Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Sapropterin Dihydrochloride 500 mg powder for oral solution
⚠ This medicine appears to have been discontinued
The electronic medicines compendium (emc) no longer publishes a Summary of Product Characteristics for this product, which usually means it is no longer marketed in the UK. The patient leaflet below is kept for reference, but the product may not be available.
If you were prescribed this medicine, other products containing Sapropterin dihydrochloride may still be available. Do not stop your treatment — ask your pharmacist or GP what to use instead.
What it is and what it is used for
for
Sapropterin Dihydrochloride contains the active substance sapropterin which 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. Sapropterin Dihydrochloride is used to treat hyperphenylalaninaemia (HPA) or phenylketonuria (PKU) in patients of all ages. HPA and PKU are due to abnormally high levels of phenylalanine in the blood which can be harmful. Sapropterin Dihydrochloride 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. This medicine is also used to treat an inherited disease called BH4 deficiency in patients of all ages, 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, Sapropterin Dihydrochloride reduces the harmful excess of phenylalanine in the blood and increases the dietary tolerance to phenylalanine. 2.
What you need to know before you take it
e Sapropterin Dihydrochloride
Do not take Sapropterin Dihydrochloride if you are allergic to sapropterin or any of the other ingredients of this medicine (listed in section 6). Warnings and precautions Talk to your doctor or pharmacist before taking Sapropterin Dihydrochloride, particularly: If you are 65 years of age or older if you have problems with your kidney or liver if you are ill. Consultation with a physician is recommended during illness as blood phenylalanine levels may increase if you have predisposition to convulsions 1
When you are treated with Sapropterin Dihydrochloride, your doctor will test your blood to verify how much phenylalanine and tyrosine it contains and may decide to adjust the dose of Sapropterin Dihydrochloride 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. Even if you take Sapropterin Dihydrochloride, if your phenylalanine blood levels are not well controlled, you can develop severe neurologic problems. Your doctor should continue to monitor your blood phenylalanine levels often during your treatment with Sapropterin Dihydrochloride, to make sure that your blood phenylalanine levels are not too high or too low. Other medicines and Sapropterin Dihydrochloride Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. In particular you should tell your doctor if you are using: levodopa (used to treat Parkinson's disease) medicines for treatment of cancer (e.g. methotrexate) medicines for treatment of bacterial infections (e.g. trimethoprim) medicines that cause dilation of blood vessels, (such as glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), sodium nitroprusside (SNP), molsidomin, minoxidil). Pregnancy, breast-feeding and fertility 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. If you are pregnant your doctor will tell you how to control phenylalanine levels adequately. If these are not strictly controlled before or when you become pregnant, this could be harmful to you and to your baby. Your doctor will monitor the restriction of dietary phenylalanine intake prior and during pregnancy. If the strict diet does not adequately reduce phenylalanine amount in your blood your doctor will consider whether you must take this medicine. You should not take this medicine if you are breast-feeding. Driving and using machines Sapropterin Dihydrochloride is not expected to affect the ability to drive and use machines. Sapropterin Dihydrochloride contains potassium Sapropterin Dihydrochloride 100 mg powder for oral solution This medicinal product contains 0.3 mmol (11.7 mg) potassium per sachet. To be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet. Sapropterin Dihydrochloride 500 mg powder for oral solution This medicinal product contains 1.6 mmol (62.6 mg) potassium per sachet. To be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet. 3.
How to take it
Sapropterin Dihydrochloride
Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure. Sapropterin Dihydrochloride 500 mg is for use in patients above 25 kg body weight only.
2
Dosing for PKU The recommended starting dose of Sapropterin Dihydrochloride in patients with PKU is 10 mg for each kg of body weight. Take Sapropterin Dihydrochloride 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. Dosing for BH4 deficiency The recommended starting dose of Sapropterin Dihydrochloride in patients with BH4 deficiency is 2 to 5 mg for each kg of body weight. Take Sapropterin Dihydrochloride with a meal to increase the absorption. Divide the total daily dose into 2 or 3 doses, taken over the day. Your doctor may adjust your dose up to 20 mg for each kg of body weight per day, depending on your condition. The table below is an example of how an appropriate dose is calculated. Body weight (kg) 10 20 30 40 50
Number of 100 mg sachets (dose 10 mg/kg) 1 2 3 4 5
Number of 100 mg sachets (dose 20 mg/kg) 2 4 6 8 10
Number of 500 mg sachets (dose 10 mg/kg) 1
Number of 500 mg sachets (dose 20 mg/kg) 2
Method of administration For PKU patients, the total daily dose is taken once a day at the same time each day, preferably in the morning. For BH4 deficiency patients, the total daily dose is divided into 2 or 3 doses over the day. Use in patients above 20 kg body weight Be sure that you know what dose of Sapropterin Dihydrochloride powder your doctor prescribed. Sapropterin Dihydrochloride 100 mg powder for oral solution For higher doses, your doctor may also prescribe Sapropterin Dihydrochloride 500 mg powder for oral solution. Sapropterin Dihydrochloride 500 mg powder for oral solution For the exact dose, your doctor may also prescribe Sapropterin Dihydrochloride 100 mg powder for oral solution. Be sure you know whether to use Sapropterin Dihydrochloride 100 mg or 500 mg powder for oral solution, or both medicines to prepare your dose. Open the sachet(s) only when you are ready to use them. Preparing the sachet(s) • Open the sachet(s) of Sapropterin Dihydrochloride powder for oral solution by folding (1) and tearing (2), or cutting at the dotted line in the upper part of the sachet. • Empty (3) the contents of the sachet(s) into 60 ml to 240 ml of water or apple juice. After dissolving Sapropterin Dihydrochloride powder in water, the solution must be clear, colourless to yellow. The powder for oral solution may also be mixed in a small amount of soft foods, such as apple sauce or pudding.
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(1)
(2)
(3)
Taking the medicine • Drink the solution or take the mixture within 30 minutes. If necessary, Sapropterin powder for oral solution may be administered via enteral feeding tube. For details how to do so, please ask your doctor, pharmacist or nurse. Use in children up to 20 kg body weight Only use the 100 mg sachets to prepare Sapropterin Dihydrochloride for children weighing up to 20 kg body weight. The dose is based on body weight. This will change as your child grows. Your doctor will tell you: • the number of Sapropterin Dihydrochloride 100 mg sachets needed for one dose • the amount of water or apple juice needed to mix one dose of Sapropterin Dihydrochloride • the amount of solution you will need to give your child for their prescribed dose Your child should drink the solution with a meal. Give your child the prescribed amount of solution within 30 minutes after dissolving. If you are not able to give your child's dose within 30 minutes after dissolving the powder, you will need to prepare a new solution as the unused solution should not be used beyond 30 minutes. For dosage equal to 100 mg and multiples of 100 mg, the powder for oral solution may also be mixed in a small amount of soft foods, such as apple sauce or pudding. Supplies needed to prepare and give your child's dose of Sapropterin Dihydrochloride • The number of Sapropterin Dihydrochloride 100 mg sachets needed for one dose • A medicine cup with graduation markings at 20, 40, 60 and 80 ml • A glass or cup • Small spoon or clean utensil for stirring • Oral syringe (graduated in 1 ml divisions) (10 ml syringe for administration of volumes of ≤ 10 ml or 20 ml syringe for administration of volumes of >10 ml) Ask your doctor for the medicine cup for dissolving the powder and the 10 ml or 20 ml oral syringe if you do not have these supplies. Steps for preparing and taking your dose: • Place the prescribed number of Sapropterin Dihydrochloride 100 mg sachets in the medicine cup. Pour the amount of water or apple juice into the cup, as instructed by your doctor (e.g. your doctor told you to use 20 ml for dissolving one Sapropterin Dihydrochloride sachet). Check to make sure that the amount of liquid lines up with the amount that your doctor tells you. Stir with the small spoon or clean utensil until the powder dissolves. After dissolving the powder in water, the solution must be clear, colourless to yellow. • If your doctor told you to administer only a portion of the solution, point the tip of the oral syringe into the medicine cup. Slowly pull back the plunger to withdraw the amount as instructed by your doctor. • Transfer the solution by pushing on the plunger slowly until all of the solution in the oral syringe is transferred to a glass or cup for administration (e.g. if your doctor told you to dissolve two Sapropterin Dihydrochloride 100 mg sachets in 40 ml water or apple juice and administer 30 ml to your child, you would have to use the 20 ml oral syringe two times to draw up 30 ml (e.g. 20 ml + 10 ml) of the solution and transfer it to a glass or cup for administration). Use a 4
•
•
10 ml oral syringe for administration of volumes ≤ 10 ml or a 20 ml oral syringe for administration of volumes >10 ml. If your baby is too small to drink from a glass or a cup you may administer the solution via the oral syringe. Draw up the prescribed volume from the solution prepared in the medicine cup and place the tip of the oral syringe into your baby's mouth. Point the tip of the oral syringe towards either cheek. Push on the plunger slowly, a small amount at a time, until all of the solution in the oral syringe is given. Throw away any remaining solution. Remove the plunger from the barrel of the oral syringe. Wash both parts of the oral syringe and the medicine cup with warm water and air dry. When the oral syringe is dry, put the plunger back into the barrel. Store the oral syringe and the medicine cup for next use.
If you take more Sapropterin Dihydrochloride than you should If you take more Sapropterin Dihydrochloride than prescribed, you may experience side effects that could include headache and dizziness. Immediately contact your doctor or pharmacist if you take more Sapropterin Dihydrochloride than prescribed. If you forget to take Sapropterin Dihydrochloride Do not take a double dose to make up for a forgotten dose. Take the next dose at the usual time. If you stop taking Sapropterin Dihydrochloride Do not stop taking Sapropterin Dihydrochloride without prior discussion with your doctor, as phenylalanine levels in your blood may increase. If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 4.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. Few cases of allergic reactions (such as skin rash and serious reactions) have been reported. Their frequency is not known (frequency cannot be estimated from the available data). If you have red, itchy, raised areas (hives), runny nose, fast or uneven pulse, swelling of your tongue and throat, sneezing, wheezing, serious difficulty in breathing or dizziness, you may be having a serious allergic reaction to the medicine. If you notice these signs, contact your doctor immediately. Very common side effects (may affect more than 1 in 10 people) Headache and runny nose. Common side effects (may affect up to 1 in 10 people) Sore throat, nasal congestion or stuffy nose, cough, diarrhoea, vomiting, stomach ache, too low levels of phenylalanine in blood tests, indigestion and feeling sick (nausea) (see section 2: "Warnings and precautions"). Not known side effects (frequency cannot be estimated from the available data) Gastritis (inflammation of the lining of the stomach), oesophagitis (inflammation of the lining of the gullet). 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 or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine. 5
5.
How to store it
Sapropterin Dihydrochloride
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on sachet and the carton after "EXP". The expiry date refers to the last day of that month. This medicine does not require any special storage conditions. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment. 6.
Contents of the pack and other information
What Sapropterin Dihydrochloride contains The active substance is sapropterin dihydrochloride. Sapropterin Dihydrochloride 100 mg: Each sachet contains 100 mg of sapropterin dihydrochloride equivalent to 77 mg of sapropterin. Sapropterin Dihydrochloride 500 mg: Each sachet contains 500 mg of sapropterin dihydrochloride equivalent to 384 mg of sapropterin. The other ingredients are mannitol (E421), potassium citrate (E332), sucralose (E955), ascorbic acid (E300). See section 2. "Sapropterin Dihydrochloride contains potassium". What Sapropterin Dihydrochloride looks like and contents of the pack The powder for oral solution is white to yellowish. The powder is filled in sachets containing 100 mg or 500 mg sapropterin dihydrochloride. Each carton contains 30 sachets. Marketing Authorisation Holder LogixX Pharma Ltd Merlin House, Brunel Road Theale, Reading Berkshire RG7 4AB, UK Manufacturer Depo-Pack S.r.l. Via Giovanni Morandi 28 21047 Saronno (VA) Italy or Pharmadox Healthcare Ltd. KW20A Kordin Industrial Park Paola PLA3000 Malta or Patheon France 40 Boulevard De Champaret 38300 Bourgoin Jallieu France
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This leaflet was last revised in 12/2025 Other sources of information Detailed information on this medicine is available on the Medicines and Healthcare Products Regulatory Agency web site: http://www.mhra.gov.uk. Latest approved information "Preparing the sachet(s)", on this medicine is available by scanning the QR code included in the outer carton with a smartphone. The same information is also available on the following URL: https://leafletsapropterin.co.uk
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Frequently asked questions about Sapropterin Dihydrochloride 500 mg powder for oral solution
How do I take Sapropterin Dihydrochloride 500 mg powder for oral solution?
Sapropterin Dihydrochloride 500 mg powder for oral solution comes as oral solution containing 500mg. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
What is the active substance in Sapropterin Dihydrochloride 500 mg powder for oral solution?
The active substance in Sapropterin Dihydrochloride 500 mg powder for oral solution is sapropterin dihydrochloride.
Where does this information come from?
This leaflet reproduces the patient information leaflet approved for Sapropterin Dihydrochloride 500 mg powder for oral solution, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Can I get Sapropterin Dihydrochloride 500 mg powder for oral solution without a prescription?
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
About this leaflet
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
- Source: electronic medicines compendium (emc), Datapharm
- Active substance: sapropterin dihydrochloride
- Official document: view the original leaflet on emc →
⚕For healthcare professionals — Summary of Product Characteristics (SmPC)Full SmPC: dosage, interactions, contraindications, warnings+
4.1. Therapeutic indications
Sapropterin Dihydrochloride is indicated for the treatment of hyperphenylalaninaemia (HPA) in adults and paediatric patients of all ages with phenylketonuria (PKU) who have been shown to be responsive to such treatment (see section 4.2).
Sapropterin Dihydrochloride is also indicated for the treatment of hyperphenylalaninaemia (HPA) in adults and paediatric patients of all ages with tetrahydrobiopterin (BH4) deficiency who have been shown to be responsive to such treatment (see section 4.2).
4.2. Posology and method of administration
Treatment with sapropterin dihydrochloride must be initiated and supervised by a physician experienced in the treatment of PKU and BH4 deficiency.
Active management of dietary phenylalanine and overall protein intake while taking this medicinal product is required to ensure adequate control of blood phenylalanine levels and nutritional balance.
As HPA due to either PKU or BH4 deficiency is a chronic condition, once responsiveness is demonstrated, Sapropterin Dihydrochloride is intended for long-term use (see section 5.1).
Posology
PKU
The starting dose of sapropterin dihydrochloride in adult and paediatric patients with PKU is 10 mg/kg body weight once daily. The dose is adjusted, usually between 5 and 20 mg/kg/day, to achieve and maintain adequate blood phenylalanine levels as defined by the physician.
BH4 deficiency
The starting dose of sapropterin dihydrochloride in adult and paediatric patients with BH4 deficiency is 2 to 5 mg/kg body weight total daily dose. Doses may be adjusted up to a total of 20 mg/kg per day.
For patients above 20 kg body weight, the calculated daily dose based on body weight should be rounded to the nearest multiple of 100 mg.
Dose adjustment
Treatment with sapropterin may decrease blood phenylalanine levels below the desired therapeutic level. Adjustment of the sapropterin dihydrochloride dose or modification of dietary phenylalanine intake may be required to achieve and maintain blood phenylalanine levels within the desired therapeutic range.
Blood phenylalanine and tyrosine levels should be tested, particularly in the paediatric population, one to two weeks after each dose adjustment and monitored frequently thereafter, under the direction of the treating physician.
If inadequate control of blood phenylalanine levels is observed during treatment with sapropterin dihydrochloride, the patient's adherence to the prescribed treatment, and diet, should be reviewed before considering an adjustment of the dose of sapropterin.
Discontinuation of treatment should be done only under the supervision of a physician. More frequent monitoring may be required, as blood phenylalanine levels may increase. Dietary modification may be necessary to maintain blood phenylalanine levels within the desired therapeutic range.
Determination of response
It is of primary importance to initiate treatment as early as possible to avoid the appearance of non-reversible clinical manifestations of neurological disorders in paediatric patients and cognitive deficits and psychiatric disorders in adults due to sustained elevations of blood phenylalanine.
Response to this medicinal product is determined by a decrease in blood phenylalanine.Blood phenylalanine levels should be checked before administering sapropterin dihydrochloride and after 1 week of use at the recommended starting dose. If an unsatisfactory reduction in blood phenylalanine levels is observed, then the dose can be increased weekly to a maximum of 20 mg/kg/day, with continued weekly monitoring of blood phenylalanine levels over a one month period. The dietary phenylalanine intake should be maintained at a constant level during this period.
A satisfactory response is defined as a ≥ 30 percent reduction in blood phenylalanine levels or attainment of the therapeutic blood phenylalanine goals defined for an individual patient by the treating physician. Patients who fail to achieve this level of response within the described one month test period should be considered non-responsive, these patients should not be treated with sapropterin dihydrochloride and administration of sapropterin dihydrochloride should be discontinued.
Once responsiveness to the medicinal product has been established, the dose may be adjusted within the range of 5 to 20 mg/kg/day according to response to therapy.
It is recommended that blood phenylalanine and tyrosine levels be tested one or two weeks after each dose adjustment and monitored frequently thereafter under the direction of the treating physician.
Patients treated with sapropterin dihydrochloride must continue a restricted phenylalanine diet and undergo regular clinical assessment (such as monitoring of blood phenylalanine and tyrosine levels, nutrient intake, and psycho- motor development).
Special populations
Elderly
Safety and efficacy of sapropterin dihydrochloride in patients above 65 years of age have not been established. Caution must be exercised when prescribing to elderly patients.
Renal or hepatic impairment
Safety and efficacy of sapropterin dihydrochloride in patients with renal or hepatic insufficiency have not been established. Caution must be exercised when prescribing to such patients.
Paediatric population
The posology is the same in adults, children, and adolescents.
Method of administration
Oral use, after dissolution.
Sapropterin Dihydrochloride should be administered with a meal, to increase the absorption.
For patients with PKU, Sapropterin Dihydrochloride should be administered as a single daily dose, and at the same time each day preferably in the morning.
For patients with BH4 deficiency, divide the total daily dose into 2 or 3 administrations, distributed over the day.
The solution should be consumed within 30 minutes of initial dissolution. Unused solution should be discarded after administration.
Patients above 20 kg body weight
The contents of the sachet(s) should be placed in 120 to 240 ml of water and stirred until dissolved.
Children up to 20 kg body weight (use only 100 mg powder sachets)
The measuring devices required for dosing in children up to 20 kg body weight (i.e. cup with graduations at 20, 40, 60, 80 ml; 10 ml and 20 ml oral syringes with graduation at 1 ml divisions) are not included in the Sapropterin Dihydrochloride pack. These devices are supplied to the specialised paediatric centres for inborn errors of metabolism to be provided to the caregivers of the patients.
The appropriate number of 100 mg sachet(s) should be dissolved in a volume of water depicted in Tables 1-4 based on the prescribed total daily dose.
If only a portion of this solution needs to be administered, an oral syringe should be used to withdraw the volume of solution to be administered. The solution may then be transferred to another cup for administration of the medicinal product. For small infants, an oral syringe can be used. A 10 ml oral syringe should be used for administration of volumes of ≤ 10 ml and a 20 ml oral syringe for administration of volumes of > 10 ml.
Table 1: 2 mg/kg per day dosing table for children weighing up to 20 kg
Weight (kg)
Total dose (mg/day)
Number of sachets to be dissolved (100 mg strength only)
Volume of dissolution (ml)
Volume of solution to be administered (ml)*
2
4
1
80
3
3
6
1
80
5
4
8
1
80
6
5
10
1
80
8
6
12
1
80
10
7
14
1
80
11
8
16
1
80
13
9
18
1
80
14
10
20
1
80
16
11
22
1
80
18
12
24
1
80
19
13
26
1
80
21
14
28
1
80
22
15
30
1
80
24
16
32
1
80
26
17
34
1
80
27
18
36
1
80
29
19
38
1
80
30
20
40
1
80
32
*Reflects volume for total daily dose.
Discard unused solution within 30 minutes for powder solution.
Table 2: 5 mg/kg per day dosing table for children weighing up to 20 kg
Weight (kg)
Total dose (mg/day)
Number of sachets to be dissolved (100 mg strength only)
Volume of dissolution (ml)
Volume of solution to be administered (ml)*
2
10
1
40
4
3
15
1
40
6
4
20
1
40
8
5
25
1
40
10
6
30
1
40
12
7
35
1
40
14
8
40
1
40
16
9
45
1
40
18
10
50
1
40
20
11
55
1
40
22
12
60
1
40
24
13
65
1
40
26
14
70
1
40
28
15
75
1
40
30
16
80
1
40
32
17
85
1
40
34
18
90
1
40
36
19
95
1
40
38
20
100
1
40
40
*Reflects volume for total daily dose.
Discard unused solution within 30 minutes for powder solution.
Table 3: 10 mg/kg per day dosing table for children weighing up to 20 kg
Weight (kg)
Total dose (mg/day)
Number of sachets to be dissolved (100 mg strength only)
Volume of dissolution (ml)
Volume of solution to be administered (ml)*
2
20
1
20
4
3
30
1
20
6
4
40
1
20
8
5
50
1
20
10
6
60
1
20
12
7
70
1
20
14
8
80
1
20
16
9
90
1
20
18
10
100
1
20
20
11
110
2
40
22
12
120
2
40
24
13
130
2
40
26
14
140
2
40
28
15
150
2
40
30
16
160
2
40
32
17
170
2
40
34
18
180
2
40
36
19
190
2
40
38
20
200
2
40
40
*Reflects volume for total daily dose.
Discard unused solution within 30 minutes for powder solution.
Table 4: 20 mg/kg per day dosing table for children weighing up to 20 kg
Weight (kg)
Total dose (mg/day)
Number of sachets to be dissolved (100 mg strength only)
Volume of dissolution (ml)
Volume of solution to be administered (ml)*
2
40
1
20
8
3
60
1
20
12
4
80
1
20
16
5
100
1
20
20
6
120
2
40
24
7
140
2
40
28
8
160
2
40
32
9
180
2
40
36
10
200
2
40
40
11
220
3
60
44
12
240
3
60
48
13
260
3
60
52
14
280
3
60
56
15
300
3
60
60
16
320
4
80
64
17
340
4
80
68
18
360
4
80
72
19
380
4
80
76
20
400
4
80
80
*Reflects volume for total daily dose.
Discard unused solution within 30 minutes for powder solution.
For cleaning, the plunger should be removed from the barrel of the oral syringe. Both parts of the oral syringe and the cup should be washed with warm water and air dry. When the oral syringe is dry, the plunger should be put back into the barrel. The oral syringe and the cup should be stored for next use.
4.3. Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4. Special warnings and precautions for use
Dietary intake
Patients treated with sapropterin dihydrochloride must continue a restricted phenylalanine diet and undergo regular clinical assessment (such as monitoring of blood phenylalanine and tyrosine levels, nutrient intake, and psycho- motor development).
Low blood phenylalanine and tyrosine levels
Sustained or recurrent dysfunction in the phenylalanine-tyrosine-dihydroxy-L-phenylalanine (DOPA) metabolic pathway can result in deficient body protein and neurotransmitter synthesis. Prolonged exposure to low blood phenylalanine and tyrosine levels during infancy has been associated with impaired neurodevelopmental outcome. Active management of dietary phenylalanine and overall protein intake while taking sapropterin dihydrochloride is required to ensure adequate control of blood phenylalanine and tyrosine levels and nutritional balance.
Health disturbances
Consultation with a physician is recommended during illness as blood phenylalanine levels may increase.
Convulsions disorders
Caution should be exercised when prescribing sapropterin dihydrochloride to patients receiving treatment with levodopa. Cases of convulsion, exacerbation of convulsion, increased excitability and irritability have been observed during co- administration of levodopa and sapropterin in BH4-deficient patients (see section 4.5).
Discontinuation of treatment
Rebound, as defined by an increase in blood phenylalanine levels above pre-treatment levels, may occur upon cessation of treatment.
Potassium content
Sapropterin Dihydrochloride 500 mg powder for oral solution
This medicinal product contains 1.6 mmol (62.6 mg) potassium per sachet. To be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.
4.5. Interaction with other medicinal products and other forms of interaction
Although concomitant administration of inhibitors of dihydrofolate reductase (e.g. methotrexate, trimethoprim) has not been studied, such medicinal products may interfere with BH4 metabolism. Caution is recommended when using such medicinal products while taking sapropterin dihydrochloride.
BH4 is a cofactor for nitric oxide synthetase. Caution is recommended during concomitant use of sapropterin dihydrochloride with all medicinal products that cause vasodilation, including those administered topically, by affecting nitric oxide (NO) metabolism or action including classical NO donors (e.g. glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), sodium nitroprusside (SNP), molsidomin), phosphodiesterase type 5 (PDE-5) inhibitors and minoxidil.
Caution should be exercised when prescribing sapropterin dihydrochloride to patients receiving treatment with levodopa. Cases of convulsion, exacerbation of convulsion, increased excitability and irritability have been observed during co- administration of levodopa and sapropterin in BH4-deficient patients.
4.6. Fertility, pregnancy and lactation
Pregnancy
There are limited amount of data from the use of sapropterin dihydrochloride in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.
Available disease-associated maternal and/or embryofoetal risk data from the Maternal Phenylketonuria Collaborative Study on a moderate amount of pregnancies and live births (between 300 - 1 000) in PKU-affected women demonstrated that uncontrolled phenylalanine levels above 600 μmol/l are associated with a very high incidence of neurological, cardiac, facial dysmorphism, and growth anomalies.
Maternal blood phenylalanine levels must therefore be strictly controlled before and during pregnancy. If maternal phenylalanine levels are not strictly controlled before and during pregnancy, this could be harmful to the mother and the foetus. 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 sapropterin dihydrochloride should be considered only if strict dietary management does not adequately reduce blood phenylalanine levels. Caution must be exercised when prescribing to pregnant women.
Breast-feeding
It is not known whether sapropterin or its metabolites are excreted in human breast milk. sapropterin dihydrochloride should not be used during breast-feeding.
Fertility
In preclinical studies, no effects of sapropterin on male and female fertility were observed.
4.7. Effects on ability to drive and use machines
Sapropterin Dihydrochloride has no or negligible influence on the ability to drive and use machines.
4.8. Undesirable effects
Summary of the safety profile
Approximately 35% of the 579 patients aged 4 years and over who received treatment with sapropterin dihydrochloride (5 to 20 mg/kg/day) in the clinical trials for sapropterin experienced adverse reactions. The most commonly reported adverse reactions are headache and rhinorrhoea.
In a further clinical trial, approximately 30% of the 27 children aged below 4 years who received treatment with sapropterin dihydrochloride (10 or 20 mg/kg/day) experienced adverse reactions. The most commonly reported adverse reactions are “amino acid level decreased” (hypophenylalaninaemia), vomiting and rhinitis.
Tabulated list of adverse reactions
In the pivotal clinical trials and in the post-marketing experience for sapropterin, the following adverse reactions have been identified.
The following definitions apply to the frequency terminology used hereafter: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1,000), very rare (< 1/10 000), not known (cannot be estimated from available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Immune system disorders
Not known:
Hypersensitivity reactions (including serious allergic reactions) and rash
Metabolism and nutrition disorders
Common:
Hypophenylalaninaemia
Nervous system disorders
Very common:
Headache
Respiratory, thoracic and mediastinal disorders
Very common:
Common:
Rhinorrhoea
Pharyngolaryngeal pain, nasal congestion, cough
Gastrointestinal disorders
Common:
Not known:
Diarrhoea, vomiting, abdominal pain, dyspepsia, nausea
Gastritis, oesophagitis
Paediatric population
Frequency, type and severity of adverse reactions in children were essentially similar to those in adults.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme.
Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9. Overdose
Headache and dizziness have been reported after the administration of sapropterin dihydrochloride above the recommended maximum dose of 20 mg/kg/day. Treatment of overdose should be directed to symptoms. A shortening of the QT interval (-8.32 msec) was observed in a study with a single supra-therapeutic dose of 100 mg/kg (5 times the maximum recommended dose); this should be taken into consideration in managing patients who have a pre-existing shortened QT interval (e.g. patients with familial short QT syndrome).
🇷🇴 Known in Romania as
Medicines sold in Romania with the same active substance: Cunoscut în România ca
- KUVAN 100 mg prescriptionSAPROPTERINUM · taken by mouth
- SAPROPTERINA DIPHARMA 100 mg prescriptionSAPROPTERINUM · taken by mouth
Same active substance. The strength, the form and whether you need a prescription can differ. Always ask a pharmacist before you switch. Romanian medicines in the UK →
🇵🇱 Known in Poland as
Medicines sold in Poland with the same active substance: W Polsce znany jako
- KuvanSapropterinum · taken by mouth
Same active substance. The strength, the form and whether you need a prescription can differ. Always ask a pharmacist before you switch. Polish medicines in the UK →
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