Sodium phenylbutyrate


Generic Medicine Info
Indications and Dosage
Oral
Adjunct for hyperammonaemia in patients with urea cycle disorders
Adult: Adjunctive therapy in chronic management of urea cycle disorders, involving deficiencies of carbamoyl phosphate synthetase, ornithine transcarbamylase or argininosuccinate synthetase; in patients with neonatal-onset deficiency (complete enzymatic deficiency, presenting within the 1st 28 days of life), or late-onset disease (partial enzymatic deficiency, presenting after the 1st month of life) who have a history of hyperammonaemic encephalopathy: Usual total daily dose: 9.9-13 g/m2 daily; given in equally divided doses and with each meal (e.g. 3-6 times daily). Max: 20 g daily. Daily dosage must be individualised and adjusted according to patient’s protein tolerance and daily dietary protein intake. Therapy must be used in combination with a protein-restricted diet, and essential amino acid or carnitine supplementation if required.
Child: Adjunctive therapy in chronic management of urea cycle disorders, involving deficiencies of carbamoyl phosphate synthetase, ornithine transcarbamylase or argininosuccinate synthetase; in patients with neonatal-onset deficiency (complete enzymatic deficiency, presenting within the 1st 28 days of life), or late-onset disease (partial enzymatic deficiency, presenting after the 1st month of life) who have a history of hyperammonaemic encephalopathy: Usual total daily dose: <20 kg: 0.45-0.6 g/kg daily; given in equally divided doses and with each meal/feeding (e.g. 3-6 times daily). Max: 20 g daily; ≥20 kg: Same as adult dose. Daily dosage must be individualised and adjusted according to patient’s protein tolerance and daily dietary protein intake. Therapy must be used in combination with a protein-restricted diet, and essential amino acid or carnitine supplementation if required.
Administration
Should be taken with food.
Contraindications
Management of acute hyperammonaemia. Pregnancy and lactation.
Special Precautions
Patient with CHF, conditions that involve Na retention with oedema, inborn errors of β-oxidation, restricted Na intake, and diabetes mellitus. Patients who require caloric supplementation should receive protein-free caloric supplements. Renal and hepatic impairment. Children.
Adverse Reactions
Significant: Na and fluid retention; signs and symptoms of neurotoxicity (e.g. somnolence, headache, lightheadedness, fatigue, hypoacusis, dysgeusia, disorientation, exacerbation of preexisting neuropathy, impaired memory).
Blood and lymphatic system disorders: Thrombocytopenia, anaemia, leucopenia, leucocytosis, thrombocytosis.
Cardiac disorders: Syncope.
Gastrointestinal disorders: Nausea, vomiting, constipation, abdominal pain.
Investigations: Decreased serum total protein, increased serum alkaline phosphatase and liver transaminases, increased weight.
Metabolism and nutrition disorders: Metabolic acidosis, alkalosis, hypoalbuminaemia, hyperbilirubinaemia, hyperuricaemia, hyperchloraemia, hypernatraemia, hypophosphataemia, hyperphosphataemia, hypokalaemia, oedema, decreased appetite.
Psychiatric disorders: Irritability, depression.
Renal and urinary disorders: Renal tubular acidosis.
Reproductive system and breast disorders: Irregular menstruation, amenorrhoea.
Skin and subcutaneous tissue disorders: Rash, abnormal skin odour.
Potentially Fatal: Acute hyperammonaemia or acute hyperammonaemic encephalopathy.
Monitoring Parameters
Monitor plasma ammonia levels, serum electrolytes, CBC with differential, serum proteins and plasma amino acid quantitation, urinalysis, hepatic and renal function tests. Monitor nutritional parameters (e.g. weight, height, albumin, head circumference), and for signs and symptoms of hyperammonaemia (e.g. vomiting, confusion, lethargy, ataxia, seizures, memory impairment).
Overdosage
Symptoms: Diarrhoea, irritability, metabolic acidosis, hypokalaemia, and manifestations of neurotoxicity. Management: Supportive and symptomatic treatment. May perform haemodialysis or peritoneal dialysis.
Drug Interactions
Concurrent use with probenecid may affect renal excretion of conjugated products which may increase serum concentrations of phenylacetate and phenylacetylglutamine. Valproates and haloperidol may increase plasma ammonia levels thus diminishing the therapeutic effect of Na phenylbutyrate. Corticosteroids may increase protein catabolism and plasma ammonia concentrations.
Action
Description: Sodium phenylbutyrate, a prodrug, is rapidly converted to phenylacetate which conjugates with glutamine to form phenylacetylglutamine. Phenylacetylglutamine then serves as a substitute for urea in excreting nitrogenous waste from the body via urine.
Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration: 1-1.35 hours (phenylbutyrate); 3.55-3.74 hours (phenylacetate); approx 3.23 hours (phenylacetylglutamine).
Distribution: Volume of distribution: 0.2 L/kg.
Metabolism: Rapidly oxidised to phenylacetate followed by conjugation with glutamine via acetylation in the liver and kidney to form phenylacetylglutamine.
Excretion: Via urine (80-100% as phenylacetylglutamine). Elimination half-life: Approx 0.8 hours (phenylbutyrate); approx 1.3 hours (phenylacetate); approx 2.4 hours (phenylacetylglutamine).
Chemical Structure

Chemical Structure Image
Sodium phenylbutyrate

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5258, Sodium phenylbutyrate. https://pubchem.ncbi.nlm.nih.gov/compound/Sodium-phenylbutyrate. Accessed Sept. 24, 2021.

Storage
Store between 15-30°C.
MIMS Class
Antidotes & Detoxifying Agents
ATC Classification
A16AX03 - sodium phenylbutyrate ; Belongs to the class of various alimentary tract and metabolism products.
References
Ammonaps 500 mg Tablets and 940 mg/g Granules (Immedica Pharma AB). European Medicines Agency [online]. Accessed 23/08/2021.

Anon. Sodium Phenylbutyrate. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 19/07/2021.

Buckingham R (ed). Glycerol Phenylbutyrate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 19/07/2021.

Buphenyl Tablet and Powder (Horizon Therapeutics USA, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 19/07/2021.

Joint Formulary Committee. Sodium Phenylbutyrate. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 19/07/2021.

Pheburane 483 mg/g Granules (Eurocept International BV). MHRA. https://products.mhra.gov.uk. Accessed 19/07/2021.

Disclaimer: This information is independently developed by MIMS based on Sodium phenylbutyrate 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 © 2022 MIMS. All rights reserved. Powered by MIMS.com
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