Voriconazol Teva 50 mg, filmomhulde tabletten

1. What are and what they are used for

<Voriconazole film-coated tablets> contain the active substance voriconazole. Voriconazole 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 cells 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 film-coated tablets> are intended for patients with worsening, possibly life-threatening, fungal infections.

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

2. What you need to know before you take

Do not take <Voriconazole film-coated tablets>

• If you are allergic to voriconazole or any of the other ingredients of <Voriconazole film-coated tablets> (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 course of treatment with <Voriconazole film-coated tablets>:

• Terfenadine (used for allergy)

Voriconazole 50/100 mg film-coated tablets

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• Astemizole (used for allergy)
• Cisapride (used for stomach problems)
• Pimozide (used for treating mental illness)
• Quinidine (used for irregular heart beat)
• Rifampicin (used for treating tuberculosis)
• Efavirenz (used for treating HIV) in doses of 400 mg and more 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)

Warnings and precautions

Talk to your doctor before taking <Voriconazole film-coated tablets> 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 film-coated tablets>. Your doctor should also monitor your liver function while you are being treated with <Voriconazole film-coated tablets> by doing blood tests.
• you are known to have cardiomyopathy, irregular heart beat, slow heart rate or an abnormality of electrocardiogram (ECG) called ‘long QT syndrome’.

You should avoid sunlight and sun exposure while being treated. It is important to cover sun exposed areas of skin and use sunscreen, as an increased sensitivity of skin to the sun’s UV rays can occur

While being treated with <Voriconazole film-coated tablets>:

• tell your doctor immediately if you develop a severe skin rash or blisters or bone pain.
• your doctor should monitor the function of your liver and kidney by doing blood tests.

Children and adolescents

<Voriconazole film-coated tablets> should not be given to children younger than 2 years of age.

Other medicines and <Voriconazole film-coated tablets>

Tell your doctor or pharmacist if you are taking/using, have recently taken/used or might take/use any other medicines.

Some medicines, when taken at the same time as <Voriconazole film-coated tablets>, may affect the way <Voriconazole film-coated tablets> work or <Voriconazole film-coated tablets> may affect the way they work.

Tell your doctor if you are taking the following medicine, as treatment with <Voriconazole film-coated tablets> at the same time can be used but should be avoided if possible:

• Ritonavir (used for treating HIV) in doses of 100 mg twice daily

Tell your doctor if you are taking either of the following medicines, as treatment with <Voriconazole film- coated tablets> 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 film- coated tablets> 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

Voriconazole 50/100 mg film-coated tablets

NL/H/2585-2586/001-002/DC - Package leaflet (Day 145 response); 28.03.13

required to check that the medicines and/ or <Voriconazole film-coated tablets> 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)
• Sulphonylureas (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 film-coated tablets> 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)
• 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 film- coated tablets>)
• 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 fungal infections)
• Everolimus (used for treating advanced kidney cancer and in transplant patients)

Pregnancy and breast-feeding

<Voriconazole film-coated tablets> must not be taken 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 taking <Voriconazole film-coated tablets>.

<Voriconazole film-coated tablets> must not be taken during breast-feeding. Ask your doctor or pharmacist for advice before taking any medicine whilst breast-feeding.

Driving and using machines

<Voriconazole film-coated tablets> may cause blurring of vision or uncomfortable sensitivity to light. While affected, do not drive or operate any tools or machines. Contact your doctor if you experience this.

<Voriconazole film-coated tablets> contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking <Voriconazole film-coated tablets>.

3. How to take

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

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

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

Tablets

Patients 40 kg and above

Patients less than 40 kg

Voriconazole 50/100 mg film-coated tablets

NL/H/2585-2586/001-002/DC - Package leaflet (Day 145 response); 28.03.13

Dose for the first 24 hours	400 mg every 12 hours for the	200 mg every 12 hours for
(Loading Dose)	first 24 hours	the first 24 hours
Dose after the first 24 hours	200 mg twice a day	100 mg twice a day
(Maintenance Dose)

Depending on your response to treatment, your doctor may increase the daily dose to 300 mg twice a day. 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:

	Tablets
	Children aged 2 to less than	Teenagers aged 12 to 14
	12 years and teenagers aged	years weighing 50 kg or
	12 to 14 years weighing less	more; and all teenagers older
	than 50 kg	than 14
Dose for the first 24 hours	The treatment will be started	400 mg every 12 hours for
(Loading Dose)	as an infusion	the first 24 hours
Dose after the first 24 hours	9 mg/kg twice a day	200 mg twice a day
(Maintenance Dose)	(a maximum dose of 350 mg
	twice daily)

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

• Tablets must only be given if the child is able to swallow tablets.

Take your tablet at least one hour before, or one hour after a meal. Swallow the tablet whole with some water.

If you take more <Voriconazole film-coated tablets> than you should

If you take more tablets than prescribed (or if someone else takes your tablets) you must seek medical advice or go to the nearest hospital casualty department immediately. Take your box of <Voriconazole film-coated tablets> with you. You may experience abnormal intolerance to light as a result of taking more <Voriconazole film-coated tablets> than you should.

If you forget to take <Voriconazole film-coated tablets>

It is important to take your <Voriconazole film-coated tablets> regularly at the same time each day. If you forget to take one dose, take your next dose when it is due. Do not take a double dose to make up for a forgotten dose.

If you stop taking <Voriconazole film-coated tablets>

It has been shown that taking all doses at the appropriate times may greatly increase the effectiveness of your medicine. Therefore unless your doctor instructs you to stop treatment, it is important to keep taking <Voriconazole film-coated tablets> correctly, as described above.

Continue taking >Voriconazole film-coated tablets> until your doctor tells you to stop. Do not stop treatment early because your infection may not be cured. Patients with a weakened immune system or those with difficult infections may require long term treatment to prevent the infection from returning.

When Voriconazole film-coated tablets treatment is stopped by your doctor you should not experience any effects.

Voriconazole 50/100 mg film-coated tablets

NL/H/2585-2586/001-002/DC - Package leaflet (Day 145 response); 28.03.13

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

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 film-coated tablets> and see a doctor immediately

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

Other side effects

Very common side effects (may affect more than 1 in 10 people) are:

• Visual disturbances (change in vision)
• Fever
• Rash
• Nausea, vomiting, diarrhoea
• Headache
• Swelling of the extremities
• Stomach pains.

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

• Flu-like symptoms, inflammation of the sinuses, chills, weakness
• Anaemia
• Low numbers of cells called platelets that help the blood to clot, low numbers of some types of white blood cells or of all types of blood cells, red or purple discoloration of the skin which may be caused by low platelet count , other blood cell changes
• Anxiety, depression, tingling, confusion, dizziness, agitation, trembling, hallucinations and other nervous symptoms
• Low blood pressure, inflammation of a vein (which may be associated with the formation of a blood clot)
• Breathing difficulty, chest pain, fluid accumulation in the lungs
• Low blood sugar, low blood potassium
• Jaundice, redness of the skin
• Swelling of the lips or face
• Allergic reactions (sometimes severe), including widespread blistering rash and skin peeling, severe skin reaction following exposure to light or sun
• Itchiness
• Hair loss
• Back pain
• Kidney failure, blood in the urine, changes in blood tests of kidney function
• Changes in blood tests of liver function
• Inflammation of the gastrointestinal tract

Uncommon side effects (may affect up to 1 in 100 people) are:

• Enlarged lymph glands (sometimes painful)
• Increase in a type of white blood cell which may be associated with allergic reaction, disorder of blood clotting system
• Heart rhythm problems including very fast heartbeat, very slow heartbeat, fainting
• Depressed function of the adrenal gland
• Problem with coordination
• Swelling of the brain

Voriconazole 50/100 mg film-coated tablets

NL/H/2585-2586/001-002/DC - Package leaflet (Day 145 response); 28.03.13

• Double vision pain and inflammation of the eyes and eyelids, involuntary movement of the eye
• Decreased sensitivity to touch
• Constipation, inflammation of upper small intestine, dyspepsia, pancreatitis, peritonitis
• Gingivitis
• Swelling and inflammation of the tongue
• Enlarged liver, hepatitis, liver failure, gallbladder disease, gallstones
• Joint pain
• Inflammation of the kidney, proteins in the urine
• Abnormal electrocardiogram (ECG)
• Blood chemistry changes
• Skin rash, which may lead to severe blistering and peeling of the skin
• Swelling or inflammation of the skin, hives, skin redness and irritation

Rare side effects (may affect up to 1 in 1000 people) are:

• Inability to sleep
• Hearing difficulties, ringing in the ears
• Abnormal sense of taste
• Increase in muscle tone, muscle weakness caused by an abnormal immune system response
• Abnormal brain function, Parkinson-like symptoms, convulsion, nerve injury resulting in numbness, pain, tingling or burning in the hands or feet.
• Severe, persistent or bloody diarrhoea associated with abdominal pain or fever
• Overactive or underactive thyroid gland
• Damage to the optic nerve resulting in vision impairment, eye bleeding, abnormal eye movement, clouding of the cornea
• Damage to the kidneys
• Heart rhythm problems including very fast heartbeat and very slow heartbeat
• Lymph infection, loss of consciousness due to liver failure

As <Voriconazole film-coated tablets> have been known to affect the liver and the kidney, your doctor should monitor the function of your liver and kidney by doing blood tests. Please advise your doctor if you have any stomach pains or if your stools have a different consistency.

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

If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet.

5. How to store

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, blister or carton after EXP. The expiry date refers to the last day of that month.

HDPE bottle: The shelf life after first opening is 8 months.

This medicinal product does not require any special storage conditions.

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.

Voriconazole 50/100 mg film-coated tablets

NL/H/2585-2586/001-002/DC - Package leaflet (Day 145 response); 28.03.13

What <Voriconazole film-coated tablets> contains

• The active substance is voriconazole. Each tablet contains 50 mg voriconazole (<Voriconazole 50 mg film-coated tablets>) or 200 mg voriconazole (<Voriconazole 200 mg film-coated tablets>).
• The other ingredients are Lactose monohydrate, Croscarmellose-Sodium, Povidone K25, Pregelatinised maize starch, Magnesium stearate, Hypromellose 5 mPa∙s, Glycerol 85 %, Titanium dioxide (E 171).

What <Voriconazole film-coated tablets> looks like and contents of the pack

Voriconazole 50 mg is supplied as white, round, biconvex film-coated tablets (diameter: approx. 7.2 mm) with imprint “V” on one and “50” on the other side.

Voriconazole 200 mg is supplied as white, oblong film-coated tablets (dimensions: approx. 17.2 mm x 7.2 mm) with imprint “V” on one and “200” on the other side.

Voriconazole 50 mg film-coated tablets are available as packs of 2, 10, 14, 20, 28, 30, 50, 56, 98 and 100 in PVC/Alu-blisters as multipack and unit pack and as packs of 2, 30 and 100 in white HDPE bottles with PP screw cap.

Voriconazole 200 mg film-coated tablets are available as packs of 2, 10, 14, 20, 28, 30, 50, 56, 98 and 100 in PVC/Alu-blisters as multipack and unit pack and as packs of 2, 30 and 100 in white HDPE bottles with PP screw cap.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Teva Nederland B.V.

Swensweg 5,

2031 GA, Haarlem

Nederland

Fabrikant

CT Arzneimittel

Graf-Arco-Straße 3

89079 Ulm

Duitsland

In het register ingeschreven onder
Voriconazol Teva 50 mg, filmomhulde tabletten	RVG 111709
Voriconazol Teva 200 mg, filmomhulde tabletten	RVG 111710

This medicinal product is authorised in the Member States of the EEA under the following names:

Germany: Voriconazol-CT 50 mg Filmtabletten

Voriconazol-CT 200 mg Filmtabletten

Netherlands: Voriconazol Teva 50 mg, filmomhulde tabletten

Voriconazol Teva 200 mg, filmomhulde tabletten

Deze bijsluiter is voor het laatst goedgekeurd in juni 2013