Vfend 200 mg powder for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

VFEND 200 mg powder for solution for infusion

voriconazole

Read the entire 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, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, since it could 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 the leaflet

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

1. What VFEND is and what it is used for

VFEND contains the active substance voriconazole. VFEND 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).

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

Prevention of fungal infections in recipients of allogeneic haematopoietic stem cell transplantation who are at high risk.

This medicine should only be used under medical supervision.

2. What you need to know before using VFEND

Do not use VFEND

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 remedies.

During treatment with VFEND, 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 heart arrhythmias).
• Ivabradine (used for symptoms of chronic heart failure).
• Rifampicin (used to treat tuberculosis).
• Efavirenz (used to treat 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 to treat HIV) at doses of 400 mg or higher twice daily.
• St. John’s wort (hypericum, a herbal remedy).
• 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 down the decline in 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

Talk to your doctor, pharmacist, or nurse before starting VFEND 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 VFEND. Your doctor should also monitor your liver function during treatment with VFEND by performing blood tests.
• you know you have cardiomyopathy, irregular heartbeat, slow heart rate, or an abnormality on 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 to 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 using other medicines that make the skin more sensitive to sunlight, such as methotrexate. These precautions also apply to children.

While being treated with VFEND:

• inform your doctor if you experience
• sunburn
• severe skin rash or blistering
• bone pain

If you develop skin disorders such as those described above, your doctor may refer you to a dermatologist, who may consider regular monitoring important. There is a small chance of developing skin cancer with long-term use of VFEND.

If you develop signs of “adrenal insufficiency,” in which the adrenal glands do not produce enough of certain steroid hormones, such as cortisol, which may cause symptoms such as: chronic or prolonged fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, inform your doctor.

If you experience 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, 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

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

Other medicines and VFEND

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

• Some medicines, when used at the same time as VFEND, may affect the action of VFEND or VFEND may affect the action of other medicines.

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

• Ritonavir (used to treat HIV) at a dose of 100 mg twice daily.
• Glasdegib (used to treat cancer); 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 VFEND should be avoided if possible, and a dose adjustment of voriconazole may be needed:

• Rifabutin (used to treat tuberculosis). If you are already being treated with rifabutin, your blood counts and adverse effects of rifabutin should be monitored.
• Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin, the concentration of phenytoin in your blood should be monitored during treatment with VFEND, 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 ensure these medicines and/or VFEND are still effective:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; used to reduce blood clotting).
• Cyclosporine (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 to treat stomach ulcers).
• Oral contraceptives (if you use VFEND 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 VFEND).
• 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 to treat bacterial infections).

Pregnancy and breastfeeding

You must not use VFEND during pregnancy unless instructed by your doctor. Women of childbearing potential being treated with VFEND should use effective contraception. Contact your doctor immediately if you become pregnant while taking VFEND.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

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

VFEND contains sodium

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

VFEND contains cyclodextrin

This medicine contains 3,200 mg of cyclodextrin in each 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 VFEND

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

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

Your doctor may 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.

VFEND powder for solution for infusion must be reconstituted and diluted to the correct concentration by pharmacy or nursing staff at the hospital (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 for 1 to 3 hours.

If you or your child are taking VFEND for prevention of fungal infections, your doctor may discontinue VFEND administration if you or your child experience adverse reactions related to treatment.

If you forget a dose of VFEND

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

If you stop treatment with VFEND

Treatment with VFEND should be maintained for as long as your doctor considers appropriate. However, the duration of treatment with VFEND powder for solution for infusion 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, intravenous infusion may be replaced with tablets.

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

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 do 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 VFEND and contact your doctor immediately

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

Other adverse effects

Very common: may affect more than 1 in 10 people

• Visual disturbance (changes in vision such as blurred vision, color vision disturbances, abnormal intolerance to visual perception of light, color blindness, eye disorder, visual halos, night blindness, oscillating vision, seeing sparks, visual aura, decreased visual acuity, reduced visual clarity, partial loss of normal 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.
• Heart rhythm problems 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 swelling.
• Jaundice (yellowing of the skin), liver inflammation, and liver damage.
• Skin rashes, which may become severe with blistering and peeling, characterized by flat red areas covered with small merging bumps, skin redness.
• Itching.
• Alopecia (hair loss).
• Back pain.
• Kidney failure, presence of blood in urine, abnormalities in kidney function tests.
• Sunburn or severe skin reaction after exposure to light or sun.
• 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.
• Reduced adrenal gland function, underactive thyroid gland.
• Abnormal brain function, symptoms resembling Parkinson’s disease, 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.
• Reduced sensitivity to touch.
• Disturbance of taste sensation.
• Hearing difficulty, ringing in the ears (tinnitus), vertigo.
• Inflammation of certain internal organs, pancreas and duodenum, tongue swelling and inflammation.
• Liver enlargement, 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 potentially life-threatening skin disease causing blisters and painful sores on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, skin redness and irritation, red or purple skin discoloration possibly due to low platelet count, eczema.
• Reaction at the infusion site.
• Allergic reaction or exaggerated immune response.
• Inflammation of 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, itchy and painful thickened red skin plaques with silvery scales, skin and mucous membrane irritation, potentially life-threatening skin disease causing large portions of the epidermis (the outermost skin layer) to detach from underlying skin layers.
• Small scaly, dry skin patches, sometimes thick with tips or "horns".

Adverse effects with unknown frequency:

• Freckles and pigmented spots.

Other important adverse effects with unknown frequency, which must be reported to your doctor immediately:

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

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

Since VFEND 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 appear different.

Cases of skin cancer have been reported in patients treated with VFEND for prolonged periods.

The frequency of sunburn or severe skin reactions after exposure to light or sun 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 follow-up is necessary. Elevated liver enzymes were also observed more frequently in children.

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

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect 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 VFEND

Keep this medicine out of 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.

After reconstitution, VFEND must be used immediately, although if necessary, it may be stored for up to 24 hours at 2°C - 8°C (in a refrigerator). Reconstituted VFEND must first be diluted with a compatible infusion diluent before infusion. (For further information, see the end of this leaflet).

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

6. Contents of the container and other information

Composition of VFEND

• The active substance is voriconazole.
• The other component is sodium sulfobutylether beta-cyclodextrin (see section 2; VFEND 200 mg powder for solution for infusion contains cyclodextrin and sodium).

Each vial contains 200 mg of voriconazole, which corresponds to a 10 mg/ml concentrated solution 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 container

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

Marketing Authorization Holder and Manufacturer

Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Brussels, Belgium.

Manufacturer

Fareva Amboise, Zone Industrielle, 29 route des Industries, 37530 Pocé-sur-Cisse, France.

For more information about this medicine, you may contact the local representative of the Marketing Authorization Holder:

Date of the most recent approval of this summary: 09/2023.

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

The following information is intended for healthcare professionals only:

Information on reconstitution and dilution

• VFEND powder for concentrate for solution for infusion 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 VFEND vial if the vacuum prevents the solvent from entering the vial.
• A standard 20 ml syringe (non-automatic) is recommended 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 VFEND solution containing 0.5 to 5 mg/ml of voriconazole.
• This medicinal product is for single use only, and any unused solution must be discarded; only clear solutions free from particles should be used.
• Must not be administered as an intravenous bolus.
• For information on storage, see section 5 “Storage of VFEND”.

Required volumes of VFEND concentrate 10 mg/ml

VFEND is a sterile, single-dose lyophilized product 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 at 2–8°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 9 mg/ml (0.9%) injection solution
• Compound sodium lactate intravenous infusion
• 5% glucose and Ringer's lactate intravenous infusion
• 5% glucose with 0.45% sodium chloride intravenous infusion
• 5% glucose intravenous infusion
• 5% glucose with 20 mEq potassium chloride intravenous infusion
• 0.45% sodium chloride intravenous infusion
• 5% glucose with 0.9% sodium chloride intravenous infusion

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

Incompatibilities:

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

Concomitant infusion of blood products must not be administered simultaneously with VFEND.

Total parenteral nutrition may be administered simultaneously with VFEND, but not through the same line or catheter.

VFEND must not be diluted with 4.2% sodium bicarbonate solution.