VORICONAZOLE AUROVITAS 200 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Voriconazole Aurovitas 200 mg film-coated tablets EFG

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Voriconazole Aurovitas and what is it used for

Voriconazole Aurovitas contains the active substance voriconazole. Voriconazole is an antifungal medicine. It works by killing 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 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 count of white blood cells).
• Severe invasive infections caused by Candida sp, when the fungus is resistant to fluconazole (another antifungal medicine).
• Severe fungal infections caused by Scedosporium sp or Fusarium sp (two different species of fungi).

Voriconazole 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 medicine should only be used under medical supervision.

2. What you need to know before you take Voriconazole Aurovitas

Do not take Voriconazole Aurovitas

• If you are allergic to voriconazole or 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 using or have recently used other medicines, including those obtained without a prescription, or herbal remedies.

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

• Terfenadine (used for allergy).
• Astemizole (used for allergy).
• Cisapride (used for digestive problems).
• Pimozide (used for mental disorders).
• Quinidine (used for heart rhythm disorders).
• Ivabradine (used for symptoms of chronic heart failure).
• Rifampicin (used for the treatment of tuberculosis).
• Efavirenz (used for the treatment of 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 patients who have received a transplant).
• Ritonavir (used for the treatment of HIV) at doses of 400 mg or higher twice daily.
• St. John's Wort (Hypericum, herbal remedy).
• Naloxegol (used to treat constipation caused by opioid painkillers [e.g., morphine, oxycodone, fentanyl, tramadol, codeine]).
• Tolvaptan (used to treat low sodium levels in the blood or to slow the worsening of 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 Voriconazole Aurovitas if:

• You have had an allergic reaction to other azoles.
• You have or have ever had liver disease. If you have liver disease, your doctor may prescribe a lower dose of voriconazole. Your doctor should also monitor your liver function while you are taking voriconazole with blood tests.
• You know that you have cardiomyopathy, irregular heartbeats, slow heart rate, or an abnormality in the electrocardiogram (ECG) called "QTc prolongation syndrome".

You should avoid any exposure to the sun and sunlight during treatment. It is essential that you cover exposed areas and use a sunscreen with a high sun protection factor (SPF), as you may experience increased sensitivity of the skin to the sun's UV rays. This can be increased further by the use of other medicines that make the skin more sensitive to sunlight, such as methotrexate. These precautions also apply to children.

While taking voriconazole:

• 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. There is a small chance that you may develop skin cancer with long-term use of voriconazole.

If you develop signs of "adrenal insufficiency" where the adrenal glands do not produce enough 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 develop 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

Voriconazole should not be given to children under 2 years of age.

Other medicines and Voriconazole Aurovitas

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

• Some medicines, when used at the same time as voriconazole, can affect the action of voriconazole or voriconazole may affect the action of other medicines.

Tell your doctor if you are using the following medicines, as concurrent treatment with voriconazole should be avoided if possible:

• Ritonavir (used for the treatment of HIV) at doses of 100 mg twice daily.
• Glasdegib (used for the treatment of cancer); if you need to use both medicines, your doctor will monitor your heart rate frequently.

Tell your doctor if you are using any of the following medicines, as concurrent treatment with voriconazole should be avoided whenever possible, and a dose adjustment of voriconazole may be necessary:

• Rifabutin (used for the treatment of tuberculosis). If you are already being treated with rifabutin, your blood count and rifabutin side effects will need to be monitored.
• Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin, your phenytoin blood levels will need to be monitored during your treatment with voriconazole, 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 check that these medicines and/or voriconazole are still working:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to reduce blood clotting).
• Cyclosporine (used in patients who have received a transplant).
• Tacrolimus (used in patients who have received a transplant).
• Sulfonylureas (e.g., tolbutamide, glipizide, and gliburide) (used for diabetes).
• Statins (e.g., atorvastatin, simvastatin) (used to lower cholesterol levels).
• Benzodiazepines (e.g., midazolam, triazolam) (used for severe insomnia and stress).
• Omeprazole (used for the treatment of stomach ulcers).
• Oral contraceptives (if you take voriconazole 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 voriconazole).
• Methadone (used to treat heroin addiction).
• Alfentanil, fentanyl, and other short-acting opioids such as sufentanil (painkillers used for operations).
• 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 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 against bacterial infections).

Pregnancy and breastfeeding

Do not take voriconazole during pregnancy unless your doctor tells you to. Women of childbearing age taking voriconazole should use effective contraception. Contact your doctor immediately if you become pregnant while taking voriconazole.

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

Voriconazole may cause blurred vision or sensitivity to light. If this happens, do not drive or use tools or machines and tell your doctor.

Voriconazole Aurovitas contains lactose

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

Voriconazole Aurovitas contains sodium

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

3. How to take Voriconazole Aurovitas

Follow exactly the instructions of your doctor for taking this medicine. If you are unsure, ask your doctor or pharmacist.

Your doctor will determine the dose depending 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

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 given 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 voriconazole to prevent fungal infections, your doctor may stop the administration of voriconazole if you or your child experience treatment-related side effects.

If you take more Voriconazole Aurovitas than you should

If you take more tablets than you have been told to take (or if someone else takes your tablets), you must immediately seek medical attention or go to the nearest hospital emergency department. Take the pack of Voriconazole Aurovitas tablets with you. You may notice abnormal sensitivity to light as a result of taking more voriconazole than you should.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Voriconazole Aurovitas

It is essential to take the tablets 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 a forgotten dose.

If you stop taking Voriconazole Aurovitas

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

Continue taking voriconazole until your doctor tells you to stop. Do not stop treatment early, as the infection may not be fully treated. Patients with compromised immune systems or complicated infections may require longer treatment to prevent the infection from coming back.

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

If you have any further questions on the use of this medicine, 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 voriconazole and consult your doctor immediately

• Skin rash.
• Jaundice, alterations in blood tests to control liver function.
• 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 halo, 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 certain types of red (sometimes immune-mediated) 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, inflammation of the veins (which may be associated with the formation of blood clots).
• 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 protrusions that converge, skin redness.
• Itching.
• Alopecia.
• Back pain.
• Kidney failure, presence of blood in urine, alterations in kidney function tests.
• Sunburn or severe skin reaction after exposure to light or sun.
• Skin cancer.

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, inflammation of the lymphatic vessels.
• 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: pain and inflammation of the eyes and eyelids, abnormal eye movements, damage to the optic nerve that causes vision alteration, inflammation of the optic papilla.
• Decreased sensitivity to touch.
• Alteration of the sense of taste.
• Difficulty hearing, ringing in the ears, vertigo.
• Inflammation of certain internal organs, pancreas, and duodenum, swelling, and inflammation of the tongue.
• Enlargement of the liver, liver failure, gallbladder disease, gallstones.
• Joint inflammation, inflammation of the veins under the skin (which may be associated with the formation of a blood clot).
• Kidney inflammation, protein in the urine, kidney damage.
• Very high heart rate or extrasystoles, sometimes with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• High cholesterol in the blood, high urea in the blood.
• Severe skin allergic reactions (sometimes life-threatening), such as a potentially fatal skin disease that causes 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 color that may be caused by low platelet count, eczema.
• Infusion site reaction.
• 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.
• Decline in brain activity as a serious complication of liver disease.
• Loss of most of the optic nerve fibers, corneal opacity, involuntary eye movement.
• Blister formation due to photosensitivity.
• Disorder in which the immune system attacks part of the peripheral nervous system.
• Serious heart rhythm or conduction problems (sometimes potentially fatal).
• Potentially fatal allergic reaction.
• Alterations in blood coagulation.
• Severe skin allergic reactions (sometimes life-threatening), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, pruritic and painful thickened and reddened skin plaques with silvery scales, skin irritation, and mucous membrane irritation, potentially fatal skin disease that causes large portions of the epidermis, the outermost skin layer, to peel off from the underlying skin layers.
• Small, scaly, and dry skin plaques, sometimes thick and with tips or "horns".

Adverse effects with unknown frequency:

• Pigmented spots and patches.

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

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

Since voriconazole 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 a different consistency.

Cases of skin cancer have been reported in patients treated with voriconazole 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, inform 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 does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Voriconazole Aurovitas

Keep this medicine out of sight and reach of children.

This medicine does not require special storage conditions.

Do not use this medicine after the expiration date that appears on the box and on the blister pack after "CAD". The expiration date is the last day of the month indicated.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE Point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Voriconazole Aurovitas

• The active ingredient is voriconazole. Each film-coated tablet contains 200 mg of voriconazole.
• The other components are:

Tablet core:lactose monohydrate, pregelatinized corn starch, corn starch, sodium croscarmellose, povidone (K-30), anhydrous colloidal silica, magnesium stearate.

Tablet coating:hypromellose 2910 (E 464), lactose monohydrate, titanium dioxide (E 171), triacetin (E 1518).

Appearance of the Product and Package Contents

White, oval, biconvex film-coated tablets, with the marks "CC" and "56" separated by a score line on one side, and smooth on the other. The tablet can be divided into equal doses.

Voriconazole Aurovitas film-coated tablets are available in transparent PVC/Aluminum blister packs. Each pack contains 14 or 28 tablets.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Aurovitas Spain, S.A.U.

Avda. de Burgos 16-D

28036 Madrid

Spain

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

Date of the Last Revision of this Prospectus:December 2023

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es).