Ucyclyd Pharma Inc.

Ucyclyd Pharma Inc. Drugs

• Buphenyl
  

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  Buphenyl

  

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  For oral use only.

  The use of BUPHENYL Tablets is indicated for children weighing more than 20 kg and for adults.

  The usual total daily dose of BUPHENYL Tablets and Powder for patients with urea cycle disorders is 450 – 600 mg/kg/day in patients weighing less than 20 kg, or 9.9 – 13.0 g/m2/day in larger patients. The tablets and powder are to be taken in equally divided amounts with each meal or feeding (i.e., three to six times per day).

  BUPHENYL Powder is indicated for oral use (via mouth, gastrostomy, or nasogastric tube) only.   The powder is to be mixed with food (solid or liquid) for immediate use; however, when dissolved in water, BUPHENYL Powder has been shown to be stable for up to one week at room temperature or refrigerated. Sodium phenylbutyrate is very soluble in water (5 grams per 10 mL). When BUPHENYL Powder is added to a liquid, only sodium phenylbutyrate will dissolve, the excipients will not. The effect of food on sodium phenylbutyrate has not been determined.

  Each level teaspoon (enclosed) dispenses 3.2 grams of powder and 3.0 grams of sodium phenylbutyrate. Each level tablespoon (enclosed) dispenses 9.1 grams of powder and 8.6 grams of sodium phenylbutyrate.

  Shake lightly before use.

  The safety or efficacy of doses in excess of 20 grams (40 tablets) per day has not been established.

  NUTRITIONAL MANAGEMENT

  To promote growth and development, plasma levels of ammonia, arginine, branched-chain amino acids, and serum protein should be maintained within normal limits while plasma glutamine is maintained at levels less than 1,000 µmol/L. Minimum daily protein intake for a patient of a particular age should be taken from, for example, "Recommended Dietary Allowances", 10th ed., Food and Nutrition Board, National Academy of Sciences, 1989. The allocation of dietary nitrogen into natural protein and essential amino acids is a function of age, residual urea-cycle enzyme activity, and the dose of sodium phenylbutyrate.

  At the recommended dose of sodium phenylbutyrate, it is suggested that infants with neonatal-onset CPS and OTC deficiencies initially receive a daily dietary protein intake limited to approximately 1.6 g/kg/day for the first 4 months of life. If tolerated, the daily protein intake may be increased to 1.9 g/kg/day during this period. Protein tolerance will decrease as the growth rate decreases, requiring a reduction in dietary nitrogen intake. From 4 months to 1 year of age, it is recommended that the infant receive at least 1.4 g/kg/day, but 1.7 g/kg/day is advisable. From 1 to 3 years of age, the protein intake should not be less than 1.2 g/kg/day; 1.4 g/kg/day is advisable during this period. For neonatal-onset patients with carbamylphosphate synthetase deficiency or ornithine transcarbamylase deficiency who are at least 6 months of age, it is recommended that the daily protein intake be equally divided between natural protein and supplemental essential amino acids.

  Patients with argininosuccinic acid synthetase deficiency and those with late-onset disease (partial deficiencies, including females heterozygous for ornithine transcarbamylase), initially may receive a diet containing the age-determined minimal daily natural protein allowance. The protein intake may be increased as tolerated and determined by plasma glutamine and other amino acid levels. However, many patients with partial deficiencies avoid dietary protein.

  Citrulline supplementation is required and recommended for patients diagnosed with neonatal-onset deficiency of carbamylphosphate synthetase or ornithine transcarbamylase; citrulline daily intake is recommended at 0.17 g/kg/day or 3.8 g/m2/day.

  The free-base form of arginine may be used instead of citrulline in patients with milder forms of carbamylphosphate synthetase and ornithine transcarbamylase deficiency (daily intake is recommended at 0.17 g/kg/day or 3.8 g/m2/day).

  Arginine supplementation is needed for patients diagnosed with deficiency of argininosuccinic acid synthetase; arginine (free base) daily intake is recommended at 0.4 – 0.7 g/kg/day or 8.8 – 15.4 g/m2/day.

  If caloric supplementation is indicated, a protein-free product is recommended. Caloric intake should be based upon the "Recommended Dietary Allowances", 10th ed., Food and Nutrition Board, National Research Council, National Academy of Sciences, 1989.

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• Ammonul
  

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  Ammonul

  

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  2.1 Recommended Dose

  AMMONUL must be diluted with sterile 10% Dextrose Injection (D10W) before administration. The dilution and dosage of AMMONUL are determined by weight for neonates, infants and young children, and by body surface area for larger patients, including older children, adolescents, and adults (Table 1).

  Table 1 Dosage and Administration Patient Population Components of Infusion SolutionAMMONUL must be diluted with sterile 10% Dextrose Injection at ≥ 25 mL/Kg before administration. Dosage Provided AMMONUL Arginine HCl Injection, 10% Sodium Phenylacetate Sodium Benzoate Arginine HCl Patients 0 to 20 kg: CPS and OTC Deficiency Dose Loading: over 90 to 120 minutes 2.5 mL/kg 2 mL/kg 250 mg/kg 250 mg/kg 200 mg/kg Maintenance: over 24 hours ASS and ASL Deficiency Dose Loading: over 90 to 120 minutes 2.5 mL/kg 6 mL/kg 250 mg/kg 250 mg/kg 600 mg/kg Maintenance: over 24 hours Patients > 20 kg: CPS and OTC Deficiency Dose Loading: over 90 to 120 minutes 55 mL/m2 2 mL/kg 5.5 g/m2 5.5 g/m2 200 mg/kg Maintenance: over 24 hours ASS and ASL Deficiency Dose Loading: over 90 to 120 minutes 55 mL/m2 6 mL/kg 5.5 g/m2 5.5 g/m2 600 mg/kg Maintenance: over 24 hours

  2.2 Administration

  AMMONUL is a concentrated solution and must be diluted before intravenous administration via a central venous catheter. Administration through a peripheral intravenous catheter may cause burns. AMMONUL may not be administered by any other route.

  AMMONUL should be administered as a loading dose infusion over 90 to 120 minutes, followed by the same dose repeated as a maintenance infusion administered over 24 hours. Because of prolonged plasma levels achieved by phenylacetate in pharmacokinetic studies, repeat loading doses of AMMONUL should not be administered. Maintenance infusions may be continued until elevated plasma ammonia levels have been normalized or the patient can tolerate oral nutrition and medications. An antiemetic may be administered during AMMONUL infusion to aid control of infusion-associated nausea and vomiting. Administration of analogous oral drugs, such as sodium phenylbutyrate, should be terminated prior to AMMONUL infusion.

  AMMONUL infusion should be started as soon as the diagnosis of hyperammonemia is made. Treatment of hyperammonemia also requires caloric supplementation and restriction of dietary protein. Non-protein calories should be supplied principally as glucose (8–10 mg/kg/min) with an intravenous fat emulsion added. Attempts should be made to maintain a caloric intake of greater than 80 kcal/kg/day. During and after infusion of AMMONUL, ongoing monitoring of the following clinical laboratory values is crucial: plasma ammonia, glutamine, quantitative plasma amino acids, blood glucose, electrolytes, venous or arterial blood gases, AST and ALT. On-going monitoring of the following clinical responses is also crucial to assess patient response to treatment: neurological status, Glasgow Coma Scale, tachypnea, CT or MRI scan or fundoscopic evidence of cerebral edema, and/or of gray matter and white matter damage. Hemodialysis should be considered in patients with severe hyperammonemia or who are not responsive to AMMONUL administration [see Warnings and Precautions (5.1)]. In the non-neonatal study patient population treated with AMMONUL, dialysis was required in 13% of hyperammonemic episodes. Standard hemodialysis was the most frequently used dialysis method. High levels of ammonia can be reduced quickly when AMMONUL is used with hemodialysis, as the ammonia-scavenging of AMMONUL suppresses the production of ammonia from catabolism of endogenous protein and hemodialysis eliminates the ammonia and ammonia conjugates.

  AMMONUL solutions are physically and chemically stable for up to 24 hours at room temperature and room lighting conditions. No compatibility information is presently available for AMMONUL infusion solutions except for Arginine HCl Injection, 10%, which may be mixed in the same container as AMMONUL. Other infusion solutions and drug products should not be administered together with AMMONUL infusion solution. AMMONUL solutions may be prepared in glass and PVC containers.

  Arginine Administration

  Intravenous arginine is an essential component of therapy for patients with carbamyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), or argininosuccinate lyase (ASL) deficiency. Because hyperchloremic acidosis may develop after high-dose arginine hydrochloride administration, chloride and bicarbonate levels should be monitored and appropriate amounts of bicarbonate administered.

  In hyperammonemic infants with suspected, but unconfirmed urea cycle disorders, intravenous arginine should be given (6 mL/kg of Arginine HCl Injection 10%, over 90 minutes followed by the same dose given as a maintenance infusion over 24 hours). If deficiencies of ASS or ASL are excluded as diagnostic possibilities, the intravenous dose of arginine HCl should be reduced to 2 mL/kg/day Arginine HCl Injection 10%.

  Converting To Oral Treatment

  Once elevated ammonia levels have been reduced to the normal range, oral therapy, such as sodium phenylbutyrate, dietary management and maintenance protein restrictions should be started or reinitiated.

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