Vimizim - patient leaflet, side effects, dosage

1. What Vimizim is and what it is used for

Vimizim contains an enzyme called elosulfase alfa, which belongs to a group of medicines known as enzyme replacement therapies. It is used to treat adults and children with mucopolysaccha­ridosis type IVA (MPS IVA disease, also known as Morquio A Syndrome).

People with MPS IVA disease either lack completely or do not have enough N-acetylgalactosamine-6-sulfatase, an enzyme which breaks down specific substances in the body such as keratan sulphate, which are found in many tissues of the body, including cartilage and bone. As a result, these substances do not get broken down and processed by the body as they should. They accumulate in the tissues interfering with their normal function and causing the symptoms of MPS IVA, such as difficulty walking, trouble breathing, short height, and hearing loss.

How Vimizim works

This medicine replaces the natural enzyme N-acetylgalactosamine-6-sulfatase which is lacking in MPS IVA patients. Treatment has been shown to improve walking and to reduce the levels of keratan sulphate in the body. This medicine may improve the symptoms of MPS IVA.

2. What you need to know before you are given Vimizim

You must not receive Vimizim

• – if you have experienced life-threatening allergic reactions to elosulfase alfa or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

• – If you are treated with Vimizim, you may develop infusion reactions. An infusion reaction is any side effect, including an allergic reaction, occurring during the infusion or within a day following infusion (see section 4). If you experience such a reaction, you should immediately contact your doctor.

• – If you have an allergic reaction during your infusion your doctor may slow down, or stop your infusion. Your doctor may also give you additional medicines to manage any allergic reactions (e.g. antihistamines and/or corticosteroids).

• – If you experience back pain, numbness in your arms or legs, or lack of control over passing urine or stools, you should immediately contact your doctor. These problems can be a part of the disease and may be caused by pressure on your spinal cord.

Other medicines and Vimizim

Please tell your doctor if you are taking, have recently taken or might take any other medicines.

Pregnancy, breast-feeding and fertility

You should not receive Vimizim during pregnancy unless clearly necessary. It is not known whether Vimizim is excreted in breast milk. Discuss with your doctor if the benefits of taking Vimizim are greater than the potential risk to your newborn while breast-feeding. It is not known if Vimizim impacts human fertility. No effect on fertility was observed in animals.

Driving and using machines

Dizziness was reported in some patients during the Vimizim infusion. Tell your doctor if you feel dizzy after your infusion, especially before driving or using any machine where dizziness might be dangerous.

Vimizim contains sodium and sorbitol (E 420)

This medicine contains 8 mg sodium (main component of cooking/table salt) in each 5 ml vial. This is equivalent to 0.4 % of the recommended daily dietary intake of sodium for an adult.

This medicine contains 100 mg sorbitol in each 5 ml vial which is equivalent to 40 mg/kg.

Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, you (or your child) must not receive this medicine unless discussed with your doctor. Patients with HFI cannot break down fructose, which may cause serious side effects.

You must tell your doctor before receiving this medicine if you (or your child) have HFI or if your child can no longer take sweet foods or drinks because they feel sick, vomit or get unpleasant effects such as bloating, stomach cramps or diarrhoea.

• 3. How Vimizim is given

Your doctor or nurse will give Vimizim to you by an infusion into a vein.

The medicine has to be diluted before being given. Your doctor or nurse will give you some medicines before your treatment to reduce allergic reactions and you may also be given medicines to help control any fever.

Dose

The dose you receive is based on your body weight. The recommended dose regimen for adults and children is 2 mg/kg body weight given once every week through a drip into a vein (intravenous infusion). Each infusion will be given over approximately 4 hours. Treatment with Vimizim may be started at as young as an age possible and is intended for long term use.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Side effects were mainly seen while patients were being given the medicine or shortly after (“infusion reactions”). The most serious side effects were severe allergic reactions (seen uncommonly – may affect up to 1 in 100 people) and mild to moderate vomiting (seen very commonly – may affect more than 1 in 10 people). Symptoms of allergic reaction include rash, itching or hives on the skin (seen commonly – may affect up to 1 in 10 people). If you experience any difficulty swallowing, talking, severe shortness of breath or wheezing, swelling of the face or lips, dizziness or weak pulse; these may represent symptoms of a severe allergic reaction and you should tell your doctor immediately. Based on the severity of the side effect, your doctor may slow or temporarily interrupt the infusion and/ or give you additional medicines to reduce the effects of a severe allergic reaction (e.g. antihistamines and/or corticosteroids) or to reduce fever (antipyretics).

Very common side effects include symptoms of infusion reactions such as headache, nausea, fever, chills and stomach ache. Other very common adverse reactions were diarrhoea, mouth and throat pain, dizziness and trouble breathing.

Common side effects observed was muscle pain.

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Vimizim

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 carton and vial after EXP. The expiry date refers to the last day of that month.

Unopened vials:

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Store in the original package in order to protect from light.

Do not use Vimizim if the solution is discoloured or it contains visible particles.

After dilution:

Once the product has been diluted it should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and should normally not be longer than 24 hours at 2oC – 8oC followed by up to 24 hours at 23oC – 27oC during administration.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Contents of the pack and other information

What Vimizim contains

• – The active substance is elosulfase alfa. Each ml of concentrate contains 1 mg elosulfase alfa.

Each vial of 5 ml contains 5 mg elosulfase alfa.

• – The other ingredients are: sodium acetate trihydrate, sodium dihydrogen phosphate monohydrate, arginine hydrochloride, sorbitol, polysorbate 20, and water for injections (see section 2 under ‘Vimizim contains sodium and sorbitol (E420)’).

What Vimizim looks like and contents of the pack

Vimizim is supplied as a concentrate for solution for infusion (sterile concentrate). The clear to slightly opalescent and colourless to pale yellow concentrate must be free of visible particles.

Pack sizes: 1 vial of 5 ml

Marketing Authorization Holder

BioMarin International Limited

Shanbally, Ringaskiddy

County Cork, P43 R298

Ireland

Manufacturer

BioMarin International Limited

Shanbally, Ringaskiddy

County Cork

Ireland

This leaflet was last revised in MM/YYYY

Detailed information on this medicine is available on the European Medicines Agency web site:. There are also links to other websites about rare diseases and treatments.

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

Vimizim should not be mixed with other medicinal products in the same infusion, except for those mentioned below.

Each vial of Vimizim is intended for single use only. Vimizim has to be diluted with sodium chloride 9 mg/ml (0.9 %) solution for infusion using aseptic technique. Diluted Vimizim solution is to be administered to patients using an infusion set. An infusion set equipped with an in-line 0.2 gm filter can be used.

Any unused product or waste material is to be disposed of in accordance with local requirements.

Preparation of the Vimizim infusion (Use aseptic technique)

• 1. The number of vials to be diluted based on the individual patient's weight must be determined and removed from the refrigerator in advance in order to allow them to reach 23°C – 27°C. Do not heat or microwave vials. The recommended dose regimen is 2 mg/kg body weight administered once every week through a drip into a vein (by intravenous infusion). Each infusion will take approximately 4 hours.

• Patient weight (kg) multiplied by 2 (mg/kg) = Patient dose (mg)
• Patient dose (mg) divided by 1 (mg/ml concentrate of Vimizim) = Total number of ml of Vimizim
• Total amount (ml) Vimizim divided by 5 ml per vial = Total number of vials

• 2. The calculated total number of vials is rounded up to next whole vial.

• 3. An infusion bag containing sodium chloride 9 mg/ml (0.9 %) solution for infusion is obtained suitable for intravenous administration. The total volume of the infusion is determined by the patient’s body weight.

• Patients weighing less than 25 kg should receive a total volume of 100 ml.
• Patients weighing 25 kg or more should receive a total volume of 250 ml.

• 4. Before dilution, each vial is to be inspected for particulate matter and discolouration. The clear to slightly opalescent and colourless to pale yellow solution must be free of visible particles. Do not shake vials.

• 5. A volume of the sodium chloride 9 mg/ml (0.9 %) solution for infusion is to be withdrawn and discarded from a 100 ml or 250 ml infusion bag equal to the total volume of Vimizim to be added.

• 6. The calculated volume of Vimizim from the appropriate number of vials is slowly withdrawn using caution to avoid excessive agitation.

• 7. The volume of Vimizim is to be slowly added to the sodium chloride 9 mg/ml (0.9 %) solution for infusion.

When diluted with 100 ml sodium chloride 9 mg/ml (0.9 %) solution for infusion; the initial rate will be 3 ml/hr. The infusion rate will be increased every 15 minutes as follows: first increase the rate to 6 ml/hr, then increase the rate every 15 minutes by 6 ml/hr increments until a maximum rate of 36 ml/hr is reached.

When diluted with 250 ml sodium chloride 9 mg/ml (0.9 %) solution for infusion; the initial rate will be 6 ml/hr. The infusion rate will be increased every 15 minutes as follows: first increase the rate to 12 ml/hr, then increase the rate every 15 minutes by 12 ml/hr increments until a maximum rate of 72 ml/hr is reached.

Patient weight (kg)	Total infusion volume (ml)	Step 1 Initial infusion rate 0–15 minutes (ml/hr)	Step 2 15–30 minutes (ml/hr)	Step 3 30–45 minutes (ml/hr)	Step 4 45–60 minutes (ml/hr)	Step 5 60–75 minutes (ml/hr)	Step 6 75–90 minutes (ml/hr)	Step 7 90+ minutes (ml/hr)
< 25	100	3	6	12	18	24	30	36
> 25	250	6	12	24	36	48	60	72

Infusion rate may be increased as tolerated by patient.

• 8. The diluted solution is to be mixed gently prior to infusion.

• 9. The diluted solution is to be visually inspected for particulate matter prior to use. Do not use if the solution is discoloured or if there is particulate matter in the solution

• 10. The diluted solution should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and should normally not be longer than 24 hours at 2°C – 8°C followed by up to 24 hours at 23°C – 27°C during administration.