Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
e Sapropterin dihydrochloride
.
has been
prescribed for you
Soluble Tablets
only. Do not pass it on to others. It may harm them, even if their signs of illness
Do
are the same as yours.
Soluble Tablets –
|f you desct
get
any bs
oc or or p
side
effects 'ef This.
armacist.
talk to your includ
Is inc u
not take
If you other
es any
the
Sapropterin
are allergic ingredients
section
dihydrochloride
to sapropterin or any of the of this medicine (listed in
6).
possible side effects not listed in this leaflet. See
section
4.
Warnings
OC
Talk to your doctor or pharmacist before taking Sapropterin dihydrochloride Soluble Tablets, particularly:
A 1.
What
Sapropterin
Tablets
2.
ee
dihydrochloride
are and what
Soluble
they are used for
–
if you
are
if you
have
3.
How
to take Sapropterin
years
of
problems
age
or
with
older
your
kidney
or
is recommended during illness as blood phenylalanine levels may increase
.
dihydrochloride
65
liver _ if you are ill. Consultation with a physician
Tablets
.
precautions
–
What do you need to know before you take Sapropterin dihydrochloride Soluble .
and
. __
j¢ you
have
predisposition
to convulsions
Soluble Tablets 4.
Possible
side
effects
5.
How to store Sapropterin dihydrochloride Soluble Tablets
When you are treated with Sapropterin dihydrochloride Soluble Tablets, your doctor will test your blood to verify how much phenylalanine and tyrosine it contains and
6.
Contents of the pack and information
may decide to adjust the dose of Sapropterin dihydrochloride Soluble Tablets or your diet if
other
needed.
.
.
.
What Sapropterin dihydrochloride Soluble Tablets are and what they are
used :
for :
:
Sapropterin
dihydrochloride Soluble Tablets
contains
active
the
substance
sapropterin
You
must
continue
your
diet treatment
as
-= p-ecommended by your doctor. Do not change | your diet without contacting your doctor. Even if you take Sapropterin dihydrochloride Soluble Tablets, if your phenylalanine blood levels are not well controlled, you can . Y develop severe neurologic problems. Your doctor should continue to monitor your blood
which is a synthetic copy of a body's own substance called tetrahydrobiopterin (BH4).
phenylalanine levels often during your treatment with Sapropterin dihydrochloride
BH4
Soluble Tablets,
is required
by the
body to use anamino
acid called phenylalanine in order to build another amino
to make
sure that your
blood
phenyinlanine lewes ane nes too high or tao
acid called tyrosine.
ow: Other
medicines
and
Sapropterin
Sapropterin dihydrochloride Soluble Tablets is dihydrochloride Soluble Tablets used to treat hyperphenylalaninaemia (HPA) Tell your doctor or pharmacist if you are or phenylketonuria (PKU) in patients of all taking, have recently taken or might take ages. HPA and PKU are due to abnormally other medicines. In particular you should high levels of phenylalanine in the blood your doctor if you are using: which
can
be harmful.
Sapropterin
–
(used
to treat Parkinson's
dihydrochloride Soluble Tablets reduces these levels in some patients who respond to BH4 ° : and can help increase the amount of
disease) meaicines ron treatment
phenylalanine that can be included in the diet.
infections (e.g. trimethoprim)
.
.
.
–
of cancer (e.g.
metnotrexate
medicines
for treatment
of
bacterial
any tell
*
medicines that cause dilation of blood vessels, (such as glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), sodium nitroprusside (SNP), molsidomin, minoxidil).
Pregnancy and breast-feeding 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. lf 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. lf 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 breast-feeding.
if you are
Driving and using machines Sapropterin dihydrochloride Soluble Tablets not expected to affect the ability to drive and use
machines.
Sapropterin dihydrochloride Soluble Tablets contains
sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.
Sapropterin dihydrochloride Soluble Tablets
Dosing for BH4 deficiency The recommended starting dose of Sapropterin dihydrochloride Soluble Tablets in patients with BH4 deficiency is 2to 5mg for each kg of body weight. Take Sapropterin dihydrochloride Soluble Tablets 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 appropriate dose is calculated Body weight (kg)
of how
an
Number of 100 mg tablets (dose
Number of 100 mg tablets (dose
10 mg/kg)
20 mg/kg)
1 2 3 4 5
= 4 6 8 10
10 20 30 40 50
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 all patients Place the prescribed number of tablets ina glass or cup of water as accurately described is below and stir until dissolved. 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 Sapropterin dihydrochloride Soluble Tablets with a meal within 15 to 20 minutes of its preparation. Do not swallow the desiccant contained in the bottle.
capsule
Use in patients above 20 kg body weight Place the tablets in a glass or cup (120 to 240 ml) of water and stir until dissolved.
Always take this medicine exactly as your doctor has told you. Check with your doctor if Use you are not sure. The Dosing for PKU The recommended starting dose of Sapropterin dihydrochloride Soluble Tablets in patients with PKU is 10 mg for each kg of body weight. Take Sapropterin dihydrochloride 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.
in children up to 20 kg body weisght dose is based on body weight. This will change as your child grows. Your doctor will tell you: ¢ the number of Sapropterin dihydrochloride Soluble Tablets needed for one dose ¢ the amount of water needed to mix one dose of Sapropterin dihydrochloride Soluble Tablets the amount of solution you will need to give your child for their prescribed dose
Your
child
meal.
should
drink
the
solution
with
a
Give your child the prescribed amount solution within 15 to 20 minutes after
dissolving.
of If your baby is too small to drink froma 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 are not able to give your
child's dose within 15 to 20 minutes after dissolving the tablets, you will need to prepare a new solution as the unused solution should not be used beyond 20 minutes. Supplies needed to prepare and give your child's dose of Sapropterin dihydrochloride Soluble Tablets The number of Sapropterin dihydrochloride Soluble Tablets needed one dose
A medicine cup with graduation at 20, 40, 60 and
for
markings
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 tablets and the 10 ml or 20 ml oral syringe supplies.
if you
do
not have
these
Steps for preparing and taking your dose: Place the prescribed number of tablets in the medicine cup. Pour the amount of water into the medicine cup, as instructed by your doctor (e.g. your doctor told you
to use 20 ml for dissolving one Sapropterin dihydrochloride Soluble Tablet). 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 tablets dissolve. 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 Soluble Tablets in 40 ml water 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 10 ml oral syringe for administration of volumes <10 ml ora 20 ml oral syringe for administration of volumes >10 ml.
If you take more Sapropterin dihydrochloride Soluble Tablets than you should If you take more Sapropterin dihydrochloride Soluble Tablets 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 Soluble Tablets than prescribed. If you forget to take Sapropterin dihydrochloride Soluble Tablets Do not take a double dose to make up fora forgotten dose. Take the next dose at the usual time. If you stop taking Sapropterin dihydrochloride Soluble Tablets Do not stop taking Sapropterin dihydrochloride Soluble Tablets without prior discussion with your doctor, as phenylalanine levels in your blood may increase. If you have any further questions of this medicine, ask your doctor pharmacist.
@
on or
the
use
Possible side effects
Like all medicines, this medicine can side effects, although not everybody them.
cause gets
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.
The
other
ingredients
are
mannitol
(E421),
pregelatinised starch, crospovidone (E1202), riboflavin (E101), ascorbic acid (E300), sodium stearyl fumarate.
Common side effects (may affect up to 1 in 10 people) What Sapropterin dihydrochloride Soluble Sore throat, nasal congestion or stuffy nose, Tablets looks like and contents of the pack cough, diarrhoea, vomiting, stomach ache, too low levels of phenylalanine in blood tests, Sapropterin dihydrochloride 100 mg Soluble
indigestion and feeling sick (nausea) (see section 2: "Warnings and precautions").
Tablets are off white to light yellow coloured, round tablets of diameter about 9.5mm
Not known side effects (frequency cannot estimated from the available data)
the
Gastritis (inflammation
of the lining of the
stomach), oesophagitis lining of the gullet).
(inflammation
engraved be
of the
Reporting of side effects If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any
not listed in this leaflet. You can also report side effects 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.
"L71"
on
one
side
and
"T"
on
side.
It is available
(HDPE)
in
high-density
bottles with
polyethylene
either a white
or green
child-resistant closure. Each bottle contains 30 or 120 tablets. The bottles are sealed with an aluminium seal. Each bottle contains a
small Not
plastic tube
all
pack
sizes
of desiccant may
be
(silica gel).
marketed.
Marketing Authorisation Holder Teva UK Limited, Ridings Point, Whistler Drive, Castleford, WF10 5HX, United Kingdom Manufacturer Teva Operations Poland Sp. z.o.o, ul. Mogilska 80, Krakow, 31-546, Poland This
Sapropterin
with
opposite
leaflet
was
last
revised
in August
2021.
PL 00289/2530
dihydrochloride Soluble Tablets 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 label and the carton after "EXP'The expiry date refers to the last day of that month. This medicinal product does not require any special temperature storage conditions. Keep
the bottle tightly closed and store in the original package
to protect from
moisture
and
light.
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.
What Sapropterin Tablets contains
dihydrochloride
Soluble
The active substance is sapropterin dihydrochloride. Each tablet contains 100 mg of sapropterin dihydrochloride (equivalent to 77 mg of sapropterin).
Lost TEVA
UK
LIMITED
EAS5427a)
Sapropterin dihydrochloride 100 mg Soluble Tablets comes as tablet containing 100mg. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
The active substance in Sapropterin dihydrochloride 100 mg Soluble Tablets is sapropterin dihydrochloride.
Medicines with the same active substance, strength and form include: Sapropterin 100 mg Soluble Tablets, Sapropterin Dihydrochloride 100 mg Soluble tablet, Sapropterin Dihydrochloride 100 mg soluble tablets. In total there are 4 equivalent products. They are interchangeable only if your prescriber or pharmacist says so.
This leaflet reproduces the patient information leaflet approved for Sapropterin dihydrochloride 100 mg Soluble Tablets, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
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.
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
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).
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.
Sapropterin dihydrochloride is provided as 100 mg tablets. The calculated daily dose based on body weight should be rounded to the nearest multiple of 100. For instance, a calculated dose of 401 to 450 mg should be rounded down to 400 mg corresponding to 4 tablets. A calculated dose of 451 mg to 499 mg should be rounded up to 500 mg corresponding to 5 tablets.
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 population
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
Sapropterin dihydrochloride tablets 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.
Patients should be advised not to swallow the desiccant capsule found in the bottle.
The prescribed number of tablets should be placed in a glass or cup of water and stirred until dissolved. It may take a few minutes for the tablets to dissolve. To make the tablets dissolve faster they can be crushed. Small particles may be visible in the solution and will not affect the effectiveness of the medicinal product. The solution should be drank within 15 to 20 minutes.
Patients above 20 kg body weight
The prescribed number of tablets should be placed in a glass or cup with 120 to 240 ml of water and stirred until dissolved.
Children up to 20 kg body weight
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.
Depending on the dose (in mg/kg/day) the appropriate number of tablets should be dissolved in a volume of water as depicted in Tables 1-4, whereby the volume of the solution to be administered is calculated according to the prescribed total daily dose. The prescribed number of tablets for a 2, 5, 10 and 20 mg/kg/day dose should be placed in a cup (that shows the appropriate graduation markings at 20, 40, 60 and 80 ml) with the amount of water as depicted in Tables 1-4 and stirred until dissolved.
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 tablets 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 20 minutes for tablet 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 tablets 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 20 minutes for tablet 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 tablets 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 20 minutes for tablet 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 tablets 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 20 minutes for tablet 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.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
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.
Sodium content
This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.
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.
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.
Sapropterin dihydrochloride has no or negligible influence on the ability to drive and use machines.
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 dihydrochloride 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 dihydrochloride, 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:
Rhinorrhoea
Common:
Pharyngolaryngeal pain, nasal congestion, cough
Gastrointestinal disorders
Common:
Diarrhoea, vomiting, abdominal pain, dyspepsia, nausea
Not known:
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.
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).
Ask anything about Sapropterin dihydrochloride 100 mg Soluble Tablets. The assistant answers only from this leaflet — if the leaflet does not cover it, it will say so. It does not give medical advice.
Answers come from the patient leaflet published on the electronic medicines compendium (emc). They are not medical advice. Ask a pharmacist or your GP if you are unsure. For urgent help call NHS 111, or 999 in an emergency.
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