BNF for Children (BNFC) 2018-2019

product entry inBNF for Children; the child or carer should
be informed of this.
Some rare formsof phenylketonuriaare caused by a
deficiency oftetrahydrobiopterin. Treatment involves oral
supplementation of tetrahydrobiopterin below; in some
severe cases, the addition of the neurotransmitter
precursors, levodopa and 5 -hydroxytryptophan, is also
necessary.
Sapropterin dihydrochloride below, a synthetic form of
tetrahydrobiopterin, is licensed as an adjunct to dietary
restriction ofphenylalaninein the management of patients
withphenylketonuriaandtetrahydrobiopterin deficiency.

Products for metabolic diseases

There is a large range of disease-specific infant formulas and
amino acid-based supplements available for use in children
with metabolic diseases (see under specific metabolic
diseases). Some of these formulas are nutritionally
incomplete and supplementation with vitamins and other
nutrients may be necessary. Many of the product names are
similar; to prevent metabolic complications in children who
cannot tolerate specific amino acids it is important to ensure
the correct supplement is supplied.

6.1a Phenylketonuria

DRUGS FOR METABOLIC DISORDERS›

TETRAHYDROBIOPTERIN AND DERIVATIVES

Sapropterin dihydrochloride

lINDICATIONS AND DOSE

Phenylketonuria (adjunct to dietary restriction of

phenylalanine) (specialist use only)

▶BY MOUTH

▶Child 4–17 years:Initially 10 mg/kg once daily, adjusted

according to response; usual dose 5 – 20 mg/kg once

daily, dose to be taken preferably in the morning

Tetrahydrobiopterin deficiency (adjunct to dietary

restriction of phenylalanine) (specialist use only)

▶BY MOUTH

▶Neonate:Initially 2 – 5 mg/kg once daily, adjusted

according to response, dose to be taken preferably in the

morning, the total daily dose may alternatively be given

in 2 – 3 divided doses; maximum 20 mg/kg per day.

▶Child:Initially 2 – 5 mg/kg once daily, adjusted

according to response, dose to be taken preferably in

the morning, the total daily dose may alternatively be

given in 2 – 3 divided doses; maximum 20 mg/kg per day

lCAUTIONSHistory of convulsions

lINTERACTIONS→Appendix 1 : sapropterin

lSIDE-EFFECTS
▶Common or very commonAbdominal pain.cough.
diarrhoea.headache.laryngeal pain.nasal congestion.
vomiting
▶Frequency not knownHypersensitivity

lPREGNANCYManufacturer advises caution—consider only
if strict dietary management inadequate.

lBREAST FEEDINGManufacturer advises avoid—no
information available.

lHEPATIC IMPAIRMENTManufacturer advises caution—no
information available.

lRENAL IMPAIRMENTManufacturer advises caution—no
information available.

lMONITORING REQUIREMENTS
▶Monitor blood-phenylalanine concentration before and
afterfirst week of treatment—if unsatisfactory response

increase dose at weekly intervals to max. dose and monitor

blood-phenylalanine concentration weekly; discontinue

treatment if unsatisfactory response after 1 month.

▶Monitor blood-phenylalanine and tyrosine concentrations

1 – 2 weeks after dose adjustment and during treatment.

lDIRECTIONS FOR ADMINISTRATIONTablets should be

dissolved in water and taken within 20 minutes.

lPRESCRIBING AND DISPENSING INFORMATIONSapropterin

is a synthetic form of tetrahydrobiopterin.

lPATIENT AND CARER ADVICEPatient or carers should be

given advice on how to administer sapropterin

dihydrochloride dispersible tablets.

lMEDICINAL FORMS

There can be variation in the licensing of different medicines

containing the same drug.

Soluble tablet

CAUTIONARY AND ADVISORY LABELS13, 21

▶Kuvan(BioMarin Europe Ltd)

Sapropterin dihydrochloride 100 mgKuvan 100 mg soluble tablets

sugar-free| 30 tabletP£ 597. 22

Tetrahydrobiopterin

lINDICATIONS AND DOSE

Monotherapy in tetrahydrobiopterin-sensitive

phenylketonuria (specialist use only)

▶BY MOUTH

▶Child: 10 mg/kg twice daily, adjusted according to

response, total daily dose may alternatively be given in

3 divided doses

In combination with neurotransmitter precursors for

tetrahydrobiopterin-sensitive phenylketonuria

(specialist use only)

▶BY MOUTH

▶Child 1 month–1 year:Initially 250 – 750 micrograms/kg

4 times a day, adjusted according to response, total

daily dose may alternatively be given in 3 divided

doses; maximum 7 mg/kg per day

▶Child 2–17 years:Initially 250 – 750 micrograms/kg

4 times a day, adjusted according to response, total

daily dose may alternatively be given in 3 divided

doses; maximum 10 mg/kg per day

lUNLICENSED USENot licensed.

lSIDE-EFFECTSDiarrhoea.sleep disorder.urinary

frequency increased

lPREGNANCYCrosses the placenta; use only if benefit

outweighs risk.

lBREAST FEEDINGPresent in milk, effects unknown.

lRENAL IMPAIRMENTUse with caution—accumulation of

metabolites.

lMEDICINAL FORMS

No licensed medicines listed.

7 Vitamin deficiency

Vitamins

Overview

Vitamins are used for the prevention and treatment of

specificdeficiency states or where the diet is known to be

inadequate; they may be prescribed in the NHS to prevent or

treat deficiency but not as dietary supplements. Except for

iron-deficiency anaemia, a primary vitamin or mineral

deficiency due to simple dietary inadequacy is rare in the

developed world. Some children may be at risk of developing

BNFC 2018 – 2019 Vitamin deficiency 623

Blood and nutrition

9