sodium phenylbutyrate (Buphenyl, phenylbutyrate sodium)
Classes: Urea Cycle Disorder Treatment Agents
Dosing and uses of Buphenyl, phenylbutyrate sodium (sodium phenylbutyrate)
Adult dosage forms and strengths
tablet
- 500mg
powder for oral suspension
- 250 g
Urea Cycle Disorders
Indicated as an adjunct to dietary protein restriction and essential amino acid supplementation for the chronic management of patients with urea cycle disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS)
It is indicated in all patients with neonatal-onset deficiency (complete enzymatic deficiency, presenting within the first 28 days of life) and for late-onset disease (partial enzymatic deficiency, presenting after the first month of life) who have a history of hyperammonemic encephalopathy
9.9-13 g/m² PO divided q4-8hr PO; not to exceed 20 g/day
Dosing Considerations
Must be combined with dietary protein restriction and, in some cases, essential amino acid supplementation
Monitor plasma amino acids, ammonia
Sickling Disorders (Orphan)
Orphan designated treatment of disorders including hemoglobinopathies S-S, S-C, and S-thalassemia
Orphan sponsor
- Medicis Pharmaceutical Corp; 8125 N. Hayden Rd; Scottsdale, AZ 85258
Malignant Glioma (Orphan)
Orphan designation for adjunct to surgery, radiation, & chemotherapy in the treatment of primary or recurrent malignant glioma
Orphan sponsor
- Elan Drug Delivery, Inc; 1300 Gould Dr; Gainesville, GA 30504
Spinal Muscular Atrophy (Orphan)
Orphan designation for treatment of spinal muscular atrophy
Orphan sponsors
- Ucyclyd Pharma, Inc; 7720 N. Dobson Rd; Scottsdale, AZ 85256
- Tikvah Therapeutics, Inc; 75 5th St, NW; Atlanta, GA 30308
- GMP-Orphan SAS; 7, rue du Pasteur Wagner, F-75011; Paris, France
Dosing Considerations
Must be combined with dietary protein restriction and, in some cases, essential amino acid supplementation
Monitor plasma amino acids, ammonia
Administration
Take with food in equally divided doses with meals (ie, 3-6 times/day)
Mix powder with solid or liquid food but NOT acidic beverages (eg, orange juice)
Pediatric dosage forms and strengths
tablet
- 500mg
powder for oral suspension
- 250 mg
Urea Cycle Disorders
Indicated as an adjunct to dietary protein restriction and essential amino acid supplementation for the chronic management of patients with urea cycle disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS)
It is indicated in all patients with neonatal-onset deficiency (complete enzymatic deficiency, presenting within the first 28 days of life) and for late-onset disease (partial enzymatic deficiency, presenting after the first month of life) who have a history of hyperammonemic encephalopathy
≥20 kg (tablet or suspension): 9.9-13 g/m² PO divided q4-8hr PO; not to exceed 20 g/day
<20 kg (suspension): 450-600 mg/kg/day divided q4 -6hr PO (solution only)
Administration
Take with food in equally divided doses with meals or feedings (ie, 3-6 times/day)
Mix powder with solid or liquid food but NOT acidic beverages (eg, orange juice)
Buphenyl, phenylbutyrate sodium (sodium phenylbutyrate) adverse (side) effects
>10%
Amenorrhea/dysmenorrhea (23%)
Hypoalbuminemia (11%)
Metabolic acidosis (14%)
1-10%
Anemia (9%)
Anorexia (4%)
Hypophosphatemia (2%)
Hypernatremia (1%)
Hyperuricemia (2%)
Hypokalemia (1%)
Leukopenia (4%)
Strong body odor (3%)
Thrombocytopenia (3%)
Warnings
Contraindications
Hypersensitivity
Acute hyperammonemia
Cautions
Renal insufficiency, hepatic insufficicency, CHF
Patients on restricted sodium intake (contains 125 mg Na/g)
Powder should not be mixed with acidic liquids
May cause sodium and fluid retention; caution in patients that poorly tolerate fluid retention like those with heart failure
Hyperammonemia and hyperammonemic encephalopathy may occur while on therapy (manage hyperammonemia as a medical emergency
Will not reverse existing hyperammonemia-inflicted neurologic damage
Low protein diet recommended with possible amino acid substitution
Pregnancy and lactation
Pregnancy category: C
Lactation: Use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Buphenyl, phenylbutyrate sodium (sodium phenylbutyrate)
Mechanism of action
Decreases elevated plasma ammonia glutamine levels
Prodrug that is rapidly metabolized to phenylacetate which conjugates with glutamine to form phenylacetylglutamine, a nitrogen waste product that is excreted renally
The phenylacetylglutamine conjugate provides an alternate vehicle to urea for waste nitrogen excretion; for each gram of sodium phenylbutyrate administered, it is estimated that between 0.12–0.15 grams of phenylacetylglutamine nitrogen are produced
Absorption
Peak plasma time: 1-1.35 hr (phenylbutyrate); 3.55-3.74 hr (phenylacetate)
Peak plasma concentration: 195-218 mcg/mL (phenylbutyrate); 45.3-48.5 mcg/mL (phenylacetate)
Metabolism
Sodium phenylbutyrate: Liver, and kidney
Elimination
Half-life: 0.8 hr (phenylbutyrate); 1.15-1.29 hr (phenylacetate)
Excretion: Urine 80-100% (as phenylacetylglutamine)
