Prospect: Information for the user

Voriconazole Aurovitas Spain 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 questions, consult your doctor, pharmacist, or nurse.

-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 side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4.

1.What is Voriconazole Aurovitas Spain and what it is used for

2.What you need to know before starting to use Voriconazole Aurovitas Spain

3.How to use Voriconazole Aurovitas Spain

4.Possible side effects

5.Storage of Voriconazole Aurovitas Spain

6.Contents of the package and additional information

Voriconazol Aurovitas Spain 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 byAspergillussp).

•candidemia (another type of fungal infection produced byCandidasp) in non-neutropenic patients (patients who do not have an abnormally low 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 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 Aurovitas Spain

If you are allergic to voriconazole or any of the other components of this medication (listed in section 6).

Do not take the following medications during treatment with voriconazole:

• Terfenadine (used for allergies).

• Astemizol (used for allergies).

• Cisapride (used for digestive problems).

• Pimozide (used for mental disorders).

• Quinidine (used for heart arrhythmias).

• 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 a day.

• Carbamazepine (used to treat seizures).

• Phenobarbital (used for severe insomnia and seizures).

• Alkaloids of ergot (e.g., ergotamine, dihydroergotamine; used for migraines).

• Sirolimus (used in patients who have received a transplant).

• Ritonavir (used for HIV treatment) at doses of 400 mg and above twice a day.

• St. John's Wort (hypericum, medicinal plant).

• Naloxegol (used to treat constipation caused specifically by opioid analgesics, e.g., 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 use this medication 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 doing 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 any exposure to the sun and sunlight during treatment. It is essential to cover exposed areas and use a high-factor sunscreen, as you may be more sensitive to UV rays from the sun. This sensitivity may be increased even more by the use of other medications that sensitize the skin to sunlight, such as methotrexate. 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 problems like those described above, your doctor may refer you to a dermatologist, who may consider regular examinations. 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 may cause symptoms like:

• Chronic or prolonged fatigue

• Muscle weakness

• Loss of appetite

• Weight loss

• Abdominal pain

Inform your doctor.

If you present signs of the "Cushing's syndrome" where the body produces too much cortisol hormone, which may cause symptoms like:

• Weight gain

• Hump of fat between the shoulders

• Round face

• Darkening of the skin on the abdomen, thighs, breasts, and arms

• Thin skin

• Easy bruising

• High blood sugar levels

• Excessive hair growth or sweating

Inform your doctor.

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

Children and Adolescents

Voriconazole should not be administered to children under 2 years old.

Other Medications and Voriconazol Aurovitas SpainVoriconazol Aurovitas Spain

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

Some medications, when used at the same time as voriconazole, 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.

• Glasdegib (used for cancer treatment); if you need to use both medications, your doctor will monitor your heart rate frequently.

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 doctor will need to monitor your blood count and rifabutin side effects.

• Phenobarbital (used for epilepsy treatment). If you are already on phenobarbital treatment, your doctor will need to monitor the concentration of phenobarbital 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 medications, as you may need to adjust your dose or have your medication monitored to ensure it continues to produce 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 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 this medication while taking 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 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 analgesia).

• Opioids with long-acting effects (e.g., oxycodone and hydrocodone) (used to treat moderate to severe pain).

• Nonsteroidal 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).

• Ivacaftor (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 medication.

You should not use voriconazole during pregnancy unless your doctor indicates it. Women of childbearing age on voriconazole treatment should use effective contraception. Contact your doctor immediately if you become pregnant during treatment with voriconazole.

Driving and Operating Machines

Voriconazole may 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 Aurovitas Spain contains sodium

This medication contains approximately 88.74 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 4.44% of the recommended daily maximum sodium intake for an adult.

Consult your doctor or pharmacist if you need 5 or more vials per day for a prolonged period, especially if you have been recommended a low-sodium diet.

Voriconazol Aurovitas Spain contains hydroxypropyl-beta-cyclodextrin

If you have kidney disease, consult your doctor before using this medication.

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:

Your doctor may reduce the dose to 3 mg/kg 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.

Voriconazol Aurovitas Spain 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 via 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 this medication for the prevention of fungal infections, your doctor may stop the administration of voriconazol if you or your child experience adverse effects related to treatment.

If you forgot to use Voriconazol Aurovitas Spain

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 the treatment with Voriconazol Aurovitas Spain

The treatment with voriconazol should be continued for as long as your doctor considers necessary, however, the duration of treatment with Voriconazol Aurovitas Spain powder for solution for infusion 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 the intravenous infusion with oral tablets.

When your doctor stops the treatment with voriconazol, 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, pharmacist, or nurse.

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 voriconazole and seek medical attention immediately if you experience:

•Skin rash.

•J jaundice, liver function test abnormalities.

•Pancreatitis.

Other side effects

Very common: may affect more than 1 in 10 people

•Visual disturbances (change in vision, including 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 white blood cell count, including severe cases, of certain types of red or white blood cells in the blood, low platelet count that helps blood to 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, drowsiness, dizziness.

•Eye hemorrhage.

•Cardiac rhythm problems that include very fast 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.

•J jaundice (yellowish skin color), liver inflammation, and liver damage.

•Skin eruptions, which can be 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, presence of blood in urine, abnormalities in renal function tests.

•Sunburn or severe skin reaction after exposure to light or the sun.

•Skin cancer.

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, abdominal wall inflammation.

•Enlargement (sometimes painful) of lymph nodes, bone marrow insufficiency, eosinophilia.

•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, abnormal eye movements, optic nerve damage that causes vision disturbances, papilledema.

•Decreased sensitivity to touch.

•Altered sense of taste.

•Difficulty hearing, tinnitus, 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 urine, kidney damage.

•Very high heart rate or extrasystoles, sometimes with erratic electrical impulses.

•Abnormal 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, skin redness, and irritation, skin discoloration or purpura that may be caused by low platelet count, eczema.

•Reaction in the perfusion area.

•Immunological response or allergic reaction.

•Periosteal inflammation.

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

•Hyperthyroidism.

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

•Optic nerve fiber loss, corneal opacity, involuntary eye movements.

•Phototoxicity blister formation.

•Peripheral neuropathy.

•Cardiac rhythm problems or conduction problems (sometimes potentially fatal).

•Severe allergic reaction.

•Coagulation disorders.

•Severe skin reactions, such as hives, edema, and skin thickening, skin irritation, and inflammation, 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 patches on the skin, sometimes thick and with points or "horns".

Side effects with unknown frequency (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:

•Red, scaly patches or skin lesions in the form of a ring that may be a symptom of an autoimmune disease called lupus erythematosus.

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

Since voriconazole 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 voriconazole 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 leaflet. 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 box and vial after CAD. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions before opening.

Chemical and physical stability has been demonstrated during use for 72 hours at 25°C and 2-8°C.

From a microbiological standpoint, once reconstituted, the medication should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and should normally not exceed 24 hours at 2-8°C (in a refrigerator), unless reconstitution was performed in controlled and validated aseptic conditions. The reconstituted medication must be diluted first with a compatible infusion diluent before being infused (for more information, see the end of this leaflet).

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need.This will help protect the environment.

Composition of Voriconazole Aurovitas Spain

-The active ingredient is voriconazole. Each vial contains 200 mg of voriconazole. After reconstitution, each ml of solution contains 10 mg of voriconazole.

-The other components are hydroxypropyl-beta-cyclodextrin, sodium chloride, hydrochloric acid (for pH adjustment).

Appearance of the product and contents of the package

Cada envase contiene un vial. Voriconazol Aurovitas Spain se presenta como un polvo liofilizado blanco o casi blanco para solución para perfusión en vial de vidrio tipo I de 25 ml con un tapón de goma gris de clorobutilo y cápsula metálica con cierre flip-off de plástico rojo.

Holder of the marketing authorization

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Responsible for manufacturing

Pharmathen International S.A.

Sapes Industrial Park, Block 5

69300 Rodopi

Greece

or

Pharmathen S.A.

Dervenakion 6

15351 Pallini

Attikis

Greece

or

Anfarm Hellas S.A

Schimatari Viotias

320 09

Greece

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

This medication is authorized 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: February 2024

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

The following information is only for healthcare professionals:

Information on reconstitution and dilution

•Voriconazole Aurovitas Spain powder for solution for infusion needs to be reconstituted first with 19 ml of water for injection or 19 ml of 0.9% sodium chloride solution for injection to obtain a 20 ml extractable volume of a transparent concentrate containing 10 mg/ml of voriconazole.

•Discard the vial of Voriconazole Aurovitas Spain 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 0.9% sodium chloride solution for injection is dispensed.

•The required volume of reconstituted concentrate is then added to a compatible intravenous solution listed below to obtain a final solution of Voriconazole Aurovitas Spain containing 0.5 to 5 mg/ml of voriconazole.

•This medication 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 rapid intravenous injection.

•Regarding the information on conservation, see section 5 “Conservation of Voriconazole Aurovitas Spain”.

Volumes required of Voriconazole Aurovitas Spain 10 mg/ml concentrate

Voriconazole Aurovitas Spain is a sterile, preservative-free single-dose lyophilisate. From a microbiological point of view, the reconstituted solution must be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and should not normally exceed 24 hours at 2-8°C (in the refrigerator), unless the reconstitution has been performed in controlled and validated aseptic conditions. Voriconazole Aurovitas Spain needs to be diluted first with a compatible solution before being infused.

Compatible infusion solutions

The reconstituted solution can be diluted with:

Solution for injection of sodium chloride 9 mg/ml (0.9%)

Intravenous infusion solution of sodium lactate compound

Intravenous infusion solution of glucose 5% and Ringer lactate solution

Intravenous infusion solution of glucose 5% and sodium chloride 0.45%

Intravenous infusion solution of glucose 5%

Intravenous infusion solution of glucose 5% in 20 mEq of potassium chloride

Intravenous infusion solution of sodium chloride 0.45%

Injectable solution of glucose 5% and sodium chloride 9 mg/ml (0.9%)

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

Incompatibilities

Voriconazole Aurovitas Spain 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 blood derivatives should not be performed with the administration of Voriconazole Aurovitas Spain.

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

Voriconazole Aurovitas Spain should not be diluted with sodium bicarbonate solution 4.2%.