SODIUM PHENYLBUTYRATE tablet

Nchi: Marekani

Lugha: Kiingereza

Chanzo: NLM (National Library of Medicine)

Viambatanisho vya kazi:

SODIUM PHENYLBUTYRATE (UNII: NT6K61736T) (PHENYLBUTYRIC ACID - UNII:7WY7YBI87E)

Inapatikana kutoka:

GLENMARK PHARMACEUTICALS INC., USA

Njia ya uendeshaji:

ORAL

Dawa ya aina:

PRESCRIPTION DRUG

Matibabu dalili:

Sodium phenylbutyrate tablets are indicated as adjunctive therapy in 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). It is also indicated in patients with late-onset disease (partial enzymatic deficiency, presenting after the first month of life) who have a history of hyperammonemic encephalopathy. It is important that the diagnosis be made early and treatment initiated immediately to improve survival. Any episode of acute hyperammonemia should be treated as a life-threatening emergency. Sodium phenylbutyrate tablets must be combined with dietary protein restriction and, in some cases, essential amino acid supplementation (see Nutritional Supplementation subsection of the DOSAGE AND ADMINISTRATION section). Previously, neonatal-onset disease was almost universally fatal within the first year of life, even when treated with peritoneal dialysis and essential amino acids or their nitrogen-free analogs. However, with hemodialysis, use of alternative waste nitrogen excretion pathways (sodium phenylbutyrate, sodium benzoate, and sodium phenylacetate), dietary protein restriction, and, in some cases, essential amino acid supplementation, the survival rate in newborns diagnosed after birth but within the first month of life is almost 80%. Most deaths have occurred during an episode of acute hyperammonemic encephalopathy. Patients with neonatal-onset disease have a high incidence of mental retardation. Those who had IQ tests administered had an incidence of mental retardation as follows: ornithine transcarbamylase deficiency, 100% (14/14 patients tested); argininosuccinic acid synthetase deficiency, 88% (15/17 patients tested); and carbamylphosphate synthetase deficiency, 57% (4/7 patients tested). Retardation was severe in the majority of the retarded patients. In patients diagnosed during gestation and treated prior to any episode of hyperammonemic encephalopathy, survival is 100%, but even in these patients, most subsequently demonstrate cognitive impairment or other neurologic deficits. In late-onset deficiency patients, including females heterozygous for ornithine transcarbamylase deficiency, who recover from hyperammonemic encephalopathy and are then treated chronically with sodium phenylbutyrate and dietary protein restriction, the survival rate is 98%. The two deaths in this group of patients occurred during episodes of hyperammonemic encephalopathy. However, compliance with the therapeutic regimen has not been adequately documented to allow evaluation of the potential for sodium phenylbutyrate tablets and dietary protein restriction to prevent mental deterioration and recurrence of hyperammonemic encephalopathy if carefully adhered to. The majority of these patients tested (30/46 or 65%) have IQ’s in the average to low average/borderline mentally retarded range. Reversal of preexisting neurologic impairment is not likely to occur with treatment and neurologic deterioration may continue in some patients. Even on therapy, acute hyperammonemic encephalopathy recurred in the majority of patients for whom the drug is indicated. Sodium phenylbutyrate tablets may be required lifelong unless orthotopic liver transplantation is elected. (See CLINICAL PHARMACOLOGY, Pharmacodynamics subsection for the biochemical effects of sodium phenylbutyrate tablets). Sodium phenylbutyrate tablets should not be used to manage acute hyperammonemia, which is a medical emergency.

Bidhaa muhtasari:

Sodium Phenylbutyrate Tablets, USP are available in 300 cc bottles which contain 250 sodium phenylbutyrate tablets, USP (NDC 68462-853-20). The bottles are equipped with child-resistant caps. Each tablet is off-white, oval shaped, and debossed with ‘G853’ on one side and plain on the other side. Each tablet contains 500 mg of sodium phenylbutyrate, USP. Store at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. AFTER OPENING, KEEP BOTTLE TIGHTLY CLOSED. Preserve in tight containers. All trademarks are the property of their respective owners. Manufactured by: Glenmark Pharmaceuticals Limited Pithampur, Madhya Pradesh 454775, India Manufactured for: Glenmark Pharmaceuticals Inc., USA Mahwah, NJ 07430 Questions? 1 [phone] www.glenmarkpharma-us.com August 2022

Idhini hali ya:

Abbreviated New Drug Application

Tabia za bidhaa

SODIUM PHENYLBUTYRATE- SODIUM PHENYLBUTYRATE TABLET
GLENMARK PHARMACEUTICALS INC., USA
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SODIUM PHENYLBUTYRATE TABLETS, USP
RX ONLY
DESCRIPTION
Sodium Phenylbutyrate Tablets, USP for oral administration contain
sodium
phenylbutyrate, USP. Sodium phenylbutyrate is a white to
yellowish-white powder which
is freely soluble in water and has a strong salty taste. Sodium
phenylbutyrate also is
freely soluble in methanol, sparingly soluble in ethanol and
practically insoluble in
methylene chloride, acetone and diethyl ether. It is known chemically
as 4-phenylbutyric
acid, sodium salt with a molecular weight of 186.18 g/mol and the
molecular formula
C
H
O Na.
Chemical Structure:
Each tablet of sodium phenylbutyrate tablets, USP contains 500 mg of
sodium
phenylbutyrate, USP and the inactive ingredients calcium stearate,
colloidal silicon
dioxide, magnesium stearate and microcrystalline cellulose.
FDA approved dissolution specifications differs from the USP.
CLINICAL PHARMACOLOGY
Sodium phenylbutyrate is a pro-drug and is rapidly metabolized to
phenylacetate.
Phenylacetate is a metabolically active compound that conjugates with
glutamine via
acetylation to form phenylacetylglutamine. Phenylacetylglutamine then
is excreted by the
kidneys. On a molar basis, it is comparable to urea (each containing
two moles of
nitrogen). Therefore, phenylacetylglutamine provides an alternate
vehicle for waste
nitrogen excretion.
PHARMACOKINETICS
GENERAL:
10
11
2
Pharmacokinetic studies have not been conducted in the primary patient
population
(neonates, infants, and children), but pharmacokinetic data were
obtained from normal
adult subjects.
ABSORPTION:
Peak plasma levels of phenylbutyrate occur within 1 hour after a
single dose of 5 grams
of sodium phenylbutyrate tablet with a C
of 218 mcg/mL under fasting conditions.
The effect of food on phenylbutyrate’s absorption is unknown.
DISPOSITION:
The overall disposition of sodium phenylbutyrate and its metabolites
has not been
characterized fully. However, the drug is known to be me