examine you regularly after the consultation. There is a small probability that you may develop skin cancer with long-term use of Voriconazol Accord.

If you develop signs of "adrenal insufficiency" where the adrenal glands do not produce sufficient amounts of certain steroid hormones, such as cortisol, which can cause symptoms such as: chronic or prolonged fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, inform your doctor.

If you present signs of "Cushing's syndrome" where the body produces too much cortisol hormone, which can cause symptoms such as: weight gain, hump of fat between the shoulders, rounded face, darkening of the skin of 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 your liver and kidney function with blood tests.

Children and adolescents

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

Taking Voriconazol Accord with other medications

Tell your doctor or pharmacist if you are taking, have recently taken, or may take other medications, including those purchased without a prescription.

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

Tell your doctor if you are using the following medications, as concurrent treatment with Voriconazol Accord should be avoided if possible:

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

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

Tell your doctor if you are using any of the following medications, as it is recommended to avoid concurrent treatment with Voriconazol Accord, and a dose adjustment of voriconazole may be necessary:

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

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

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to decrease blood clotting).
• Cyclosporine (used in transplant patients).
• Tacrolimus (used in transplant patients).
• Sulfonylureas (e.g., tolbutamide, glipizide, and gliburide) (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).

• Vinca alkaloids (e.g., vincristine and 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, and nevirapine) (used to treat HIV infection) (some doses of efavirenz should NOT be taken at the same time as Voriconazol Accord).
• Methadone (used to treat heroin addiction).
• Alfentanil, fentanyl, and other short-acting opioids such as sufentanil (pain relievers used for operations).
• Oxycodone and other long-acting opioids such as hydrocodone (used to treat moderate to severe pain).
• Non-steroidal anti-inflammatory medications (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 transplantation).
• Ivacaftor: used to treat cystic fibrosis.

• Flucloxacillin (antibiotic used against bacterial infections)

Pregnancy and breastfeeding

Do not take Voriconazol Accord during pregnancy unless your doctor advises you to. Women of childbearing age taking Voriconazol Accord should use effective contraceptives.

Contact your doctor immediately if you become pregnant during treatment with 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 medication.

Driving and using machines

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

Voriconazol Accord contains lactose

If your doctor has informed you that you have an intolerance to some sugars, talk to your doctor before taking Voriconazol Accord.

Voriconazol Accord contains sodium

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

This medication 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 your doctor's instructions for taking this medication exactly. If you are unsure, 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 daily.

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.

• 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 a little water.

If you or your child are taking Voriconazol Accord to prevent fungal infections, your doctor may stop the administration of Voriconazol Accord if you or your child experience treatment-related side effects.

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 attention or go to the nearest hospital emergency department. Bring the package of Voriconazol Accord tablets with you. You may experience 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 the tablets of Voriconazol Accord regularly at the same time each day. If you forget to take a dose, take the next dose when it is due. Do not take a double dose to make up for the forgotten dose.

If you stop taking Voriconazol Accord

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

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

When your doctor stops treatment with Voriconazol Accord, you should not experience any effects from stopping the treatment.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

If any appear, it is most likely to be mild and transient. Nevertheless, some can be serious and require medical attention.

Severe Adverse Effects - Stop taking Voriconazol Accord and see a doctor immediately

immediately

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

Other Adverse Effects

Very frequent: may affect more than 1 in 10 people

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

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

Frequent: may affect up to 1 in 10 people

• Sinusitis, gum inflammation, chills, weakness.
• Low count, including severe, of some types of red blood cells (sometimes immune-related) and/or white blood cells (sometimes accompanied by fever) in the blood, low platelet count that helps blood clot.
• 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, somnolence, dizziness.
• Eye hemorrhage.
• Heart rhythm problems, including very fast heartbeat, very slow heartbeat, fainting, hypotension, vein inflammation (which may be associated with blood clot formation).
• Acute difficulty breathing, chest pain, swelling of the face (mouth, lips, and around the eyes), fluid retention in the lungs.
• Constipation, indigestion, lip inflammation.
• Jaundice (yellowish skin color), liver inflammation, and liver damage.
• Skin eruptions, which can be severe, with blisters and peeling, characterized by a flat and reddened area, covered with small bumps that converge, skin redness.
• Itching.
• Alopecia.
• Back pain.
• Kidney failure, blood in urine, alterations in blood tests to control kidney function.

Infrequent: may affect up to 1 in 100 people

• Flu-like symptoms, irritation, and inflammation of the gastrointestinal tract, gastrointestinal tract inflammation that causes antibiotic-associated diarrhea, lymphatic vessel inflammation.
• Inflammation of the thin tissue that lines the inner wall of the abdomen and covers the abdominal organs.
• Enlargement (sometimes painful) of the lymph nodes, bone marrow failure, increased eosinophils.

• Decreased function of the adrenal gland, underactive thyroid gland.
• Abnormal brain function, symptoms similar to Parkinson's disease, nerve damage causing numbness, pain, tingling, or burning in the hands or feet.
• Problems with balance or coordination.
• Brain swelling.
• Double vision, serious eye diseases, such as: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage that causes vision changes, optic papilla inflammation.

• Decreased sensitivity to touch.
• Alteration of the sense of taste.
• Inflammation of certain internal organs, pancreas, and duodenum, swelling, and inflammation of the tongue.
• Liver enlargement, 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 the urine, kidney damage.
• Very high or extra heart rate, sometimes with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• High cholesterol in the blood, high urea in the blood.

Allergic skin reactions (sometimes severe), such as a potentially fatal skin disease that causes painful blisters and ulcers on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, sunburn, or severe skin reaction after exposure to light or sun, skin redness, and irritation, reddish or purplish skin color that may be caused by low platelet count, eczema.

• Infusion site reaction.
• Allergic reaction or exaggerated immune response.

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

• Overactive thyroid gland.
• Worsening of brain activity as a serious complication of liver disease.

• Loss of most of the optic nerve fibers, corneal opacity, involuntary eye movement.
• Blisters 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 fatal allergic reaction.
• Blood coagulation disorders.
• Allergic skin reactions (sometimes severe), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, pruritic and painful skin plaques with silvery scales, skin irritation, and mucous membrane irritation, potentially fatal skin disease that causes large portions of the epidermis to peel off from the underlying skin layers.
• Small, scaly, and dry skin patches, sometimes thick and with tips or "horns".

Adverse effects with unknown frequency:

• Pigmented spots and patches.

Other important adverse effects whose frequency is not known but should be reported to the doctor immediately:

• Skin cancer.
• Inflammation of the tissue surrounding the bone.
• Red, scaly skin patches or ring-shaped lesions that may be a symptom of an autoimmune disease called cutaneous lupus erythematosus.

Since Voriconazol Accord has been observed to affect the liver and kidneys, your doctor should monitor liver and kidney function through blood tests. Warn your doctor if you have stomach 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.

The frequency of sunburn or severe skin reactions after exposure to light or sun was higher in children. If you or your child have 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 undergo regular follow-up. Elevated liver enzymes were also observed more frequently in children.

If any of these adverse effects persist or are bothersome, report them to your doctor.

Reporting Adverse Effects

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

5. Storage of Voriconazol Accord

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date shown on the label. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Voriconazol Accord Composition

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

Product Appearance and Package Contents

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

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

Voriconazol Accord 50 mg film-coated tablets and Voriconazol Accord 200 mg film-coated tablets are available in packs of 2, 10, 14, 20, 28, 30, 50, 56, and 100 or blister packs (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 6ª planta,

08039 Barcelona,

Spain

Manufacturing

Manufacturers:

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 prospectus was approved on {MM/YYYY}.

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