Prospect: information for the user

Voriconazole Teva 200 mg powder for solution for infusion EFG

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

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult yourdoctor, pharmacist or nurse.

- This medicine has been prescribedonlyto you, and you must not give it to other people althoughtheymay havethe same symptomsas you,as it may harm them.

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

1.Voriconazole Teva 200 mg powder for solution for infusion and its use

2.What you need to knowbeforestarting touse Voriconazole Teva 200 mg powder for solution for infusion

3.How to use Voriconazole Teva 200 mg powder for solution for infusion

4.Possible adverse effects

5Storage of Voriconazole Teva 200 mg powder for solution for infusion

6.Contents of the package and additional information

Voriconazol Teva 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 to treat 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 count of white blood cells)
• 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 may put their lives at risk.

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

This medication must be used only under medical supervision.

No useVoriconazol Teva

• 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, pharmacist, or nurse if you are taking or have recently taken other medications, including those purchased without a prescription, or herbal remedies.

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 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 painkillers, called opioids [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 take 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 being treated with voriconazole by performing blood tests.

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

• You have kidney failure
• You know you have a heart condition, irregular heartbeats, slow heart rate, or an electrocardiogram (ECG) anomaly called "prolonged QT syndrome".

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 rays from the sun. This may be exacerbated by the use of other medications that sensitize the skin to sunlight, such as methotrexate. These precautions also apply to children.

Inform your doctor immediately if you develop the following symptoms while being treated with voriconazole:

• Sunburn
• Severe skin rash or blisters
• Bone pain

If you develop skin problems as described above, your doctor may refer you to a dermatologist, who may consider regular examinations. There is a small probability 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 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" where 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 on the abdomen, thighs, breasts, and arms, fine skin, easy bruising, high blood sugar, excessive hair growth, or excessive sweating, inform your doctor.

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

Children and adolescents

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

Use of Voriconazol Teva with other medications

Inform your doctor or pharmacist if you are taking/using or have taken/used or may need to take/use other medications, including those purchased without a prescription.

Some medications, when taken at the same time as this medication, may affect the action of voriconazole or vice versa, voriconazole may affect the action of other medications.

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 this medication should be avoided as much as possible, and you may need to adjust the dose of voriconazole:

• Rifabutin (used for tuberculosis treatment). If you are already being treated with rifabutin, your doctor will need to monitor your blood count and monitor the side effects of rifabutin.
• Phenitoin (used to treat epilepsy). If you are already being treated with phenitoin, your doctor will need to monitor the concentration of phenitoin in your blood during your treatment with this medication 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 monitor to ensure that these medications and/or voriconazole continue to produce 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 received a transplant).
• Sulfonilureas (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 to treat stomach ulcers).
• Oral contraceptives (if you use voriconazole while taking oral contraceptives, you may experience side effects such as nausea and menstrual disorders).
• Alkaloids of vincristine (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).
• Saquinavir and other HIV protease inhibitors (used to treat HIV infection).
• Inhibitors of reverse transcriptase non-nucleosides (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 (painkillers used for surgery).
• 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).
• Flucloxacillin (antibiotic used to treat bacterial 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.

Pregnancy and breastfeeding

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

Stop breastfeeding before starting to use Voriconazol Teva 200 mg powder for solution for infusion.

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

Driving and operating machinery

Voriconazole may cause blurred vision or discomfort due to increased sensitivity to light. If this occurs, do not drive or operate tools or machines. Inform your doctor if this occurs.

Voriconazol Teva 200 mg powder for solution for infusion contains hydroxypropyl betadex

This medication contains 2500 mg of cyclodextrin in each vial, which is equivalent to 125 mg / ml when reconstituted in 20 ml.

Do not use in children under 2 years of age unless recommended by your doctor

If you have kidney failure, consult your doctor before taking this medication.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. 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.

Voriconazole must be reconstituted and diluted to the correct concentration by hospital pharmacy or nursing staff (for more information, see section 5 and 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 adverse effects related to treatment.

If you forgot a dose of Voriconazole Teva

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

If you interrupt treatment with Voriconazole Teva

Treatment with voriconazole should be continued for as long as your doctor considers necessary, but the duration of treatment with voriconazole 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 can 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, 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 may be serious and require medical attention.

Severe side effects - Stop taking Voriconazol Teva 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, such as blurred vision, visual disturbances of colors, 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 the usual visual field, spots in the visual field)
• Fever
• Skin rash
• Nausea, vomiting, and diarrhea
• Headache
• Swelling of the extremities
• Abdominal pain
• Respiratory difficulties
• Elevated liver enzymes

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

• Gastrointestinal tract irritation and inflammation, sinusitis, gum inflammation, chills, weakness
• Low count, including severe, of certain types of red blood cells (sometimes of an immunological nature) and/or white blood cells (sometimes 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
• 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
• 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, renal function test abnormalities
• 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 and inflammation, antibiotic-associated diarrhea, lymphatic vessel inflammation
• Peritoneal 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
• Diplopia, severe eye diseases, such as: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage causing vision impairment, 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, gallbladder disease, gallstones
• Joint inflammation, inflammation of veins under the skin (which may be associated with the formation of a blood clot)
• Renal inflammation, proteinuria, renal damage
• Very high or extrasystolic heart rate, sometimes with erratic electrical impulses
• Abnormal electrocardiogram (ECG)
• Elevated blood cholesterol, elevated blood urea
• Dermatological reactions (sometimes severe) 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
• Allergic reaction or excessive immune response
• Periosteal inflammation

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

• Hyperactive thyroid gland
• Cerebral activity deterioration 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
• Condition in which the immune system attacks part of the peripheral nervous system
• Cardiac rhythm problems or conduction (sometimes potentially fatal)
• Potentially fatal allergic reaction
• Blood coagulation abnormalities
• Dermatological reactions (sometimes severe), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, pruritic and painful skin plaques with scaly skin that may be potentially fatal, causing large areas of the epidermis, the most superficial layer of the skin, to detach from the layers of skin beneath it, generalized eruption, elevated body temperature, and enlarged lymph nodes
• Small, scaly, and dry skin plaques, sometimes thick and with points or "horns"

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

• Spots and pigmented patches

• Other important side effects whose frequency is unknown, but which should be reported to the doctor immediately:Red scaly plaques or skin lesions in the form of a ring that may be a symptom of a skin autoimmune disease called lupus erythematosus

During perfusion, infrequently, there have been reactions withvoriconazol(including redness, fever, sweating, increased heart rate, difficulty breathing, nausea, itching, and skin rash). The doctor may interrupt the perfusion if this happens.

Since it has been observed thatvoriconazolaffects 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 withvoriconazolfor 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, 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 a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use: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 sight and reach of children.

Do not use this medication after the expiration date that appears on the label or container after CAD. The expiration date is the last day of the month indicated.

Do not store at a temperature above 25 °C.

Once reconstituted, this medication must be used immediately, although, if necessary, it can be stored for up to 24 hours between 2 °C – 8 °C (in a refrigerator). Voriconazole Teva 200 mg powder for solution for infusion reconstituted must be diluted first with a compatible infusion diluent before being infused. (For more information see the end of this leaflet).

Medicines should not be disposed of through the drains or in the trash. Dispose of the containers and medicines that you no longer need at the SIGRE Point. If in doubt, ask your pharmacist how to dispose of the containers and medicines that you no longer need. In this way, you will help protect the environment.

Composition of Voriconazole Teva 200 mg powder for solution for infusion

• The active ingredient is voriconazole.
• The other components (excipients) are hydroxypropyl betadex and hydrochloric acid (for pH adjustment).

Each vial contains 200 mg of voriconazole, which corresponds 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 Teva 200 mg powder for solution for infusion is presented in a single-use glass vial in the form of a white to off-white powder for solution for infusion.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

TEVA PHARMA, S.L.U.

C/ Anabel Segura, 11, Edificio Albatros B, 1st floor,

Alcobendas, 28108 Madrid, Spain

Responsible for manufacturing

Merckle GmbH

Ludwig-Merckle-Straße 3, Blaubeuren, 89143

Germany

Or

PLIVA HRVATSKA D.O.O.

Prilaz Baruna Filipovica 25

10000 Zagreb, Croatia

This medicine is authorized in the member states of the European Economic Area with the following names:

Last review date of this leaflet: July 2024

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

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The following information is only intended for medical professionals and healthcare professionals:

Information on reconstitution and dilution

• Voriconazole needs to be reconstituted with 19 ml of water for injectable preparations or 19 ml of sodium chloride 9 mg/ml (0.9%) for infusion to obtain a 20 ml extractable volume of a transparent concentrate containing 10 mg/ml of voriconazole.
• It is recommended to use a standard 20 ml syringe (not automatic) to ensure that the exact amount (19.0 ml) of water for injectable preparations 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 containing 0.5 to 5 mg/ml of voriconazole.
• This specialty is for single use and any unused solution must be discarded and only transparent solutions without particles should be used.
• It should not be administered by rapid intravenous injection.
• Regarding information on conservation, see section 5 "Conservation of Voriconazole Teva 200 mg powder for solution for infusion ."

Volumes required of Voriconazole Teva 200 mg powder for solution for infusion concentrate 10 mg/ml

Voriconazole is a lyophilized sterile product without preservatives of single dose. From a microbiological point of view, the solution must be used immediately once reconstituted. If not used immediately, the time and conditions of conservation before its use are the responsibility of the user, and it must be kept between 2 and 8 ° C (in a refrigerator) for a maximum period of 24 hours.

Compatible infusion solutions :

The reconstituted solution can be diluted with:

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

Infusion solution of lactate sodium compound

Solution for infusion of Ringer lactate

Solution for infusion of glucose 5% and Ringer lactate

Solution for infusion of glucose 5% and sodium chloride 0.45% for infusion

Solution for infusion of glucose 5% for infusion

Solution for infusion of glucose 5% and potassium chloride 20 mEq for infusion

Solution for infusion of sodium chloride 0.45% for infusion

Solution for infusion of glucose 5% and sodium chloride 0.9% for infusion

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

Incompatibilities :

Voriconazole should not be infused through the same route or cannula simultaneously with other drug infusions, including parenteral nutrition (e.g. Aminofusin 10% Plus).

Simultaneous administration of hemoderivatives and infusion of concentrated solutions of electrolytes for a short period should not be performed with the administration of voriconazole .

Parenteral nutrition can be administered simultaneously with the administration of voriconazole , but not through the same route or cannula.

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