Sapropterin


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Hyperphenylalaninaemia due to phenylketonuria Initial: 10 mg/kg once daily, preferably in the morning, adjusted according to desired phenylalanine levels. Usual maintenance dose: 5-20 mg/kg once daily. Hyperalaninaemia due to tetrahydrobiopterin (BH4) deficiency Initial: 2-5 mg/kg once daily, adjusted according to desired phenylalanine levels. Max total dose: 20 mg/kg daily, may be given in 2-3 divided doses.
Dosage Details
Oral
Hyperphenylalaninaemia due to phenylketonuria
Adult: As sapropterin dihydrochloride: Initially, 10 mg/kg once daily, preferably in the morning, adjusted according to desired phenylalanine levels. Usual maintenance dose: 5-20 mg/kg once daily.
Child: ≥4 years Same as adult dose.

Oral
Hyperphenylalaninaemia due to tetrahydrobiopterin (BH4) deficiency
Adult: As sapropterin dihydrochloride: Initially, 2-5 mg/kg once daily, preferably in the morning, adjusted according to desired phenylalanine levels. Max total dose: 20 mg/kg daily, may alternatively be given in 2-3 divided doses.
Child: ≥4 years Same as adult dose.
Reconstitution
Dissolve with 120-240 mL of water or apple juice.
Special Precautions
Patient with history of convulsions. Hepatic and renal impairment. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Gastritis, hyperactivity, hypersensitivity reactions, hypophenylalaninaemia.
Gastrointestinal disorders: Diarrhoea, vomiting, abdominal pain, dyspepsia, nausea.
Nervous system disorders: Headache.
Respiratory, thoracic and mediastinal disorders: Upper respiratory tract infection, rhinorrhoea, cough, nasal congestion, pharyngolaryngeal pain.
MonitoringParameters
Monitor serum phenylalanine and tyrosine levels at baseline, 1 week after treatment, then periodically and regularly thereafter; blood pressure, nutrient intake, psycho-motor development, signs and symptoms of gastritis, hyperactivity.
Overdosage
Symptoms: Headache and dizziness. Management: Symptomatic treatment.
Drug Interactions
Increased excitability, irritability and exacerbation of convulsion with levodopa. May increase the vasodilating effect of phosphodiesterase type-5 (PDE-5) inhibitors, glyceryl trinitrate, isosorbide dinitrate (ISDN). Decreased serum concentration with methotrexate, trimethoprim.
Food Interaction
Increased absorption with food.
Action
Description: Sapropterin is a synthetic form of tetrahydrobiopterin (BH4), an endogenous cofactor for phenylalanine hydroxylase (PAH). PAH enzyme hydroxylates phenylalanine through an oxidative reaction to form tyrosine; PAH activity is absent or deficient in patients with phenylketonuria. Sapropterin enhances the activity of residual PAH hence, improves normal phenylalanine metabolism and decreases serum phenylalanine level concentration.
Onset: Within 24 hours.
Duration: 24 hours.
Pharmacokinetics:
Absorption: Increased absorption with food. Time to peak plasma concentration: 3-4 hours.
Distribution: Distributed mainly to the kidneys, adrenal glands, spleen and liver.
Metabolism: Metabolised in the liver by dihydrofolate reductase and dihydropteridine reductase to dihydrobiopterin and dihydroxanthopterin as main metabolites.
Excretion: Mainly via faeces; urine (small amount). Elimination half-life: Approx 7 hours (range: 4-17 hours).
Chemical Structure

Chemical Structure Image
Sapropterin

Source: National Center for Biotechnology Information. PubChem Database. Sapropterin, CID=135398654, https://pubchem.ncbi.nlm.nih.gov/compound/Sapropterin (accessed on Jan. 23, 2020)

Storage
Store between 20-25°C. Protect from moisture.
Any unused portions should be disposed of in accordance with local requirements.
ATC Classification
A16AX07 - sapropterin ; Belongs to the class of various alimentary tract and metabolism products.
References
Anon. Sapropterin. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 04/06/2018.

Anon. Sapropterin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/06/2018.

Buckingham R (ed). Sapropterin Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/06/2018.

Joint Formulary Committee. Sapropterin Dihydrochloride. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/06/2018.

Kuvan 100 mg Soluble Tablets (BioMarin International Limited). European Medicines Agency [online]. Accessed 04/06/2018.

Kuvan Tablet (BioMarin Pharmaceutical Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 04/06/2018.

Disclaimer: This information is independently developed by MIMS based on Sapropterin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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