Sodium phenylbutyrate

Corticosteroids may cause the breakdown of body protein and thus increase plasma ammonia levels. More frequent monitoring of plasma ammonia levels is advised when these medicinal products have to be used.

Since the metabolism and excretion of sodium phenylbutyrate involves the liver and kidneys, sodium phenylbutyrate should be used with caution in patients with hepatic or renal insufficiency.

There have been published reports of hyperammonaemia being induced by haloperidol and by valproate.

Concurrent administration of probenecid may affect renal excretion of the conjugation product of sodium phenylbutyrate.

There are no or limited amount of data from the use of sodium phenylbutyrate in pregnant women. Studies in animals have shown reproductive toxicity. Sodium phenylbutyrate is contra-indicated during pregnancy. Women of childbearing potential must use effective contraception during treatment.

Available pharmacodynamic/toxicological data in animals have shown excretion of sodium phenylbutyrate/metabolites in milk. It is unknown whether sodium phenylbutyrate/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. Sodium phenylbutyrate is contra-indicated during breast-feeding.

Women of childbearing potential/Contraception in males and females

Effective contraceptive measures must be taken by women of child-bearing potential.

Fertility

There is no evidence available on the effect of sodium phenylbutyrate on fertility

Sodium phenylbutyrate has negligible influence on the ability to drive and use machines.

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.

List of adverse reactions

In the list below all adverse reactions are listed 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.

Blood and lymphatic system disorders

Common: anaemia, thrombocytopenia, leukopenia, leukocytosis, thrombocytosis

Uncommon: aplastic anaemia, ecchymosis

Metabolism and nutrition disorders

Common: metabolic acidosis, alkalosis, decreased appetite

Psychiatric disorders

Common: depression, irritability

Nervous system disorders

Common: syncope, headache

Cardiac disorders

Common: oedema

Uncommon: arrhythmia

Gastrointestinal disorders

Common: abdominal pain, vomiting, nausea, constipation, dysgeusia

Uncommon: pancreatitis, peptic ulcer, rectal haemorrhage, gastritis

Skin and subcutaneous tissue disorders

Common: rash, abnormal skin odor

Renal and urinary disorders

Common: renal tubular acidosis

Reproductive system and breast disorders

Very common: amenorrhea, irregular menstruation

Investigations

Common: Decreased blood potassium, albumin, total protein and phosphate. Increased blood 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.