Voriconazole Hameln

Package leaflet: Information for the user

Voriconazole hameln

200 mg powder for solution for infusion
Voriconazole
Generic medicine
Please read all of this leaflet carefully before you start taking 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 give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effect, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

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

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

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

This product should only be used under medical supervision.

2. What you need to know before using Voriconazole hameln

Do not use Voriconazole hameln

• if you are allergic to voriconazole or to any of the other ingredients of this medicine (listed in section 6). It is very important that you inform your doctor or pharmacist if you are taking or have taken other medicines,
  including those without a prescription, or herbal medicines.
  The following medicines must 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) at doses equal to or greater than 400 mg 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) at doses of 400 mg or more twice daily

• St. John’s Wort (hypericum – a herbal supplement)

• Naloxegol (for the treatment of constipation specifically caused by pain medicines 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 in kidney function in patients with polycystic kidney disease)

• Lurasidone (for the treatment of depression)

• Finerenone (for the treatment of chronic kidney disease)

• 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 have or have had liver disease. If you have liver problems, your doctor may prescribe a lower dose of voriconazole. Your doctor will need to monitor your liver function during treatment with voriconazole by performing blood tests.
• you know you have heart disease, an irregular heartbeat, a slow heartbeat, or an abnormality on the electrocardiogram (ECG) called "long QTc syndrome".

You must avoid any exposure to sunlight and solar radiation during treatment. It is important
to cover skin areas exposed to sunlight and to use high-protection-factor sunscreens (SPF),
as increased sensitivity of the skin to UV rays from sunlight may occur. This sensitivity may be
further increased by other medicines that make the skin sensitive to sunlight, such as
methotrexate. These precautions also apply to children.
During treatment with voriconazole:

• inform your doctor immediately if you develop sunburn, severe skin reaction, 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 regular check-ups are necessary. 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 may cause symptoms such as
chronic or persistent fatigue, muscle weakness, loss of appetite, weight loss, or 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 may cause symptoms such as weight gain,
fat accumulation between the shoulders, 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 body hair growth, and excessive sweating.
Your doctor will need to monitor your liver and kidney function by performing blood tests.
Children and adolescents
Voriconazole hameln must not be administered to children under 2 years of age.
Other medicines and Voriconazole hameln
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
Some medicines, when taken together with voriconazole, may alter the activity of voriconazole, or voriconazole may alter the activity of these medicines.
Inform 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) at doses of 100 mg twice daily
• Glasdegib (for the treatment of cancer): if you need to use both medicines, your doctor will frequently monitor your heart rhythm

Inform 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, blood cell counts and rifabutin-related side effects should be closely monitored.
• Phenytoin (for the treatment of epilepsy). If you are already being treated with phenytoin, blood levels of phenytoin should be monitored during treatment with voriconazole, and your dose may need to be adjusted.

Inform your doctor if you are taking any of the following medicines because dose adjustments or monitoring may be necessary to ensure these medicines and/or voriconazole remain effective:

• Warfarin and other anticoagulants (e.g., phenprocoumon, acenocoumarol; to slow down the blood clotting process)
• Ciclosporin (for transplant patients)
• Tacrolimus (for transplant patients)
• Sulfonylureas (e.g., tolbutamide, glipizide, glibenclamide; 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 while using oral contraceptives, side effects such as nausea and menstrual disturbances may occur)
• Vinca alkaloids (e.g., vincristine, 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 must not be taken together with voriconazole)
• Methadone (for the treatment of heroin addiction)
• Alfentanil and fentanyl and other short-acting opioids such as sufentanil (analgesics used in surgical procedures)
• Oxycodone and other long-acting opioids such as hydrocodone (used for the treatment of moderate to severe pain)
• Non-Steroidal 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 renal cell carcinoma and in transplant patients)
• Letermovir (used to prevent cytomegalovirus (CMV) disease following bone marrow transplantation)
• Ivacaftor: used for the treatment of cystic fibrosis
• Flucloxacillin (an antibiotic indicated for bacterial infections)

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Voriconazole hameln must not be used during pregnancy unless specifically indicated by your doctor. Women of childbearing potential must use an effective contraceptive method. Contact your doctor immediately if you become pregnant during treatment with Voriconazole hameln.
Driving and using machines
Voriconazole hameln may cause blurred vision or increased sensitivity to light. In this case, you must not drive and must not operate tools or machinery. In such cases, contact your doctor.
Voriconazole hameln contains sodium
This medicine contains 88.74 mg of sodium (the main component of table salt) per vial. This corresponds to 4.44% of the maximum recommended daily dietary intake for an adult.
Talk to your doctor or pharmacist if you need to take 5 or more vials per day for a prolonged period, especially if you have been advised to follow a low-salt (sodium) diet.
Voriconazole hameln contains hydroxypropylbetadex
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, speak with your doctor before taking this medicine.

3. How to take Voriconazole hameln

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor.
Your doctor will determine the appropriate dose for you based on your body weight and the type of infection diagnosed.
Your doctor may adjust the dose according to 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 have 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 a pharmacist or hospital nurse to obtain the correct concentration. (For further information, see the final section of the package leaflet.)
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 is taking Voriconazolo hameln to prevent fungal infections, your doctor may decide to discontinue treatment if you or your child develops treatment-related adverse effects.

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 a dose has been missed, inform your doctor or pharmacist.

If you stop using Voriconazolo hameln
Treatment with Voriconazolo hameln must continue for as long as your doctor decides; however, the duration of treatment with Voriconazolo hameln powder for solution for intravenous infusion must not exceed 6 months.
Patients with a weakened immune system or those with difficult-to-treat infections may require long-term treatment to prevent the infection from returning. When your condition improves, treatment may be switched from intravenous to oral tablets.
When treatment with Voriconazolo hameln is discontinued on the doctor's decision, no adverse effects should occur.
If you have any doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If side effects occur, most will probably be mild and temporary. However, some may be serious and require immediate medical attention.
Serious side effects – Stop taking Voriconazole hameln and contact a doctor immediately:

• Rash
• Jaundice, changes in liver function tests
• Pancreatitis

Other side effects

Very common: may affect more than 1 in 10 people

• Visual disturbances (including blurred vision, altered colour vision, abnormal tolerance to light perception, colour blindness, eye disorders, seeing halos, night blindness, fluctuating vision, seeing sparks, visual aura, reduced visual acuity, visual brightness, partial loss of visual field, spots in front of the eyes)
• Fever
• Skin rashes
• Nausea, vomiting, diarrhoea
• Headache
• Swelling of extremities
• Stomach ache
• Difficulty breathing
• Elevated liver enzymes

Common: may affect up to 1 in 10 people

• Sinus inflammation, gum inflammation, chills, fatigue
• Reduction, sometimes severe, in the number of certain types of red blood cells (sometimes immune-mediated) and/or white blood cells (sometimes with fever), reduction in the number of platelets (blood cells that help blood clotting)
• Low blood sugar levels, low blood potassium levels, low blood sodium levels
• Anxiety, depression, confusion, agitation, sleep disorders, hallucinations
• Seizures, 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 blood clot formation)
• Acute breathing difficulty, chest pain, facial swelling (mouth, lips and around eyes), fluid accumulation in the lungs
• Constipation, indigestion, inflammation of the lips
• Jaundice, liver inflammation and liver damage
• Skin rash which may lead to severe blistering and skin peeling, characterised by flat red areas of skin with small merging bumps, skin redness
• Itching
• Hair loss
• Back pain
• Kidney failure, blood in urine, changes in kidney function tests
• Sunburn or severe skin reaction following 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 which may cause antibiotic-associated diarrhoea, inflammation of lymphatic vessels
• Inflammation of the thin tissue lining the abdominal wall and covering abdominal organs
• Enlargement of lymph glands (sometimes painful), bone marrow failure, increase in eosinophils
• Reduced function of adrenal glands, reduced activity of the thyroid gland
• Changes in brain function, Parkinson-like symptoms, nerve damage leading to numbness, pain, tingling or burning in hands or feet
• Problems with balance and coordination
• Brain swelling
• Double vision, serious eye conditions including: eye and eyelid pain and inflammation, abnormal eye movements, optic nerve damage with visual impairment, swelling of the optic disc
• Reduced sensitivity to touch
• Altered taste
• Hearing disorders, ringing in the ears, vertigo
• Inflammation of certain internal organs, pancreas and duodenum, swelling and inflammation of the tongue
• Enlarged liver, liver failure, gallbladder diseases, gallstones
• Joint inflammation, inflammation of subcutaneous veins (which may be associated with blood clot formation)
• Kidney inflammation, presence of protein in urine, kidney damage
• Increased heart rate or missed heartbeats, sometimes with irregular electrical impulses
• Abnormal electrocardiogram (ECG)
• Increased blood cholesterol, increased blood urea
• Allergic skin reactions (sometimes severe), including potentially life-threatening skin condition causing blisters and painful sores of the skin and mucous membranes, especially in the mouth, skin inflammation, hives, redness and skin irritation, red or purplish skin discolouration which may be caused by low platelet count, eczema
• Infusion site reaction
• Allergic reactions or exaggerated immune response
• Inflammation of tissues surrounding the bones

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 fibres 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 clotting system
• Allergic skin reactions (sometimes severe), including rapid swelling (oedema) of the dermis, subcutaneous tissue, mucosa and submucosal tissues, itchy or painful patches of thickened, red and scaly skin with silvery scales, skin and mucous membrane irritation, potentially life-threatening skin condition causing detachment of large portions of the epidermis (the outer layer of the skin) from the underlying skin layers
• Small patches of dry, scaly skin, sometimes thickened with tips or 'horns'

Side effects with unknown frequency: (frequency cannot be determined from available data):

• Freckles and pigmented spots

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

• Red, scaly patches or ring-shaped skin lesions which may be symptoms of an autoimmune disease called systemic lupus erythematosus

Reactions during Voriconazole hameln infusion have occurred uncommonly (including skin flushing, fever, sweating, increased heart rate and shortness of breath). If this occurs, your doctor may stop the infusion.
Since Voriconazole hameln has been observed to affect the liver and kidneys, your doctor will need to 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 hameln for prolonged periods.
Sunburn or severe skin reaction following exposure to light or sunlight has been reported more frequently in children. If you or your child develops skin problems, your doctor may refer you to a dermatologist who may decide whether regular dermatological check-ups are necessary for you or your child. Elevated liver enzymes have also been observed more frequently in children.
If any of these side effects persist or are bothersome, inform your doctor.
Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Voriconazole hameln

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Exp". 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 in-use stability has been demonstrated for 72 hours at 25 °C and at 2 °C - 8 °C. From a microbiological standpoint, the product should be used immediately. If the product is not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at a temperature of 2°C to 8°C (in the refrigerator), unless reconstitution/dilution has been carried out under controlled and validated aseptic conditions.

Once reconstituted, Voriconazole hameln must be diluted with a compatible diluent for intravenous infusion prior to administration. (For further information, see the final section of the package leaflet.)

Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Voriconazolo hameln contains

• The active substance is voriconazole. Each vial contains 200 mg of voriconazole. After reconstitution, each ml of solution contains 10 mg of voriconazole.
• The other components are hydroxypropylbetadex, sodium chloride, hydrochloric acid, and concentrates (for pH adjustment).

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

Marketing Authorization 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 authorized in the European Economic Area member states under the following names:
Austria Voriconazol hameln 200 mg Powder for solution for infusion
Belgium Voriconazol hameln 200 mg poeder voor oplossing voor infusie / 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 for healthcare professionals only:
Voriconazolo hameln
200 mg powder for solution for infusion
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 9 mg/ml (0.9%) sodium chloride infusion solution to obtain an extractable volume of 20 ml of a clear concentrate containing 10 mg/ml of voriconazole.
• Discard the vial of Voriconazolo hameln if the internal negative vacuum pressure prevents the diluent from being drawn into the vial.
• It is recommended to use a standard 20 ml syringe (non-automatic) to ensure accurate administration of the required volume of water for injections (19.0 ml) or 9 mg/ml (0.9%) sodium chloride infusion solution.
• The required volume of the reconstituted concentrate is then added to one of the compatible infusion solutions listed below to obtain a final Voriconazolo hameln solution containing 0.5–5 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.
• The product must not be administered as an intravenous bolus.
• For information on storage of the product, refer to Section 5 “How to store Voriconazolo hameln”.

Required volumes of Voriconazolo hameln concentrate at 10 mg/ml

Voriconazole hameln is a sterile, single-dose lyophilisate without preservatives. Therefore, from a microbiological standpoint, the reconstituted/diluted solution must be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and should normally not exceed 24 hours at a temperature of 2–8 °C (refrigerated), unless reconstitution/dilution has been carried out under controlled and validated aseptic conditions.
Reconstituted Voriconazole hameln must be diluted with a compatible infusion solution prior to infusion.

Compatible infusion solutions:
The reconstituted solution may be diluted with:

• Sodium Chloride 9 mg/ml (0.9 %) Injection
• Compound Sodium Lactate for Intravenous Infusion
• Glucose 5 % and Sodium Lactate (Ringer's Lactate) for Intravenous Infusion
• Glucose 5 % and Sodium Chloride 0.45 % for Intravenous Infusion
• Glucose 5 % for Intravenous Infusion
• Glucose 5 % with 20 mEq Potassium Chloride for Intravenous Infusion
• Sodium Chloride 0.45 % for Intravenous Infusion
• Glucose 5 % and Sodium Chloride 9 mg/ml 0.9 % Injection for Intravenous Infusion

The compatibility of Voriconazole hameln with diluents other than those listed above (or listed in the section “Incompatibilities”) is unknown.

Incompatibilities:
Voriconazole hameln must not be administered through the same line or cannula as other infusion medicines, including parenteral nutrition (e.g., Aminofusin 10 % Plus).
Transfusion of blood products must not be performed simultaneously with the administration of Voriconazole hameln.
Total parenteral nutrition may be administered simultaneously with Voriconazole hameln, but not through the same line or cannula.
Voriconazole hameln must not be diluted with Sodium Bicarbonate 4.2 % Infusion.