VORICONAZOL SALA 200 mg POWDER FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Voriconazole Sala 200 mg Powder for Solution for Infusion EFG

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

Keep this leaflet, you may need to read it again.

If you have any further questions, ask your doctor, pharmacist, or nurse.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

• Save this leaflet, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed to you only, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Voriconazole Sala 200 mg Powder for Solution for Infusion and what is it used for
2. What you need to know before you use Voriconazole Sala 200 mg Powder for Solution for Infusion
3. How to use Voriconazole Sala 200 mg Powder for Solution for Infusion
4. Possible side effects
5. Storage of Voriconazole Sala 200 mg Powder for Solution for Infusion
6. Contents of the pack and other information

1. What is Voriconazole Sala 200 mg Powder for Solution for Infusion and what is it used for

This medication contains the active ingredient voriconazole. Voriconazole is an antifungal medication. It works 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 caused by Aspergillus sp),
• candidemia (another type of fungal infection caused by Candida sp) in non-neutropenic patients (patients who do not have an abnormally low count of white blood cells),

severe invasive infections caused by Candida sp, when the fungus is resistant to fluconazole (another antifungal medication),

• severe fungal infections caused by Scedosporium spor by Fusarium sp(two different species of fungi).

This medication is used in patients with severe fungal infections that can be life-threatening.

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

This medication should only be used under medical supervision.

2. What you need to know before you use Voriconazole Sala 200 mg Powder for Solution for Infusion

Do not usethis medication:

• if you are allergic to voriconazole or to sulfobutylether beta-cyclodextrin sodium (included in section 6).

It is very important that you 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).
• Astemizole (used for allergies).
• Cisapride (used for digestive problems).
• Pimozide (used for mental disorders).
• Quinidine (used for cardiac arrhythmias).
• Ivabradine (used for symptoms of chronic heart failure).

• Rifampicin (used for tuberculosis treatment).
• Efavirenz (used for HIV treatment) at doses of 400 mg or higher 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 or higher twice a day.
• St. John's Wort (hypericum, herbal remedy).
• Naloxegol (used to treat constipation caused 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 to treat 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 this medication. Your doctor should also monitor your liver function while you are being treated with this medication through blood tests.
• you know you have cardiomyopathy, irregular heartbeats, slow heart rate, or an abnormality in the electrocardiogram (ECG) called "prolonged QTc syndrome".

You should avoid any exposure to the sun and sunlight during treatment. It is essential that you cover exposed areas and use a sunscreen with a high sun protection factor (SPF), as your skin may be more sensitive to the sun's UV rays. This sensitivity may be increased further by the use of other medications that make your skin more sensitive to sunlight, such as methotrexate. These precautions also apply to children.

While you are being treated with this medication, inform your doctor if you experience:

• sunburn
• severe skin rash or blisters
• bone pain

If you develop skin disorders such as those described above, your doctor may refer you to a dermatologist, who may consider it essential to examine you regularly after the consultation. There is a small probability that you may develop skin cancer with long-term use of this medication.

If you develop signs of "adrenal insufficiency" in which the adrenal glands do not produce sufficient amounts of certain steroid hormones, such as cortisol, which can cause symptoms such as: chronic or prolonged fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, inform your doctor.

If you present signs of "Cushing's syndrome" in which the body produces too much cortisol hormone, which can cause symptoms such as: weight gain, hump of fat between the shoulders, rounded face, darkening of the skin of the abdomen, thighs, breasts, and arms, thin skin, easy bruising, high blood sugar levels, excessive hair growth or excessive sweating, inform your doctor.

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

Children and adolescents.

This medication should not be administered to children under 2 years of age.

Use ofvoriconazole with other medications

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

Some medications, when used at the same time as voriconazole, can affect the action of this medication or voriconazole may affect the action of other medications.

Inform your doctor if you are using the following medications, as concurrent 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 treatment at the same time as this medication should be avoided as much as possible, and a dose adjustment of voriconazole may be necessary:

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

Inform your doctor if you are taking any of the following medications, as you may need a dose adjustment or monitoring to check that these medications and/or voriconazole are still producing the desired effect:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to decrease blood clotting).
• Cyclosporine (used in transplant patients).
• Tacrolimus (used in transplant patients).
• Sulfonylureas (e.g., tolbutamide, glipizide, and gliburide) (used for diabetes).
• Statins (e.g., atorvastatin, simvastatin) (used to reduce cholesterol levels).
• Benzodiazepines (e.g., midazolam, triazolam) (used for severe insomnia and stress).
• Omeprazole (used to treat stomach ulcers).
• Oral contraceptives (if you use this medication while using oral contraceptives, you may experience side effects such as nausea and menstrual disorders).
• Vinca alkaloids (e.g., vincristine and vinblastine) (used to treat cancer).
• Indinavir and other HIV protease inhibitors (used to treat HIV infection).
• 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).
• Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, and nevirapine) (used to treat HIV infection) (some doses of efavirenz should NOT be taken at the same time as this medication).
• Methadone (used to treat heroin addiction).
• Alfentanil, fentanyl, and other short-acting opioids such as sufentanil (pain relievers used for operations).
• Oxycodone and other long-acting opioids such as hydrocodone (used to treat moderate to severe pain).
• Non-steroidal anti-inflammatory medications (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 transplant patients).
• Letermovir (used to prevent cytomegalovirus (CMV) infection after bone marrow transplantation).
• Ivacaftor: used to treat cystic fibrosis.
• Flucloxacillin (antibiotic used against bacterial infections).

Pregnancy and breastfeeding

Do not use this medication during pregnancy unless your doctor advises you to. Women of childbearing age using this medication should use effective contraceptives. Contact your doctor immediately if you become pregnant during treatment with this medication.

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

Driving and using machines

This medication 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.

This medicationcontains sodium

This medication contains 220.8 mg of sodium (main component of table/cooking salt) per vial. This is equivalent to 11% of the maximum recommended daily intake of sodium for an adult.

This medicationcontains cyclodextrin

This medication contains 3,200 mg of cyclodextrin per vial, equivalent to 160 mg/ml when reconstituted in 20 ml. If you have kidney failure, consult your doctor before taking this medication.

3. How to use Voriconazole Sala 200 mg Powder for Solution for Infusion

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 the dose according to your situation.

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

Depending on your response to treatment, your doctor may decrease 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.

This medication 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 by intravenous infusion (in a 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 to prevent fungal infections, your doctor may stop the administration of voriconazole if you or your child experience treatment-related side effects.

If you forget a dose of Voriconazole Sala 200 mg Powder for Solution for Infusion

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

If you interrupt treatment with Voriconazole Sala 200 mg Powder for Solution for Infusion

Treatment with this medication should be maintained for as long as your doctor considers it necessary, however, the duration of treatment with this medication should not exceed 6 months.

Patient with compromised immune systems or those with complicated infections may require longer treatments to prevent the infection from coming back. Once your condition improves, intravenous infusion may be replaced by oral tablets.

When your doctor stops treatment with this medication, you should not experience any effects from stopping the treatment.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. If any appear, it is most likely to be mild and transient. Nevertheless, some may be serious and require medical attention.

Severe Adverse Effects - Stop using this medicine and consult your doctor immediately

• Skin rash.
• Jaundice, alterations in blood tests to control liver function.
• Pancreatitis.

Other Adverse Effects

Very frequent: may affect more than 1 in 10 people

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

Frequent: may affect up to 1 in 10 people

• Sinusitis, gum inflammation, chills, weakness.
• Low count, including severe, of certain types of red blood cells (sometimes of an immune type) or white blood cells (sometimes accompanied by fever) in the blood, low platelet count that helps blood 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, somnolence, dizziness.
• Eye hemorrhage.
• Heart rhythm problems that include very fast heartbeat, very slow heartbeat, fainting.
• Hypotension, inflammation of the veins (which may be associated with the formation of blood clots).
• Acute difficulty breathing, chest pain, swelling of the face (mouth, lips, and around the eyes), fluid retention in the lungs.
• Constipation, indigestion, lip inflammation.
• Jaundice (yellowish skin color), liver inflammation, and liver damage.
• Skin eruptions, which can be severe, with blisters and peeling characterized by a flat and reddened area, covered with small protrusions that converge, skin redness.
• Itching.
• Alopecia.
• Back pain.
• Kidney failure, presence of blood in urine, alterations in kidney function tests.
• Sunburn or severe skin reaction after exposure to light or sun.
• Skin cancer.

Uncommon: may affect up to 1 in 100 people

• Flu-like symptoms, irritation, and inflammation of the gastrointestinal tract, gastrointestinal tract inflammation that causes antibiotic-associated diarrhea, inflammation of the lymphatic vessels.
• Inflammation of the tissue that lines the inner wall of the abdomen and covers the abdominal organs.

abdominal organs.

• Enlargement (sometimes painful) of the lymph nodes, bone marrow failure, increased eosinophils.
• Decreased function of the adrenal gland, underactive thyroid gland.
• Abnormal brain function, symptoms similar to Parkinson's disease, nerve damage causing numbness, pain, tingling, or burning in the hands or feet.
• Problems with balance or coordination.
• Brain swelling.
• Double vision, severe eye diseases, such as: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage that causes vision alteration, inflammation of the optic papilla.
• Decreased sensitivity to touch.
• Alteration of the sense of taste.
• Difficulty hearing, ringing in the ears, vertigo.
• Inflammation of certain internal organs, pancreas, and duodenum, swelling, and inflammation of the tongue.
• Enlargement of the liver, liver failure, gallbladder disease, gallstones.
• Joint inflammation, inflammation of the veins under the skin (which may be associated with the formation of a blood clot).
• Kidney inflammation, protein in the urine, kidney damage.
• Very high heart rate or extrasystoles, sometimes with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• High cholesterol in the blood, high urea in the blood.
• Skin allergic reactions (sometimes severe), such as skin disease, potentially life-threatening, which causes painful blisters and ulcers on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, skin redness, and irritation, reddish or purplish skin color that may be caused by low platelet count, eczema.

potentially life-threatening, which causes painful blisters and ulcers on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, skin redness, and irritation, reddish or purplish skin color that may be caused by low platelet count, eczema.

• Infusion site reaction.
• Allergic reaction or exaggerated immune response.
• Inflammation of the tissue surrounding the bone.

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

• Overactive thyroid gland.
• Worsening of brain activity as a severe complication of liver disease.
• Loss of most of the optic nerve fibers, corneal opacity, involuntary eye movement.
• Blisters due to photosensitivity.
• Disorder in which the immune system attacks part of the peripheral nervous system.
• Heart rhythm or conduction problems (sometimes potentially life-threatening).
• Potentially life-threatening allergic reaction.
• Alterations in blood coagulation.
• Skin allergic reactions (sometimes severe), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, itchy and painful plates of thickened and reddened skin with silvery skin scales, skin and mucous membrane irritation, potentially life-threatening skin disease that causes large portions of the epidermis, the outermost layer of the skin, to peel off from the layers of skin underneath.
• Small, scaly, and dry plates on the skin, sometimes thick and with tips or "horns".

Adverse Effects with Unknown Frequency

• Freckles and pigmented spots.

Other Important Adverse Effects whose Frequency is Unknown, but which must be Communicated to the Doctor Immediately:

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

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

Since it has been observed that this medicine affects the liver and kidneys, your doctor should monitor liver and kidney function through blood tests. Inform your doctor if you have stomach pain or if the stools have a different consistency.

Cases of skin cancer have been reported in patients treated with this medicine for long periods.

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

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

Reporting of Adverse Effects

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

5. Conservation of Voriconazol Sala 200 mg Powder for Solution for Infusion

Keep this medicine out of sight and reach of children.

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

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

Medicines should not be thrown away through drains or into the trash. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Voriconazol Sala 200 mg Powder for Solution for Infusion

• The active ingredient is voriconazole.
• The other component is sulfobutyl ether beta-cyclodextrin sodium (see section 2, Voriconazol Sala 200mg powder for solution for infusion contains cyclodextrin and sodium).

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 hospital pharmacy or nursing staff (see the information at the end of this prospectus).

Appearance of the Product and Package Contents

This medicine is presented in the form of powder for solution for infusion in single-dose glass vials.

Marketing Authorization Holder and Manufacturer

Laboratorio Reig Jofre, S.A.

Gran Capitán, 10 – 08970

Sant Joan Despí, Barcelona

Spain

Date of the Last Revision of this Prospectus:January 2024

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es.

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This information is intended only for doctors and healthcare professionals:

Information on Reconstitution and Dilution

• This medicine 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 an extractable volume of 20 ml of clear concentrate that contains 10 mg/ml of voriconazole.

• Discard the vial of this medicine if the vacuum does not allow the solvent to be introduced into the vial.
• The use of a standard 20 ml syringe (not automatic) is recommended 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, including those listed below, to obtain a final solution of this medicine that contains 0.5 to 5 mg/ml of voriconazole.

• This specialty is for single use, and any unused solution must be discarded, and only clear solutions without particles should be used.
• It should not be administered as a bolus.
• Regarding information on conservation, see section 5 "Conservation of Voriconazol Sala 200 mg Powder for Solution for Infusion".

Required Volumes of Voriconazol Sala 200 mg Concentrate 10 mg/ml

This medicine is a sterile lyophilized product without preservatives for single use. 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 use are the responsibility of the user, and it must be kept between 2 and 8°C 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 0.9%.

Lactated Ringer's solution at concentrations of 0.5 mg/ml and 5 mg/ml.

5% glucose solutions and lactated Ringer's solution at concentrations of 0.5 mg/ml and 5 mg/ml.

5% glucose solution and 0.45% sodium chloride solution at concentrations of 0.5 mg/ml and 5 mg/ml.

5% glucose solution at concentrations of 0.5 mg/ml and 5 mg/ml.

5% glucose solution with 20 mEq of potassium chloride at concentrations of 0.5 mg/ml and 5 mg/ml.

0.45% sodium chloride solution at concentrations of 0.5 mg/ml and 5 mg/ml.

5% glucose solution and 0.9% sodium chloride solution at concentrations of 0.5 mg/ml and 5 mg/ml.

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

Incompatibilities:

This medicine should not be infused in the same vein or cannula simultaneously with other drug infusions, including parenteral nutrition (e.g., Aminofusin 10% Plus).

Hemoderivatives should not be infused simultaneously with the administration of this medicine.

Total parenteral nutrition can be administered simultaneously with this medicine, but not in the same vein or cannula.

This medicine should not be diluted with 4.2% sodium bicarbonate solution.