VORICONAZOLE NORMON 200 mg FILM-COATED TABLETS

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

This medicine 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),
• serious invasive infections caused by Candida spwhen the fungus is resistant to fluconazole (another antifungal medicine),
• serious fungal infections caused by Scedosporium spor Fusarium sp(two different species of fungi).

Voriconazole 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 you take Voriconazol Normon

Do not take Voriconazol Normon

• 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 Voriconazol Normon, 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 tuberculosis treatment).
• Efavirenz (used for HIV treatment) at doses of 400 mg and above 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 HIV treatment) at doses of 400 mg and above 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 decline in kidney function in patients with polycystic kidney disease).
• Lurasidone (used to treat depression).
• Venetoclax (used to treat patients with chronic lymphocytic leukaemia [CLL]).

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to take voriconazole 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 with blood tests while you are taking voriconazole.
• you know that you have cardiomyopathy, irregular heartbeats, slow heart rate or an abnormality in your electrocardiogram (ECG) called “QTc prolonged syndrome”.

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

While you are taking Voriconazol:

• tell your doctor if you get:
• • 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 important 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, tell 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, tell your doctor.

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

Children and adolescents

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

Other medicines and Voriconazol Normon

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 HIV treatment) at doses of 100 mg twice daily.
• Glasdegib (used for cancer treatment); 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 Voriconazol Normon should be avoided whenever possible, and a dose adjustment of Voriconazol Normon 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 and may need to adjust your dose.

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 Voriconazol Normon are still working:

• 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).
• Sulphonylureas (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 Normon 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 leukaemia).
• 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 MUST NOT be taken at the same time as Voriconazol Normon).
• 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 medicines (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 bone marrow transplantation).
• Ivacaftor: used to treat cystic fibrosis.
• Flucloxacillin (antibiotic used against bacterial infections).

Pregnancy and breast-feeding

Do not take this medicine during pregnancy unless your doctor has told you to. Women of childbearing age taking Voriconazol must use effective contraception. Contact your doctor immediately if you become pregnant during treatment with voriconazole.

If you are pregnant or breast-feeding, 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

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

Voriconazol Normon contains lactose

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

Voriconazol Normon contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per film-coated tablet, i.e. it is essentially “sodium-free”.

3. How to take Voriconazol Normon

Follow exactly the instructions of your doctor. If you are in doubt, consult your doctor or pharmacist again.

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. For patients weighing less than 40 kg, the oral dose may be increased to 150 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 tablets whole.

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

If you take more Voriconazol Normon than you should

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

It is important to take the tablets of Voriconazol regularly at the same time each day. If you forget to take a dose, take the next one when it is due. Do not take a double dose to make up for a forgotten dose.

If you stop taking Voriconazol Normon

It has been shown that strictly 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 important that you continue to take Voriconazol correctly as indicated above.

Continue to take Voriconazol Normon 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 Voriconazol, 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 side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If they do occur, they are most likely to be mild and temporary. However, some can be serious and require medical attention.

Serious side effects - Stop taking Voriconazol Normon and see a doctor immediately

• Skin rash.
• Jaundice, changes in blood tests to check 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 limbs.
• 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 of an immune nature) 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.
• Ocular 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).
• 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 rashes, which can be severe, with blisters and peeling, characterized by a flat and reddened area, covered with small protuberances 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 fine 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, severe eye diseases, such as: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage that causes vision changes, inflammation of the optic papilla.
• 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, 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.
• Skin allergic 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, 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.
• Deterioration of brain activity as a severe 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.
• Heart rhythm or conduction problems (sometimes potentially fatal).
• Potentially fatal allergic reaction.
• Alterations in blood coagulation.
• Skin allergic 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 and mucous membrane irritation, potentially fatal skin disease that causes large portions of the epidermis, the outermost layer of skin, 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 not known, 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 of time.

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 of 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 Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Voriconazol Normon

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

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines that you no longer need in the SIGRE point of the pharmacy. Ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Voriconazol Normon

• The active ingredient is voriconazole.

Voriconazol Normon 50 mg film-coated tablets: each tablet contains 50 mg of voriconazole

Voriconazol Normon 200 mg film-coated tablets: each tablet contains 200 mg of voriconazole

• The other components are:

Core of the tablet: lactose monohydrate, sodium croscarmellose, povidone, pregelatinized corn starch, and magnesium stearate (E-572).

Tablet coating: hypromellose (E-464), titanium dioxide (E-171), macrogol 6000, and talc.

Appearance of the Product and Package Contents

Voriconazol Normon 50 mg tablets are presented in the form of white, round, biconvex film-coated tablets marked with V50 on one face.

Voriconazol Normon 50 mg film-coated tablets are available in packages of 30, 56, and 100.

Voriconazol Normon 200 mg tablets are presented in the form of white, elongated, biconvex film-coated tablets marked with V200 on one face.

Voriconazol Normon 200 mg film-coated tablets are available in packages of 30, 56, and 100.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

LABORATORIOS NORMON, S.A.

C/ Ronda de Valdecarrizo, 6

28760 Tres Cantos, Madrid

Spain.

Manufacturer

LABORATORIOS NORMON, S.A.

C/ Ronda de Valdecarrizo, 6

28760 Tres Cantos, Madrid

Spain.

This medicine is authorized in the EEA Member States under the following names:

Spain: Voriconazol Normon 50 mg film-coated tablets EFG

Voriconazol Normon 200 mg film-coated tablets EFG

Portugal: Voriconazol Normon

Date of the last revision of this prospectus: September 2024

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