Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - voriconazole

Document Subject

Generated Narrative: MedicinalProductDefinition mpa2d91e093ece9c0d3351fd31285a05ea

identifier: http://ema.europa.eu/identifier/EU/1/15/1004/001 1 Pack

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: Voriconazole Hikma 200 mg powder for solution for infusion

type: Full name

part

part: nan

type: Invented name part

part

part: nan

type: Scientific name part

part

part: nan

type: Strength part

part

part: nan

type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-a2d91e093ece9c0d3351fd31285a05ea

identifier: http://ema.europa.eu/identifier/EU/1/15/1004/001 1 Pack

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - voriconazole

Attesters

What is in this leaflet

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

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

It is used for the treatment of patients (adults and children over the age of 2) with:

• invasive aspergillosis (a type of fungal infection due to Aspergillus sp.),
• candidaemia (another type of fungal infection due to Candida sp.) in non-neutropenic patients (patients without abnormally low white blood cell count),
• serious invasive Candida sp. infections 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 Hikma is intended for patients with worsening, possibly life-threatening, fungal infections.

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

This medicinal product should only be used under the supervision of a doctor.

Do not take Voriconazole Hikma:

• If you are allergic to the active ingredient voriconazole or to sulfobutylether beta cyclodextrin sodium (listed in section 6).

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

The medicines in the following list must not be taken during your Voriconazole Hikma treatment:

• Terfenadine (used for allergy)
• Astemizole (used for allergy)
• Cisapride (used for stomach problems)
• Pimozide (used for treating mental illness)
• Quinidine (used for irregular heart beat)
• Ivabradine (used for symptoms of chronic heart failure)
• Rifampicin (used for treating tuberculosis)
• Efavirenz (used for treating HIV) in doses of 400 mg and above 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 treating HIV) in doses of 400 mg and more twice daily
• St John s Wort (herbal supplement)
• Naloxegol (used to treat constipation specifically caused by pain medicines, called opioids, (e.g., morphine, oxycodone, fentanyl, tramadol, codeine))
• Tolvaptan (used to treat hyponatremia (low levels of sodium in your blood) or to slow kidney function decline in patients with polycystic kidney disease)
• Lurasidone (used to treat depression)
• Venetoclax (used to treat patients with chronic lymphocytic leukaemia-CLL)

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

• You have had an allergic reaction to other azoles.
• You are suffering from, or have ever suffered from liver disease. If you have liver disease, your doctor may prescribe a lower dose of Voriconazole Hikma. Your doctor should also monitor your liver function while you are being treated with Voriconazole Hikma by doing blood tests.
• You are known to have cardiomyopathy, irregular heart beat, slow heart rate or an abnormality of electrocardiogram (ECG) called long QTc syndrome .

You should avoid any sunlight and sun exposure while being treated. It is important to cover sun exposed areas of skin and use sunscreen with high sun protection factor (SPF), as an increased sensitivity of skin to the sun s UV rays can occur. These precautions are also applicable to children.

While being treated with Voriconazole Hikma:

• Tell your doctor immediately if you develop * sunburn * severe skin rash or blisters * bone pain.

If you develop skin disorders as described above, your doctor may refer you to a dermatologist, who after consultation may decide that it is important for you to be seen on a regular basis. There is a small chance that skin cancer could develop with long term use of Voriconazole Hikma.

If you develop signs of adrenal insufficiency where the adrenal glands do not produce adequate amounts of certain steroid hormones such as cortisol which may lead to symptoms such as: chronic, or long lasting fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, please tell your doctor.

If you develop signs of Cushing s syndrome where the body produces too much of the hormone cortisol which may lead to symptoms such as: weight gain, fatty hump between the shoulders, a rounded face, darkening of the skin on the stomach, thighs breasts, and arms, thinning skin, bruising easily, high blood sugar, excessive hair growth, excessive sweating, please tell your doctor.

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

Children and adolescents Voriconazole Hikma should not be given to children younger than 2 years of age.

Other medicines and Voriconazole Hikma Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those that are obtained without a prescription.

Some medicines, when taken at the same time as Voriconazole Hikma, may affect the way that Voriconazole Hikma works or Voriconazole Hikma may affect the way they work.

Tell your doctor if you are taking the following medicine, as treatment with Voriconazole Hikma at the same time should be avoided if possible:

• Ritonavir (used for treating HIV) in doses of 100 mg twice daily Glasdegib (used for treating cancer) if you need to use both drugs your doctor will monitor your heart rhythm frequently

Tell your doctor if you are taking either of the following medicines, as treatment with Voriconazole Hikma at the same time should be avoided if possible, and a dose adjustment of voriconazole may be required:

• Rifabutin (used for treating tuberculosis). If you are already being treated with rifabutin, your blood counts and side effects to rifabutin will need to be monitored.
• Phenytoin (used to treat epilepsy). If you are already being treated with phenytoin, your blood concentration of phenytoin will need to be monitored during your treatment with Voriconazole Hikma and your dose may be adjusted.

Tell your doctor if you are taking any of the following medicines, as a dose adjustment or monitoring may be required to check that the medicines and/or Voriconazole Hikma are still having the desired effect:

• Warfarin and other anticoagulants (e.g. phenprocoumon, acenocoumarol; used to slow down clotting of the blood)
• Ciclosporin (used in transplant patients)
• Tacrolimus (used in transplant patients)
• Sulfonylureas (e.g., tolbutamide, glipizide and glyburide) (used for diabetes)
• Statins (e.g., atorvastatin, simvastatin) (used for lowering cholesterol)
• Benzodiazepines (e.g., midazolam, triazolam) (used for severe insomnia and stress)
• Omeprazole (used for treating ulcers)
• Oral contraceptives (if you take Voriconazole Hikma whilst using oral contraceptives, you may get side effects such as nausea and menstrual disorders)
• Vinca alkaloids (e.g., vincristine and vinblastine) (used in treating cancer)
• Tyrosine kinase inhibitors (e.g., axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (used for treating cancer)
• Tretinoin (used to treat leukaemia)
• Indinavir and other HIV protease inhibitors (used for treating HIV)
• Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, delavirdine, nevirapine) (used for treating HIV) (some doses of efavirenz can NOT be taken at the same time as Voriconazole Hikma)
• Methadone (used to treat heroin addiction)
• Alfentanil and fentanyl and other short acting opiates such as sufentanil (painkillers used for surgical procedures)
• Oxycodone and other long acting opiates such as hydrocodone (used for moderate to severe pain)
• Non-steroidal anti-inflammatory drugs (e.g., ibuprofen, diclofenac) (used for treating pain and inflammation)
• Fluconazole (used for treating fungal infections)
• Everolimus (used for treating advanced kidney cancer and in transplant patients)
• Letermovir (used for preventing cytomegalovirus (CMV) disease after bone marrow transplant)
• Ivacaftor (used to treat cystic fibrosis)
• Flucloxacillin (antibiotic used against bacterial infections) Pregnancy and breast-feeding
  Voriconazole Hikma must not be used during pregnancy, unless indicated by your doctor. Effective contraception must be used in women of childbearing potential. Contact your doctor immediately if you become pregnant while being treated with Voriconazole Hikma.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines Voriconazole Hikma may cause blurring of vision or uncomfortable sensitivity to light. While affected, do not drive or operate any tools or machines. Tell your docotor if you experience this.

Voriconazole Hikma contains sodium This medicine contains 217.6 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 10.9% of the recommended maximum daily dietary intake of sodium for an adult.

Voriconazole Hikma contains cyclodextrins This medicine contains 3200 mg cyclodextrins in each vial which is equivalent to 160 mg/ml when reconstituted in 20 ml. If you have a kidney disease, talk to your doctor before you receive this medicine.

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

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

Your doctor may change your dose depending upon your condition.

The recommended dose for adults (including elderly patients) is as follows:

Intravenous Dose for the first 24 hours (Loading Dose) 6 mg/kg every 12 hours for the first 24 hours Dose after the first 24 hours (Maintenance Dose) 4 mg/kg twice a day

Depending on your response to treatment, your doctor may decrease the dose to 3 mg/kg twice daily.

The doctor may decide to decrease the dose if you have mild to moderate cirrhosis.

Use in children and adolescents The recommended dose for children and teenagers is as follows:

Intravenous Children aged 2 to less than years and teenagers aged 12 to years weighing less than 50 kg Teenagers aged 12 to 14 years weighing 50 kg or more; and all teenagers older than Dose for the first 24 hours (Loading Dose) 9 mg/kg every 12 hours for the first 24 hours 6 mg/kg every 12 hours for the first 24 hours Dose after the first 24 hours (Maintenance Dose) 8 mg/kg twice a day 4 mg/kg twice a day

Depending upon your response to treatment, your doctor may increase or decrease the daily dose.

Voriconazole Hikma powder for solution for infusion will be reconstituted and diluted to the correct concentration by your hospital pharmacist or nurse. (Please refer to the end of this leaflet for further information).

This will be given to you 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 Voriconazole Hikma for prevention of fungal infections, your doctor may stop giving Voriconazole Hikma if you or your child develop treatment related side effects.

If a dose of Voriconazole Hikma has been forgotten: As you will be given this medicine under close medical supervision, it is unlikely that a dose would be missed. However, tell your doctor or pharmacist if you think that a dose has been forgotten.

If you stop taking Voriconazole Hikma Voriconazole Hikma treatment will continue for as long as your doctor advises, however the duration of treatment with voriconazole should be no more than 6 months.

Patients with a weakened immune system or those with difficult infections may require long term treatment to prevent the infection from returning. You may be switched from the intravenous infusion to tablets once your condition improves.

When Voriconazole Hikma treatment is stopped by your doctor you should not experience any effects.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If any side effects occur, most are likely to be minor and temporary. However, some may be serious and need medical attention.

Serious side effects Stop taking Voriconazole Hikma and see a doctor immediately

• Rash
• Jaundice; changes in blood tests of liver function
• Pancreatitis

Other side effects

Very common: may affect more than 1 in 10 people

Visual impairment (change in vision including blurred vision, visual color alterations, abnormal intolerance to visual perception of light, colour blindness, eye disorder, halo vision, night blindness, swinging vision, seeing sparks, visual aura, visual acuity reduced, visual brightness, loss of part of the usual field of vision, spots before the eyes) Fever Rash Nausea, vomiting, diarrhoea Headache Swelling of the extremities Stomach pains Breathing difficulties. Elevated liver enzymes

Common: may affect up to 1 in 10 people

Inflammation of the sinuses, inflammation of the gums, chills, weakness Low numbers of some types, including severe, of red (sometimes immune-related) and/or white blood cells (sometimes with fever), low numbers of cells called platelets that help blood to clot Low blood sugar, low blood potassium, low sodium in the blood Anxiety, depression, confusion, agitation, inability to sleep, hallucinations Seizures, tremors or uncontrolled muscle movements, tingling or abnormal skin sensations, increase in muscle tone, sleepiness, 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 breathing difficulty, chest pain, swelling of the face (mouth, lips and around eyes), fluid accumulation in the lungs Constipation, indigestion, inflammation of the lips Jaundice, inflammation of the liver and liver injury Skin rashes which may lead to severe blistering and peeling of the skin characterized by a flat, red area on the skin that is covered with small confluent bumps, redness of the skin Itchiness 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 causing antibiotic associated diarrhoea, inflammation of the lymphatic vessels Inflammation of the thin tissue that lines the inner wall of the abdomen and covers the abdominal organs Enlarged lymph glands (sometimes painful), failure of blood marrow, increased eosinophil Depressed function of the adrenal gland, underactive thyroid gland Abnormal brain function, Parkinson-like symptoms, nerve injury resulting in numbness, pain, tingling or burning in the hands or feet Problems with balance or coordination Swelling of the brain Double vision, serious conditions of the eye including: pain and inflammation of the eyes and eyelids, abnormal eye movement, damage to the optic nerve resulting in vision impairment, optic disc swelling Decreased sensitivity to touch Abnormal sense of taste Hearing difficulties, ringing in the ears, vertigo Inflammation of certain internal organs- pancreas and duodenum, swelling and inflammation of the tongue Enlarged liver, liver failure, gallbladder disease, gallstones Joint inflammation, inflammation of the veins under the skin (which may be associated with the formation of a blood clot) Inflammation of the kidney, proteins in the urine, damage to the kidney
Very fast heart rate or skipped heartbeats, sometimes with erratic electrical impulses Abnormal electrocardiogram (ECG) Blood cholesterol increased, blood urea increased Allergic skin reactions (sometimes severe), including life-threatening skin condition that causes painful blisters and sores of the skin and mucous membranes, especially in the mouth, inflammation of the skin, hives, sunburn or severe skin reaction following exposure to light or sun, skin redness and irritation, red or purple discoloration of the skin which may be caused by low platelet count, eczema Infusion site reaction Allergic reaction or exaggerated immune response Rare: may affect up to 1 in 1000 people

Overactive thyroid gland Deterioration of brain function that is a serious complication of liver disease Loss of most fibers in the optic nerve clouding of the cornea, involuntary movement of the eye Bullous photosensitivity A disorder in which the body s immune system attacks part of the peripheral nervous system Heart rhythm or conduction problems that (sometimes life threatening) Life threatening allergic reaction
Disorder of blood clotting system Allergic skin reactions (sometimes severe), including rapid swelling (oedema) of the dermis, subcutaneous tissue, mucosa and submucosal tissues, itchy or sore patches of thick, red skin with silvery scales of skin, irritation of the skin and mucous membranes, life-threatening skin condition that causes large portions of the epidermis, the skin's outermost layer, to detach from the layers of skin below Small dry scaly skin patches, sometimes thick with spikes or horns

Side effects with frequency not known: Freckles and pigmented spots

Other significant side effects whose frequency is not known, but should 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 a symptom of an autoimmune disease called cutaneous lupus erythematosus

Reactions during the infusion have occurred uncommonly with Voriconazole Hikma (including flushing, fever, sweating, increased heart rate and shortness of breath). Your doctor may stop the infusion if this occurs.

As Voriconazole Hikma has been known to affect the liver and the kidney, your doctor should monitor the function of your liver and kidneys by doing blood tests. Please advise your doctor if you have any stomach pains or if your stools have a different consistency.

There have been reports of skin cancer in patients treated with voriconazole for long periods of time

Sunburn or severe skin reaction following exposure to light or sun was experienced more frequently in children. If you or your child develops skin disorders, your doctor may refer you to a dermatologist, who after consultation may decide that it is important for you or your child to be seen on a regular basis. Elevated liver enzymes were also observed more frequently in children.

If any of these side effects persist or are troublesome, please tell your doctor.

Reporting of side effects If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

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 label after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special temperature storage conditions. Store in the original package in order to protect from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Voriconazole Hikma contains

• The active substance is voriconazole. Each vial contains 200 mg voriconazole, equivalent to 10 mg/ml solution when reconstituted as directed by your hospital pharmacist or nurse.
• The other ingredient is sulfobutylether beta cyclodextrin sodium.

What Voriconazole Hikma looks like and contents of the pack

Voriconazole Hikma is a white to off-white lyophilised cake.

Voriconazole Hikma is presented in packs of 1 or 5 glass vials as a powder for solution for infusion. Not all pack sizes may be marketed.

Marketing Authorisation Holder Hikma Farmac utica (Portugal), S.A. Estrada do Rio da M n. 8, 8A e 8B, Ferven a 2705-906 Terrugem SNT Portugal

Manufacturer Hikma Italia S.p.A. Viale Certosa, 27100 Pavia Italy

Pfizer Service Company BVBA Hoge Wei 10, Zaventen, 1930, Belgium

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

AT / BE / DE / NL Hikma Pharma GmbH Tel: +49 89-45450-IT Hikma Italia S.p.A. T l/Tel: + 39 0382 1751BG / CY / CZ / DK / EE / ES / EL / FI / HR / HU / IE / IS / LI / LT / LU / LV / MT / NO / PL / PT / RO / SE / SI / SK Hikma Farmac utica (Portugal), S.A. Tel.: +351 219 608 UK Consilient Health Ltd Tel.: +44(0)203 751 1FR Hikma France +33(0) 1 87 69 98 This leaflet was last revised in 05/2Detailed information on this medicine is available on the European Medicines Agency web site: