Adverse reactions : תופעות לוואי

4.8       Undesirable effects

Summary of safety profile
In clinical trials with sodium phenylbutyrate, 56 % of the patients experienced at least one adverse event and 78 % of these adverse events were considered as not related to sodium phenylbutyrate.
Adverse reactions mainly involved the reproductive and gastrointestinal system.

Tabulated list of adverse reactions
In the table below all adverse reactions are listed below, by system organ class and by frequency. Frequency is defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
System Organ Class              Frequency                       Adverse reaction anaemia, thrombocytopenia, leukopenia,
Blood and lymphatic system           Common leukocytosis, thrombocytosis disorders
Uncommon                aplastic anaemia, ecchymosis
Metabolism and nutrition                              metabolic acidosis, alkalosis, decreased Common disorders                                                       appetite Psychiatric disorders              Common                     depression, irritability Nervous system disorders            Common                       syncope, headache Common                             oedema
Cardiac disorders
Uncommon                          arrhythmia abdominal pain, vomiting, nausea,
Common constipation, dysgeusia
Gastrointestinal disorders pancreatitis, peptic ulcer, rectal
Uncommon haemorrhage, gastritis
Skin and subcutaneous
Common                     rash, abnormal skin odor tissue disorders
Renal and urinary disorders          Common                      renal tubular acidosis Reproductive system and
Very common             amenorrhea, irregular menstruation breast disorders
Decreased blood potassium, albumin, total protein and phosphate. Increased blood
Investigations                Common              alkaline phosphatase, transaminases, bilirubin, uric acid, chloride, phosphate and sodium. Increased weight

Description of selected adverse reactions
A probable case of toxic reaction to sodium phenylbutyrate (450 mg/kg/d) was reported in an 18-year-old anorectic female patient who developed a metabolic encephalopathy associated with lactic acidosis, severe hypokalaemia, pancytopaenia, peripheral neuropathy, and pancreatitis. She recovered following dose reduction except for recurrent pancreatitis episodes that eventually prompted treatment discontinuation.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il