Buphenyl (Sodium Phenylbutyrate) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

The assessment of clinical adverse events came from 206 patients treated with sodium phenylbutyrate. Adverse events (both clinical and laboratory) were not collected systematically in these patients, but were obtained from patient-visit reports by the 65 co-investigators. Causality of adverse effects is sometimes difficult to determine in this patient population because they may result from either the underlying disease, the patient's restricted diet, intercurrent illness, or BUPHENYL^®. Furthermore, the rates may be under-estimated because they were reported primarily by parent or guardian and not the patient.

Clinical Adverse Events

In female patients, the most common clinical adverse event reported was amenorrhea/menstrual dysfunction (irregular menstrual cycles), which occurred in 23% of the menstruating patients.

Decreased appetite occurred in 4% of all patients. Body odor (probably caused by the metabolite, phenylacetate) and bad taste or taste aversion were each reported in 3% of patients.

Other adverse events reported in 2% or fewer patients were:

Gastrointestinal: abdominal pain, gastritis, nausea and vomiting; constipation, rectal bleeding, peptic ulcer disease, and pancreatitis each occurred in one patient.

Hematologic: aplastic anemia and ecchymoses each occurred in one patient.

Cardiovascular: arrhythmia and edema each occurred in one patient.

Renal: renal tubular acidosis

Psychiatric: depression

Skin: rash

Miscellaneous: headache, syncope, and weight gain

Neurotoxicity was reported in cancer patients receiving intravenous phenylacetate, 250–300 mg/kg/day for 14 days, repeated at 4-week intervals. Manifestations were predominately somnolence, fatigue, and lightheadedness; with less frequent headache, dysgeusia, hypoacusis, disorientation, impaired memory, and exacerbation of a pre-existing neuropathy. These adverse events were mainly mild in severity. The acute onset and reversibility when the phenylacetate infusion was discontinued suggest a drug effect.

Laboratory Adverse Events

In patients with urea cycle disorders, the frequency of laboratory adverse events by body system were:

Metabolic: acidosis (14%), alkalosis and hyperchloremia (each 7%), hypophosphatemia (6%), hyperuricemia and hyperphosphatemia (each 2%), and hypernatremia and hypokalemia (each 1%).

Nutritional: hypoalbuminemia (11%) and decreased total protein (3%).

Hepatic: increased alkaline phosphatase (6%), increased liver transaminases (4%), and hyperbilirubinemia (1%).

Hematologic: anemia (9%), leukopenia and leukocytosis (each 4%), thrombocytopenia (3%), and thrombocytosis (1%).

The clinician is advised to routinely perform urinalysis, blood chemistry profiles, and hematologic tests.

REPORTS OF SUSPECTED BUPHENYL SIDE EFFECTS / ADVERSE REACTIONS

Possible Buphenyl side effects / adverse reactions in 17 year old female

Reported by a individual with unspecified qualification from Japan on 2011-10-25

Patient: 17 year old female weighing 40.8 kg (89.8 pounds)

Reactions: General Physical Condition Abnormal, Vomiting, Ataxia, Stress, Aggression, Irritability, Hyperammonaemia, Dizziness, Gait Disturbance, Salivary Hypersecretion

Adverse event resulted in: hospitalization

Suspect drug(s):
Buphenyl
    Dosage: 1350 mg;qd;po ; 1000 mg;qd
    Administration route: Oral
    Indication: Amino Acid Metabolism Disorder
    Start date: 2011-10-04
    End date: 2011-10-10

Buphenyl
    Dosage: 1350 mg;qd;po ; 1000 mg;qd
    Administration route: Oral
    Indication: Amino Acid Metabolism Disorder
    Start date: 2011-09-22
    End date: 2011-10-03

Other drugs received by patient: Hokunalin Tape 2 MG (Tulobuterol); Cravit Ophthalmic Solution 0.5% (Levofloxacin Hydrate); Asverin Powder (Tipepidine Hibenzate); Amiyu Granule (Essential Amino Acids FOR Renal Insufficiency); Allelock Tablets (Olopatadine Hydrochloride); Pulsmarin A DRY Syrup FOR Pediatric (Ambroxol Hydrochloride); Mucodyne DRY Syrup 50% (L-Carbocisteine); Sulfur and Camphor Lotion (Sulfur and Camphor; Solunim Cream (Fluocinonide)

Possible Buphenyl side effects / adverse reactions in 17 year old female

Reported by a individual with unspecified qualification from Japan on 2011-11-17

Patient: 17 year old female weighing 40.8 kg (89.8 pounds)

Reactions: Irritability, Vomiting, Hyperammonaemia, Dizziness, Ataxia, Gait Disturbance, Salivary Hypersecretion, Aggression

Adverse event resulted in: hospitalization

Suspect drug(s):
Buphenyl
    Dosage: 13500;10000 mg, qd, po
    Administration route: Oral
    Indication: Amino Acid Metabolism Disorder
    Start date: 2011-10-04
    End date: 2011-10-10

Buphenyl
    Dosage: 13500;10000 mg, qd, po
    Administration route: Oral
    Indication: Amino Acid Metabolism Disorder
    Start date: 2011-09-22
    End date: 2011-10-03

Other drugs received by patient: Allelock Tablets (Olopatadine Hydrochloride); Sulfur and Camphor Lotion (Sulfur and Camphor); Asverin Powder (Tipepidine Hibenzate); Amiyu Granule (Essential Amino Acids FOR Renal Insufficiency); Pylsmarin A DRY Syrup Fopr Pediatric (Ambroxol Hydrochloride); Solunim Cream (Flucononide); Mucodyne DRY Syrup (L-Carbocisteine); Hokunalin Tape 2 MG (Tulobuterol); Cravit Ophthalmic Solution (Levofloxacin Hydrate)

Possible Buphenyl side effects / adverse reactions in 17 year old female

Reported by a consumer/non-health professional from Japan on 2011-12-28

Patient: 17 year old female weighing 40.8 kg (89.8 pounds)

Reactions: Personality Change, Vomiting, Ataxia, Impulsive Behaviour, Stress, Aggression, Irritability, Hyperammonaemia, Alopecia, Dizziness, Salivary Hypersecretion, Gait Disturbance

Adverse event resulted in: hospitalization

Suspect drug(s):
Buphenyl
    Dosage: 13500 mg;qd;po 10000 mg;qd;po
    Administration route: Oral
    Indication: Amino Acid Metabolism Disorder
    Start date: 2011-09-22
    End date: 2011-10-03

Buphenyl
    Dosage: 13500 mg;qd;po 10000 mg;qd;po
    Administration route: Oral
    Indication: Amino Acid Metabolism Disorder
    Start date: 2011-10-04
    End date: 2011-10-10

Other drugs received by patient: Mucodyne DRY Syrup 50% (L-Carbocisteine); Amiyu Granule (Essential Amino Acids FOR Renal Insufficiency); Allelock Tablets (Olopatadine Hydrochloride); Hokunalin Tape 2 MG (Tulobuterol); Solunim Cream (Fluocinonide); Pulsmarin A DRY Syrup FOR Pediatric (Ambroxol Hydrochloride); Sulfur and Camphor Lotion (Sulfur and Camphor); Asverin Powder (Tipepidine Hibenzate); Cravit Ophthalmic Solution 0.5% (Levofloxacin Hydrate)