Leaflet: Information for the user

Voriconazole Accord 200 mg powder for solution for infusion EFG

Voriconazole

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

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

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

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

1.What is Voriconazole Accord 200mg powder for solution for infusion EFG and how it is used.

2.What you need to know before starting to use Voriconazole Accord 200mg powder for solution for infusion EFG.

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

4.Possible side effects.

5.Storage of Voriconazole Accord 200mg powder for solution for infusion EFG.

6.Contents of the pack and additional information.

Theactiveingredientofthismedicineisvoriconazol.Itisanantifungalmedicine.Itactsbysuppressingorpreventingthe

growth offungithatproduceinfections.

Itisusedforthetreatmentofpatients(adultsandchildrenolderthan2yearsofage)

with:

·invasive aspergillosis (a type of fungal infection produced byAspergillus sp),

·candidemia (another type of fungal infection produced byCandida sp) in non-neutropenic patients (patients with an abnormally low count of white blood cells),

·serious invasive infections produced byCandida sp,when the fungus is resistant to fluconazole (another antifungal medicine),

·serious fungal infections produced byScedosporium spor byFusarium sp(two different species of fungi).

Voriconazol Accord is used in patients with serious fungal infections that can be life-threatening.

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

This medicine should be used only under medical supervision.

No use Voriconazol Accord

-If you are allergic to voriconazole or any of the other ingredients in this medication (listed in section 6.1).

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

During treatment with Voriconazol Accord, do not take the following medications:

·Terfenadine (used for allergies).

·Astemizol (used for allergies).

·Cisapride (used for digestive problems).

·Pimozide (used for mental disorders).

·Quinidine (used for heart arrhythmias).

·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, herbal remedy).

·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, or nurse before starting to take 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 Voriconazol Accord. Your doctor should also monitor your liver function while you are taking this medication by performing blood tests.

·You know you have heart disease, irregular heartbeats, slow heart rate, or an electrocardiogram (ECG) anomaly called "prolonged QTc syndrome."

You should avoid 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. These precautions also apply to children.

While taking Voriconazol Accord:

·Inform your doctor if you experience:

or sunburn

or severe skin rash or blisters

or bone pain

If you develop skin disorders such as those 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 this medication.

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 present signs of the "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

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 performing blood tests.

Children and adolescents

Voriconazol Accord should not be administered to children under 2 years old.

Use of Voriconazol Accord with other medications

Inform your doctor if you are taking, have recently taken, or may need to take any other medication, including those purchased without a prescription.

·Some medications, when used at the same time as Voriconazol Accord, may affect the action of this medication or vice versa.

Inform your doctor or pharmacist if you are using the following medications, as simultaneous treatment with Voriconazol Accord 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 Voriconazol Accord should be avoided as much as possible, and you may need to adjust the voriconazole dose:

·Rifabutin (used for tuberculosis treatment). If you are already being treated with rifabutin, your doctor will need to monitor your blood count and rifabutin side effects.

·Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin, your doctor will need to monitor the concentration of phenytoin 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 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 to treat stomach ulcers).
• Oral contraceptives (if you use Voriconazol Accord while using oral contraceptives, you may experience side effects such as nausea and menstrual disorders).
• Vincristine and vinblastine alkaloids (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).
• 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 Voriconazol Accord).
• 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).
• 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

You should not use Voriconazol Accord 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 Voriconazol Accord.

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

Voriconazol Accord 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.

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:

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

Your doctor may decide to reduce the dose if you have mild to moderate cirrhosis.

Use in children and adolescents

The recommended dose in children and adolescents is as follows:

Depending on your response to treatment, your doctor may increase or decrease the daily dose.

Voriconazol Accord 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 Voriconazol Accord for the prevention of fungal infections, your doctor may stop administering Voriconazol Accord if you or your child experience adverse effects related to treatment.

If you forgot a dose of Voriconazol Accord

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 Voriconazol Accord

Treatment with this medication should be continued for as long as your doctor considers necessary.
The duration of treatment with Voriconazol Accord 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 can switch from intravenous infusion to taking tablets.

When your doctor stops treatment with Voriconazol Accord, 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.

If you take more Voriconazol Accord than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, telephone: 91 562 04 20, indicating the medication and the amount ingested.

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 using Voriconazol Accord and seek medical attention immediately

-Skin rash

-J jaundice, liver function abnormalities detected in blood tests.

-Pancreatitis

Other side effects

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

-Visual disturbances (change in vision, blurred vision, visual color disturbances, abnormal light perception intolerance, color blindness, eye 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):

-Gastrointestinal inflammation, sinusitis, gum inflammation, chills, weakness.

-Low 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, somnolence, 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, inflammation of the lips.

-J jaundice (yellow discoloration of the skin), 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,redness of the skin.-Itching.

-Hair loss.

-Back pain.

-Renal failure, presence of blood in urine, abnormalities in renal function tests.

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

-Grip-like symptoms, gastrointestinal tract irritation that causes diarrhea associated with antibiotics, lymphatic vessel inflammation.

-Peritoneal inflammation, the thin tissue that lines the abdominal cavity and covers the abdominal organs.

-Enlargement (sometimes painful) of the 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.

-Cerebral edema.

-Diplopia, 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.

-Alteration of the sense of taste.

-Difficulty hearing, tinnitus, vertigo.

-Internal organ inflammation, pancreas and duodenum, tongue swelling and inflammation.

-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).

-Renal inflammation, protein in urine, kidney damage.

-Very high or irregular heart rate, sometimes with erratic electrical impulses.

-Abnormal ECG.

-High blood cholesterol, elevated blood urea.

-Severe skin reactions, such as Stevens-Johnson syndrome, which can cause painful blisters and sores on the skin and mucous membranes, especially in the mouth, inflammation of the skin, sunburn or severe skin reaction after exposure to light or the sun, skin redness and irritation, red or purple discoloration of the skin that may be caused by low platelet count, eczema.

-Reactionat the infusion site.

- Allergic reaction or excessive immune response.

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

-Hyperthyroidism.

-Severe brain damage as a complication of liver disease.

-Optic nerve damage, corneal opacity, involuntary eye movements

-Phototoxicity, blistering.

-Peripheral neuropathy.

-Severe cardiac rhythm problemsor conduction (sometimes potentially fatal).

• Severe allergic reaction.
• Bleeding disorders.
• Severe skin reactions, such as hives, angioedema, or Stevens-Johnson syndrome, which can cause painful blisters and sores on the skin and mucous membranes, especially in the mouth, inflammation of the skin, sunburn or severe skin reaction after exposure to light or the sun, skin redness and irritation, red or purple discoloration of the skin that may be caused by low platelet count, eczema.
• Small, scaly, and dry patches on the skin, sometimes thick and with points or“horns”.

Unknown frequency side effects:

• Age spots and pigmented spots.

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

-Skin cancer.

-Periosteal inflammation.

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

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

Since Voriconazol Accord 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 voriconazol 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.

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 or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly throughtheSpanish System for the Pharmacovigilance of Medicinal Products 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 and the box after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

After reconstitution, chemical and physical stability has been demonstratedfor24 hours at

2 – 8 °C. From a microbiological standpoint, the product must be used immediately. If not used immediately, the time and storage conditions before use are the responsibility

of the user.

After dilution, chemical and physical stability during use has been demonstrated for 6 hours at 25 °C. From a microbiological standpoint, the product must be used immediately. If not used immediately, the time and storage conditions before use are the responsibility of the user.

Medications should not be disposed of through drains or in the trash. Ask your pharmacisthow to dispose ofthecontainers and medications that you no longerneed.This will help protect the environment.

Composition of Voriconazole Accord

-The active ingredient isvoriconazole

-The other components are hydroxypropyl-β-cyclodextrin (HPBCD) and lactose monohydrate

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

Appearance of the product and contents of the package

Powder white, lyophilized for solution for infusion.

It is presented in single-use glass vials.

Package with 1 vialof30ml.

Marketing authorization holder and responsible for manufacturing

Marketing authorization holder

Accord Healthcare, S.L.U.

World Trade Center

Moll de Barcelona s/n,

Edifici Est, 6th floor,

08039 Barcelona

Responsible for manufacturing

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park,

Paola, PLA 3000

Malta

O

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,95-200

Pabianice, Poland

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

CZ:Voriconazole Accord 200 mg powder for infusion solution

DE:Voriconazol Accord 200 mg Powder for the preparation of an infusion solution

FR:Voriconazole Accord 200 mg powder for solution for infusion

ES:Voriconazol Accord 200 mg powder for solution for infusionEFG

BG:Voriconazole Accord 200 mg Powder for solution for infusion

HU:Voriconazole Accord 200 mg Powder for infusion solution

PL:Voriconazole Accord

RO:Voriconazol Accord 200 mg powder for infusion solution

SI:Vorikonazol Accord 200 mg powder for infusion solution

AT:Voriconazol Accord 200 mg Powder for the preparation of an infusion solution

BE:Voriconazole Accord Healthcare 200 mg, Powder for solution for infusion

DK:Voriconazole Accord 200 mg

EE:Voriconazole Accord

FI:Voriconazole Accord 200 mg infusion powder, for solution

IS:Vórikónazóli 200 mg infusion powder, for solution

LV:Voriconazole Accord 200 mg powder for infusion solution

LT:Voriconazole Accord 200 mg powder for infusion solution

NL:Voriconazol Accord 200 mg Powder for solution for infusion

NO:Voriconazole Accord 200 mg

SE:Voriconazole 200 mg Powder for infusion solution, solution

CY:Voriconazole Accord 200 mg Powder for solution for infusion

PT:Voriconazol Accord 200 mg

IE:Voriconazole Accord 200 mg Powder for Solution for Infusion

Last review date of this leaflet: April 2023.

Other sources of information

The detailed information on this medicine is available on the website oftheSpanish AgencyofMedicinesand

Medical Products(AEMPS)http://www.aemps.es

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This information is intended solely for healthcare professionals:

Information on reconstitution and dilution

·Voriconazole Accord powder for solution for infusion needs to be reconstituted with 19 ml of water for injection or 19 ml of sodium chloride 9 mg/ml (0.9%) for infusion to obtain a usable volume of 20 ml of concentrated solution containing 10 mg/ml of voriconazole.

·Reconstitution may take up to 4 minutes

·Discard the vial of Voriconazole Accord if the vacuum does not allow the solvent to be introduced into the vial.

·It is recommended to use a standard 20 ml syringe (not automatic) to ensure that the exact amount (19.0 ml) of water for injection or sodium chloride 9 mg/ml (0.9%) is dispensed.

·The required volume of reconstituted concentrate is then added to a compatible infusion solution listed below, to obtain a final solution of Voriconazole Accord 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 as a bolus.

-Regarding the information on conservation, see section 5 “Conservation of Voriconazole Accord”.

Required volumes of Voriconazole Accord concentrated 10 mg/ml

Voriconazole Accord is a sterile, preservative-free, single-dose powder.
After reconstitution, the chemical and physical stability has been demonstratedfor24 hours at 2 - 8°C. From a microbiological point of view, the product must be used immediately. If not used immediately, the time and conditions of conservation before use are the responsibility of the user.

After dilution, the chemical and physical stability during use has been demonstrated for 6 hours at 25°C. From a microbiological point of view, the product must be used immediately. If not used immediately,the time and conditions of conservation before use are the responsibility of the user.

Compatible infusion solutions:

The reconstituted solution can be diluted with:

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

Intravenous infusion of lactate sodium compound solution

Glucose solution at 5% and Ringer lactate solution for intravenous infusion

Glucose solution at 5% and sodium chloride at 0.45% for intravenous infusion

Glucose solution at 5% for intravenous infusion

Glucose solution at 5% with 20 mEq of potassium chloride for intravenous infusion

Sodium chloride at 0.45% for intravenous infusion

Glucose solution at 5% and sodium chloride at 0.9% for intravenous infusion

Ringer lactate solution for intravenous infusiona

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

Incompatibilities:

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

Simultaneous infusion of blood derivatives should not be performed with the administration of Voriconazole Accord.

Parenteral nutrition can be performed simultaneously with the administration of Voriconazole Accord but not through the same vein or cannula.

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