Glycerol phenylbutyrate oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of glycerol phenylbutyrate.
Drugs List
Therapeutic Indications
Uses
Adjunctive therapy in the chronic management of urea cycle disorders
Dosage
Glycerol phenylbutyrate must be used with dietary protein restrictions. Sometimes supplemental amino acid formulations may be necessary to maintain essential amino acids within normal range.
The daily dose should be individually adjusted according to the patient's protein tolerance and the daily dietary protein intake needed.
For dosage information for patients switching from sodium phenylbutyrate or sodium phenylacetate/sodium benzoate injection to glycerol phenylbutyrate and for dose adjustments based on specific measurements (e.g. plasma ammonia, glutamine, urinary phenylacetylglutamine (U-PAGN), phenylacetic acid (PAA)) please refer to product information.
Adults
Body surface area less than 1.3 square metre
Initial: 9.4g per square metre daily in divided doses with meals.
Maintenance: 5.3g per square metre to 12.4g per square metre daily in divided doses with meals.
Body surface area 1.3 square metre and above
Initial: 8g per square metre daily in divided doses with meals.
Maintenance: 5.3g per square metre to 12.4g per square metre daily in divided doses with meals.
The dose should be rounded up to the nearest 0.5ml.
Children
Body surface area less than 1.3 square metre
Initial: 9.4g per square metre daily in divided doses with meals or feeding.
Maintenance: 5.3g per square metre to 12.4g per square metre daily in divided doses with meals or feeding.
Body surface area 1.3 square metre and above
Initial: 8g per square metre daily in divided doses with meals.
Maintenance: 5.3g per square metre to 12.4g per square metre daily in divided doses with meals.
The dose should be rounded up to the nearest 0.1ml for patients less than 2 years of age and 0.5ml for patients 2 years and older.
Patients with Hepatic Impairment
Dosage should be initiated at 5.3g per square metre per day and kept at the lowest dose necessary to control the patient's ammonia levels.
Contraindications
Breastfeeding
Pregnancy
Precautions and Warnings
Elderly
Infection
Post operatively
Hepatic impairment
Malabsorption syndrome
Pancreatic insufficiency
Severe renal impairment
Hepatic impairment: Use the lowest dose to maintain control
Not suitable for treatment of hyperammonaemia
Renal impairment: Use the lowest dose to maintain control
Advise patient dizziness may affect ability to drive or operate machinery
Treatment to be initiated and supervised by a specialist
Monitor ammonia levels in patients with intestinal malabsorption
Monitor ammonia levels in patients with pancreatic insufficiency
Dietary restrictions should be maintained
Female: Ensure adequate contraception during treatment
Advise patient to report nausea, vomiting or feeling confused
Glycerol phenylbutyrate may be required life long unless the patient has a successful liver transplantation.
Acute hyperammonaemia including hyperammonaemic encephalopathy may occur despite being on treatment with glycerol phenylbutyrate.
In patients reporting unexplained somnolence, confusion, nausea and lethargy and who have normal or low ammonia, investigate if high PAA levels are present as reversible clinical manifestations suggestive of neurotoxicity have been reported. In such cases, measure plasma PAA and plasma PAA to phenylacetylglutamine (PAGN) and consider a reduction of the glycerol phenylbutyrate dosage. Alternatively, increase the frequency of dosing if the PAA level exceeds 500mcg/L and the plasma PAA to PAGN ratio exceeds 2.5.
Pregnancy and Lactation
Pregnancy
Glycerol phenylbutyrate is contraindicated during pregnancy.
At the time of writing there is limited data regarding the use of glycerol phenylbutyrate in pregnant women.
Studies in animals have shown reproductive toxicity.
The manufacturer does not recommend glycerol phenylbutyrate during pregnancy.
Lactation
Glycerol phenylbutyrate is contraindicated during breastfeeding.
At the time of writing, it is unknown whether glycerol phenylbutyrate or its metabolites are excreted in breast milk. A risk to the newborn/infant cannot be excluded.
The manufacturer advises a decision must be made to discontinue breastfeeding or to discontinue/abstain from glycerol phenylbutyrate therapy taking into account the benefit of the breastfeeding for the child and the benefit of therapy for the woman.
Side Effects
Abdominal discomfort
Abdominal distension
Abdominal pain
Abnormal faeces
Acne
Alanine aminotransferase increased
Alopecia
Amenorrhoea
Amino acid level decreased
Anaemia
Aspartate aminotransferase increased
Back pain
Biliary pain
Bladder pain
Confusion
Constipation
Decreased appetite
Decreased vitamin D
Depressed mood
Diarrhoea
Dizziness
Dry mouth
Dysgeusia
Dyspepsia
Dysphonia
ECG changes
Eczema
Elevated serum potassium
Elevated triglyceride levels
Epistaxis
Eructation
Faecal urgency
Fatigue
Flatulence
Food aversion
Gamma glutamyl transferase (GGT) increased
Gastro-intestinal infection
Gastroesophageal reflux disease
Headache
Hot flushes
Hunger
Hyperhidrosis
Hypoalbuminaemia
Hypokalaemia
Hypophagia
Hypothyroidism
Increased anion gap
Increased appetite
Increased low density lipoprotein (LDL)
Increases in hepatic enzymes
Irregular menstruation
Joint swelling
Lethargy
Lower abdominal pain
Metrorrhagia
Muscle spasm
Nail ridges
Nasal congestion
Nausea
Oedema of the extremities (arms and legs)
Oral discomfort
Oropharyngeal pain
Painful defaecation
Painful extremities
Paraesthesia
Plantar fasciitis
Prothrombin time increased
Pruritic rash
Psychomotor hyperactivity
Pyrexia
Rash
Reduced lymphocyte count
Retching
Skin odour changes
Somnolence
Speech disturbances
Steatorrhoea
Stomatitis
Throat irritation
Thrombocytosis
Tremor
Upper abdominal pain
Ventricular arrhythmias
Vomiting
Weight gain
Weight loss
White blood cell count raised
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: April 2019
Reference Sources
Summary of Product Characteristics: Ravicti 1.1g/ml oral liquid. Swedish Orphan Biovitrum Ltd. Revised December 2018.
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