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Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety data were obtained from 316 patients who received AMMONUL as emergency (rescue) or prospective treatment for hyperammonemia as part of an uncontrolled, open-label study. The study population included patients between the ages of 0 to 53 years with a mean (SD) of 6.2 (8.54) years; 51% were male and 49% were female who had the following diagnoses: OTC (46%), ASS (22%), CPS (12%), ASL (2%), ARG ( < 1%), THN ( < 1%), and other (18%).
Table 2: Adverse Reactions Occurring in ≥ 3% of
Patients Treated with AMMONUL
|Number of patients with any adverse event||163 (52%)|
|Blood and lymphatic system disorders||35 (11%)|
|Disseminated intravascular coagulation||11 (3%)|
|Cardiac disorders||28 (9%)|
|Gastrointestinal disorders||42 (13%)|
|General disorders and administration-site conditions||45 (14%)|
|Injection-site reaction||11 (3%)|
|Urinary tract infection||9 (3%)|
|Injury, poisoning and procedural complications||12 (4%)|
|Metabolism and nutrition disorders||67 (21%)|
|Metabolic acidosis||13 (4%)|
|Nervous system disorders||71 (22%)|
|Brain edema||17 (5%)|
|Mental impairment||18 (6%)|
|Psychiatric disorders||16 (5%)|
|Renal and urinary disorders||14 (4%)|
|Respiratory, thoracic and mediastinal disorders||47 (15%)|
|Respiratory distress||9 (3%)|
|Skin and subcutaneous tissue disorders||19 (6%)|
|Vascular disorders||19 (6%)|
Adverse reactions were reported with similar frequency in patients with OTC, ASS, CPS, and diagnoses categorized as “other.” Nervous system disorders were more frequent in patients with OTC and CPS, compared with patients with ASS and patients with “other” diagnoses. Convulsions and mental impairment were reported in patients with OTC and CPS. These observations are consistent with literature reports that patients with enzyme deficiencies occurring earlier in the urea cycle (i.e., OTC and CPS) tend to be more severely affected.
Adverse reactions profiles differed by age group. Patients ≤ 30 days of age had more blood and lymphatic system disorders and vascular disorders (specifically hypotension), while patients > 30 days of age had more gastrointestinal disorders (specifically nausea, vomiting and diarrhea).
Less common adverse reactions ( < 3% of patients) that are characterized as severe are listed below by body system.
EYE DISORDERS: blindness
GASTROINTESTINAL DISORDERS: abdominal distension, gastrointestinal hemorrhage
GENERAL DISORDERS AND ADMINISTRATION-SITE CONDITIONS: asthenia, brain death, chest pain, multiorgan failure, edema
NERVOUS SYSTEM DISORDERS: areflexia, ataxia, brain infarction, brain hemorrhage, cerebral atrophy, clonus, depressed level of consciousness, encephalopathy, nerve paralysis, intracranial pressure increased, subdural hematoma, tremor
PSYCHIATRIC DISORDERS: acute psychosis, aggression, confusional state, hallucinations
RENAL AND URINARY DISORDERS: anuria, renal failure, urinary retention
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS: acute respiratory distress syndrome, dyspnea, hypercapnia, hyperventilation, Kussmaul respiration, pneumonia aspiration, pneumothorax, pulmonary hemorrhage, pulmonary edema, respiratory acidosis or alkalosis, respiratory arrest/failure
Read the Ammonul (sodium phenylacetate and sodium benzoate injection) Side Effects Center for a complete guide to possible side effects
Formal drug interaction studies have not been performed with AMMONUL.
Probenecid is known to inhibit the renal transport of many organic compounds, including aminohippuric acid, and may affect renal excretion of phenylacetylglutamine and hippurate.
There have been reports that valproic acid can induce hyperammonemia through inhibition of the synthesis of N-acetylglutamate, a co-factor for carbamyl phosphate synthetase. Therefore, administration of valproic acid to patients with urea cycle disorders may exacerbate their condition and antagonize the efficacy of AMMONUL.
Use of corticosteroids may cause a protein catabolic state and, thereby, potentially increase plasma ammonia levels in patients with impaired ability to form urea.
Read the Ammonul Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 3/23/2016
Additional Ammonul Information
- Ammonul Drug Interactions Center: sodium benzoate-sod phenylacet iv
- Ammonul Side Effects Center
- Ammonul FDA Approved Prescribing Information including Dosage
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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