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VORICONAZOLE ACTAVIS 200 MG POWDER FOR SOLUTION FOR INFUSION

Active substance(s): VORICONAZOLE

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Package leaflet: Information for the user
Voriconazole 200mg Powder for Solution for Infusion

Read all of this leaflet carefully before you start using this medicine because it contains
important information for you.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,
even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. See section 4.
The full name of this medicine is Voriconazole 200mg Powder for Solution for Infusion but
within the leaflet it will be referred to as Voriconazole.
What is in this leaflet
1.
What Voriconazole is and what it is used for
2.
What you need to know before you use Voriconazole
3.
How to use Voriconazole
4.
Possible side effects
5.
How to store Voriconazole
6.
Contents of the pack and other information

1.

What Voriconazole is and what it is used for

Voriconazole 200mg Powder for Solution for Infusion contains 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 is intended for patients with worsening, possibly life-threatening, fungal infections.
Prevention of fungal infections in high risk bone marrow transplant recipients.
This product should only be used under the supervision of a doctor.

2.

What you need to know before you use Voriconazole

Do not use Voriconazole
if you are allergic to the active ingredient voriconazole, or to hydroxypropylbetadex or 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 any
other medicines, even those that are obtained without a prescription, or herbal medicines.
1

The medicines in the following list must not be taken during your course of Voriconazole 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)
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 400mg and more twice daily
St. John’s Wort (herbal supplement).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Voriconazole




if you have had an allergic reaction to other azoles.
if 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. Your doctor should also monitor your
liver function while you are being treated with Voriconazole by doing blood tests.
if you are known to have cardiomyopathy, irregular heartbeat, 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:

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.
Your doctor should monitor the function of your liver and kidney by doing blood tests.
Children and adolescents
Voriconazole should not be given to children younger than 2 years of age.
Other medicines and Voriconazole
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.
Some medicines, when taken at the same time as Voriconazole, may affect the way Voriconazole
works or Voriconazole may affect the way they work.
Tell your doctor if you are taking the following medicine, as treatment with Voriconazole at the same
time should be avoided if possible:

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

2

Tell your doctor if you are taking either of the following medicines, as treatment with Voriconazole 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
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 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 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)
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 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.
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 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.
Voriconazole contains sodium
This medicinal product contains less than 1mmol sodium (23mg) per vial, i.e. essentially ‘sodiumfree’.

3.

How to use Voriconazole

Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not
sure.
3

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:

Dose for the first 24 hours
(Loading Dose)
Dose after the first 24 hours
(Maintenance Dose)

Intravenous
6mg/kg every 12 hours for the
first 24 hours
4mg/kg twice a day

Depending on your response to treatment, your doctor may decrease the dose to 3mg/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:

Dose for the first
24 hours
(Loading Dose)
Dose after the first
24 hours
(Maintenance Dose)

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

4mg/kg twice a day

Depending on your response to treatment, your doctor may increase or decrease the daily dose.
Voriconazole Powder for Solution for Infusion will be reconstituted and further 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 3mg/kg per hour
over 1 to 3 hours.
If you or your child are taking Voriconazole for prevention of fungal infections, your doctor may stop
giving Voriconazole if you or your child develop treatment related side effects.
If a dose of Voriconazole 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 using Voriconazole
Voriconazole treatment will continue for as long as your doctor advises, however duration of
treatment with Voriconazole 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.
4

When Voriconazole 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.

4.

Possible side effects

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 using Voriconazole 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):
Visual impairment (change in vision including blurred vision, visual colour 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 side effects (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 the blood to
clot
Allergic reaction or exaggerated immune response
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
5

-

Back pain
Kidney failure, blood in the urine, changes in kidney function tests.

Uncommon side effects (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 organ
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 impulse
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.
Rare side effects (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 (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 know (frequency cannot be estimated from the available data):
Freckles and pigmented spots.

6

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 (including flushing,
fever, sweating, increased heart rate and shortness of breath). Your doctor may stop the infusion if
this occurs.
As voriconazole 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.
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, pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. You can also report side effects directly via the
Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard
By reporting side effects you can help provide more information on the safety of this medicine.

5.

How to store Voriconazole

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 immediate and outer label after
EXP. The expiry date refers to the last day of that month.
Do not store above 30°C. Store in the original package in order to protect from light.
Once reconstituted, Voriconazole should be used immediately, but if necessary may be stored for up
to 24 hours at 2°C - 8°C (in a refrigerator) or in room temperature (15°C-25°C). Reconstituted
Voriconazole needs to be further diluted with a compatible infusion solution first before it is infused.
(Please refer to the end of this leaflet for further information).
Once diluted, the solutions can be stored for up to 48 hours at 2°C - 8°C (in a refrigerator) or up to
24 hours at 15-25°C (room temperature).
From a microbiological point of view, the product 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°C to 8°C, unless reconstitution/dilution has taken place in controlled
and validated aseptic conditions.
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.
7

6.

Contents of the pack and other information

What Voriconazole contains
-

The active substance is voriconazole.
The other ingredients are hydroxypropylbetadex, arginine hydrochloride, sodium hydroxide (for
pH adjustment), hydrochloric acid concentrated (for pH adjustment).

Each vial contains 200mg voriconazole, equivalent to a 10mg/ml solution when reconstituted as
directed by your hospital pharmacist or nurse (see the information at the end of this leaflet).
What Voriconazole looks like and contents of the pack
Voriconazole is a white or almost white powder for solution for infusion presented in 30ml single use
glass vials.
Marketing Authorisation Holder
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður
Iceland
Manufacturer
Actavis Italy S.p.A., Nerviano Plant
Via Pasteur 10
20014 Nerviano (Milan)

S.C. Sindan-Pharma S.R.L.
11th Ion Mihalache Blvd.
011171 Bucharest 1
Romania

This leaflet was last revised in March 2016.

----------------------------------------------------------------------------------------------------------------------------The following information is intended for healthcare professionals only:
Voriconazole 200mg Powder for Solution for Infusion
Reconstitution and Dilution information

Voriconazole Powder for Solution for Infusion needs to first be reconstituted with either 19ml
of Water for Injections or 19ml of 9mg/ml (0.9%) Sodium Chloride for Infusion to obtain an
extractable volume of 20ml of clear concentrate containing 10mg/ml voriconazole.

Discard the Voriconazole vial if the vacuum does not pull the diluent into the vial.

It is recommended that a standard 20ml (non-automated) syringe be used to ensure that the
exact amount (19.0ml) of Water for Injections or of 9mg/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 Voriconazole solution containing 0.5
to 5mg/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.

For intravenous infusion only.
8



For storage information, please refer to Section 5 ‘How to store Voriconazole.

Required Volumes of 10mg/ml Voriconazole Concentrate

Body
Weight
(kg)
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
90
95
100

Volume of Voriconazole Concentrate (10mg/ml) required for:
3mg/kg dose
4mg/kg dose
6mg/kg dose
8mg/kg dose
9mg/kg dose
(number of
(number of
(number of
(number of
(number of
vials)
vials)
vials)
vials)
vials)
4.0ml (1)
8.0ml (1)
9.0ml (1)
6.0ml (1)
12.0ml (1)
13.5ml (1)
8.0ml (1)
16.0ml (1)
18.0ml (1)
10.0ml (1)
20.0ml (1)
22.5ml (2)
9.0ml (1)
12.0ml (1)
18.0ml (1)
24.0ml (2)
27.0ml (2)
10.5ml (1)
14.0ml (1)
21.0ml (2)
28.0ml (2)
31.5ml (2)
12.0ml (1)
16.0ml (1)
24.0ml (2)
32.0ml (2)
36.0ml (2)
13.5ml (1)
18.0ml (1)
27.0ml (2)
36.0ml (2)
40.5ml (3)
15.0ml (1)
20.0ml (1)
30.0ml (2)
40.0ml (2)
45.0ml (3)
16.5ml (1)
22.0ml (2)
33.0ml (2)
44.0ml (3)
49.5ml (3)
18.0ml (1)
24.0ml (2)
36.0ml (2)
48.0ml (3)
54.0ml (3)
19.5ml (1)
26.0ml (2)
39.0ml (2)
52.0ml (3)
58.5ml (3)
21.0ml (2)
28.0ml (2)
42.0ml (3)
22.5ml (2)
30.0ml (2)
45.0ml (3)
24.0ml (2)
32.0ml (2)
48.0ml (3)
25.5ml (2)
34.0ml (2)
51.0ml (3)
27.0ml (2)
36.0ml (2)
54.0ml (3)
28.5ml (2)
38.0ml (2)
57.0ml (3)
30.0ml (2)
40.0ml (2)
60.0ml (3)
-

Voriconazole is a single dose unpreserved sterile lyophilisate. 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 (in a refrigerator), unless reconstitution has taken place in controlled and
validated aseptic conditions.
Compatible Infusion Solutions:
The reconstituted solution can be diluted with:
Sodium Chloride 9mg/ml (0.9%) Solution for Injection
5% (50mg/ml) Glucose and Lactated Ringer's Intravenous Infusion
5% (50mg/ml) Glucose and 0.45% (4.5mg/ml) Sodium Chloride Intravenous Infusion
5% (50mg/ml) Glucose Intravenous Infusion
5% (50mg/ml) Glucose in 20 mEq Potassium Chloride Intravenous Infusion
5% (50mg/ml) Glucose and 0.9% (9mg/ml) Sodium Chloride Intravenous Infusion
The compatibility of Voriconazole with diluents other than listed above (or listed below under
‘Incompatibilities’) is unknown.
Incompatibilities:
Voriconazole must not be infused into the same line or cannula concomitantly with other drug
infusions, including parenteral nutrition.
Infusions of blood products must not occur simultaneously with Voriconazole.

9

Infusion of total parenteral nutrition can occur simultaneously with Voriconazole but not in the same
line or cannula.
Voriconazole must not be diluted with 4.2% (42mg/ml) Sodium Bicarbonate Infusion.
When reconstituted with Water for Injections, Voriconazole cannot be used in combination with
Sodium Chloride 0.45% (4.5mg/ml) Solution for Injection and Compound Sodium Lactate
Intravenous Infusion, due to low osmolality.

10

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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