VORICONAZOL ACCORD 200 mg POWDER FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Voriconazole Accord 200 mg powder for solution for infusion EFGEFG

Voriconazole

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.
• 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.

Contents of the pack

1. What Voriconazole Accord 200mg powder for solution for infusion EFG is and what it is used for.
2. What you need to know before you 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 other information.

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

The active substance of this medicine is voriconazole. It is an antifungal medicine. It works by stopping or preventing the growth of fungi that cause infections.

It is used for the treatment of patients (adults and children over 2 years of age) 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 medicine),

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

Voriconazole Accord is used in patients with severe fungal infections that can be life-threatening.

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

This medicine should only be used under medical supervision.

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

Do not use Voriconazole Accord

• if you are allergic to voriconazole or any of the other ingredients of this medicine (listed in section 6.1).

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

During treatment with Voriconazole Accord, you must not take the following medicines:

• Terfenadine (used for allergy).
• Astemizole (used for allergy).
• Cisapride (used for digestive problems).
• Pimozide (used for mental disorders).
• Quinidine (used for heart rhythm disorders).
• 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 daily.
• Carbamazepine (used to treat seizures).
• Phenobarbital (used for severe insomnia and seizures).
• Ergot alkaloids (e.g., ergotamine, dihydroergotamine; used for migraine).
• Sirolimus (used in patients who have received a transplant).
• Ritonavir (used for HIV treatment) at doses of 400 mg and above twice daily.
• 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 or nurse before starting to take this medicine if:

• you have had an allergic reaction to other azoles.
• you have or have ever had liver disease. If you have liver disease, your doctor may prescribe a lower dose of Voriconazole Accord. Your doctor should also monitor your liver function while you are taking this medicine with blood tests.
• you know that you have cardiomyopathy, irregular heartbeats, slow heart rate, or an abnormality in the electrocardiogram (ECG) called "QTc prolongation".

You should avoid any exposure to the sun and sunlight during treatment. It is important that you cover exposed areas and use a sunscreen with a high sun protection factor (SPF), as you may have increased skin sensitivity to the sun's UV rays. These precautions also apply to children.

While taking Voriconazole Accord:

• tell your doctor if you get

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 it important to examine you regularly. There is a small probability that you may develop skin cancer with long-term use of this medicine.

If you develop signs of "adrenal insufficiency" where 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, tell your doctor.

If you develop signs of "Cushing's syndrome" where 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, tell your doctor.

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

Children and adolescents

Voriconazole Accord should not be given to children under 2 years of age.

Using Voriconazole Accord with other medicines

Tell your doctor if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

• Some medicines, when used at the same time as Voriconazole Accord, can affect the action of this medicine or this medicine can affect the action of other medicines.

Tell your doctor or pharmacist if you are using any of the following medicines, as concurrent treatment with Voriconazole Accord should be avoided if possible:

• Ritonavir (used for HIV treatment) at doses of 100 mg twice daily.
• Glasdegib (used for cancer treatment); if you need to use both medicines, your doctor will monitor your heart rate frequently.

Tell your doctor if you are using any of the following medicines, as concurrent treatment with Voriconazole Accord should be avoided if 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, your phenytoin blood levels will need to be monitored during treatment with this medicine, and your dose may need to be adjusted.

Tell your doctor if you are taking any of the following medicines, as you may need a dose adjustment or monitoring to check that these medicines and/or Voriconazole Accord are still working as they should:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to decrease blood clotting).
• Cyclosporine (used in patients who have received a transplant).
• Tacrolimus (used in patients who have received a transplant).
• Sulfonylureas (e.g., tolbutamide, glipizide, and gliburide) (used for diabetes).
• Statins (e.g., atorvastatin, simvastatin) (used to lower cholesterol levels).
• Benzodiazepines (e.g., midazolam, triazolam) (used for severe insomnia and stress).
• Omeprazole (used for stomach ulcer treatment).
• Oral contraceptives (if you use Voriconazole Accord 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).
• Tyrosine kinase inhibitors (e.g., axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (used to treat cancer).
• Tretinoin (used to treat leukemia).
• Indinavir and other HIV protease inhibitors (used to treat HIV infection).
• Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, and nevirapine) (used to treat HIV infection) (some doses of efavirenz should NOT be taken at the same time as Voriconazole Accord).
• Methadone (used to treat heroin addiction).
• Alfentanil, fentanyl, and other short-acting opioids such as sufentanil (painkillers used for operations).
• 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).
• Everolimus (used to treat advanced kidney cancer and in patients who have received a transplant).
• 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

You should not use Voriconazole Accord during pregnancy unless your doctor advises you to. Women of childbearing age using this medicine should use effective contraception. Contact your doctor immediately if you become pregnant during treatment with Voriconazole Accord.

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Driving and using machines

Voriconazole Accord may cause blurred vision or discomfort due to increased sensitivity to light. If this happens, do not drive or operate tools or machines and tell your doctor.

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

Follow exactly the instructions for administration of this medicine given by your doctor.

If you are unsure, 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 depending 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 daily.

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.

Voriconazole Accord powder for solution for infusion should 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 (into a vein) at a maximum rate of 3 mg/kg per hour over 1 to 3 hours.

If you or your child are taking Voriconazole Accord to prevent fungal infections, your doctor may stop the administration of Voriconazole Accord if you or your child experience treatment-related side effects.

If you miss a dose of Voriconazole Accord

Given that you will receive this medicine under close medical supervision, it is unlikely that you will miss a dose. However, tell your doctor or pharmacist if you think you have missed a dose.

If you stop treatment with Voriconazole Accord

Treatment with this medicine should be continued for as long as your doctor considers necessary; however, the duration of treatment with Voriconazole Accord powder for solution for infusion should not exceed 6 months.

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

When your doctor stops treatment with Voriconazole Accord, you should not experience any effects from stopping treatment.

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

If you take more Voriconazole Accord than you should

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

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 can be serious and require medical attention.

Severe Adverse Effects - Stop using Voriconazol Accord and consult your doctor immediately

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

Other Adverse 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 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 extremities
• Stomach pain
• Difficulty breathing
• Elevated liver enzymes

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

• Inflammation of the gastrointestinal tract, sinusitis, inflammation of the gums, chills, weakness.
• Low count, including severe, of certain types of red blood cells (sometimes of an immune nature) 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, including 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, inflammation of the lips.
• 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 bumps that merge, skin redness. - Itching.
• Alopecia.
• Back pain.
• Kidney failure, blood in urine, alterations in kidney function tests.

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

• Flu-like symptoms, irritation, and inflammation of the gastrointestinal tract that causes antibiotic-associated diarrhea, inflammation of the lymphatic vessels.
• Inflammation of the thin tissue that lines the inner wall of the abdomen and covers the 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: pain and inflammation of the eyes and eyelids, abnormal eye movements, damage to the optic nerve that causes vision changes, 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 or extra heart rate, sometimes with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• High cholesterol in the blood, high urea in the blood.
• Allergic skin reactions (sometimes severe), such as a potentially life-threatening skin disease that causes painful blisters and ulcers on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, sunburn, or severe skin reaction after exposure to light or sun, skin redness, and irritation, reddish or purplish skin color that may be caused by low platelet count, eczema.
• Reaction at the infusion site.
• Allergic reaction or exaggerated immune response.

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

• Overactive thyroid gland.
• Deterioration of brain activity as a serious 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.
• Serious heart rhythm or conduction problems (sometimes potentially fatal).
• Potentially fatal allergic reaction.
• Alterations in blood coagulation.
• Allergic skin reactions (sometimes severe), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, pruritic, and painful thickened and reddened skin plaques 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 skin, to peel off from the underlying skin layers.
• Small, scaly, and dry skin patches, sometimes thick and with tips or "horns".

Adverse effects with unknown frequency:

• Pigmented spots and patches.

Other important adverse effects whose frequency is not known, but which should be reported to the doctor immediately:

• Skin cancer.
• Inflammation of the tissue surrounding the bone.
• Red, scaly skin patches or ring-shaped lesions that may be a symptom of an autoimmune disease called cutaneous lupus erythematosus.

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

Since Voriconazol Accord has been shown to affect 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 your stools have a different consistency.

Cases of skin cancer have been reported in patients treated with voriconazole 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.

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

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, 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. Storage of Voriconazol Accord 200mg powder for solution for infusion EFG

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the label and 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 demonstrated for 24 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 storage 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 point of view, the product must be used immediately. If not used immediately, the time and conditions of storage before use are the responsibility of the user.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Container Content and Additional Information

Composition of Voriconazol Accord

• The active ingredient is voriconazole
• The other components are hydroxypropyl-β-cyclodextrin (HPBCD) and lactose monohydrate

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

Appearance of the Product and Container Content

White powder, lyophilized for solution for infusion.

It is presented in single-use glass vials.

Container with 1 vial of 30ml.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Accord Healthcare, S.L.U.

World Trade Center

Moll de Barcelona s/n,

Edifici Est, 6ª planta,

08039 Barcelona

Manufacturer

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park,

Paola, PLA 3000

Malta

Or

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,95-200

Pabianice, Poland

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

CZ: Voriconazole Accord 200 mg powder for infusion solution

DE: Voriconazol Accord 200 mg powder for solution for infusion

FR: Voriconazole Accord 200 mg powder for solution for perfusion

ES: Voriconazol Accord 200 mg powder for solution for perfusion EFG

BG: Voriconazole Accord 200 mg powder for solution for infusion

HU: Voriconazole Accord 200 mg powder for solution for infusion

PL: Voriconazole Accord

RO: Voriconazol Accord 200 mg powder for perfusion solution

SI: Vorikonazol Accord 200 mg powder for solution for infusion

AT: Voriconazol Accord 200 mg powder for solution for infusion

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 dry substance, for solution

IS: Vórikónazóli 200 mg infusion substance, solution

LV: Voriconazole Accord 200 mg powder for infusion solution preparation

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

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

Date of the last revision of this prospectus: April 2023.

Other sources of information

Detailed information on this medicinal product is available on the website of theSpanishAgencyforMedicinesandHealthcareProducts(AEMPS)http://www.aemps.es

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This information is intended only for healthcare professionals:

Information on reconstitution and dilution

• Voriconazol Accord powder for solution for perfusion 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 containing 10 mg/ml of voriconazole.
• Reconstitution could take up to 4 minutes
• Discard the Voriconazol Accord vial if the vacuum does not allow the introduction of the solvent 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 Voriconazol Accord solution containing 0.5 to 5 mg/ml of voriconazole.
• This specialty is for single use, and any unused solution must be discarded. Only clear solutions without particles should be used.
• It should not be administered as a bolus.

• Regarding information on storage, see section 5 "Storage of Voriconazol Accord".

Required volumes of Voriconazol Accord concentrate 10 mg/ml

Voriconazol Accord is a sterile, preservative-free, single-dose lyophilized product. After reconstitution, the chemical and physical stability has been demonstrated for 24 hours at 2 - 8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, the time and conditions of storage 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 should be used immediately. If not used immediately, the time and conditions of storage before use are the responsibility of the user.

Compatible infusion solutions:

The reconstituted solution can be diluted with:

Sodium chloride 9 mg/ml (0.9%) injection solution

Compound sodium lactate intravenous infusion

5% glucose solutions and lactated Ringer's solution for intravenous infusion

5% glucose and 0.45% sodium chloride solution for intravenous infusion

5% glucose solution for intravenous infusion

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

0.45% sodium chloride solution for intravenous infusion

5% glucose and 0.9% sodium chloride solution for intravenous infusion

Lactated Ringer's solution for intravenous infusion

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

Incompatibilities:

Voriconazol Accord should not be infused in the same line 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 Voriconazol Accord.

Total parenteral nutrition can be administered simultaneously with Voriconazol Accord, but not in the same line or cannula.

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