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

Hyperammonemia

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%

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
  

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. 

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-
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.