VORICONAZOL KERN PHARMA 50 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Voriconazole Kern Pharma 50 mg film-coated tablets EFG

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

1. What Voriconazole Kern Pharma is and what it is used for

Voriconazole Kern Pharma contains the active substance voriconazole. Voriconazole Kern Pharma 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 Aspergillussp),

? candidaemia (another type of fungal infection caused by Candidasp) in non-neutropenic patients (patients who do not have an abnormally low count of white blood cells),

? serious invasive infections caused by Candidasp, when the fungus is resistant to fluconazole (another antifungal medicine),

? serious fungal infections caused by Scedosporiumsp or Fusariumsp (two different species of fungi).

Voriconazole Kern Pharma 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 Voriconazole Kern Pharma

Do not take Voriconazole Kern Pharma

? if you are allergic to voriconazole or any of the other ingredients of Voriconazole Kern Pharma (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 this medicine, you should 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 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 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 opioid pain medicines, e.g., morphine, oxycodone, fentanyl, tramadol, codeine)
• Tolvaptan (used to treat low sodium levels in the blood or to slow kidney function decline 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 this medicine 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 Kern Pharma;

? you know that you have cardiomyopathy, irregular heartbeats, slow heart rate, or an abnormality in your electrocardiogram (ECG) called "QTc prolongation".

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 skin sensitivity to the sun's UV rays. These precautions also apply to children.

While taking voriconazole:

• inform 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 sufficient amounts of certain steroid hormones, such as cortisol, which can cause symptoms like 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 like weight gain, hump of fat between the shoulders, rounded face, darkening of the skin on the stomach, thighs, breasts, and arms, thinning of the skin, easy bruising, high blood sugar, excessive hair growth, and excessive sweating, inform your doctor.

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

Children and adolescents

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

Taking Voriconazole Kern Pharma with other medicines

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 this medicine, 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 voriconazole should be avoided whenever possible, 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 monitor your blood count and rifabutin side effects.

? Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin, your doctor will monitor the phenytoin concentration in your blood during treatment with voriconazole 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 voriconazole are still working as intended:

? Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to reduce 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 to treat 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 (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 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 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

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.

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

Driving and using machines

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

Voriconazole Kern Pharma contains lactose

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

Voriconazole Kern Pharma 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 Kern Pharma

Follow exactly the instructions for administration of this medicine given by your doctor. 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

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 this medicine 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 Kern Pharma than you should

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

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

If you forget to take Voriconazole Kern Pharma

It is essential to take the tablets of Voriconazole Kern Pharma 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 Voriconazole Kern Pharma

It has been shown that correctly following the prescribed dosage, administering 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 this medicine 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 Kern Pharma, you should not experience any effects from stopping the 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. However, some may be serious and require medical attention.

Severe Adverse Effects - Stop taking Voriconazol Kern Pharma and consult your doctor immediately

? Skin rash.

? Jaundice or alterations in blood tests to control liver function.

? Pancreatitis.

Other Adverse Effects

The very frequent adverse effects (may affect more than 1 in 10 people) are:

? 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.

The frequent adverse effects (may affect up to 1 in 10 people) are:

? Sinusitis, gum inflammation, chills, weakness.

? Low count, including severe, of some types of red (sometimes immune-related) or white blood cells (sometimes accompanied by fever) in the blood, low platelet count that helps blood 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, 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 kidney function tests.

The infrequent adverse effects (may affect up to 1 in 100 people) are:

? Flu-like symptoms, irritation, and inflammation of the gastrointestinal tract, antibiotic-associated gastrointestinal tract inflammation that causes 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 lymph nodes, bone marrow failure, increased eosinophils.

• Decreased adrenal gland function, underactive thyroid gland.

? 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.

? Double vision, severe eye diseases, such as: eye and eyelid pain and inflammation, involuntary eye movement, optic nerve damage that causes vision alteration, optic papilla inflammation.

? Decreased touch sensitivity.

? 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 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.

? Skin allergic reactions (sometimes severe), such as skin disease, potentially life-threatening disease 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 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.

The rare adverse effects (may affect up to 1 in 1,000 people) are:

? 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 life-threatening).

? Potentially life-threatening 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 thickened and reddened skin plaques with silvery scales, skin and mucous membrane irritation, potentially life-threatening skin disease that causes large portions of the epidermis to peel off from the underlying skin layers.

? Small, scaly, dry patches on the skin, sometimes thick and with points or "horns".

Adverse effects with unknown frequency (cannot be estimated from available data):

? Freckles and pigmented spots.

Other important adverse effects whose frequency is unknown, but which 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 Kern Pharma 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 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 does not appear 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 Kern Pharma

Keep this medicine out of 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.

No special storage conditions are required.

Bottles: use within 30 days after the first opening

Medicines should not be thrown away through drains or into the trash. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Voriconazol Kern Pharma

? The active ingredient is voriconazole.

Each 50 mg film-coated tablet of Voriconazol Kern Pharma contains 50 mg of voriconazole.

Each 200 mg film-coated tablet of Voriconazol Kern Pharma contains 200 mg of voriconazole.

? The other components are: tablet core (lactose monohydrate, pregelatinized corn starch, sodium croscarmellose, povidone K30, anhydrous colloidal silica, magnesium stearate) and tablet coating (opadry II white OY-LS 28908).

The opadry II white OY-LS 28908 coating contains: hypromellose, titanium dioxide (E171), lactose monohydrate, and macrogol 4000/PEG.

Appearance of the Product and Package Contents

Voriconazol Kern Pharma 50 mg film-coated tablets are presented in the form of film-coated tablets, white to off-white in color, and round in shape, with "V50" engraved on one face, 7.1 ± 0.2 mm in diameter.

Voriconazol Kern Pharma 200 mg film-coated tablets are presented in the form of film-coated tablets, white to off-white in color, and oval in shape, with "V200" engraved on one face, 15.7 ± 0.2 mm in length and 7.9 ± 0.2 mm in width.

Voriconazol Kern Pharma 50 mg film-coated tablets and 200 mg film-coated tablets are presented in PVC/Aluminum blisters and are available in packages of 2, 10, 14, 20, 28, 30, 50, 56, or 100 tablets, or in HDPE white opaque bottles with a child-resistant polypropylene screw cap, containing 30 tablets.

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Kern Pharma, S.L.

Venus, 72 – Pol. Ind. Colón II

08228 Terrassa - Barcelona

Spain

Manufacturer

Pharmathen S.A.

6, Dervenakion Str.

15351 Pallini Attikis

Greece

or

Pharmathen International S.A.

Sapes Industrial Park, Block 5

69300 Rodopi

Greece

or

Heumann Pharma GmbH & Co. Generica KG

Südwestpark 50 Nürnberg

90449 Germany

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Date of the last revision of this prospectus: June 2023

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