VORICONAZOLE ACCORDPHARMA 200 MG POWDER FOR SOLUTION FOR INFUSION - patient leaflet, side effects, dosage

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 1 mmol sodium (23mg) per vial, i.e. essentially'sodium- free'.

3. Howto use Voriconazole

Always use 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:

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.

The following information is intended for healthcare professionals only:

Voriconazole Accordpharma 200mg Powder for Solution for Infusion

Reconstitution and Dilution information w

• 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 lOmg/ml voriconazole. I

• This medicinal product is for single use only and any ; unused solution should be discarded and only clear I solutions without particles should be used.
• For intravenous infusion only.
• For storage information, please refer to Section 5'How to ; store Voriconazole'. I

Required Volumes of 10mg/ml Voriconazole Concentrate

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 userand 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:

Use in children and adolescents

You should avoid exposure to direct sunlight during Voriconazole treatment. It is important to cover sun- exposed areas of skin and use sufficient sunscreen with high sun protection factor (SPF) as an increased sensitivity to the sun’s UV rays can occur. There is a small chance that skin cancer could develop over time.

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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.

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.

The recommended dose for children and teenagers is as follows:

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.

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.

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.

M> 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 characterised 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 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 1,000 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 known (frequency cannot be estimated from the available data):

• 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 (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 kidneys 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:

By reporting side effects you can help provide more information on the safety of this medicine.

This leaflet was last revised in December 2019.

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