Label: information for the user

Voriconazol Seacross200 mg powder for solution for infusion EFG

Read this label carefully before starting to use this medicine, because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed to you alone, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section 4.

Voriconazol Seacross 200 mg powder for solution for infusion contains the active ingredient voriconazol. Voriconazol is an antifungal medication. It acts by eliminating or preventing the growth of fungi that cause infections.

It is used for the treatment of patients (adults and children 2 years of age or older) with:

• invasive aspergillosis (a type of fungal infection produced byAspergillus sp),
• candidemia (another type of fungal infection produced byCandida sp) in non-neutropenic patients (patients who do not have an abnormally low white blood cell count),
• serious invasive infections produced byCandida sp., when the fungus is resistant to fluconazol (another antifungal medication),
• serious fungal infections produced byScedosporium sp.or byFusarium sp.(two different species of fungi).

Voriconazol is used in patients with serious fungal infections that may put their lives at risk.

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

This medication must be used only under medical supervision.

No use Voriconazol Seacross

• If you are allergic to the active ingredient voriconazole or to sodium sulfobutylether beta-cyclodextrin (included in section 6).

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

During treatment with voriconazole, 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 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 (herbal remedy).
• Naloxegol (used to treat constipation caused specifically by 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 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 voriconazole. Your doctor should also monitor your liver function while you are taking voriconazole by performing blood tests.
• You know you have heart disease, irregular heartbeats, slow heart rate, or an electrocardiogram (ECG) anomaly called "prolonged QTc syndrome."

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 be more sensitive to UV rays from the sun. This sensitivity may be increased even more by the use of other medications that sensitize the skin to sunlight, such as methotrexate. These precautions also apply to children.

While taking voriconazole:

• Inform your doctor immediately if you develop:
• • Sunburn
  • Severe skin rash or blisters
  • Bone pain

If you develop skin problems like 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 chance that you may develop skin cancer with long-term use of voriconazole.

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 like: 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 like: 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, excessive hair growth or sweating, inform your doctor.

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

Children and adolescents

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

Other medications and Voriconazol Seacross

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

Some medications, when used at the same time as voriconazole, may affect the action of voriconazole or vice versa.

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

• 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 your phenytoin blood levels during your treatment with voriconazole 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 monitor to ensure that these medications and/or voriconazole 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 to treat 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 are using voriconazole while taking oral contraceptives, you may experience side effects such as nausea and menstrual disorders).
• Vincristine and vinblastine alkaloids (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 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 surgical procedures).
• Oxycodone and other long-acting opioids (e.g., 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 this medication during pregnancy unless your doctor indicates it. Women of childbearing age taking voriconazole 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

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

Voriconazol Seacross contains sodium

This medication contains 221 mg of sodium (main component of table salt/for cooking) per vial. This is equivalent to 11% of the recommended daily maximum sodium intake for an adult.

Voriconazol Seacross 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 renal insufficiency, 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 again.

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

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

If you take more Voriconazole Seacross than you should

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

If you forgot a dose of Voriconazole Seacross

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 Seacross

Treatment with voriconazole should be continued for as long as your doctor considers necessary, however, 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, the intravenous infusion may be replaced with oral tablets.

When your doctor stops treatment with voriconazole, you should not experience any effects resulting from 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 of the side effects occur, it is likely to be mild and temporary. However, some may be serious and require medical attention.

Severe side effects - Stop using voriconazole and seek medical attention immediately

• Skin rash.
• Jaundice, liver function test abnormalities.
• 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 disorders, halo vision, night blindness, oscillating vision, spark vision, visual aura, decreased visual acuity, visual clarity, partial loss of the 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 blood cells (occasionally of an immunological nature) and/or white blood cells (occasionally accompanied by fever) 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, drowsiness, 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, lip inflammation.
• Jaundice, 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, presence of blood in urine, renal function test abnormalities.
• 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 and inflammation, gastrointestinal tract inflammation that causes diarrhea associated with antibiotics, lymphatic vessel inflammation.
• Peritoneal inflammation, the thin tissue that lines the inner wall of the abdomen and covers the abdominal organs.
• Enlargement (occasionally 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.
• Balance or coordination problems.
• Brain swelling.
• Dual vision, severe eye diseases, such as: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage that causes 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, swelling and inflammation of the tongue.
• Enlarged 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 urine, kidney damage.
• Very high heart rate or extrasystoles, occasionally with erratic electrical impulses.
• Abnormal electrocardiogram (ECG).
• Elevated blood cholesterol, elevated blood urea.
• Severe skin reactions (occasionally life-threatening) such as skin disease, potentially fatal that causes blisters and painful 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.
• Severe allergic reaction or excessive immune response.
• Inflammation of the tissue surrounding the bone.

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

• Hyperactive thyroid gland.
• Severe brain activity deterioration as a complication of liver disease.
• Loss of most of the optic nerve fibers, corneal opacity, involuntary eye movements.
• Blister formation due to photosensitivity.
• Disease in which the immune system attacks part of the peripheral nervous system.
• Cardiac rhythm problems or conduction problems (occasionally potentially fatal).
• Potentially life-threatening allergic reaction.
• Blood coagulation abnormalities.
• Severe skin reactions (occasionally life-threatening) such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, pruritic and painful skin plaques with 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 beneath it.
• Small, scaly, and dry skin patches, occasionally thick and with points or "horns".

Side effects with unknown frequency:

• Moles and pigmented spots.

Other important side effects whose frequency is unknown, but which should be reported to the 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 with voriconazole (including facial redness, fever, sweating, increased heart rate, and difficulty breathing). The doctor may interrupt the perfusion if this happens.

Since voriconazole 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 voriconazole 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. Elevated liver enzymes were also observed more frequently in children.

If any of these side effects persist or are bothersome, report them to 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 the Spanish System for the 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 medication must be used immediately, although, if necessary, it can be stored for up to 24 hours between 2?- 8?(in a 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).

Medications should not be thrown down the drains or into thewaste. Ask your pharmacist how to dispose of the containers and medications that you no longer need. By doing so, you will help protect the environment.

Composition of Voriconazole Seacross

• The active principle is voriconazole.
• The other component is sodium sulfobutyl ether beta-cyclodextrin (see section 2, Voriconazole Seacross contains cyclodextrin and sodium).

Each vial contains 200 mg of voriconazole, which is equivalent to a solution of 10 mg/ml once reconstituted following the instructions given 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

Voriconazole Seacross is presented as a lyophilized sterile powder for solution for infusion in glass vials for single use.

Marketing Authorization Holder and Responsible Manufacturer

Seacross Pharma (Europe) Limited

POD 13, The Old Station House

15A Main Street, Blackrock

Dublin, A94 T8P8

Ireland

Local Representative

Pharmavic Ibérica, S.L.

C/ Compositor Lehmberg Ruiz

6 Edificio Ibiza, Office 7

29007 Málaga, (Spain)

Tel: 676295501

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

Date of the last review of this leaflet:June 2024

Further information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

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This information is intended solely for healthcare professionals:

Information on reconstitution and dilution

• Voriconazole Seacross powder for solution for infusion must 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 clear, transparent concentrate containing 10 mg/ml of voriconazole.
• Discard the vial of this medicinal product 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%) for infusion is dispensed.
• The required volume of reconstituted concentrate is then added to one of the following compatible infusion solutions to obtain a final solution of this medicinal product containing 0.5 to 5 mg/ml of voriconazole.
• This specialty is for single use only and any unused solution must be discarded and only clear, particle-free solutions should be used.
• It must not be administered as a bolus.
• Regarding the information on conservation, see section 5 “Conservation of Voriconazole Seacross”.

Volumes of Voriconazole Seacross concentrate 10 mg/ml required

Voriconazole Seacross is a sterile, preservative-free, single-dose lyophilized powder. From a microbiological point of view, the solution must be used immediately once reconstituted. If not used immediately, the time and conditions of conservation before use are the responsibility of the user, and it must be kept between 2 and 8°C for a maximum period of 24 hours unless the reconstitution has been carried out in controlled, validated aseptic conditions.

After reconstitution:It has been demonstrated that the chemical and physical stability in use is 24 hours between 2°C and 8°C.

After dilution:It has been demonstrated that the chemical and physical stability in use is 7 days between 2°C and 8°C and 72 hours at 25°C.

Compatible infusion solutions:

The reconstituted solution can be diluted with:

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

Intravenous infusion of lactate sodium compound

Glucose 5% and Ringer lactate infusion solution

Glucose 5% and sodium chloride 0.45% for intravenous infusion

Glucose 5% for intravenous infusion

Glucose 5% in 20 mEq of potassium chloride for intravenous infusion

Sodium chloride 0.45% for intravenous infusion

Glucose 5% and sodium chloride 0.9% for intravenous infusion

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

Incompatibilities:

This medicinal product must not be infused in the same vein or cannula simultaneously with other infusions of drugs, including parenteral nutrition (e.g. Aminofusin 10% Plus).

Simultaneous infusion of blood derivatives must not be performed with the administration of voriconazole.

Parenteral nutrition can be infused simultaneously with the administration of voriconazole, but not in the same vein or cannula.

This medicinal product must not be diluted with sodium bicarbonate solution 4.2%.