Drugs List

Therapeutic Indications

Uses

Phenylketonuria
Tetrahydrobiopterin deficiency

Administration

Adults
The prescribed number of tablets should be placed in a glass with 120 to 240 ml of water and stirred until dissolved. The tablets may be crushed to encourage the tablets to dissolve faster. The solution should be drunk within 15 to 20 minutes.

Children above 20 kg body weight
The prescribed number of tablets should be placed in a glass with up to 120 ml of water and stirred until dissolved. The tablets may be crushed to encourage the tablets to dissolve faster. The solution should be drunk within 15 to 20 minutes.

Children up to 20 kg body weight
Depending on the dose (in mg/kg/day) the appropriate number of tablets should be dissolved in a volume of water as stated in the product information, whereby the volume of the solution to be administered is calculated according to the prescribed daily dose.

For small infants who cannot drink from a glass or cup the solution corresponding to the prescribed daily dose may be administered into the mouth via the oral dosing syringe.

Contraindications

Breastfeeding

Precautions and Warnings

Patients over 65 years
Hepatic impairment
History of seizures
Pregnancy
Renal impairment

Treatment to be initiated and supervised by a specialist
Take with food at the same time every day, preferably in the morning
Monitor blood pressure pre-treatment and periodically thereafter
Monitor blood phenylalanine and tyrosine levels
Advise patients on adequate dietary control

Blood phenylalanine and tyrosine levels should be tested one to two weeks after each dose adjustment and monitored frequently thereafter.

There is limited data regarding the long term use of the tablets.

Consultation with a physician is recommended during illness as blood phenylalanine levels may increase.

Pregnancy and Lactation

Pregnancy

Sapropterin dihydrochloride should be used with caution in pregnancy.

There is no clinical data on exposed pregnancies. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.

Maternal phenylalanine levels need to be strictly controlled before and during pregnancy so as to not harm the mother or foetus. The first choice of treatment prior to and throughout pregnancy is supervised restriction of dietary phenylalanine. Sapropterin should only be considered if strict dietary management does not adequately reduce blood phenylalanine levels (Briggs 2011).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Sapropterin dihydrochloride is contraindicated in breastfeeding.

The manufacturer recommends that sapropterin dihydrochloride tablets should not be used during breast feeding as it is not known whether sapropterin or its metabolites are excreted in human breast milk. Briggs states that due to the molecular weight (about 241 for the free base) and long half life make it likely to be excreted in human breast milk and so should not be used in breast feeding mothers.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Allergic reaction
Convulsions
Cough
Diarrhoea
Headache
Hypophenylalaninaemia
Increased urination
Nasal congestion
Pharyngolaryngeal pain
Rash
Rebound hyperphenylalaninaemia on withdrawal
Rhinorrhoea
Sleep disorders
Vomiting

Presentation

Soluble tablets containing sapropterin dihydrochloride.

Drugs List

Therapeutic Indications

Uses

Phenylketonuria
Tetrahydrobiopterin deficiency

Dosage

The calculated daily dose is based on a patient's body weight and should be rounded to the nearest multiple of 100.

Adults

Children

Neonates

Additional Dosage Information

Administration

Adults
The prescribed number of tablets should be placed in a glass with 120 to 240 ml of water and stirred until dissolved. The tablets may be crushed to encourage the tablets to dissolve faster. The solution should be drunk within 15 to 20 minutes.

Children above 20 kg body weight
The prescribed number of tablets should be placed in a glass with up to 120 ml of water and stirred until dissolved. The tablets may be crushed to encourage the tablets to dissolve faster. The solution should be drunk within 15 to 20 minutes.

Children up to 20 kg body weight
Depending on the dose (in mg/kg/day) the appropriate number of tablets should be dissolved in a volume of water as stated in the product information, whereby the volume of the solution to be administered is calculated according to the prescribed daily dose.

For small infants who cannot drink from a glass or cup the solution corresponding to the prescribed daily dose may be administered into the mouth via the oral dosing syringe.

Contraindications

Breastfeeding

Precautions and Warnings

Patients over 65 years
Hepatic impairment
History of seizures
Pregnancy
Renal impairment

Treatment to be initiated and supervised by a specialist
Take with food at the same time every day, preferably in the morning
Monitor blood pressure pre-treatment and periodically thereafter
Monitor blood phenylalanine and tyrosine levels
Advise patients on adequate dietary control

Blood phenylalanine and tyrosine levels should be tested one to two weeks after each dose adjustment and monitored frequently thereafter.

There is limited data regarding the long term use of the tablets.

Consultation with a physician is recommended during illness as blood phenylalanine levels may increase.

Pregnancy and Lactation

Pregnancy

Sapropterin dihydrochloride should be used with caution in pregnancy.

There is no clinical data on exposed pregnancies. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.

Maternal phenylalanine levels need to be strictly controlled before and during pregnancy so as to not harm the mother or foetus. The first choice of treatment prior to and throughout pregnancy is supervised restriction of dietary phenylalanine. Sapropterin should only be considered if strict dietary management does not adequately reduce blood phenylalanine levels (Briggs 2011).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Sapropterin dihydrochloride is contraindicated in breastfeeding.

The manufacturer recommends that sapropterin dihydrochloride tablets should not be used during breast feeding as it is not known whether sapropterin or its metabolites are excreted in human breast milk. Briggs states that due to the molecular weight (about 241 for the free base) and long half life make it likely to be excreted in human breast milk and so should not be used in breast feeding mothers.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Allergic reaction
Convulsions
Cough
Diarrhoea
Headache
Hypophenylalaninaemia
Increased urination
Nasal congestion
Pharyngolaryngeal pain
Rash
Rebound hyperphenylalaninaemia on withdrawal
Rhinorrhoea
Sleep disorders
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: September 2015

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Kuvan 100mg soluble tablets. BioMarin International Limited. Revised January 2021.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 23 September 2022