Voriconazole Normon 200 mg powder for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Voriconazole Normon 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 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 this leaflet

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

1. What Voriconazol Normon is and what it is used for

Voriconazol Normon contains the active substance voriconazole. Voriconazol Normon 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).

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

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

This medicine should only be used under medical supervision.

2. What you need to know before starting to use Voriconazol Normon

Do not use Voriconazol Normon

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

It is very important that you inform your doctor, pharmacist, or nurse if you are currently using, or have recently used, other medicines—including those obtained without a prescription—or medicinal herbs.

During treatment with this medicine, 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 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 perforatum, a medicinal herb).
• Naloxegol (used to treat constipation specifically caused by painkillers known as 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 for the treatment of patients with chronic lymphocytic leukemia [CLL]).

Warnings and precautions

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

• have ever had an allergic reaction to other azoles.
• have or have ever had liver disease. If you have liver disease, your doctor may prescribe a lower dose of voriconazol. Your doctor should also monitor your liver function during treatment with voriconazol by performing blood tests.
• know that you have cardiomyopathy, irregular heartbeats, 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 skin and to use sunscreen with a high sun protection factor (SPF), as your skin may become more sensitive to UV radiation from sunlight. These precautions also apply to children.

Contact your doctor immediately if you experience any of the following symptoms while taking this medicine:

• 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 necessary. There is a small risk of developing skin cancer with long-term use of voriconazol.

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 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 levels, excessive hair growth, or excessive sweating, inform your doctor.

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

Children and adolescents

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

Other medicines and Voriconazol Normon

Inform 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 voriconazol, may affect the action of voriconazol, or voriconazol may affect the action of other medicines.

Inform your doctor if you are using the following medicines, as concomitant treatment with voriconazol 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 using any of the following medicines, as concomitant treatment with voriconazol should be avoided if possible, and a dose adjustment of voriconazol may be required:

• Rifabutin (used for the treatment of tuberculosis). If you are already being treated with rifabutin, your blood count 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 voriconazol, 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 that these medicines and/or voriconazol remain effective:

• 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 voriconazol 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 cannot be taken simultaneously with voriconazol).
• 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

Do not use this medicine during pregnancy unless instructed by your doctor. Women of childbearing age receiving Voriconazol Normon must use effective contraception. Contact your doctor immediately if you become pregnant while being treated with this medicine.

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

Voriconazol Normon 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.

Voriconazol Normon contains sodium

This medicine contains 35.38 mg of sodium (a main component of table/cooking salt) per vial. This corresponds to 1.76% of the maximum daily sodium intake recommended for an adult.

Voriconazol Normon contains cyclodextrins

This medicine contains 3200 mg of hydroxypropylbetadex per vial, equivalent to 160 mg/ml in the solution reconstituted with 20 ml.

Do not use in children under 2 years of age unless recommended by your doctor.

If you have renal impairment, consult your doctor before taking this medicine.

3. How to use Voriconazol Normon

Follow exactly the instructions for use of this medicine given by your doctor or pharmacist. 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 according to 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 section 5 and 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 administration if you or your child experience treatment-related adverse effects.

If you forget to use Voriconazol Normon

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

If you stop treatment with Voriconazol Normon

Treatment with this medicine should be maintained for as long as your doctor considers appropriate; however, treatment duration 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 by tablet administration.

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

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 experiences them.

If any occur, they are most likely to be mild and transient. 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 adverse effects (may affect more than 1 in 10 people):

• Visual disturbances (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 extremities.
• Stomach pain.
• Difficulty breathing.
• Elevated liver enzymes.

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

• Sinusitis, gum inflammation, chills, weakness.
• Low blood 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.
• Allergic reaction or exaggerated immune response.
• 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 rapid 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.

Uncommon adverse effects (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 the 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 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.
  • Altered sense of taste.
  • Hearing difficulty, ringing in the ears, 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, sunburn or severe skin reaction after exposure to light or sun, skin redness and irritation, reddish or purplish skin discoloration possibly caused by low platelet count, eczema.
  • Reaction at the infusion site.

Rare adverse effects (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 abnormalities.
• 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 whose frequency is unknown, but which must be reported to your doctor immediately:

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

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

Since voriconazole 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 voriconazole over long periods.

The frequency of sunburns 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 monitoring is necessary. 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 not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaRAM.es/. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Voriconazol Normon

Store below 25 °C.

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

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

After reconstitution, Voriconazol Normon should be used immediately; however, if necessary, it may be stored for up to 24 hours between 2 °C and 8 °C (in a refrigerator). Reconstituted Voriconazol Normon must first be diluted with a compatible infusion diluent before being administered by 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 need. This will help protect the environment.

6. Package contents and other information

Composition of Voriconazol Normon

• The active substance is voriconazole.
• The other components are hydroxypropylbetadex and sodium chloride.

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

Appearance of the product and contents of the pack

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

Marketing Authorisation Holder and Manufacturer

LABORATORIOS NORMON, S.A.
Ronda de Valdecarrizo, 6
28760, Tres Cantos – Madrid (Spain)

Date of the most recent review of this leaflet: May 2023

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

You can access detailed information about this medicine by scanning with your mobile phone (smartphone) the QR code included in the package leaflet and outer packaging. You can also access this information at the following internet address: https://cima.aemps.es/cima/dochtml/p/80941/P_80941.html

The following information is intended for medical and healthcare professionals only:

Information on reconstitution and dilution:

• Voriconazol Normon powder 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 clear concentrate containing 10 mg/ml of voriconazole.
• Discard the vial of Voriconazol Normon if the vacuum does not allow the solvent to be introduced into the vial.
• The use of a standard 20 ml syringe (non-automatic) is recommended to ensure the exact volume (19.0 ml) of water for injections or sodium chloride 9 mg/ml (0.9%) is used.
• The required volume of reconstituted concentrate is then added to a compatible infusion solution listed below, to obtain a final solution of Voriconazol Normon containing 0.5 to 5 mg/ml of voriconazole.
• This medicine is for single use only, and any unused solution must be discarded. Only clear solutions free from particles should be used.
• Do not inject as a bolus. Infuse at a maximum rate of 3 mg/kg per hour.
• For information on storage, see section 5 “Storage of Voriconazol Normon”.

Required volumes of Voriconazol Normon concentrate 10 mg/ml

This medicinal product is a sterile, single-dose lyophilisate without preservatives. Therefore, from a microbiological standpoint, the solution should be used immediately after reconstitution. If not used immediately, the storage time and conditions prior to use are the responsibility of the user and the solution should be stored between 2°C 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 9 mg/mL (0.9%) injection solution.
• Compound sodium lactate intravenous infusion.
• 5% glucose and Ringer's lactate intravenous infusion solutions.
• 5% glucose and 0.45% sodium chloride intravenous infusion solution.
• 5% glucose intravenous infusion solution.
• 5% glucose intravenous infusion solution with 20 mEq potassium chloride.
• 0.45% sodium chloride intravenous infusion solution.
• 5% glucose and 0.9% sodium chloride intravenous infusion solution.

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

Incompatibilities:

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

Hemoderivative infusions must not be administered simultaneously with Voriconazol Normon.

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

Voriconazol Normon must not be diluted with 4.2% sodium bicarbonate solution.