VORICONAZOLO 200 mg Powder For Intravenous Infusion Solution

Зміст інструкції

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

Voriconazolo hameln
200 mg powder for solution for infusion

Voriconazolo

Generic medicine

Read this leaflet carefully before you start to use this medicine because it contains important information for you.

• Keep this leaflet. 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. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What is Voriconazolo hameln and what it is used for

Voriconazolo hameln contains the active substance voriconazole. Voriconazole is an antifungal medicine.
It works by stopping the growth or killing fungi that cause infections.
It is used for the treatment of patients (adults and children over 2 years of age) suffering from:

• invasive aspergillosis (a type of fungal infection caused by Aspergillusspecies),
• candidemia (another type of fungal infection caused by Candidaspecies) in non-neutropenic patients (patients who do not have an unusually low white blood cell count),
• serious and invasive infections caused by Candidaspecies, when the fungus is resistant to fluconazole (another antifungal medicine),
• serious fungal infections caused by Scedosporiumand Fusariumspecies (two different species of fungi). Voriconazole is indicated for patients with worsening fungal infections and potentially life-threatening conditions. Prevention of fungal infections in patients undergoing high-risk bone marrow transplantation.

This product must be used only under medical supervision.

2. What you need to know before using Voriconazolo hameln

Do not use Voriconazolo hameln

• if you are allergic to voriconazole or any of the other ingredients of this medicine (listed in section 6). The medicines included in the list below should not be used during

treatment with voriconazole:

• Terfenadine (for allergies)
• Astemizole (for allergies)
• Cisapride (for stomach problems)
• Pimozide (for the treatment of mental illnesses)
• Quinidine (for irregular heartbeat)
• Ivabradine (for symptoms of chronic heart failure)
• Rifampicin (for the treatment of tuberculosis)
• Efavirenz (for the treatment of HIV) in doses of 400 mg or more once daily
• Carbamazepine (for the treatment of seizures)
• Phenobarbital (for severe insomnia and seizures)
• Ergot alkaloids (e.g., ergotamine, dihydroergotamine; for migraine)
• Sirolimus (for transplant patients)
• Ritonavir (for the treatment of HIV) in doses of 400 mg and above, twice daily
• St. John's Wort (hypericum - herbal medicine supplement)
• Naloxegol (for the treatment of constipation specifically caused by pain medications, called opioids [e.g. morphine, oxycodone, fentanyl, tramadol, codeine])
• Tolvaptan (for the treatment of hyponatremia, i.e. low sodium levels in the blood, or to slow the decline of kidney function in patients with polycystic kidney disease)
• Lurasidone (for the treatment of depression)
• Venetoclax (for the treatment of patients with chronic lymphocytic leukemia-CLL)

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking voriconazole if:

• you have had an allergic reaction to other azoles.
• you suffer from or have suffered from a liver disease. If you have liver problems, your doctor may prescribe a lower dose of voriconazole. Your doctor will need to check your liver function during treatment with voriconazole by performing blood tests.
• you know you have heart disease, an irregular heartbeat, a slowed heartbeat, or an abnormality in your electrocardiogram (ECG) called “long QT syndrome”. You should avoid any exposure to the sun and sunlight during treatment. It is important to cover exposed skin areas and use sunscreens with a high protection factor (SPF), as increased skin sensitivity to the sun’s UV rays can occur. These precautions also apply to children.

During treatment with voriconazole:

• immediately inform your doctor if you develop sunburn or severe skin reaction or blisters or bone pain. If you develop any of the skin conditions described above, your doctor may refer you to a dermatologist, who after consultation may decide that it is important to have you undergo regular visits. With prolonged use of voriconazole, there is a small risk of developing skin cancer.

If you develop signs of “adrenal insufficiency”, in which the adrenal glands do not produce
adequate amounts of certain steroid hormones such as cortisol, which can cause symptoms such as
chronic or persistent fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, inform
your doctor.
Inform your doctor if you develop signs of “Cushing’s syndrome” in which the body produces
excessive amounts of the hormone cortisol, which can cause symptoms such as weight gain,
accumulation of fat between the shoulders, a rounded face, darkening of the skin on the stomach,
thinning of thighs, breasts and arms, thinning of the skin, easy bruising, high
blood sugar levels, excessive hair growth on the body, excessive sweating.
Your doctor will need to check your liver and kidney function by performing blood tests.

Children and adolescents
Voriconazolo hameln should not be given to children under 2 years of age.

Other medicines and Voriconazolo hameln
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines.
Some medicines, when taken at the same time as voriconazole, can change the activity
of voriconazole or voriconazole can change the activity of these medicines.
Tell your doctor if you are taking the following medicine because, if possible, concomitant treatment
with voriconazole should be avoided:

• Ritonavir (for the treatment of HIV) in doses of 100 mg twice daily
• Glasdegib (for the treatment of cancer): if you need to use both drugs, your doctor will often check your heart rate

Tell your doctor if you are taking any of the following medicines because, if possible, concomitant treatment
with voriconazole should be avoided and a dose adjustment of
voriconazole may be necessary:

• Rifabutin (for the treatment of tuberculosis). If you are already being treated with rifabutin, your blood cell count and side effects to rifabutin will need to be monitored.
• Phenytoin (for the treatment of epilepsy). If you are already being treated with phenytoin, phenytoin concentrations in the blood will need to be checked during treatment with voriconazole and the dose you are taking may be adjusted.

Tell your doctor if you are taking any of the following medicines because a dose adjustment or dose monitoring may be necessary to ensure that these medicines and/or voriconazole
continue to have the desired effect:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; to slow down blood clotting)
• Cyclosporine (for transplant patients)
• Tacrolimus (for transplant patients)
• Sulfonylureas (e.g., tolbutamide, glipizide and gliburide) (for diabetes)
• Statins (e.g., atorvastatin, simvastatin) (to reduce cholesterol)
• Benzodiazepines (e.g., midazolam, triazolam) (for severe insomnia and stress)
• Omeprazole (for the treatment of ulcers)
• Oral contraceptives (if you take voriconazole during treatment with oral contraceptives, side effects such as nausea and menstrual disorders may occur)
• Vinca alkaloids (e.g., vincristine and vinblastine) (for the treatment of cancer)
• Tyrosine kinase inhibitors (e.g. axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (for the treatment of cancer)
• Tretinoin (for the treatment of leukemia)
• Indinavir and other HIV protease inhibitors (for the treatment of HIV)
• Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, nevirapine) (for the treatment of HIV) (some doses of efavirenz cannotbe taken at the same time as voriconazole)
• Methadone (for the treatment of heroin addiction)
• Alfentanil and fentanyl and other short-acting opioids such as sufentanil (pain relievers used for surgical techniques)
• Oxycodone and other long-acting opioids such as hydrocodone (used for the treatment of moderate to severe pain)
• Nonsteroidal Anti-Inflammatory Drugs (e.g., ibuprofen, diclofenac) (used for the treatment of pain and inflammation)
• Fluconazole (used to treat fungal infections)
• Everolimus (used for the treatment of advanced kidney cancer and in transplant patients)
• Letermovir (used to prevent cytomegalovirus (CMV) disease following bone marrow transplantation)
• Ivacaftor: used for the treatment of cystic fibrosis
• Flucloxacillin (antibiotic indicated in bacterial infections)

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning to become pregnant or are breastfeeding
ask your doctor or pharmacist for advice before taking this medicine.
Voriconazolo hameln should not be used during pregnancy unless indicated
by your doctor. Women of childbearing potential should use effective contraception. Contact
your doctor immediately if you become pregnant during treatment with Voriconazolo hameln.

Driving and using machines
Voriconazolo hameln can cause blurred vision or an annoying sensitivity to light. If this happens, you should not drive and should not use tools or machinery. Contact your doctor in these cases.

Voriconazolo hameln contains sodium
This medicine contains 88.74 mg of sodium (the main component of table salt) per
vial. This is equivalent to 4.44% of the recommended maximum daily intake of salt
for an adult.
Talk to your doctor or pharmacist if you need 5 or more vials per day for a prolonged
period, especially if you have been advised to follow a low-salt (sodium)
diet.

Voriconazolo hameln contains hydroxypropyl betadex
This medicine contains 2,400 mg of cyclodextrin per vial equivalent to 120 mg/ml when
reconstituted to obtain 20 ml of transparent concentrate.
If you have kidney problems, talk to your doctor before taking this medicine.

3. How to take Voriconazolo hameln

Take this medicine following exactly the instructions of your doctor. If you have any doubts, consult your
doctor.
The doctor will establish the appropriate dose for you based on your weight and the type of infection diagnosed.
The doctor may adjust the dose based on your condition.
The recommended dose for adults (including elderly patients) is as follows:
Depending on the response to treatment, your doctor may reduce the dose to 3 mg/kg twice daily.
If you suffer from mild to moderate cirrhosis, your doctor may decide to reduce the dose.

Use in children and adolescents
The recommended dose in children and adolescents is as follows:
Depending on the response to treatment, your doctor may increase or decrease the daily dose.
Voriconazolo hameln powder for solution for intravenous infusion will be reconstituted and diluted by the
pharmacist or the hospital nurse to obtain the correct concentration. (For further
The medicine will be administered to you by intravenous infusion (into a vein) at a maximum infusion rate of
3 mg/kg/h over 1 – 3 hours.
If you or your child are taking Voriconazolo hameln for the prevention of fungal infections,
your doctor may decide to discontinue the administration of Voriconazolo hameln if you or your
child should develop adverse effects related to treatment.

If you forget to use Voriconazolo hameln
Since this medicine will be administered under medical supervision, it is unlikely that a dose will be missed.
However, if you think that a dose has been forgotten, report it to your doctor or pharmacist.

If you stop taking Voriconazole hameln
Treatment with Voriconazolo hameln must continue as long as your doctor decides; however,
the duration of treatment with Voriconazolo hameln powder for solution for intravenous infusion
should not exceed 6 months.
Patients with a weakened immune system or those who have infections that are difficult to treat
may require long-term treatment to prevent the infection from returning. When your
conditions improve, you may be switched from intravenous treatment to tablets.
When treatment with Voriconazolo hameln is stopped at the doctor's decision, no effects should
occur.
If you have any doubts about the use of this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
If side effects occur, most will likely be mild and
transient. However, some may be serious and require medical attention.

Serious side effects - Stop taking Voriconazolo hameln and consult your doctor immediately:

• Skin rash
• Jaundice, changes in liver function tests
• Pancreatitis Other side effectsVery common: may affect more than 1 in 10 people
• Impaired vision (changes in vision including blurred vision, altered color vision, abnormal intolerance to the visual perception of light, color blindness, eye disorders, halo vision, night blindness, flickering vision, visual aura, reduced visual acuity, visual brightness, partial loss of visual field, spots in front of the eyes)
• Fever
• Skin rashes
• Nausea, vomiting, diarrhea
• Headache
• Swelling of the extremities
• Stomach pain
• Difficulty breathing
• Elevated liver enzymes Common: may affect up to 1 in 10 people
• Inflammation of the paranasal sinuses, inflammation of the gums, chills, fatigue
• Reduction, even severe, in the number of some types of red blood cells (sometimes immune-related) and/or white blood cells (sometimes with fever), reduction in the number of cells called platelets that help blood clotting
• Low blood sugar levels, low blood potassium levels, low blood sodium levels
• Anxiety, depression, confusion, agitation, sleep disorders, hallucinations
• Convulsions, tremor or uncontrolled muscle movements, tingling or abnormal skin sensations, increased muscle tone, drowsiness, dizziness
• Bleeding in the eye
• Heart rhythm problems including very fast heartbeat, very slow heartbeat, fainting
• Low blood pressure, inflammation of a vein (which may be associated with the formation of a blood clot)
• Acute difficulty breathing, chest pain, swelling of the face (mouth, lips and around the eyes), fluid accumulation in the lungs
• Constipation, indigestion, inflammation of the lips
• Jaundice, inflammation of the liver and liver damage
• Skin rash that may involve the formation of blisters and severe skin peeling, characterized by a flat and reddened area of skin with confluent small bumps, skin redness
• Itching
• Hair loss
• Back pain
• Kidney failure, blood in the urine, changes in kidney function tests Uncommon: may affect up to 1 in 100 people
• Flu-like symptoms, irritation and inflammation of the gastrointestinal tract, inflammation of the gastrointestinal tract that can cause antibiotic-associated diarrhea, inflammation of the lymphatic vessels
• Inflammation of the thin tissue lining the inner wall of the abdomen and covering the abdominal organ
• Enlargement of the lymph glands (sometimes painful), bone marrow failure, increased eosinophils
• Reduced function of the adrenal glands, reduced activity of the thyroid gland
• Changes in brain function, Parkinson-like symptoms, nerve damage resulting in numbness, pain, tingling or burning in the hands or feet
• Problems with balance and coordination
• Brain edema
• Double vision, serious eye conditions including: pain and inflammation of the eyes and eyelids, abnormal eye movement, damage to the optic nerve with impaired vision, swelling of the optic disc
• Reduced sensitivity to touch
• Altered taste
• Hearing disorders, ringing in the ears, dizziness
• Inflammation of some internal organs, pancreas and duodenum, swelling and inflammation of the tongue
• Enlargement of the liver, liver failure, gallbladder diseases, gallstones
• Inflammation of the joints, inflammation of the subcutaneous veins (which may be associated with the formation of blood clots)
• Inflammation of the kidneys, presence of protein in the urine, kidney damage
• Fast heart rate or missed heartbeats, sometimes with irregular electrical impulses
• Altered electrocardiogram (ECG)
• Increased blood cholesterol, increased blood urea
• Allergic skin reactions (sometimes severe) including a potentially life-threatening skin condition causing blisters and painful sores on the skin and mucous membranes, especially in the mouth, skin inflammation, hives, sunburn or severe skin reaction following exposure to light or sun, skin redness and irritation, skin discoloration red or purple which may be caused by a low platelet count, eczema
• Infusion site reaction
• Allergic reactions or exaggerated immune response Rare: may affect up to 1 in 1,000
• Hyperactive thyroid gland
• Deterioration of brain function as a serious complication of liver disease
• Loss of most of the fibers in the optic nerve, corneal opacity, involuntary eye movement
• Bullous photosensitivity
• Disorder in which the body's immune system attacks part of the peripheral nervous system
• Heart rhythm or conduction problems (sometimes fatal)
• Potentially life-threatening allergic reaction
• Disorders of the blood coagulation system
• Allergic skin reactions (sometimes severe), including rapid swelling (edema) of the dermis, subcutaneous tissue, mucous membranes and submucosal tissues, itchy or painful patches of thickened and scaly skin with silvery scales, skin irritation and mucous membranes, a potentially life-threatening skin condition causing the detachment of large areas of the epidermis (the outer layer of skin) from the underlying skin layers
• Small patches of dry, scaly skin, sometimes thick with points or ‘horns’ Side effects with frequency not known: (frequency cannot be estimated on the basis of available data):
• Freckles and pigmented spots

Other significant side effects, whose frequency is unknown but which should be reported immediately to the doctor are:

• Skin cancer
• Inflammation of the tissues surrounding the bones
• Red, scaly or ring-shaped skin lesions that may be symptoms of an

autoimmune disease called systemic lupus erythematosus
Reactions during the infusion of Voriconazolo hameln have occurred uncommonly
(including skin redness, fever, sweating, increased heart rate and shortness of breath.
If this occurs, the doctor may interrupt the infusion.
Since Voriconazolo hameln has been shown to have effects on the liver and kidneys, the doctor will need to
check liver and kidney function by performing blood tests. Inform your doctor if you have
stomach pain or if your stools have a different consistency than usual.
Cases of skin cancer have been reported in patients treated with Voriconazolo hameln for prolonged
periods.
Sunburn or a severe skin reaction following exposure to light or sun has been
reported more frequently in children. If you or your child develops skin disorders, your
doctor may have you or your child visit a dermatologist who can decide whether it is important for you or
your child to continue regular visits with the dermatologist. Elevated liver enzymes have also been
observed more frequently in children.
If any of these side effects persist or are bothersome, tell your doctor.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please tell
your doctor, pharmacist or nurse. You can also report side effects directly to
reazioni-avverse . By reporting side effects you can help provide more information
on the safety of this medicine.

5. How to store Voriconazolo hameln

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and vial after
“Expiry”. The expiry date refers to the last day of that month.
Closed vial
This medicine does not require any special storage conditions before opening.
Reconstituted and diluted product
Chemical and physical stability in use has been demonstrated for 72 hours at 25 °C and at 2 °C - 8 °C. From a
microbiological point of view, the product must be used immediately. If the product is not
used immediately, the storage times and conditions before use are
the responsibility of the user and should normally not exceed 24 hours at a temperature between
2°C and 8°C (in a refrigerator), unless the reconstitution/ dilution has been carried out in
controlled and validated aseptic conditions.
Once reconstituted Voriconazolo hameln must be diluted with a compatible diluent for
intravenous infusion before administration. (For further information see the
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Voriconazolo hameln contains

• The active ingredient is voriconazole. Each vial contains 200 mg of voriconazole. After reconstitution, each ml of solution contains 10 mg of voriconazole.
• The other ingredients are hydroxypropyl betadex, sodium chloride, hydrochloric acid, concentrates (for pH adjustment)

Description of the appearance of Voriconazolo hameln and contents of the pack
Each pack contains one vial. Voriconazolo hameln presents as a lyophilized powder
from white to off-white for solution for infusion in a transparent type I glass vial of 25 ml
with a grey type I chlorobutyl rubber stopper and an aluminium crimp cap with a red plastic flip-off seal.

Marketing Authorisation Holder
hameln pharma gmbh
Inselstraße 1
31787 Hameln
Germany

Manufacturer
Anfarm Hellas S.A.
61 Km National Road Athens Lamia
320 09 Schimatari Viotias
Greece
Pharmathen S.A.
6, Dervenakion street
Pallini 153 51 Attiki
Greece

This medicinal product is authorised in the Member States of the European Economic Area with the
following denominations:
Austria Voriconazol hameln 200 mg Pulver zur Herstellung einer Infusionslösung
Belgium Voriconazol hameln 200 mg powder for solution for infusion/Pulver zur
Herstellung einer Infusionslösung/poudre pour solution pour perfusion
Bulgaria Вориконазол hameln 200mg Прах за инфузионен разтвор
Denmark Voriconazole „hameln”
Finland Voriconazole hameln 200 mg infuusiokuiva-aine, liuosta varten
Germany Voriconazol hameln 200 mg Pulver zur Herstellung einer Infusionslösung
Ireland Voriconazole 200mg powder for solution for infusion
Italy Voriconazolo hameln
Norway Voriconazole hameln
Netherlands Voriconazol hameln 200 mg poeder voor oplossing voor infusie
Poland Voriconazole hameln
Portugal Voriconazol hameln 200 mg pó para solução para perfusão
Czech Republic Voriconazole hameln
Romania Voriconazol hameln 200 mg pulbere pentru soluţie perfuzabilă
Slovakia Voriconazole hameln 200 mg prášok na infúzny roztok
Slovenia Vorikonazol hameln 200 mg prašek za raztopino za infundiranje
Sweden Voriconazole hameln 200 mg pulver till infusionsvätska, lösning
The following information is intended exclusively for healthcare professionals:

Information on Reconstitution and Dilution

• Voriconazolo hameln powder for solution for infusion must initially be reconstituted with 19 ml of water for injections or with 19 ml of a sodium chloride 9 mg/ml (0.9 %) solution for infusion to obtain a withdrawable volume of 20 ml of a clear concentrate containing 10 mg/ml of voriconazole.
• Discard the vial of Voriconazolo hameln if the internal vacuum pressure does not allow the diluent to be drawn into the vial.
• It is recommended to use a standard 20 ml syringe (non-automatic) to ensure the administration of the exact amount of water for injections (19.0 ml) or of the sodium chloride 9 mg/ml (0.9 %) solution for infusion.
• The required volume of reconstituted concentrate is then added to one of the compatible infusion solutions listed below to obtain a final solution of Voriconazolo hameln containing 0.5 - 5 mg/ml of voriconazole.
• This medicinal product is for single use only; unused solution must be discarded and only clear solutions free from particles must be used.
• The product must not be administered as a bolus.
• For information on product storage, refer to Paragraph 5 “How to store Voriconazolo hameln”.

Required Volumes of Voriconazolo hameln Concentrate 10 mg/ml

Voriconazolo hameln is a sterile lyophilized single-dose product without preservatives. Therefore, from a
microbiological point of view, the reconstituted / diluted solution must be used immediately. If
not used immediately, the storage times in use and conditions prior to use
are the responsibility of the user and should not normally exceed 24 hours at a temperature of

• 2 – 8 °C (in refrigerator), unless the reconstitution / dilution has been carried out under controlled and validated aseptic conditions. Reconstituted Voriconazolo hameln must be diluted with a compatible infusion solution before being infused.

Compatible Infusion Solutions:
The reconstituted solution can be diluted with:
Sodium Chloride 9 mg/ml (0.9 %) Solution for Injection
Sodium Lactate Compound Solution for Intravenous Infusion
Glucose 5 % and Ringer Lactate for Intravenous Infusion
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 9mg/ml 0.9% Solution for Injection for Intravenous Infusion
The compatibility of Voriconazolo hameln with diluents other than those listed above
(or listed in the “Contraindications” section) is not known.

Contraindications:
Voriconazole hameln must not be administered through the same line or cannula with other
infusion medicines, including parenteral nutrition (e.g., Aminofusin 10 % Plus).
The infusion of blood products must not be carried out simultaneously with the administration of
Voriconazolo hameln.
The infusion of total parenteral nutrition can be carried out simultaneously with the
administration of Voriconazolo hameln, but not through the same line or cannula.
Voriconazolo hameln must not be diluted with Sodium Bicarbonate 4.2 % Infusion.

Detailed and up-to-date information on this product (checklist for healthcare
professionals and a booklet with questions and answers on phototoxicity, SCC and hepatic toxicity)
smartphone. The same information is also available at the following URL:www.hameln-
pharma.infoon the website of
[Proposed QR code location].