Prospect: Information for the User

Voriconazole Kern Pharma 200 mg Powder for Solution for Infusion EFG

Read this prospect carefully before starting to use this medicine, as it contains important information for you.

-Keep this prospect, as you may need to read it again.

-If you have any doubts, consult your doctor or pharmacist.

-This medicine has been prescribed only for you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.

-If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

1.What is Voriconazole Kern Pharma and how is it used

2.What you need to know before starting to use Voriconazole Kern Pharma

3.How to use Voriconazole Kern Pharma

4.Possible adverse effects

5Storage of Voriconazole Kern Pharma

6.Contents of the package and additional information

Voriconazol Kern Pharma contains the active ingredient voriconazol. Voriconazol is an antifungal medication. It acts by eliminating or preventing the growth of fungi that cause infections.

It is used for the treatment of patients (adults and children 2 years of age or older) with:

• invasive aspergillosis (a type of fungal infection produced byAspergillusspp),
• candidemia (another type of fungal infection produced byCandidaspp) in non-neutropenic patients (patients who do not have an abnormally low count of white blood cells),
• serious invasive infections produced byCandidaspp, when the fungus is resistant to fluconazol (another antifungal medication),
• serious fungal infections produced byScedosporiumspp or byFusariumspp (two different species of fungi).

Voriconazol Kern Pharma is used in patients with serious fungal infections that can put their lives at risk.

Prevention of fungal infections in bone marrow transplant recipients with a high risk.

This medication must be used only under medical supervision.

No use Voriconazol Kern Pharma

-if you are allergic to voriconazole or any of the other ingredients of this medication (listed in section 6).

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

During treatment with voriconazole, you should not take the following medications:

• Terfenadine (used for allergies).
• Astemizol (used for allergies).
• Cisapride (used for digestive problems).
• Pimozide (used for mental disorders).
• Quinidine (used for heart arrhythmias).
• Rifampicin (used for tuberculosis treatment).
• Efavirenz (used for HIV treatment) at doses of 400 mg and above once a day.
• Carbamazepine (used to treat seizures).
• Phenobarbital (used for severe insomnia and seizures).
• Ergot alkaloids (e.g., ergotamine, dihydroergotamine; used for migraines).
• Sirolimus (used in transplant patients).
• Ritonavir (used for HIV treatment) at doses of 400 mg and above twice a day.
• St. John's Wort (Hypericum, herbal remedy).

Warnings and Precautions

Consult your doctor before starting to use voriconazole 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 on treatment with voriconazole by performing blood tests,
• you know you have heart disease, irregular heartbeats, slow heart rate, or an electrocardiogram (ECG) anomaly called "prolonged QTc syndrome".

You should avoid exposure to the sun and sunlight during treatment. It is essential to cover exposed areas and use a high-factor sunscreen, as you may experience increased skin sensitivity to UV sunlight. These precautions also apply to children.

While on treatment with voriconazole, inform your doctor if you experience:

• sunburn,
• severe skin rash or blisters,
• bone pain.

If you develop skin disorders as described above, your doctor may refer you to a dermatologist, who may consider regular examinations. There is a small chance of developing 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 medication should not be administered to children under 2 years old.

Use of Voriconazol Kern Pharma with Other Medications

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

• Some medications, when used at the same time as Voriconazol Kern Pharma, may affect the action of voriconazole or vice versa.

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

• Ritonavir (used for HIV treatment) at doses of 100 mg twice a day.

Inform your doctor if you are using any of the following medications, as simultaneous treatment with voriconazole should be avoided as much as possible, and the dose of voriconazole may need to be adjusted:

• Rifabutin (used for tuberculosis treatment). If you are already on rifabutin treatment, your blood count and rifabutin side effects will need to be monitored.
• Phenytoin (used to treat epilepsy). If you are already on phenytoin treatment, your phenytoin blood concentration will need to be monitored during your treatment with voriconazole, and your dose may need to be adjusted.

Inform your doctor if you are taking any of the following medications, as you may need to adjust your dose or have your medication levels checked:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to reduce blood clotting).
• Ciclosporin (used in transplant patients).
• Tacrolimus (used in transplant patients).
• 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 stomach ulcer treatment).
• Oral contraceptives (if you use voriconazole while taking oral contraceptives, you may experience side effects such as nausea and menstrual disorders).
• Vincristine and vinblastine alkaloids (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 efavirenz doses cannot be taken at the same time as voriconazole).
• Methadone (used to treat heroin addiction).
• Alfentanil, fentanyl, and other short-acting opioids (e.g., sufentanil) (used for surgical procedures).
• Oxycodone and other long-acting opioids (e.g., 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 transplant patients).
• Flucloxacillin (antibiotic used to treat bacterial infections).

Pregnancy and Breastfeeding

You should not use voriconazole 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.

If you are pregnant or breastfeeding, or think you may be pregnant or plan to become pregnant, consult your doctor before using this medication.

Driving and Operating Machinery

This medication may cause blurred vision or discomfort due to increased light sensitivity. If this happens, do not drive or operate tools or machinery and inform your doctor.

Voriconazol Kern Pharma contains sodium

Patients on low-sodium diets should note that this medication contains 88.74 mg (3.86 mmol) of sodium per vial

Follow exactly the administration instructions of this medication 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.

Your doctor may change your dose based on your situation.

The recommended dose in adults (including elderly patients) is as follows:

Depending on your response to treatment, your doctor may reduce the dose to 3 mg/kg twice a day.

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.

Voriconazole powder for solution for infusion must be reconstituted and diluted to the correct concentration by hospital pharmacy or nursing staff (for more information see the end of this leaflet).

It will be administered through intravenous infusion (in vein) at a maximum rate of 3 mg/kg per hour for 1 to 3 hours.

If you or your child are taking voriconazole for the prevention of fungal infections, your doctor may stop administering voriconazole if you or your child experience treatment-related adverse effects.

If you forgot to use Voriconazole Kern Pharma

Given that you will receive this medication under close medical supervision, it is unlikely that you will forget a dose. However, inform your doctor or pharmacist if you think you have forgotten a dose.

If you interrupt treatment with Voriconazole Kern Pharma

Voriconazole treatment should be continued for as long as your doctor considers necessary, although the duration of voriconazole powder for solution for infusion treatment should not exceed 6 months.

Patients with compromised immune systems or those with complicated infections may require longer treatments to prevent the infection from recurring. Once your condition improves, you may substitute intravenous infusion with oral tablets.

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

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them. If any occur, they are likely to be mild and temporary. However, some can be serious and require medical attention.

Severe side effects - Stop using this medicine and seek medical attention immediately

• Skin rash.
• Jaundice, liver function test abnormalities.
• Pancreatitis.

Other side effects

Very common (may affect more than 1 in 10 people):

• Visual disturbances (change in vision, blurred vision, visual color disturbances, abnormal light perception intolerance, color blindness, eye disorders, halo vision, night blindness, oscillating vision, spark vision, visual aura, decreased visual acuity, visual clarity, partial loss of the usual visual field, visual field spots).
• Fever.
• Skin rash.
• Nausea, vomiting, and diarrhea.
• Headache.
• Swelling of the extremities.
• Abdominal pain.
• Difficulty breathing.
• Elevated liver enzymes.

Common (may affect up to 1 in 10 people):

• 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.
• Allergic reaction or excessive immune response.
• 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, drowsiness, dizziness.
• Eye hemorrhage.
• Cardiac rhythm problems that include very fast heart rate, very slow heart rate, fainting.
• Hypotension, vein inflammation (which may be associated with blood clot formation).
• Acute difficulty breathing, chest pain, facial swelling (mouth, lips, and around the eyes), fluid retention in the lungs.
• Constipation, indigestion, lip inflammation.
• Jaundice (yellow skin discoloration), 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, skin redness.
• Itching.
• Alopecia.
• Back pain.
• Renal failure, blood in urine, renal function test abnormalities.

Uncommon (may affect up to 1 in 100 people):

• Flu-like symptoms, gastrointestinal tract irritation, gastrointestinal tract inflammation that causes diarrhea associated with antibiotics, lymphatic vessel inflammation.
• Peritoneal inflammation.
• Enlargement (occasionally painful) of lymph nodes, bone marrow insufficiency, eosinophil increase.
• Adrenal gland dysfunction, hypothyroidism.
• Abnormal cerebral function, Parkinson's disease-like symptoms, nerve damage causing numbness, pain, tingling, or burning in the hands or feet.
• Coordination problems.
• Brain swelling.
• Diplopia, severe eye diseases, such as: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage causing vision disturbances, papillary optic inflammation.
• Decreased sensitivity to touch.
• Altered sense of taste.
• Difficulty hearing, tinnitus, vertigo.
• Inflammation of certain internal organs, pancreas and duodenum, tongue swelling and inflammation.
• Enlarged liver, liver failure, biliary tract disease, gallstones.
• Joint inflammation, vein inflammation under the skin (which may be associated with blood clot formation).
• Renal inflammation, protein in urine, renal damage.
• Very high heart rate or extrasystoles, occasionally with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• Elevated blood cholesterol, elevated blood urea.
• 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 in the perfusion area.

Rare (may affect up to 1 in 1,000 people):

• Hyperactive thyroid gland.
• Severe cerebral activity deterioration as a complication of liver disease.
• Partial loss of optic nerve fibers, corneal opacity, involuntary eye movements.
• Blister formation due to photosensitivity.
• Autoimmune disease that attacks part of the peripheral nervous system.
• Cardiac rhythm problems or conduction (occasionally potentially fatal).
• Severe allergic reaction.
• Blood coagulation abnormalities.
• Severe skin reactions, such as hives, rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, pruritic and painful skin plaques with thickened and red skin with scaly skin plates, skin and mucous membrane irritation, potentially fatal skin disease 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 skin plates, occasionally thick and with points or“horns”.

Side effects with unknown frequency:

• Moles and pigmented spots.

Other important side effects whose frequency is unknown, but which 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.

During perfusion, infrequently, there have been reactions withvoriconazole(including facial redness, fever, sweating, increased heart rate, and difficulty breathing). The doctor may interrupt the perfusion if this occurs.

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

Cases of skin cancer have been reported in patients treated withvoriconazolefor long periods of time.

The frequency of sunburns or severe skin reactions after exposure to light

or the sun was much 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 important for you or your child to undergo regular follow-up. Elevated liver enzymes were observed

more frequently in children.

If any of these side effects persist or are bothersome, report them to your doctor.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for human use: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.

Once reconstituted, this medication must be used immediately, although, if necessary, it can be stored for up to 24 hours between 2°C and 8°C (in the refrigerator). Reconstituted Voriconazole Kern Pharma must be diluted first with a compatible infusion diluent before being infused. (For more information, see the end of this prospectus).

Medications should not be disposed of through drains or in the trash.Ask your pharmacist how to dispose of the packaging and medications that you do not need. This will help protect the environment.

Composition of VoriconazoleKern Pharma

-The active ingredient is voriconazole.

-The other components are hydroxypropyl-beta-cyclodextrin, sodium chloride, and hydrochloric acid.

Each vial contains 200 mg of voriconazole, which is equivalent to a concentrated solution of 10 mg/ml once reconstituted following the instructions indicated by the pharmacy or nursing staff of the hospital (see the information at the end of this leaflet).

Appearance of the product and contents of the package

Voriconazole Kern Pharma is presented in the form of a powder for solution for infusion in glass vials of type I of 25 ml for single use provided with a rubber stopper and an aluminum cap with a plastic seal.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Kern Pharma, S.L.

Venus, 72 - Pol. Ind.Colón II

08228 Terrassa - Barcelona

Spain

Responsible for manufacturing

Anfarm Hellas S.A.

Schimatari Viotias

320 09

Greece

or

Pharmathen S.A.

Dervenakion 6

15351 Pallini

Attikis - Greece

or

Pharmathen International S.A.

Sapes Industrial Park, Block 5

69300 Rodopi - Greece

Last review date of this leaflet: June 2023.

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

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This information is intended solely for doctors or healthcare professionals:

Information on reconstitution and dilution

• Voriconazole Kern Pharma powder for solution for infusion needs to be reconstituted with 19 ml of water for injection or 19 ml of sodium chloride 9 mg/ml (0.9%) for infusion to obtain a volume of 20 ml of a transparent concentrate containing 10 mg/ml of voriconazole.
• Discard the vial of Voriconazole Kern Pharma if the vacuum does not allow the solvent to be introduced into the vial.
• It is recommended to use a standard 20 ml syringe (not automatic) to ensure that the exact amount (19.0 ml) of water for injection or sodium chloride 9 mg/ml (0.9%) is dispensed.
• The required volume of reconstituted concentrate is then added to a compatible infusion solution listed below to obtain a final solution of Voriconazole Kern Pharma containing 0.5 to 5 mg/ml of voriconazole.
• This specialty is for single use only and any unused solution must be discarded and only transparent solutions without particles should be used.
• It should not be administered as a bolus.
• Regarding the information on conservation, see section 5 “Conservation of Voriconazole Kern Pharma”.

Volumes required of Voriconazole Kern Pharma concentrated 10 mg/ml

Voriconazole Kern Pharma is a sterile, preservative-free, single-dose lyophilisate. From a microbiological point of view, the solution must be used immediately once reconstituted. If not used immediately, the time and conditions for conservation before use are the responsibility of the user, and it should be kept between 2 and 8°C (in the refrigerator) for a maximum period of 24 hours unless the reconstitution has been carried out in controlled and validated aseptic conditions.

Compatible infusion solutions:

The reconstituted solution can be diluted with:

• Sodium chloride 9 mg/ml (0.9%) for injection.
• Intravenous lactate sodium compound infusion.
• Glucose 5% solution for intravenous infusion.
• Ringer lactate solution for intravenous infusion.
• Glucose 5% solution with sodium chloride 0.45% for intravenous infusion.
• Glucose 5% solution with potassium chloride 20 mEq for intravenous infusion.
• Sodium chloride 0.45% solution for intravenous infusion.
• Glucose 5% solution with sodium chloride 0.9% for intravenous infusion.

The compatibility of voriconazole with other diluents other than those specifically mentioned above (or mentioned below in “Incompatibilities”) is unknown.

Incompatibilities:

Voriconazole Kern Pharma should not be infused in the same vein or cannula simultaneously with other medication infusions, including parenteral nutrition (e.g. Aminofusin 10% Plus).

Simultaneous infusion of hemoderivatives should not be performed with the administration of Voriconazole Kern Pharma.

Parenteral total nutrition can be performed simultaneously with the administration of Voriconazole Kern Pharma but not in the same vein or cannula.

Voriconazole Kern Pharma should not be diluted with sodium bicarbonate 4.2% solution.