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Sodium phenylbutyrate oral

Updated 2 Feb 2023 | Urea cycle disorders

Presentation

Oral formulations containing sodium phenylbutyrate

Drugs List

  • AMMONAPS 500mg tablets
  • PHEBURANE 483mg/1g granules
  • sodium phenylbutyrate 483mg/g granules
  • sodium phenylbutyrate 500mg tablets
  • Therapeutic Indications

    Uses

    Adjunctive therapy in the chronic management of urea cycle disorders

    Adjunctive therapy in the chronic management of urea cycle disorders, involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase, or argininosuccinate synthetase. It is indicated in all patients with neonatal-onset presentation (complete enzyme deficiencies, presenting within the first 28 days of life). It is also indicated in patients with late-onset disease (partial enzyme deficiencies, presenting after the first month of life) who have a history of hyperammonaemic encephalopathy.

    Dosage

    The daily dose should be individually adjusted according to the patient's protein tolerance and the daily dietary protein intake needed to promote growth and development.

    Adults

    Total daily dose: 9.9g/square metre to 13g/square metre taken in divided doses with meals.

    The safety and efficacy of total daily doses of greater than 20g have not been studied.

    Children

    Children weighing more than 20kg
    9.9g/square metre to 13g/square metre per day, taken in divided doses with meals.

    The safety and efficacy of total daily doses of greater than 20g have not been studied.

    Children weighing less than 20kg
    450mg/kg to 600mg/kg daily, taken in divided doses with meals.

    The safety and efficacy of total daily doses of greater than 20g have not been studied.

    The following alternative dosing schedule may be suitable:

    Children weighing more than 20kg
    5g/square metre daily, taken in three or four divided doses with meals.
    Maximum dose: 12g daily.

    Children weighing less than 20kg
    Up to 250mg/kg daily, taken in three or four divided doses with meals.

    Neonates

    450mg/kg to 600mg/kg daily (granules only).

    The following alternative dosing schedule may be suitable:

    Up to 250mg/kg daily, taken in three to four divided doses with feeds.

    Additional Dosage Information

    Tablets should be taken with a large volume of water.

    When taken orally, granules should be mixed with solid foods (e.g. mashed potato or apple sauce) or liquid foods (e.g. water, apple or orange juice or protein-free infant formulas). Granules prepared for oral administration should be taken immediately.

    The sodium phenylbutyrate 940mg/g granules can be administered via gastrostomy or nasogastric tube. For administration by tube, mix with water.

    Contraindications

    Breastfeeding
    Pregnancy

    Precautions and Warnings

    Predisposition to sodium and water retention
    Restricted sodium intake
    Congestive cardiac failure
    Glucose-galactose malabsorption syndrome
    Hepatic impairment
    Hereditary fructose intolerance
    Renal impairment

    Treatment to be initiated and supervised by a specialist
    Contains 124mg (5.4mmol) of sodium per gram of sodium phenylbutyrate
    Some brands contain sucrose. Consult specific brand literature
    Monitor haematological parameters periodically
    Monitor serum potassium periodically
    Plasma glutamine should be maintained at levels less than 1000 micromoles/l
    Female: Ensure adequate contraception during treatment

    Pregnancy and Lactation

    Pregnancy

    Sodium phenylbutyrate is contraindicated during pregnancy.

    At the time of writing there is insufficient information available to assess the effect/s of sodium phenylbutyrate on the foetus. Animal studies have shown that sodium phenylbutyrate has reproductive toxicity. Exposure to the active metabolite of sodium phenylbutyrate (phenyl acetate) caused lesions on cortical pyramidal cells, as well as, longer, thinner and fewer dendritic spines in rat pups.

    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

    Sodium phenylbutyrate is contraindicated in breastfeeding.

    At the time of writing there is insufficient information to asses the effect/s of sodium phenylbutyrate on a breastfeeding infant. It is not known whether sodium phenylbutyrate is excreted in breast milk.

    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
    Acidosis
    Alkalosis
    Amenorrhoea
    Anaemia
    Aplastic anaemia
    Body odour
    Cardiac arrhythmias
    Constipation
    Decreased appetite
    Depression
    Dysgeusia
    Ecchymosis
    Gastritis
    Headache
    Hyperbilirubinaemia
    Hyperchloraemia
    Hypernatraemia
    Hyperphosphataemia
    Hyperuricaemia
    Hypoalbuminaemia
    Hypokalaemia
    Hypophosphataemia
    Hypoproteinaemia
    Increase in alkaline phosphatase
    Increase of liver transaminases
    Irregular menstruation
    Irritability
    Leucocytosis
    Leucopenia
    Nausea
    Oedema
    Pancreatitis
    Peptic ulceration
    Rash
    Rectal bleeding
    Renal tubular acidosis
    Syncope
    Taste disturbances
    Thrombocytopenia
    Thrombocytosis
    Unpleasant taste
    Vomiting
    Weight gain

    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: May 2014

    Reference Sources

    Summary of Product Characteristics: AMMONAPS 500 mg tablets. Swedish Orphan International AB, Sweden. Revised March 2014.
    Summary of Product Characteristics: AMMONAPS 940 mg/g granules. Swedish Orphan International AB, Sweden. Revised March 2014.

    Summary of Product Characteristics: PHEBURANE 483 mg/g granules. Lucane Pharma. Revised August 2013.

    NICE Evidence Services Available at: www.nice.org.uk Last accessed: 05 September 2017

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