Index of drugs

The drug is indicated as an adjunctive treatment in chronic therapy of urea cycle disorders, including deficiency of carbamoylphosphate synthetase, ornithine carbamoyltransferase or argininosuccinate synthetase. This drug is indicated for all patients with a disease that manifests in the neonatal period (total enzyme deficiencies occurring within the first 28 days of life). The drug is also indicated in patients whose disease appeared later (partial enzyme deficiency, occurring after the first month of life), with hyperammonaemic encephalopathy.

1 tabl contains 500 mg of sodium phenylbutyrate; 1 tabl contains 62 mg of sodium. 1 g of the granulate contains 940 mg of sodium phenylbutyrate; 1 small spoon of granules contains 149 mg of sodium; 1 medium spoon of granulate contains 408 mg of sodium; 1 large spoon of granules contains 1200 mg of sodium.

Sodium phenylbutyrate is a pro-drug that is rapidly converted to phenylacetate. Phenylacetate is a metabolically active compound that binds to glutamine through acetylation and forms phenylacetyl glutamine, which is then excreted through the kidneys. Phenylacetylglutamine is an alternative carrier for the excretion of excess nitrogen. Based on studies of phenylacetylglutamine excretion in patients with urea cycle disorders, it is possible to estimate that for each gram of the given sodium phenylbutyrate, 0.12-0.15 g of phenylacetylglutamine nitrogen is formed. Therefore, sodium phenylbutyrate reduces elevated levels of ammonia and glutamine in the blood plasma in patients with urea cycle disorders. Phenylbutyrate is rapidly absorbed after administration on an empty stomach. Average time to reach C_max is 1.35 h after tablet administration and 1 h after granule administration. T_0,5 in the elimination phase, estimated at 0.8 h. After a single dose of 5 g sodium phenylbutyrate, the average time to reach C_max phenylacetyl and phenylacetylglutamine are 3.74 h and 3.43 h (tablets) and 3.55 h and 3.23 h (granules), respectively. T_0,5 in the phase of elimination of phenylacetate and phenylacetylglutamine were estimated for 1.2 h and 2.4 h (tablets) and 1.3 h and 2.4 h (granules), respectively. Approx. 80-100% of the drug is excreted by the kidneys within 24 hours in the form of phenylacetylglutamine.

Hypersensitivity to the active substance or any of the excipients. Pregnancy and breastfeeding.

The drug should be used with caution in patients with impaired liver or kidneys. During the course of treatment, serum potassium should be monitored because excretion of phenylacetylglutamine through the kidneys may cause loss of potassium in the urine. Also during treatment, acute hyperammonaemic encephalopathy may occur in many patients. The drug is not recommended for the treatment of acute hyperammonaemia, which is an emergency medical emergency requiring immediate medical attention. For children who are unable to swallow the tablet, it is recommended to administer the medicine as granules. The tablets should not be used in patients with dysphagia (difficult swallowing) due to the potential risk of oesophageal ulcerations if the tablets are not rapidly transferred to the stomach. 1 tabl contains 62 mg (2.7 mmol) of sodium, and 1 g of granules contains 124 mg (5.4 mmol) of sodium corresponding to 2.5 g (108 mmol) of sodium per 20 g of sodium phenylbutyrate - these amounts constitute the maximum daily dose. Therefore, caution should be exercised when using the product in patients with congestive heart failure or severe renal failure and in clinical conditions where sodium retention occurs with edema.

The use of the drug during pregnancy and breastfeeding is contraindicated. Women of childbearing age must use effective methods of contraception.

Very common: lack of menstruation, irregular menstruation. Common: anemia, thrombocytopenia, leukopenia, leukocytosis, thrombocytosis, metabolic acidosis, alkalosis, decreased appetite, depression, irritability, fainting, headache, edema, abdominal pain, vomiting, nausea, constipation, disorder of taste, rash, other than usual skin odor , renal tubular acidosis, reduction of potassium, albumin, total protein and phosphate in the blood, increase in alkaline phosphatase in the blood, transaminases, increased bilirubin, uric acid, chloride, phosphate and sodium, weight gain. Uncommon: aplastic anemia, ecchymosis, arrhythmia, pancreatitis, peptic ulcers, rectal bleeding, gastritis.A likely toxic response to drug administration (450 mg / kg / day) was observed in an 18-year-old woman suffering from anorexia, who developed metabolic encephalopathy in association with lactic acidosis, severe hyperkalemia, aplastic anemia, peripheral neuropathy and pancreatitis. After reducing the dose, the patient improved, except for episodes of recurrent pancreatitis, which eventually resulted in discontinuation of therapy with the product.

Treatment should be supervised by a doctor who has experience in the treatment of urea cycle disorders. The daily dose should be individually adjusted taking into account the patient's protein tolerance and the daily intake of protein necessary for normal growth and development. Usually the total daily dose of sodium phenylbutyrate in the clinical trial is: in newborns, infants and children at birth. less than 20 kg - 450-600 mg / kg / day; in children about the month of more than 20 kg, youth and adults - 9.9-13.0 g / m² pc./dobę. The safety and efficacy of doses greater than 20 g / day have not been established. Concentrations of ammonia, arginine, essential amino acids (especially branched chain amino acids), Carnitine and proteins in the blood plasma should be normal. The concentration of glutamine in the blood plasma should be less than 1000 μmol / l. The drug should be used together with a diet limiting protein intake, and in some cases with supplementation of essential amino acids and carnitine. In patients with a deficiency of carbamylphosphate synthetase or ornithine carbamoyltransferase diagnosed in the neonatal period, supplementation of citrulline or arginine in the amount of 0.17 g / kg / day or 3.8 g / m² pc./dobę. In patients diagnosed with arginine succinate synthetase deficiency, arginine supplementation in the amount of 0.4-0.7 g / kg / day or 8.8 - 15.4 g / m2 is required.² pc./dobę. If additional calories are indicated, a protein-free product is recommended. The total daily dose should be divided into equal parts and administered with each meal (eg 3 times a day or 4-6 times a day for young children). The granules should be administered orally (infants and children who are unable to swallow tablets and patients with dysphagia) or gastrostomy or gastric tube. For oral administration, the granules should be mixed with a solid food (such as mashed potatoes or apple mousse) or with a liquid (such as water, apple juice, orange juice or ready-made baby food that does not contain protein). The tablets should be taken with plenty of water.