VORICONAZOL FOSUN PHARMA 200 mg POWDER FOR SOLUTION FOR INFUSION

2. What you need to know before you use Voriconazole Fosun Pharma

Do not use Voriconazole Fosun Pharma:

• If you are allergic to voriconazole or any of the other ingredients of this medicine (listed in section 6).

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

During treatment with voriconazole, 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 the treatment of tuberculosis)
• Efavirenz (used for the treatment of HIV) 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 the treatment of HIV) at doses of 400 mg and above twice daily
• St. John's Wort (herbal remedy)
• Venetoclax (used for the treatment of patients with chronic lymphocytic leukemia [CLL])

Warnings and precautions

Consult your doctor or nurse before starting to take Voriconazole Fosun Pharma 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 this medicine. Your doctor should also monitor your liver function while you are being treated with this medicine by performing blood tests.
• you know that you have cardiomyopathy, irregular heartbeats, slow heart rate or an abnormality in the electrocardiogram (ECG) called "QTc prolonged syndrome".

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 you are being treated with Voriconazole Fosun Pharma:

• tell your doctor immediately if you develop

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, after consultation, may consider it important for you to be examined 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" in which the adrenal glands do not produce adequate 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, and abdominal pain, inform your doctor.

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

Children and adolescents

This medicine must not be given to children under 2 years of age.

Other medicines and Voriconazole Fosun Pharma 200 mg

Tell your doctor or pharmacist 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, can affect the action of this medicine or voriconazole may affect the action of other medicines.

Tell your doctor if you are using the following medicine, as simultaneous treatment with voriconazole should be avoided if possible:

• Ritonavir (used for the treatment of HIV) at doses of 100 mg twice daily.

Tell your doctor if you are using any of the following medicines, as simultaneous treatment with voriconazole should be avoided as much as possible, and a dose adjustment of voriconazole may be necessary:

• Rifabutin (used for the treatment of tuberculosis). If you are already being treated with rifabutin, your blood count and rifabutin side effects should be monitored.
• Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin, your phenytoin blood levels should be monitored during your treatment with voriconazole 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 are still working as expected:

• Warfarin and other anticoagulants (e.g. phenprocoumon, acenocoumarol; used to reduce 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 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 the treatment of stomach ulcers)
• Oral contraceptives (if you use voriconazole 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)
• Non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz, delavirdine, nevirapine) (used to treat HIV) (some doses of efavirenz MUST NOT be taken at the same time as this medicine)
• Methadone (used to treat heroin addiction)
• Alfentanil and fentanyl and other short-acting opiates such as sufentanil (painkillers used for operations)
• Oxycodone and other long-acting opiates such as hydrocodone (used to treat moderate to severe pain)
• Non-steroidal anti-inflammatory medicines (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)
• Tolvaptan (used to treat hyponatremia [low sodium levels in the blood] or to delay the deterioration of kidney function in patients with polycystic kidney disease)
• Letermovir (used to prevent cytomegalovirus [CMV] disease after bone marrow transplantation)
• Naloxegol (used to treat constipation caused by opioid painkillers [e.g. morphine, oxycodone, fentanyl, tramadol, codeine])
• Ivacaftor (used to treat cystic fibrosis)
• Corticosteroids, including inhaled corticosteroids (used to treat asthma)

Pregnancy and breast-feeding

Do not use this medicine during pregnancy unless your doctor has told you to. Women of childbearing age should use effective contraception. Contact your doctor immediately if you become pregnant during treatment with this medicine.

If you are pregnant or breast-feeding, 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

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

Voriconazole Fosun Pharma contains sodium and cyclodextrin

This medicine contains 217.6 mg of sodium (the main component of cooking/table salt) in each vial. This is equivalent to 11% of the maximum recommended daily intake of sodium for an adult.

This medicine contains sulfobutyl ether beta-cyclodextrin sodium. Each vial contains 3.2 g of sulfobutyl ether beta-cyclodextrin sodium. If you have kidney disease, consult your doctor before taking this medicine.

3. How to use Voriconazole Fosun Pharma

Follow the instructions for administration of this medicine exactly as told 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.

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 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 medicine 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 (into a vein) at a maximum rate of 3 mg/kg per hour over 1 to 3 hours.

If you or your child are using this medicine to prevent fungal infections, your doctor may stop the administration of voriconazole if you or your child experience treatment-related side effects.

This medicine must not be given to children under 2 years of age.

If you miss a dose of Voriconazole Fosun Pharma

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 are given more Voriconazole Fosun Pharma than you should

Given that you will receive this medicine under close medical supervision, it is unlikely that you will receive more doses than you should. However, tell your doctor or pharmacist if you think you have received more 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.

If you stop treatment with Voriconazole Fosun Pharma

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

Patient with compromised immune system 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 medicine, 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.

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. However, 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 disorders, 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 (sometimes immune-related) or white blood cells (sometimes accompanied by fever) in the blood, low platelet count that helps blood clot
• Low blood sugar levels, low blood potassium levels, low blood sodium levels
• Anxiety, depression, confusion, agitation, insomnia, hallucinations
• Seizures, tremors or uncontrolled muscle movements, tingling or abnormal sensations in the skin, increased muscle tone, somnolence, dizziness
• Ocular 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, lip inflammation
• Jaundice, 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, redness of the skin
• Itching
• Alopecia
• Back pain
• Kidney failure, presence of blood in the urine, alterations in kidney function tests

Infrequent: may affect up to 1 in 100 people

• Flu-like symptoms, irritation, and inflammation of the gastrointestinal tract, antibiotic-associated gastrointestinal tract inflammation that causes diarrhea, lymphatic vessel inflammation
• Inflammation of the 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 (peripheral neuropathy)
• Problems with balance or coordination
• Brain swelling
• Double vision, serious 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 heartbeats, 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 a potentially life-threatening skin disease that causes blisters and painful sores on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, sunburn or severe skin reaction after exposure to light or sun, redness of the skin, and irritation, reddish or purplish coloration of the skin 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
• Heart rhythm or conduction problems (sometimes potentially fatal)
• 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 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 underlying skin layers
• Small, scaly, and dry patches on the skin, sometimes thick and with tips or "horns"

Adverse effects of unknown frequency (frequency cannot be estimated from available data):

• Freckles and pigmented spots

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

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

During infusion, infrequently, there have been 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 leaflet. 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 Fosun Pharma

Store below 25°C.

Keep this medicine out of the sight and reach of children.

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

Chemical and physical stability in use has been demonstrated for 24 hours between 2°C and 8°C.

From a microbiological point of view, unless the opening method excludes the risk of microbial contamination, the reconstituted solution should be used immediately. If not used immediately, the storage times and conditions are the responsibility of the user.

This reconstituted medicine must be diluted first with a compatible infusion diluent before being administered (for more information, see the end of this leaflet).

Medicines should not be disposed of via wastewater or household waste. 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 Fosun Pharma

• The active ingredient is voriconazole.
• The other component is sulfobutylether beta cyclodextrin sodium.

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

Appearance of the Product and Package Contents

Voriconazol Fosun Pharma 200 mg is presented in single-use glass vials in the form of a white lyophilized cake or powder for solution for infusion. Voriconazol Fosun Pharma 200 mg powder for solution for infusion is available in a carton box containing 1 vial.

Marketing Authorization Holder and Manufacturer

Fosun Pharma Sp. z o.o.

Zajecza 15, Warsaw (00-351), Poland

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

Austria: Voriconazol Fosun Pharma

Belgium: Voriconazol Fosun Pharma 200 mg Pulver zur Herstellung einer Infusionslösung

Voriconazol Fosun Pharma 200 mg poeder voor oplossing voor infusie

Voriconazol Fosun Pharma 200 mg poudre pour solution pour perfusion

Germany: Voriconazol Fosun Pharma 200 mg Pulver zur Herstellung einer Infusionslösung

France: Voriconazole Fosun Pharma

Italy: Voriconazolo Fosun Pharma

Netherlands: Voriconazol Fosun Pharma

Poland: Voriconazole Fosun Pharma

Portugal: Voriconazole Fosun Pharma

Spain: Voriconazol Fosun Pharma

Date of the Last Revision of this Leaflet:August 2021

Detailed 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 healthcare professionals:

Voriconazol Fosun Pharma 200 mg powder for solution for infusion:

• The powder is reconstituted with 19 ml of water for injectable preparations or with 19 ml of sodium chloride 9 mg/ml (0.9%) to obtain an extractable volume of 20 ml of clear concentrate that contains 10 mg/ml of voriconazole.
• Discard the Voriconazol Fosun Pharma vial 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 the dispensing of the exact amount (19.0 ml) of water for injectable preparations or sodium chloride (9 mg/ml [0.9%]).
• The required volume of reconstituted concentrate is then added to a compatible infusion solution recommended from the following to obtain a final solution of this medicine that contains 0.5 to 5 mg/ml of voriconazole.
• This medicine is for single use and any unused solution should be discarded, and only clear solutions without particles should be used.
• It should not be administered as a bolus.
• Regarding storage information, see section 5 "Storage of Voriconazol Fosun Pharma”.

Volumes of Voriconazol Fosun Pharma 200 mg Concentrate 10 mg/ml Required

Voriconazol Fosun Pharma is a sterile, preservative-free, single-dose lyophilized powder.

Therefore, from a microbiological point of view, the solution should be used immediately once reconstituted. If not used immediately, the storage time and conditions 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 solution and lactated Ringer's solution for intravenous infusion

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

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 infused simultaneously with the administration of this medicine, but not in the same vein or cannula.

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