Leaflet: Information for the User

Voriconazole Kern Pharma 50 mg Film-Coated Tablets

Voriconazole Kern Pharma 200 mg Film-Coated Tablets

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

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

2.What you need to know before you start taking 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 additional information

Voriconazol Kern Pharma contains the active ingredient voriconazol. Voriconazol Kern Pharmais an antifungal medication. It acts 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 produced byAspergillussp),

?candidemia (another type of fungal infection produced byCandidasp) in non-neutropenic patients (patients with a normal white blood cell count),

?serious invasive infections produced byCandidasp, when the fungus is resistant to fluconazol (another antifungal medication),

?serious fungal infections produced byScedosporiumsp or byFusariumsp (two different species of fungi).

Voriconazol Kern Pharmais used in patients with serious fungal infections that can be life-threatening.

Prevention of fungal infections in high-risk bone marrow transplant recipients. This medication must be used only under medical supervision.

Do not take Voriconazol Kern Pharma

?if you are allergic to voriconazole or any of the other components of Voriconazol Kern Pharma(listed in section 6).

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

Do not take the following medicines during treatment with this medicine:

?Terfenadine (used for allergies)

?Astemizole (used for allergies)

?Cisapride (used for digestive problems)

?Pimozide (used for mental disorders)

?Quinidine (used for heart arrhythmias)

?Ivabradina (used for symptoms of chronic heart failure).

?Rifampicin(used for the treatment of tuberculosis)

?Efavirenz (used for the treatment of HIV) in doses of 400 mg and above once a day

?Carbamazepine (used to treat seizures)

?Fenobarbital (used for severe insomnia and seizures)

?Ergot alkaloids (e.g. ergotamine, dihydroergotamine; used for migraines).

?Sirolimus (used in patients who have received a transplant)

?Ritonavir (used for the treatment of HIV) in doses of 400 mg and above twice a day

?St. John's Wort (Hypericum, medicinal herb)

• Naloxegol (used to treat constipation caused specifically by pain medicines called opioids, (for example, morphine, oxycodone, fentanyl, tramadol, codeine))
• Tolvaptan (used to treat hyponatremia (low sodium levels in the blood) or to slow the deterioration of kidney function in patients with polycystic kidney disease)
• Lurasidone (used to treat depression)
• Venetoclax (used for the treatment of 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 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 Voriconazol Kern Pharma by doing blood tests;

?you know that you have heart disease, irregular heartbeats, slow heart rate or an abnormality in the electrocardiogram (ECG) called "prolonged QTc syndrome".

Avoid any exposure to the sun and sunlight during treatment. It is important to cover exposed areas and use a high-factor sunscreen, as you may be more sensitive to UV rays from the sun. 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 problems 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 chance that you may develop skin cancer with long-term use of voriconazole.

If you develop signs of "adrenal insufficiency" in which the adrenal glands do not produce enough of certain steroid hormones, such as cortisol, which may 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", in which the body produces too much cortisol hormone, which may cause symptoms such as: weight gain, hump of fat between the shoulders, rounded face, darkening of the skin of the stomach, thighs, breasts, and arms, thinning of the skin, easy bruising, high blood sugar, excessive hair growth, excessive sweating, inform your doctor.

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

Children and adolescents

Voriconazol Kern Pharmashould not be administered to children under 2 years.

Taking Voriconazol Kern Pharma with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken or may need to take any other medicine.

Some medicines, when used at the same time as this medicine, may affect the action of voriconazole or vice versa.

Inform your doctor ifyou are using the following medicines, as simultaneous treatment with voriconazole should be avoided if possible:

?Ritonavir (used for the treatment of HIV) in doses of 100 mg twice a day.

• Glasdegib (used for the treatment of cancer): if you need to use both medicines, your doctor will monitor your heart rate frequently

Inform your doctor if you are using any of the following medicines, as simultaneous treatment with voriconazole should be avoided as much as possible and may require adjustment of the voriconazole dose:

?Rifabutin (used for the treatment of tuberculosis). If you are already taking rifabutin, your doctor will need to monitor your blood count and the side effects of rifabutin.

?Fenitoin (used to treat epilepsy). If you are already taking fenitoin, your doctor will need to monitor the concentration of fenitoin in your blood during your treatment with

voriconazole and may need to adjust your dose.

Inform your doctor if you are taking any of the following medicines, as you may need to adjust your dose or have your medicines monitored to ensure they are still producing the desired effect:

?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 receiveda transplant)

?Sulfonylureas (e.g. tolbutamide, glipizide and glibenclamide) (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)

?Ergot alkaloids (e.g. vincristine and vinblastine) (used to treat cancer)

• Inhibitors of tyrosine kinase (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 cannot be taken at the same time as voriconazole)

?Methadone (used to treat heroin addiction)

?Alfentanil, fentanyl and other short-acting opioids such as sufentanil (anesthetics 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)

?Ivacaflor: used to treat cystic fibrosis

• Flucloxacillin (antibiotic used to treat bacterial infections)

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medicine.

Do not take this medicine 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.

Driving and operating machinery

Voriconazol Kern Pharmamay cause blurred vision or discomfort due to increased sensitivity to light. If this happens, do not drive or operate tools or machines and inform your doctor.

Voriconazol Kern Pharma contains lactose

If your doctor has told you that you have a certain sugar intolerance, contact them before taking this medicine.

Voriconazol Kern Pharma contains sodium

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

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, 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:

Your doctor may increase the daily dose to 300 mg twice a day depending on your response to treatment.

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:

Your doctor may increase or decrease the daily dose depending on your response to treatment.

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 this medication for the prevention of fungal infections, your doctor may suspend voriconazole Kern Pharma administration if you or your child experience adverse effects related to treatment.

If you take more Voriconazol Kern Pharma than you should

If you take more tablets than prescribed (or if someone else takes your tablets), immediately seek medical assistance or go to the nearest emergency hospital. Bring the box of Voriconazol Kern Pharma tablets with you. You may notice an abnormal sensitivity to light as a result of taking more Voriconazol Kern Pharma than you should.

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

If you forgot to take Voriconazol Kern Pharma

It is essential to take Voriconazol Kern Pharma tablets regularly at the same time of day. If you forget to take a dose, take the next one when it is due. Do not take a double dose to compensate for the missed dose.

If you interrupt treatment with Voriconazol Kern Pharma

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

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

When your doctor suspends treatment with Voriconazol Kern Pharma, you should not experience any effects resulting from the interruption.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

If any occur, it is likely to be mild and temporary. However, some may be serious and require medical attention.

Severe side effects - Stop taking Voriconazol Kern Pharma and seek medical attention immediately

?Skin rash.

?Jaundice or changes in liver function blood tests.

?Pancreatitis.

Other side effects

The very common side effects (may affect more than 1 in 10 people) are:

?Visual disturbance (change in vision, such as blurred vision, visual color disturbances, abnormal light perception intolerance, color blindness, eye disorder, halo vision, 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.

?Abdominal pain.

?Difficulty breathing

• Elevated liver enzymes.

The common side effects (may affect up to 1 in 10 people) are:

?Sinusitis, gum inflammation, chills, weakness.

?Low count, including severe, of some types of red blood cells (occasionally of an immunological nature) or white blood cells (occasionally accompanied by fever) in the blood, low platelet count that helps blood to coagulate.

• Low blood sugar levels, low potassium levels in the blood, low sodium levels in the blood.

?Anxiety, depression, confusion, agitation, insomnia, hallucinations.

?Convulsions, tremors, or uncontrolled muscle movements, tingling or abnormal sensations in the skin, increased muscle tone, drowsiness, dizziness.

?Eye hemorrhage.

?Problems with heart rhythm that include rapid heart rate, very slow heart rate, fainting.

?Hypotension, inflammation of the veins (which may be associated with the formation of blood clots).

?Acute difficulty breathing, chest pain, facial swelling (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, potentially severe, with blisters and peeling, characterized by a flat, red area covered with small protuberances that converge, facial redness.

?Itching.

?Hair loss.

?Back pain.

?Renal failure, presence of blood in urine, changes in renal function tests.

The uncommon side effects (may affect up to 1 in 100 people) are:

?Flu-like symptoms, gastrointestinal tract irritation and inflammation, gastrointestinal tract inflammation that causes antibiotic-associated diarrhea, lymphatic vessel inflammation.

?Peritoneal inflammation.

?Enlargement (occasionally painful) of lymph nodes, bone marrow insufficiency, eosinophilia increase.

• Adrenal gland dysfunction, hypothyroidism.

?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.

?Dual vision, severe eye diseases, such as: eye and eyelid pain and inflammation, involuntary eye movement, optic nerve damage that causes vision disturbance, papillary optic inflammation.

?Decreased sensitivity to touch.

?Alteration of the sense of taste.

?Difficulty hearing, tinnitus, vertigo.

?Inflammation of certain internal organs, pancreas, and duodenum, tongue swelling and inflammation.

?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).

?Renal inflammation, protein in urine, kidney damage.

?Very high heart rate or extrasystoles, occasionally with erratic electrical impulses.

?Abnormal electrocardiogram (ECG).

?Elevated blood cholesterol levels, elevated blood urea levels.

?Severe skin reactions, such as skin disease, potentially fatal that causes blisters and painful sores on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, sunburn, or severe skin reaction after exposure to light or the sun, skin redness and irritation, skin discoloration or purpura that may be caused by low platelet count, eczema.

?Reaction at the infusion site.

• Alergic reaction or excessive immune response.

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

?Hyperthyroidism.

?Severe brain activity deterioration as a complication of liver disease.

?Optic nerve fiber loss, corneal opacity, involuntary eye movement.

?Photosensitivity blister formation.

?Peripheral nervous system autoimmune disease.

?Cardiac rhythm or conduction problems (occasionally potentially fatal.

?Severe allergic reaction.

?Blood coagulation alterations.

?Severe skin reactions, such as skin disease, potentially fatal that causes large areas of the epidermis, the skin's outermost layer, to peel off from the layers of skin beneath it.

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

Unknown frequency side effects (cannot be estimated from available data):

?Moles and pigmented spots.

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

?Skin cancer.

?Periosteal inflammation.

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

Since Voriconazol Kern Pharma has been observed to affect the liver and kidneys, your doctor should monitor liver and renal function through blood tests. Inform your doctor if you have abdominal pain or if your stools have a different consistency.

Cases of skin cancer have been reported in patients treated with voriconazol for long periods of time.

The frequency of sunburns or severe skin reactions after exposure to light or the sun was higher in children. If you or your child experience skin problems, your doctor may refer you to a dermatologist who, after consultation, may decide that it is necessary for you or your child to undergo regular follow-up. Elevated liver enzymes were also observed more frequently in children.

If any of these side effects persist or are bothersome, inform your doctor.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish Medicines System for Human Use Pharmacovigilance: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication 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.

Flasks: use within 30 days after the first opening

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. In this way, you will help protect the environment.

Composition of Voriconazol Kern Pharma

?The active ingredient is voriconazole.

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

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

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

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

Appearance of the product and contents of the pack

Voriconazol Kern Pharma 50 mg film-coated tablets are presented in the form of white to off-white, round, film-coated tablets, 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 white to off-white, oval, film-coated tablets, 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/Aluminium blisters and are available in packs of 2, 10, 14, 20, 28, 30, 50, 56 or 100 film-coated tablets or in HDPE white opaque bottles with a polypropylene child-resistant cap, containing 30 film-coated tablets.

Only some pack sizes may be marketed.

Holder of the marketing authorisation and manufacturer responsible

Holder of the marketing authorisation

Kern Pharma, S.L.

Venus, 72 – Pol.Ind. Colón II

08228 Terrassa - Barcelona

Spain

Manufacturer responsible

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 medicinal product is authorised in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Last review date of this leaflet: June 2023

The detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es