Voriconazole Sala 200 mg powder for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Voriconazole Sala 200 mg powder for solution for infusion EFG

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

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

Contents of this leaflet

1. What Voriconazole Sala 200 mg powder for solution for infusion is and what it is used for
2. What you need to know before using Voriconazole Sala 200 mg powder for solution for infusion
3. How to use Voriconazole Sala 200 mg powder for solution for infusion
4. Possible side effects
5. How to store Voriconazole Sala 200 mg powder for solution for infusion
6. Contents of the pack and other information

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

This medicine contains the active substance voriconazole. Voriconazole is an antifungal medicine. It works by killing or stopping the growth of fungi that cause infections.

It is used to treat patients (adults and children aged 2 years and older) with:

• invasive aspergillosis (a type of fungal infection caused by Aspergillus sp.),
• candidaemia (another type of fungal infection caused by Candida sp.) in non-neutropenic patients (patients who do not have an abnormally low white blood cell count),
• serious invasive infections caused by Candida sp., when the fungus is resistant to fluconazole (another antifungal medicine),
• serious fungal infections caused by Scedosporium sp. or Fusarium sp. (two different species of fungi).

This medicine is used in patients with serious fungal infections that may be life-threatening.

Prevention of fungal infections in haematopoietic stem cell transplant recipients at high risk.

This medicine should only be used under medical supervision.

2. What you need to know before using Voriconazole Sala 200 mg powder for solution for infusion

Do not use this medicine:

• if you are allergic to voriconazole or to sulfobutylether beta-cyclodextrin sodium (included in section 6).

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

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

• Terfenadine (used for allergies).
• Astemizole (used for allergies).
• Cisapride (used for digestive problems).
• Pimozide (used for mental disorders).
• Quinidine (used for cardiac arrhythmias).
• 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 or higher 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 transplant patients).
• Ritonavir (used for the treatment of HIV) at doses of 400 mg or higher twice daily.
• St. John’s wort (hypericum, herbal medicine).
• Naloxegol (used to treat constipation specifically caused by painkillers called opioids [e.g., morphine, oxycodone, fentanyl, tramadol, codeine]).
• Tolvaptan (used to treat hyponatremia [low sodium levels in blood] or to slow the decline in 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

Talk to your doctor, pharmacist, or nurse before starting this medicine if:

• you have had an allergic reaction to other azoles.
• you have or have previously 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 during treatment with this medicine by performing blood tests.
• you know you have cardiomyopathy, irregular heartbeat, slow heart rate, or an abnormality on the electrocardiogram (ECG) known as “prolonged QTc syndrome”.

You should avoid any exposure to sunlight and UV light during treatment. It is important to cover exposed areas and use sunscreen with a high sun protection factor (SPF), as your skin may become more sensitive to UV rays from the sun. This sensitivity may be further increased by the use of other medicines that make the skin sensitive to sunlight, such as methotrexate. These precautions also apply to children.

While being treated with this medicine, inform your doctor if you experience:

• sunburn
• severe skin rash or blisters
• bone pain

If you develop skin disorders as described above, your doctor may refer you to a dermatologist, who may consider it important for you to have regular check-ups. There is a small chance 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 sufficient amounts of certain steroid hormones, such as cortisol, which may cause symptoms such as: prolonged or chronic fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, inform your doctor.

If you develop signs of “Cushing's syndrome”, in which the body produces too much cortisol hormone, which may cause symptoms such as: weight gain, fatty hump 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 excessive sweating, inform your doctor.

Your doctor should monitor the function of your liver and kidneys by performing blood tests.

Children and adolescents

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

Using voriconazole with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Some medicines, when used at the same time as voriconazole, may affect the action of this medicine or voriconazole may affect the action of other medicines.

Inform your doctor if you are taking the following medicines, as concomitant treatment with voriconazole should be avoided if possible:

• Ritonavir (used for the treatment of HIV) at a dose of 100 mg twice daily.
• Glasdegib (used for cancer treatment); if you need to take both medicines, your doctor will frequently monitor your heart rhythm.

Inform your doctor if you are taking any of the following medicines, as concomitant treatment with this medicine should be avoided as much as possible, and a dose adjustment of voriconazole may be needed:

• Rifabutin (used for the treatment of tuberculosis). If you are already being treated with rifabutin, your blood count and adverse effects of rifabutin will need to be monitored.
• Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin, the concentration of phenytoin in your blood will need to be monitored during treatment with this medicine, and your dose may need to be adjusted.

Inform your doctor if you are taking any of the following medicines, as you may need a dose adjustment or monitoring to ensure these medicines and/or voriconazole continue to have the desired effect:

• Warfarin and other anticoagulants (e.g.: phenprocoumon, acenocoumarol; used to reduce blood clotting).
• Ciclosporin (used in transplant patients).
• Tacrolimus (used in transplant patients).
• Sulfonylureas (e.g.: tolbutamide, glipizide, glyburide) (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 this medicine while taking oral contraceptives, you may experience adverse effects such as nausea and menstrual disorders).
• Vinca alkaloids (e.g.: vincristine, vinblastine) (used to treat cancer).
• Indinavir and other HIV protease inhibitors (used to treat HIV infection).
• Tyrosine kinase inhibitors (e.g., axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (used to treat cancer).
• Tretinoin (used to treat leukemia).
• Non-nucleoside reverse transcriptase inhibitors (e.g.: efavirenz, delavirdine, nevirapine) (used to treat HIV infection) (some doses of efavirenz must NOT be taken at the same time as this medicine).
• Methadone (used to treat heroin addiction).
• Alfentanil, fentanyl, and other short-acting opioids such as sufentanil (analgesics used during surgery).
• 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 transplant patients).
• Letermovir (used to prevent cytomegalovirus [CMV] infection after bone marrow transplant).
• Ivacaftor: used to treat cystic fibrosis.
• Flucloxacillin (an antibiotic used against bacterial infections).

Pregnancy and breast-feeding

Do not use this medicine during pregnancy unless instructed by your doctor. Women of childbearing age being treated with this medicine 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 become pregnant, consult your doctor or pharmacist 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 operate tools or machinery, and inform your doctor.

This medicine contains sodium

This medicine contains 220.8 mg of sodium (the main component of table/cooking salt) per vial. This corresponds to 11% of the maximum daily recommended sodium intake for an adult.

This medicine contains cyclodextrin

This medicine contains 3,200 mg of cyclodextrin per vial, equivalent to 160 mg/ml when reconstituted in 20 ml. If you have renal impairment, consult your doctor before taking this medicine.

3. How to use Voriconazol Sala 200 mg powder for solution for infusion

Follow exactly the instructions given by your doctor for administering this medicine. If in doubt, consult your doctor or pharmacist again.

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

Your doctor may adjust your dose depending on your condition.

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.

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 taking this medicine to prevent fungal infections, your doctor may stop the administration of voriconazole if you or your child experience adverse effects related to treatment.

If you miss a dose of Voriconazol Sala 200 mg powder for solution for infusion

Since you will be receiving this medicine under close medical supervision, it is unlikely that you will miss a dose. However, inform your doctor or pharmacist if you think you have missed a dose.

If you stop treatment with Voriconazol Sala 200 mg powder for solution for infusion

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

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

When your doctor discontinues treatment with this medicine, you should not experience any effects due to stopping.

If you have any further questions about 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 everyone will experience them. If they occur, they are most likely to be mild and temporary. However, some may be serious and require immediate medical attention.

Serious adverse effects – Stop using this medicine and contact your doctor immediately

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

Other adverse effects

Very common: may affect more than 1 in 10 people

• Visual disturbances (changes in vision such as blurred vision, color vision disturbances, abnormal sensitivity to light, color blindness, eye disorders, visual halos, night blindness, oscillating vision, seeing sparks, visual aura, decreased visual acuity, reduced 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.

Common: may affect up to 1 in 10 people

• Sinusitis, gum inflammation, chills, weakness.
• Low blood cell counts, including severe cases, of certain types of red blood cells (sometimes immune-mediated) or white blood cells (sometimes accompanied by fever), low platelet count affecting blood clotting.
• 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, drowsiness, dizziness.
• Ocular hemorrhage.
• Problems with heart rhythm including very fast heartbeat, very slow heartbeat, fainting.
• Hypotension, inflammation of veins (which may be associated with blood clot formation).
• Acute breathing difficulty, chest pain, facial swelling (mouth, lips, and around the eyes), fluid accumulation in the lungs.
• Constipation, indigestion, lip inflammation.
• Jaundice (yellowing of the skin), liver inflammation, and liver damage.
• Skin rashes, which may become severe, with blisters and peeling characterized by flat, red areas covered with small merging bumps, skin redness.
• Itching.
• Alopecia.
• Back pain.
• Kidney failure, presence of blood in urine, abnormalities in tests monitoring kidney function.
• Sunburn or severe skin reaction after exposure to light or sunlight.
• Skin cancer.

Uncommon: may affect up to 1 in 100 people

• Flu-like symptoms, irritation and inflammation of the gastrointestinal tract, gastrointestinal inflammation causing antibiotic-associated diarrhea, inflammation of lymphatic vessels.

• Inflammation of the thin tissue lining the abdominal wall and covering abdominal organs.

• Enlargement (sometimes painful) of lymph nodes, bone marrow failure, increased eosinophils.

• Decreased adrenal gland function, underactive thyroid gland.

• Abnormal brain function, Parkinson-like symptoms, nerve damage causing numbness, pain, tingling, or burning sensations in hands or feet.

• Problems with balance or coordination.

• Brain swelling.

• Double vision, serious eye disorders such as eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage causing vision disturbances, optic disc inflammation.

• Decreased sensitivity to touch.

• Disturbance of taste sensation.

• Hearing difficulty, ringing in the ears, 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 veins under the skin (which may be associated with blood clot formation).

• Kidney inflammation, protein in urine, kidney damage.

• Very high heart rate or extrasystoles, sometimes with erratic electrical impulses.

• Abnormal electrocardiogram (ECG).

• Elevated blood cholesterol, elevated blood urea.

• Skin allergic reactions (sometimes severe), such as skin disorders, potentially life-threatening conditions causing blisters and painful sores on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, skin redness and irritation, reddish or purplish skin discoloration possibly due to low platelet count, eczema.

• Reaction at the infusion site.

• Allergic reaction or exaggerated immune response.

• Inflammation of the tissue surrounding the bone.

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

• Overactive thyroid gland.
• Deterioration of brain function as a serious complication of liver disease.
• Loss of most of the optic nerve fibers, corneal opacity, involuntary eye movements.
• Blister formation 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.
• Blood clotting disorders.
• Skin allergic reactions (sometimes severe), such as rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa, and submucosal layers, painful and itchy thickened and reddened skin plaques with silvery scales, skin and mucous membrane irritation, potentially life-threatening skin disorder causing large portions of the epidermis, the outermost skin layer, to detach from underlying skin layers.
• Small scaly and dry skin patches, sometimes thick with tips or "horns".

Adverse effects with unknown frequency

• Freckles and pigmented spots.

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

• Scaly red patches or ring-shaped skin lesions, which may be a sign of an autoimmune disease called cutaneous lupus erythematosus.

During infusion, reactions with this medicine have occurred infrequently (including facial flushing, fever, sweating, increased heart rate, and difficulty breathing). Your doctor may interrupt the infusion if this occurs.

Since this medicine has been observed 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 an unusual consistency.

Cases of skin cancer have been reported in patients treated with this medicine over long periods.

The frequency of sunburns or severe skin reactions after exposure to light or sunlight was higher in children. If you or your child develop skin disorders, your doctor may refer you to a dermatologist who, after evaluation, may decide that regular monitoring is necessary. Increased 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 they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Voriconazole Sandoz 200 mg powder for solution for infusion

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

Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of the month indicated.

Once reconstituted, this medicine must be used immediately, although if necessary, it may be stored for up to 24 hours at 2°C – 8°C (in a refrigerator). The reconstituted medicine must first be diluted with a compatible infusion diluent before administration. (For further 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 medicines and containers you no longer need. This will help protect the environment.

6. Contents of the package and other information

Composition of Voriconazole Sala 200 mg powder for solution for infusion

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

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

Presentation of the product and contents of the pack

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

Marketing Authorization Holder and Manufacturer

Laboratorio Reig Jofre, S.A.

Gran Capitán, 10 – 08970
Sant Joan Despí, Barcelona
Spain

Date of the most recent review of this leaflet: January 2024

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS): http://www.aemps.gob.es.

This information is intended for healthcare professionals only:

Information on reconstitution and dilution

• This medicine must be reconstituted with 19 ml of water for injections or 19 ml of sodium chloride 9 mg/ml (0.9%) for infusion to obtain an extractable volume of 20 ml of a clear concentrate containing 10 mg/ml of voriconazole.

• Discard the 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 (non-automatic) to ensure the exact amount (19.0 ml) of water for injections 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 this medicine containing 0.5 to 5 mg/ml of voriconazole.

• This medicinal product is for single use only; any unused solution must be discarded, and only clear solutions free from particles should be used.
• It must not be administered as an intravenous bolus.
• For information on storage, see section 5 “Storage of Voriconazole Sala 200 mg powder for solution for infusion”.

Required volumes of Voriconazole Sala 200 mg concentrate 10 mg/ml

This medicine is a sterile, single-dose lyophilized preparation without preservatives. Therefore, from a microbiological standpoint, the solution should be used immediately after reconstitution. If not used immediately, the time and storage conditions prior to use are the responsibility of the user and the solution should be stored between 2 and 8°C for a maximum of 24 hours, unless reconstitution has been carried out under controlled and validated aseptic conditions.

Compatible infusion solutions:

The reconstituted solution may be diluted with:

• Sodium chloride 0.9%
• Lactated Ringer's solution at concentrations of 0.5 mg/ml and 5 mg/ml
• 5% dextrose solution and lactated Ringer's solution at concentrations of 0.5 mg/ml and 5 mg/ml
• 5% dextrose solution with 0.45% sodium chloride at concentrations of 0.5 mg/ml and 5 mg/ml
• 5% dextrose solution at concentrations of 0.5 mg/ml and 5 mg/ml
• 5% dextrose solution with 20 mEq potassium chloride at concentrations of 0.5 mg/ml and 5 mg/ml
• 0.45% sodium chloride solution at concentrations of 0.5 mg/ml and 5 mg/ml
• 5% dextrose solution with 0.9% sodium chloride at concentrations of 0.5 mg/ml and 5 mg/ml

The compatibility of voriconazole with diluents other than those specifically listed above (or those listed below under "Incompatibilities") is unknown.

Incompatibilities:

This medicine must not be infused through the same line or cannula simultaneously with other drug infusions, including parenteral nutrition (e.g., Aminofusin 10% Plus).

Hemoderivatives must not be infused simultaneously during administration of this medicine.

Total parenteral nutrition infusion may be administered simultaneously with this medicine, but not through the same line or cannula.

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