Drug Interaction:
Drug intreactions- summary-
+ Sodium phenylacetate/sodium benzoate-
Penicillin -
some antibiotics such as penicillin may compete with phenylacetylglutamine and hippurate
for active secretion of renal tubules which affect thte overall dispostion of the infused drug.
Probenecid-
probenecid inhibits the renal transport of amminohippuric acid and affect renal excretion.
Valproic acid-
valproic acid given to patients with UCD may exacerbate the conditions and antagonise the
efficacy of sodiun phenylacetate
Indication:
Hyperammonemia
Adverse Reaction:
CNS- agitation 3% brain edema 5% CNS disorders 22% coma 3%
convulsions NOS 6% mental impairment NOS 6% psychiatric disorders 5%
Dermatologic- skin andsubcutaneous tissue 6%
GI - diarrhea 3% GI disorders 13% nausea 3% vomiting 12%
GU- renal and urinary disorders 4% urinary tract infection 3%
Hematologic/lymphatic - anemia 4% dissemated intravascular coagulation 3%
Metabolic /nutrional - acidosis 3% hyperammonemia 5% hyperglycemia 7%
hypokalemia 7% metabolic acidosis 4%
metbolism and nutrition disorders 21%
Respiratory - respiratory distress 3%
respiratory , thoraic and mediastinal disorders 15%
Miscellaneous- general disorders and administration site conditions 14%
infections 12% infection site reactions 3%
injury poisioning and procedural complications 10%
pyrexia 5%
Contra-Indications:
Hypersensitivity to the drugs
Special Precautions-
Acute symptomatic hyperammonemia- treat any acute episode of symptomatic hyperammonemia
as a life- threatening emergency. Treatment may require dialysis , preferably hemodialysis to remove
a large burden of ammonia. Uncontrolled hyperammonnemia can result in brain damage or death.
Appropiate management of hyperammonemia - perform management of hyperammonemia caused
by inborn errors of metabolism in coordination with medical personnel familiar with these diseases.
The multidisciplinary nature of the treatment usually requires the facilities of a tertiary or quarternary
care center.
Sodium- Use sodium phenylacetate and sodium benzoate with great care., if at all in patients
with congestive heart failure or severe renal insufficiency and in clinical states in which sodium
retention with edema
Extravasation- extravasation of sodium phenylacetate and sodium benzoate into intravenous
tissues may lead to skin necrosis. If extravasation is suspected discontinue the infusion and
resume at a different site, if necessary.
The infusion rate must be monitored closely for possible infiltration during drug administration.
Nausea and vomiting- the infusion has been associated with nausea and vomiting. An antiemetic
may be administered during sodium phenylacetate and sodium benzoate infusion.
Loading doses- because of prolonged plasma levels acheived by phenylacetate in
pharmacokinetic studies do not administer repeat loading doses of sodium phenylacetate
and sodium benzoate.
Use of corticosteroids- may cause breakdown of body protein and thereby potentially increase
plasma ammmonia levels in patients with impaired ability to form urea.
Renal/hepatic function impairment- because sodium phenylacetate and sodium benzoate are
metabolised in the liver and kidney and because phenylacetyglutamine and hippuric acid are
excreted primararily by the kidney, use caution when administering phenylacetate and
sodium benzoate to patients with hepatic and renal impairment.
Pregnancy- give sodium phenylacetate and sodium benzoate to a pregnant woman only if
clearly needed.
Lactation- excercise caution when sodium phenylacetate and sodium benzoate is administered to
a breast feeding woman.
Children- sodium phenylacetate and sodium benzoate has been used for treatment of
hyperammonemia in pediatric patients including patients in the early neonatal period.
Monitoring- ongoing monitoring of neurological status, plasma ammonia levels, clinical
laboratory values, and clinical responses are crucial to assess patient response to treatment.
Perfom blood chemistry profiles and frequent blood pH and pCO2 monitoring
Dosages/ Overdosage Etc:
Indication-
Hyperammonemia
Dosage-
sodium phenylacetate and sodium acetate should be started as soon as diagnosis of
hyperammonemia is made.
Addministered intravenously IV as a loading dose infusion administered over 90 to 120 minutes ,
followed by an equivalent maintenance dose infusion administered over 24 hours.
Patient Information:
Ref - USP PDI Vol II 17th Edition
SODIUM BENZOATE AND SODIUM PHENYLACETATE- SYSTEMIC
1.Allergies-
Tell your doctor if you have ever had any unusual or allergic reaction to
Sodium benzoate and Sodium Phenyl acetate. Also tell your healthcare
care professional if you are allergic to any other substances such
as foods. preservatives or dyes.
2.Pregnancy-
Sodium Benzoate and Sodium Phenylacetate combination has not been
studied in pregnant women and in animls.
3. Breast-feeding-
It is not known whether sodium benzoate and sodium phenylacetate
combination passes into breast milk. Mothers who are taking this
medicine and who wish to breast feed should discuss this with their doctor.
4.Children-
Sodium Benzoate and Sodium phenylacetate may cause serious unwanted
effects if given to infants of low birthweight
5.Older adults-
There is no specific information comparing use of sodium benzoate and
Sodium Phenylacetate in the elderly with use in other age groups.
6. Other medicines-
Tell your doctor if you are using any of the following -
Edema or
Heart disease or
Kidney disease or
Toxemia of pregnancy - Increased retention of water may make the
conditions worse.
Pharmacology/ Pharmacokinetics:
Pharmacology-
Sodium phenylacetate and sodium benzoate are metabolically active compounds that can serve as
alternative to urea for the excretion of waste nitrogen. It can serve as active vehicle effectively
reduce waste nitrogen levels in patients with deficiencies of ureacycle enzymes and thus attentuate
the risk of ammonia and glutamine neurotoxicity
Pregnancy and lactation:
Pregnancy-
Give sodium phenylacetate and sodium benzoate to a pregnant woman only if
clearly needed.
Lactation-
Excercise caution when sodium phenylacetate and sodium benzoate is administered to
a breast feeding woman.
Children-
Sodium phenylacetate and sodium benzoate has been used for treatment of
hyperammonemia in pediatric patients including patients in the early neonatal period.