Kuvan 100 mg soluble tabletsPatient’s LeafletSummary for the - United Kingdom[英国药品]

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Kuvan 100 mg soluble tabletsPatient’s LeafletSummary for the

2014-01-28 19:25:59 来源: 作者: 【大中小】浏览:499次评论:0条

For doctors

What is it and how is it used?

Kuvan is a synthetic copy of a body’s own substance called tetrahydrobiopterin (BH4). BH4 is required by the body to use an amino acid called phenylalanine in order to build another amino acid called tyrosine.

Kuvan is used for the treatment of hyperphenylalaninaemia (HPA) or phenylketonuria (PKU), due to abnormally high levels of phenylalanine in the blood, which can be harmful. Kuvan reduces these levels in some patients who respond to BH4 and can help increase the amount of phenylalanine that can be included in the diet.

Kuvan is also used for the treatment of an inherited disease called BH4 deficiency, in which the body cannot produce enough BH4. Because of very low BH4 levels phenylalanine is not used properly and its levels rise, resulting in harmful effects. By replacing the BH4 that the body cannot produce, Kuvan reduces the harmful excess of phenylalanine in the blood and increases the dietary tolerance to phenylalanine.

What do you have to consider before using it?

Do not take KuvanIf you are allergic (hypersensitive) to sapropterin or any of the other ingredients of Kuvan.

Take special care with Kuvan
You should consult your doctor:

When you are treated with Kuvan, your doctor will test your blood to verify how much phenylalanine and tyrosine it contains and may decide to adjust the dose of Kuvan or your diet if needed.

You must continue your diet treatment as recommended by your doctor. Do not change your diet without contacting your doctor.

Taking other medicines
You should consult your doctor if you are taking:

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

Taking Kuvan with food and drink
Kuvan should be taken with food at the same time each day preferably in the morning.

Pregnancy and breast-feeding
For Kuvan no information is available for human pregnancies. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy , embryonal/foetal development, birth or postnatal development.

If maternal phenylalanine levels are not strictly controlled before and during pregnancy, this could be harmful to the mother and the foetus. In case of pregnancy your doctor will tell you how to control phenylalanine levels adequately. Physician-supervised restriction of dietary phenylalanine intake prior to and throughout pregnancy is the first choice of treatment in this patient group.
The use of Kuvan should be considered only if strict dietary management does not adequately reduce blood phenylalanine levels.

Be sure to tell your doctor if you are pregnant or breast-feeding, if you think you might be pregnant, or if you are planning to become pregnant or are planning to begin breast-feeding.
You should not take Kuvan if you are breast-feeding.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
No studies on the effects on the ability to drive and use machines have been performed. Kuvan is not expected to affect the ability to drive and use machines.'

How is it used?

Always take Kuvan exactly as your doctor has told you. You should check with your doctor if you are not sure.

Dosage

PKU
The usual starting dose of Kuvan in adult and paediatric patients with PKU is 10 mg for each kg of body weight. Take the soluble tablets as a single daily dose with a meal to increase the absorption, and at the same time each day, preferably in the morning. Your doctor may adjust your dose, usually between 5 and 20 mg for each kg of body weight per day, depending on your condition.

BH4 deficiency
The usual starting dose of Kuvan in adult and paediatric patients with BH4 deficiency is 2 to 5 mg for each kg of body weight. Take the soluble tablets as a single daily dose, with a meal to increase the absorption, and at the same time each day, preferably in the morning. Your doctor may adjust your dose up to 20 mg for each kg of body weight per day, depending on your condition. It may be necessary to divide the total daily dose into 2 or 3 doses, distributed over the day, to achieve the best therapeutic effect.

The table below is an example of how an appropriate dose is calculated:

Body weight kg Number of tablets Kuvan dose 10 mgkg Number of tablets Kuvan dose 20 mgkg 10 1 2 20 2 4 30 3 6 40 4 8 50 5 10

Method of Administration

Adults
Place the tablets in a glass or cup (120 to 240 ml) of water and stir until dissolved.

Paediatric patients
The prescribed number of tablets should be placed in a glass or cup (up to 120 ml) of water and stir until dissolved.

For doses below 100 mg, one tablet should be dissolved in 100 ml of water. Your doctor will tell you to administer only a certain volume of the solution corresponding to the appropriate dose. An accurate measuring device with suitable graduations should be used for this purpose.

It may take a few minutes for the tablets to dissolve. To make the tablets dissolve faster you can crush them. Small particles may be visible in the solution, but they will not affect the effectiveness of the medicine. Drink the dissolved preparation of Kuvan with a meal, at the same time each day, preferably in the morning within 15 to 20 minutes of its preparation.

Make sure you do not swallow the desiccant capsule contained in the bottle.

If you take more Kuvan than you should
If you take more Kuvan than prescribed, you may experience side effects that could include headache and dizziness. You should immediately contact your doctor or pharmacist if you take more Kuvan than prescribed.

If you forget to take Kuvan
Do not take a double dose to make up for a forgotten dose.

If you stop taking Kuvan
Do not stop taking Kuvan without prior discussion with your doctor, as phenylalanine levels in the blood may increase.

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

What are possible side effects?

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

Frequencies of side effects are defined as:

Very common side effects: headache and runny nose.

Common side effects: sore throat, nasal congestion or stuffy nose, cough, diarrhoea, vomiting, stomach ache and too low levels of phenylalanine in blood tests.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How should it be stored?

Keep out of the reach and sight of children.

Do not use Kuvan after the expiry date which is stated on the bottle and the carton after “EXP”. The expiry date refers to the last day of that month.

Store below 25°C.
Keep the bottle tightly closed in order to protect from moisture.

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.

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For doctors

What is it?

Kuvan is a medicine that contains the active substance sapropterin dihydrochloride. It is available as light yellow soluble tablets (100 mg).

What is it used for?

Kuvan is used to treat hyperphenylalaninaemia (HPA, high levels of phenylalanine in the blood) in patients with the genetic disorders phenylketonuria (PKU) or tetrahydrobiopterin (BH4) deficiency. Patients with these disorders cannot convert the amino acid phenylalanine (found in protein in the diet) into tyrosine (another amino acid). This causes a build-up of phenylalanine in the blood, which can lead to problems with the brain and nervous system.

Kuvan can be used in adults and children who have shown to respond adequately to the medicine. Kuvan is intended for use in children with HPA due to PKU who are at least four years old. Kuvan may be used in children of all ages with HPA due to BH4 deficiency.

Because the number of patients with HPA is low, the disease is considered ‘rare’, and Kuvan was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 8 June 2004.

The medicine can only be obtained with a prescription.

How is it used?

Treatment with Kuvan must be started and supervised by a doctor who has experience in the treatment of PKU and BH4 deficiency. The amount of phenylalanine and protein in the patient’s diet needs to be monitored, to make sure that blood phenylalanine levels and nutritional balance are controlled. Kuvan is intended for long-term use.

The dose of Kuvan depends on the patient’s weight. Patients with PKU should start with 10 mg per kilogram body weight once a day and those with BH4 deficiency should start with 2 to 5 mg/kg once a day. After a week, the dose can be adjusted up to 20 mg/kg once a day if the patient has not responded to treatment. A satisfactory response is defined as a reduction in blood phenylalanine levels of at least 30% or to a level determined by the doctor. If this has been achieved after one month, the patient is classified as a ‘responder’ and can continue taking Kuvan.

Kuvan is taken with a meal at the same time every day, preferably in the morning. The tablets are dissolved in a glass of water before the patient drinks the solution. For some patients with BH4 deficiency, the dose may need to be divided into two or three doses over the course of the day to get the best effect.

How does it work?

The high levels of phenylalanine in the blood are due to a problem with the conversion of phenylalanine into tyrosine by the enzyme ‘phenylalanine hydroxylase’. Patients with PKU have defective versions of the enzyme, and patients with BH4 deficiency have low levels of BH4, a ‘cofactor’ that this enzyme needs to work properly. The active substance in Kuvan, sapropterin dihydrochloride, is a synthetic copy of BH4. In PKU, it works by enhancing the activity of the defective enzyme, and in BH4 deficiency it replaces the missing cofactor. This helps to restore the ability of the enzyme to convert phenylalanine into tyrosine, reducing phenylalanine levels in the blood.

How has it been studied?

For the treatment of patients with PKU, Kuvan has been studied in two main studies that compared Kuvan with placebo. All of the patients included in the studies had shown a response to an initial eight-day course of Kuvan but had a period of at least one week without the medicine before the studies started.

The first study involved 89 patients aged eight years or more who were not following a strict diet. The main measure of effectiveness was the reduction in blood phenylalanine levels over six weeks.

The second study involved 46 children aged between four and 12 years, who were on a diet with a controlled level of phenylalanine. From the third week of treatment, the diet was adjusted every two weeks based on blood phenylalanine levels. The main measure of effectiveness was the change in how much phenylalanine the children could eat while keeping blood phenylalanine at target levels. The study lasted for 10 weeks.

For the treatment of patients with BH4 deficiency, the company presented the results of three studies from the published literature with sapropterin dihydrochloride. One of these studies involved 16 patients who were treated for an average of 15.5 months.

What benefits has it shown during the studies?

For the treatment of PKU, Kuvan was more effective than placebo. In the first study, blood phenylalanine levels were around 867 ‘micromoles per litre’ at the start of the study. Normal levels are around 60 micromoles per litre in people without PKU. After six weeks, phenylalanine levels had fallen by 236 micromoles per litre in the patients taking Kuvan and had risen by 3 micromoles per litre in the patients taking placebo. In the second study, the children taking Kuvan could eat an average of 17.5 mg more phenylalanine per kilogram body weight every day after 10 weeks, compared with 3.3 mg more in the children taking placebo.

In the studies of patients with BH4 deficiency, patients showed an improvement in blood phenylalanine levels and other markers of the disease when they were taking sapropterin dihydrochloride.

What is the risk associated?

The most common side effects with Kuvan (seen in more than 1 patient in 10) are headache and rhinorrhoea (runny nose). For the full list of all side effects reported with Kuvan, see the package leaflet.

Kuvan should not be used in patients who may be hypersensitive (allergic) to sapropterin hydrochloride or any of the other ingredients.

Why has it been approved?

The CHMP decided that Kuvan’s benefits are greater than its risks and recommended that it be given marketing authorisation.

Further information

The European Commission granted a marketing authorisation valid throughout the European Union for Kuvan on 2 December 2008. The marketing authorisation holder is Merck Serono Europe Limited. The marketing authorisation is valid for five years, after which it can be renewed.

The summary of opinion of the Committee for Orphan Medicinal Products for Kuvan can be found on the Agency’s website: ema.europa.eu/Find medicine/Human medicines/Rare disease designations. europa.eu/Find medicine/Human medicines/European Public Assessment Reports. For more information about treatment with Kuvan, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 01-2011.

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