VORICONAZOL PHARMAKERN 50 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Voriconazole Pharmakern 50 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 Pharmakern is and what it is used for
2. What you need to know before you take Voriconazole Pharmakern
3. How to take Voriconazole Pharmakern
4. Possible side effects
5. Storing Voriconazole Pharmakern
6. Contents of the pack and other information

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

Voriconazole contains the active substance voriconazole. This medicine 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),
• candidemia (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).

This medicine is used in patients with serious 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 Pharmakern

Do not take Voriconazole Pharmakern

• if you are allergic to voriconazole or any of the other ingredients of voriconazole (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 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).
• Rifampicin (used for the treatment of tuberculosis).
• Efavirenz (used for the treatment of HIV) 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 the treatment of HIV) at doses of 400 mg and above twice daily.
• St. John's Wort (hypericum, herbal remedy).

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 this medicine. Your doctor should also monitor your liver function while you are being treated with voriconazole by performing blood tests;
• you know that you have cardiomyopathy, irregular heartbeats, slow heart rate, or an abnormality in the 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 sensitivity of the skin to the sun's UV rays. These precautions also apply to children.

While being treated with this medicine, 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 necessary to examine you regularly. There is a small probability that you may develop skin cancer with long-term use of voriconazole.

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

Children and adolescents

This medicine must not be given to children under 2 years of age.

Taking Voriconazole Pharmakern with other medicines

Inform 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, may affect the action of this medicine or voriconazole may affect the action of other medicines.

Inform 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.

Inform 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 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 this medicine 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 producing the desired effect:

• 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 reduce 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).
• 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 opiates such as sufentanil (painkillers used for operations).
• Oxycodone and other long-acting opiates 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).
• Flucloxacillin (an antibiotic used against bacterial infections).

Pregnancy and breast-feeding

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.

Do not take this medicine during pregnancy unless your doctor has told 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 may cause blurred vision or sensitivity to light. If this happens, do not drive or use tools or machines and tell your doctor.

Voriconazole Pharmakern contains lactose

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

Voriconazole Pharmakern contains sodium

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

3. How to take Voriconazole Pharmakern

Always take this medicine exactly as your doctor has told you. If you are not sure, check with 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 liver 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 side effects related to treatment.

If you take more Voriconazole Pharmakern than you should

If you take more tablets than you have been prescribed (or if someone else takes your tablets), you must seek medical attention or go to the nearest hospital emergency department immediately. Take the pack of voriconazole 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, contact your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, stating the medicine and the amount taken.

If you forget to take Voriconazole Pharmakern

It is essential to take the tablets of voriconazole 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 the forgotten dose.

If you stop taking Voriconazole Pharmakern

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 essential that you continue to take this medicine as prescribed.

Continue to take this medicine until your doctor tells you to stop. Do not stop treatment early, as the infection may not be fully treated. Patients with a compromised immune system 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 Voriconazol Pharmakern 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:

• Gingival 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 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 rapid 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 protuberances that converge, skin redness.
• Itching.
• Alopecia.
• Back pain.
• Kidney failure, presence of 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, 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 adrenal gland function, 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: pain and inflammation of the eyes and eyelids, abnormal eye movements, optic nerve damage 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 or extra heart rate, 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 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.
• Reaction at the infusion site.
• 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 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, pruriginous and painful plates of thickened and reddened skin with silvery scales, skin and mucous membrane irritation, potentially fatal skin disease that causes large portions of the epidermis, the outermost layer of the skin, to peel off from the underlying skin layers.
• Small scaly and dry plates on the skin, sometimes thick and with tips or "horns".

Adverse effects with unknown frequency:

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

Since it has been observed that voriconazol affects 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 the 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. Conservation of Voriconazol Pharmakern

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.

This medicine does not require special storage conditions.

Medicines should not be thrown away through drains or into the trash. Deposit the packaging and medicines that are no longer needed in the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Voriconazol Pharmakern

• The active ingredient is voriconazol. Each film-coated tablet contains 50 mg of voriconazol.
• The other components are: tablet core(lactose monohydrate, pregelatinized corn starch, sodium croscarmellose, povidone K25, and magnesium stearate) and tablet coating(opadry II white 85F18422).

The opadry II white 85F18422 coating film contains: Partially hydrolyzed polyvinyl alcohol, titanium dioxide (E171), talc (E-553b), and macrogol 4000/PEG.

Product Appearance and Package Contents

Voriconazol 50 mg film-coated tablets are presented in the form of film-coated tablets, white to off-white in color, and rounded in shape, with "V50" engraved on one face.

This medicine is presented in PVC/Aluminum blisters and is available in packages of 28 and 56 film-coated tablets and a clinical package of 100 film-coated tablets.

Marketing Authorization Holder and Manufacturer

Kern Pharma, S.L.

Venus, 72 – Pol. Ind. Colón II

08228 Terrassa - Barcelona

Spain

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.