SPIONIC 40 mg/ml poeder voor orale suspensie

SPIONIC contains the active substance voriconazole. SPIONIC 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).

SPIONIC is intended for patients with worsening, possibly life-threatening, fungal infections.

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

Do not take SPIONIC

If you are allergic to voriconazole or any of the other ingredients of SPIONIC (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 SPIONIC 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)

• Rifampicin (used for treating tuberculosis)
• 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 400mg and more twice daily
• St John’s Wort (herbal supplement)

Warnings and precautions

Talk to your doctor before taking SPIONIC 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 SPIONIC. Your doctor should also monitor your liver function while you are being treated with SPIONIC 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 SPIONIC:

• 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

SPIONIC should not be given to children younger than 2 years of age.

Other medicines and SPIONIC

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including those that are obtained without a prescription.

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

Tell your doctor if you are taking the following medicine, as treatment with SPIONIC at the same time 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 SPIONIC 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 SPIONIC 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 SPIONIC 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 SPIONIC 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 SPIONIC)
• Methadone (used to treat heroin addiction)
• Alfentanil and fentanyland 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

SPIONIC 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 SPIONIC.

SPIONIC 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

SPIONIC 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.

SPIONIC contains sucrose

SPIONIC suspension contains 0.54g sucrose per ml of suspension. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking SPIONIC.

Always take this medicine exactly as your doctor 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:

	Oral suspension
	Patients 40 kg and above	Patients less than 40 kg
Dose for the first 24	400 mg (10 ml) every 12	200 mg (5 ml) every 12
hours
(Loading Dose)	hours for the first 24	hours for the first 24
	hours	hours
Dose after the first 24	200 mg (5 ml) twice a	100 mg (2.5 ml) twice a
hours (Maintenance Dose)	day	day

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:

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

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

Take your suspension at least one hour before, or two hours after a meal.

SPIONIC suspension should not be mixed with any other medicine. The suspension should not be further diluted with water or any other liquids.

Instructions to constitute the suspension:

It is recommended that your pharmacist constitutes SPIONIC suspension before giving it to you. SPIONIC suspension is constituted if it is in a liquid form. If it appears to be a dry powder you should constitute the oral suspension by following the instructions below.

1. Tap the bottle to release the powder.
2. Remove the cap.
3. Measure 23 ml of water by filling the measuring cup (included in the carton) to the top of the marked line then pour the water into the bottle. Using the cup measure another 23 ml of water and add this to the bottle. You should always add a total of 46 ml (2 x 23 ml) of water irrespective of the dose you are taking.
4. Replace the cap and shake the bottle vigorously for about 1 minute.
5. Remove the cap. Press the bottle adaptor into the neck of the bottle (as shown on figure below). The adaptor is provided so that you can fill the oral syringe with medicine from the bottle. Replace the cap on the bottle.
6. Write the date of expiry of the constituted suspension on the bottle label (the shelf-life of the constituted suspension is 14 days). Any unused suspension should be discarded after this date.

Instructions for use:

Your pharmacist should advise you how to measure the medicine using the multi-dosing oral syringe provided in the pack. Please see instructions below before using SPIONIC suspension.

1. Shake the closed bottle of constituted suspension for approximately 10 seconds before use. Remove the cap.
2. While the bottle is upright, on a flat surface, insert the tip of the oral syringe into the adaptor.
3. Turn the bottle upside down while holding the oral syringe in place. Slowly pull back the plunger of the oral syringe to the graduation mark that marks the dose for you. To measure the dose accurately, the top edge of the black ring should be lined up with the graduated mark on the oral syringe.
4. If large bubbles can be seen, slowly push the plunger back into the syringe. This will force the medicine back into the bottle. Repeat step 3 again.
5. Turn the bottle back upright with the oral syringe still in place. Remove the oral syringe from the bottle.
6. Put the tip of the oral syringe into the mouth. Point the tip of the oral syringe towards the inside of the cheek. SLOWLY push down the plunger of the oral syringe. Do not squirt the medicine out quickly. If the medicine is to be given to a child, make sure the child is sitting, or is held, upright before giving the medicine.
7. Replace the cap on the bottle, leaving the bottle adaptor in place. Wash the oral syringe as instructed below.

1

2

3/4

5

6

Cleaning and storing the syringe:

1. The syringe should be washed after each dose. Pull the plunger out of the syringe and wash both parts in warm soapy water. Then rinse with water.
2. Dry the two parts. Push the plunger back in to the syringe. Keep it in a clean safe place with the medicine.

If you take more SPIONIC than you should:

If you take more suspension than prescribed (or if someone else takes your suspension) you must seek medical advice or go to the nearest hospital casualty department immediately. Take your bottle of SPIONIC suspension with you. You may experience abnormal intolerance to light as a result of taking more SPIONIC than you should.

If you forget to take SPIONIC:

It is important to take your SPIONIC suspension 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 the forgotten dose.

If you stop taking SPIONIC:

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 SPIONIC correctly, as described above.

Continue taking SPIONIC 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 SPIONIC 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 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 SPIONIC 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
• Low blood sugar, low blood potassium
• 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
• 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
• 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 SPIONIC has 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 specific side effects not listed in this leaflet.

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 and on the carton. The expiry date refers to the last day of that month.

Powder for oral suspension: store at 2°C - 8°C (in a refrigerator) before constitution. For the constituted suspension:

Do not store above 30°C. Do not refrigerate or freeze.

Store in the original container Keep the container tightly closed.

Any remaining suspension should be discarded 14 days after constitution.

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

What SPIONIC contains:

• The active substance is voriconazole. Each bottle contains 45 g of powder providing 70 ml of suspension when constituted with water as recommended. One ml of the constituted suspension contains 40 mg voriconazole. (See section 3 ‘How to take SPIONIC’).
• The other ingredients are sucrose; silica colloidal; titanium dioxide; xanthan gum; sodium citrate; sodium benzoate; citric acid; natural orange flavour.

What SPIONIC looks like and contents of the pack

SPIONIC is supplied as a white to off-white powder for oral suspension providing a white to off-white, orange flavoured suspension when constituted with water. One pack contains one 100 ml high-density polyethylene (HDPE) bottle (with a polypropylene child resistant closure), a measuring cup (graduated to indicate 23 ml), one 5 ml oral syringe and a press-in bottle adaptor.

Marketing Authorisation Holder

Pfizer bv, Rivium Westlaan 142, 2909 LD Capelle a/d IJssel, Nederland

Manufacturer

Pfizer PGM, Zone Industrielle, 29 Route des Industries, 37530 Pocé-sur-Cisse, Frankrijk.

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

Belgium	SPIONIC 40 mg/ml powder for oral suspension
France	SPIONIC 40 mg/ml poudre pour suspension buvable
Netherlands	SPIONIC 40 mg/ml poeder voor orale suspensie
Luxembourg	SPIONIC 40 mg/ml powder for oral suspension

In het register ingeschreven onder: RVG 112006

Deze bijsluiter is voor het laatst goedgekeurd in juni 2013