SPIONIC 200 mg poeder voor oplossing voor infusie

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 used under the supervision of a doctor.

Do not take SPIONIC

• If you are allergic to the active ingredient voriconazole, or to sulphobutylether 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 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 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

SPIONIC 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 SPIONIC.

SPIONIC must not be used 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. Tell your doctor if you experience this.

SPIONIC contains sodium

Each vial of SPIONIC contains 217.6 mg of sodium per vial. This should be taken into consideration if you are on a strictly controlled sodium diet.

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 on your condition.

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

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

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	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	9 mg/kg every 12 hours	6 mg/kg every 12 hours
hours
(Loading Dose)	for the first 24 hours	for the first 24 hours
Dose after the first 24	8 mg/kg twice a day	4 mg/kg twice a day
hours
(Maintenance Dose)

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

SPIONIC 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 a dose of SPIONIC 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 SPIONIC:

SPIONIC treatment will continue for as long as your doctor advises, however duration of treatment with SPIONIC powder for solution for infusion 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 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.

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
• Inflammation at injection sites
• 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.
• Sleepiness during infusion
• 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

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

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

Once reconstituted, SPIONIC should be used immediately, but if necessary may be stored for up to 24 hours at 2°C - 8°C (in a refrigerator). Reconstituted SPIONIC needs to be diluted with a compatible infusion solution first before it is infused. (Please refer to the end of this leaflet for further information).

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.

-The other ingredient is sulphobutylether beta cyclodextrin sodium.

Each vial contains 200 mg voriconazole, equivalent to a 10 mg/ml solution when reconstituted as directed by your hospital pharmacist or nurse (see the information at the end of this leaflet).

What SPIONIC looks like and contents of the pack

SPIONIC is presented in single use glass vials as a powder for solution for infusion.

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 200mg powder for solution for infusion
France	SPIONIC 200 mg poudre pour solution pour
	perfusion
Netherlands	SPIONIC 200 mg poeder voor oplossing voor infusie
Luxembourg	SPIONIC 200mg powder for solution for infusion

In het register ingeschreven onder: RVG 112008

Deze bijsluiter is voor het laatst goedgekeurd in juni 2013

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The following information is intended for medical or healthcare professionals only:

Reconstitution and Dilution information

• SPIONIC powder for solution for infusion needs to first be reconstituted with either 19 ml of Water for Injections or 19 ml of 9 mg/ml (0.9%) Sodium Chloride for Infusion to obtain an extractable volume of 20 ml of clear concentrate containing 10 mg/ml voriconazole.
• Discard the SPIONIC vial if the vacuum does not pull the diluent into the vial.
• It is recommended that a standard 20 ml (non-automated) syringe be used to ensure that the exact amount (19.0 ml) of Water for Injections or of 9 mg/ml (0.9%) Sodium Chloride for Infusion is dispensed.
• The required volume of the reconstituted concentrate is then added to a recommended compatible infusion solution listed below to obtain a final SPIONIC solution containing 0.5 to 5 mg/ml of voriconazole.
• This medicinal product is for single use only and any unused solution should be discarded and only clear solutions without particles should be used.
• Not for administration as a bolus injection.
• For storage information, please refer to Section 5 ‘How to store SPIONIC’.

Required Volumes of 10 mg/ml SPIONIC Concentrate

Body	Volume of SPIONIC Concentrate (10 mg/ml) required for:
3 mg/kg dose	4 mg/kg dose	6 mg/kg dose	8 mg/kg dose	9 mg/kg dose
Weight	(number of	(number of	(number of	(number of	(number of
(kg)	vials)	vials)	vials)	vials)	vials)
10	-	4.0 ml (1)	-	8.0 ml (1)	9.0 ml (1)
15	-	6.0 ml (1)	-	12.0 ml (1)	13.5 ml (1)
20	-	8.0 ml (1)	-	16.0 ml (1)	18.0 ml (1)
25	-	10.0 ml (1)	-	20.0 ml (1)	22.5 ml (2)

30	9.0 ml (1)	12.0 ml (1)	18.0 ml (1)	24.0 ml (2)	27.0 ml (2)
35	10.5 ml (1)	14.0 ml (1)	21.0 ml (2)	28.0 ml (2)	31.5 ml (2)
40	12.0 ml (1)	16.0 ml (1)	24.0 ml (2)	32.0 ml (2)	36.0 ml (2)
45	13.5 ml (1)	18.0 ml (1)	27.0 ml (2)	36.0 ml (2)	40.5 ml (2)
50	15.0 ml (1)	20.0 ml (1)	30.0 ml (2)	40.0 ml (2)	45.0 ml (2)
55	16.5 ml (1)	22.0 ml (2)	33.0 ml (2)	44.0 ml (3)	49.5 ml (3)
60	18.0 ml (1)	24.0 ml (2)	36.0 ml (2)	48.0 ml (3)	54.0 ml (3)
65	19.5 ml (1)	26.0 ml (2)	39.0 ml (2)	52.0 ml (3)	58.5 ml (3)
70	21.0 ml (2)	28.0 ml (2)	42.0 ml (3)	-	-
75	22.5 ml (2)	30.0 ml (2)	45.0 ml (3)	-	-
80	24.0 ml (2)	32.0 ml (2)	48.0 ml (3)	-	-
85	25.5 ml (2)	34.0 ml (2)	51.0 ml (3)	-	-
90	27.0 ml (2)	36.0 ml (2)	54.0 ml (3)	-	-
95	28.5 ml (2)	38.0 ml (2)	57.0 ml (3)	-	-
100	30.0 ml (2)	40.0 ml (2)	60.0 ml (3)	-	-

SPIONIC is a single dose unpreserved sterile lyophile. Therefore, from a microbiological point of view, the reconstituted solution must be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.

Compatible Infusion Solutions:

The reconstituted solution can be diluted with:

Sodium Chloride 9 mg/ml (0.9%) Solution for Injection Compound Sodium Lactate Intravenous Infusion

5 % Glucose and Lactated Ringer’s Intravenous Infusion

5 % Glucose and 0.45 % Sodium Chloride Intravenous Infusion 5 % Glucose Intravenous Infusion

5 % Glucose in 20 mEq Potassium Chloride Intravenous Infusion 0.45 % Sodium Chloride Intravenous Infusion

5 % Glucose and 0.9 % Sodium Chloride Intravenous Infusion

The compatibility of SPIONIC with diluents other than listed above (or listed below under ‘Incompatibilities’) is unknown.

Incompatibilities:

SPIONICmust not be infused into the same line or cannula concomitantly with other drug infusions, including parenteral nutrition (e.g., Aminofusin 10 % Plus).

Infusions of blood products must not occur simultaneously with SPIONIC.

Infusion of total parenteral nutrition can occur simultaneously with SPIONIC but not in the same line or cannula.

SPIONIC must not be diluted with 4.2 % Sodium Bicarbonate Infusion.