Prospect: information for the patient

Voriconazole Solution for Infusion EFG 200 mg powder

Read this prospect carefully before starting to use this medication, because

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, pharmacist, or nurse.
• This medication has been prescribed only to 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, pharmacist, or nurse, even if they do not appear in this prospect. See section 4.

1. What isVoriconazole Solution for Infusion EFG 200 mg powderand for what it is used

2. What you need to know before starting to useVoriconazole Solution for Infusion EFG 200 mg powder

3. How to useVoriconazole Solution for Infusion EFG 200 mg powder

4. Possible adverse effects

5. Storage ofVoriconazole Solution for Infusion EFG 200 mg powder

6. Contents of the package and additional information

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 to treat patients (adults and children 2 years of age or older) with:

• invasive aspergillosis (a type of fungal infection produced by Aspergillus sp ),
• candidemia (another type of fungal infection produced by Candida sp ) in non-neutropenic patients (patients who do not have an abnormally low white blood cell count),

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

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

This medication is used in patients with severe fungal infections that can put their lives at risk.

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

This medication should only be used under medical supervision.

Do not use this medication:if you are allergic to voriconazole or to sulfobutyl ether beta-cyclodextrin sodium (included in section 6).

• if you are allergic to voriconazole or to sulfobutyl ether 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, even 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 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).
• Ergot alkaloids (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 renal 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 this medication. Your doctor should also monitor your liver function while you are taking this medication by performing blood tests.
• you know that 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 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.

While taking 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 necessary to have you examined regularly. 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 may 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 the "Cushing's syndrome" in which the body produces too much cortisol hormone that may 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, fine skin, easy bruising, high blood sugar levels, excessive hair growth, excessive sweating, inform your doctor.

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 voriconazole 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 voriconazole, may affect the action of this medication 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 should 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 taking rifabutin, you will need to monitor your blood count and rifabutin side effects.
• Phenytoin (used to treat epilepsy). If you are already taking phenytoin, you will need to monitor the concentration of phenytoin in your blood during 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 have your medications monitored to ensure they 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).
• 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).
• Vincristine and vinblastine alkaloids (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 nevirapina) (used to treat HIV infection) (some doses of efavirenz cannot be taken at the same time as this medication).
• Methadone (used to treat heroin addiction).
• Alfentanil, fentanyl, and other short-acting opioids (e.g., sufentanil) (used for analgesia during surgery).
• 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).

(used to treat pain and inflammation).

• Fluconazole (used to treat fungal infections).
• Everolimus (used to treat advanced kidney cancer and in patients who have received a transplant).
• Letermovir (used to prevent cytomegalovirus (CMV) infection after a bone marrow transplant).
• Ivacaflor: used to treat cystic fibrosis.
• Flucloxacillin (antibiotic used to treat bacterial infections).

Pregnancy and breastfeeding

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

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

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

This medication contains sodium

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

This medication contains cyclodextrin

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

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Your doctor will determine the dose based on your weight and the type of infection you have.

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.

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

If you forgot a dose of Voriconazole 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. However, inform your doctor or pharmacist if you think you have forgotten a dose.

If you interrupt treatment with Voriconazole 200 mg powder for solution for infusion

Treatment with this medication should be continued for as long as your doctor considers necessary, but the duration of treatment with this medication 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 this medication, you should not experience any effects related to 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.

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

• Skin rash.
• Jaundice, changes in liver function blood tests.
• Pancreatitis.

Other side effects

Very common: may affect more than 1 in 10 people

• Visual disturbance (change in vision, such as blurred vision, visual colour changes, abnormal light perception intolerance, colour blindness, eye disorder, halo vision, night blindness, oscillating vision, spark vision, visual aura, decreased visual acuity, visual clarity, partial loss of 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 or white blood cells in the blood, low platelet count that helps blood to clot.
• Low blood sugar, 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 or very slow heart rate, fainting.
• Hypotension, inflammation of the veins (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, which may 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, blood in urine, changes 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.

• Enlargement (sometimes painful) of the lymph nodes, bone marrow insufficiency, eosinophil increase.
• Adrenal gland dysfunction, hypothyroidism.
• Abnormal brain function, Parkinson's disease-like symptoms, nerve damage causing numbness, pain, tingling, or burning in the hands or feet.
• Coordination or balance problems.
• Brain swelling.
• Dual vision, severe eye diseases, such as: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage causing vision changes, 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 the veins under the skin (which may be associated with blood clot formation).
• Renal inflammation, protein in urine, kidney damage.
• Very high or irregular heart rate, sometimes with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• Elevated blood cholesterol, elevated blood urea.
• Severe skin reactions (sometimes life-threatening), such as skin disease,

potentially fatal that causes painful blisters and sores on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, 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.
• Optic nerve fiber loss, corneal opacity, involuntary eye movement.
• Photosensitivity blister formation.
• Disease in which the immune system attacks part of the peripheral nervous system.
• Cardiac rhythm problems or conduction (sometimes potentially life-threatening).
• Potentially life-threatening allergic reaction.
• Blood coagulation alterations.
• Severe skin reactions (sometimes life-threatening), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, pruritic and painful skin plaques with thickened and scaly skin, skin irritation and mucous membranes, potentially fatal skin disease that causes large areas of the epidermis, the skin's outermost layer, to peel off from the layers of skin underneath.
• Small, dry, scaly skin plaques, sometimes thick and with points or "horns".

Side effects of unknown frequency

• Moles and pigmented spots.

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

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

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

Since it has been observed thatthis medicineaffects 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 withthis medicinefor long periods of time.

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

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

Reporting side effects

If you experience any type of side effect, consult your doctor,pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through theSpanish 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 label. The expiration date is the last day of the month indicated.

Once reconstituted,this medicationmust 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 medication 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. Ask your pharmacist how to dispose of the containers and the medication that you no longer need. By doing so, you will help protect the environment.

Composition of Voriconazole Solution for Infusion 200 mg powder for solution for infusion

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

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 pack

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

Marketing authorization holder and manufacturer responsible

Laboratorio Reig Jofre, S.A.

Gran Capitán, 10 – 08970

Sant Joan Despí, Barcelona

Spain

Last review date of this leaflet: January 2024January 2024

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

--------------------------------------------------------------------------------------------------------------------

This information is intended solely for doctors and healthcare professionals:

Information on reconstitution and dilution

• This medicineneeds 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 ofthis medicineif 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 ofthis medicinecontaining 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 Solution for Infusion 200 mg powder for solution for infusion”.

Required volumes of Voriconazole Solution for Infusion 200 mgconcentrate 10 mg/ml

This medicineis a sterile, preservative-free, single-dose lyophilisate. From a microbiological point of view, the solution must be used immediately after reconstitution. 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%

Lactate Ringer solution at concentrations 0.5 mg/ml and 5 mg/ml.

Glucose solutions with lactate Ringer solution at concentrations 0.5 mg/ml and 5 mg/ml.

Glucose solutions with sodium chloride 0.45% at concentrations 0.5 mg/ml and 5 mg/ml.

Glucose solutions at concentrations 0.5 mg/ml and 5 mg/ml.

Glucose solutions with 20 mEq of potassium chloride at concentrations 0.5 mg/ml and 5 mg/ml.

Sodium chloride 0.45% solutions at concentrations 0.5 mg/ml and 5 mg/ml.

Glucose solutions with sodium chloride 0.9% at concentrations 0.5 mg/ml and 5 mg/ml.

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

Incompatibilities:

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

Parenteral nutrition should not be administered simultaneously with the administration ofthis medicine.

Parenteral total nutrition can be administered simultaneously with the administration ofthis medicine, but not in the same vein or cannula.

This medicineshould not be diluted with sodium bicarbonate solution 4.2%.