Pheburane · 4.1 Therapeutic indications · 2

HOS-155533 · has-adverse-reaction-information · PDF-Seite 13

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. 13  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 haemorrhage, Uncommon gastritis Skin and subcutaneous tissue Common rash, abnormal skin door disorders Renal

Auszug; vollständigen Abschnitt im Original lesen.

HOS-155527 · has-adverse-reaction-information · PDF-Seite 5

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 haemorrhage, Uncommon gastritis Skin and subcutaneous tissue Common rash, abnormal skin odor disorders Renal and urinary disorders Common

Auszug; vollständigen Abschnitt im Original lesen.

HOS-155523 · has-contraindication-information · PDF-Seite 3

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Pregnancy. • Breast-feeding.

HOS-155529 · has-contraindication-information · PDF-Seite 12

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Pregnancy. • Breast-feeding.

HOS-155528 · has-indication-information · PDF-Seite 10

PHEBURANE is indicated as adjunctive therapy in the chronic management of urea cycle disorders, involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase or argininosuccinate synthetase. It is indicated in all patients with neonatal-onset disease (complete enzyme deficiencies, presenting within the first 28 days of life). It is also indicated in patients with late-onset disease (partial enzyme deficiencies, presenting after the first month of life) who have a history of hyperammonaemic encephalopathy.

HOS-155522 · has-indication-information · PDF-Seite 2

PHEBURANE is indicated as adjunctive therapy in the chronic management of urea cycle disorders, involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase or argininosuccinate synthetase. It is indicated in all patients with neonatal-onset disease (complete enzyme deficiencies, presenting within the first 28 days of life). It is also indicated in patients with late-onset disease (partial enzyme deficiencies, presenting after the first month of life) who have a history of hyperammonaemic encephalopathy.

HOS-155525 · has-interaction-information · PDF-Seite 4

Concurrent administration of probenecid may affect renal excretion of the conjugation product of sodium phenylbutyrate. There have been published reports of hyperammonaemia being induced by haloperidol and by valproate. 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.

HOS-155531 · has-interaction-information · PDF-Seite 12

12 Concurrent administration of probenecid may affect renal excretion of the conjugation product of sodium phenylbutyrate. There have been published reports of hyperammonaemia being induced by haloperidol and by valproate. 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.

HOS-155532 · has-pregnancy-information · PDF-Seite 13

Women of childbearing potential/contraception in males and females Effective contraceptive measures must be taken by women of child-bearing potential. Pregnancy There are no or limited amount of data from the use of sodium phenylbutyrate in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). PHEBURANE is contra- indicated during pregnancy (see section 4.3). Women of childbearing potential must use effective contraception during treatment. Breast-feeding Available pharmacodynamic/toxicological data in animals have shown excretion of sodium phenylbutyrate/metabolites in milk (see section 5.3). It is unknown whether sodium phenylbutyrate/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. PHEBURANE is contra-indicated during breast-feeding (see section 4.3). Fertility There is no evidence available on the effect of sodium phenylbutyrate on fertility.

HOS-155526 · has-pregnancy-information · PDF-Seite 4

Women of childbearing potential/Contraception in males and females Effective contraceptive measures must be taken by women of child-bearing potential. Pregnancy There are no or limited amount of data from the use of sodium phenylbutyrate in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Pheburane is contra-indicated during pregnancy (see section 4.3). Women of childbearing potential must use effective contraception during treatment. Breast-feeding Available pharmacodynamic/toxicological data in animals have shown excretion of sodium phenylbutyrate/metabolites in milk (see section 5.3). It is unknown whether sodium phenylbutyrate/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. Pheburane is contra-indicated during breast-feeding (see section 4.3). Fertility There is no evidence available on the effect of sodium phenylbutyrate on fertility.

HOS-155524 · has-warning-information · PDF-Seite 3

Content of clinically important electrolytes • PHEBURANE contains 124 mg (5.4 mmol) of sodium per gram of sodium phenylbutyrate, corresponding to 2.5 g (108 mmol) of sodium per 20 g of sodium phenylbutyrate, which is the maximum daily dose. PHEBURANE should therefore be used with caution in patients with congestive heart failure or severe renal insufficiency, and in clinical conditions where there is sodium retention with oedema. • Serum potassium should be monitored during therapy since renal excretion of phenylacetylglutamine may induce a urinary loss of potassium. 3 General considerations • Even on therapy, acute hyperammonaemic encephalopathy may occur in a number of patients. • PHEBURANE is not recommended for the management of acute hyperammonaemia, which is a medical emergency. Excipients with known effect • This medicinal product contains 124 mg (5.4 mmol) sodium per gram of sodium phenylbutyrate, equivalent to 6.2% of the WHO recommended maximum daily intake of 2 g sodium for an adult. The maximum daily dose of this medicinal product contains 2.5 g sodium per 20 gram of sodium phenylbutyrate, equivalent to 125% of the WHO recommended maximum daily intake of 2 g sodium for an adult. PHEBURANE is considered high in sodium. This should be particularly taken into account for those on a low salt diet. • This medicinal product contains 768 mg sucrose per gram of sodium phenylbutyrate. This should be taken into account in patients with diabetes mellitus. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product.

HOS-155530 · has-warning-information · PDF-Seite 12

Content of clinically important electrolytes • Each gram of sodium phenylbutyrate (2.86 mL of PHEBURANE oral solution) contains 124 mg (5.4 mmol) of sodium. The maximum daily dose of sodium phenylbutyrate is 20 g (57.14 mL of PHEBURANE oral solution), this would bring an associated amount of: 2.5 g (108 mmol) of sodium per 20 g of sodium phenylbutyrate, which is the maximum daily dose. PHEBURANE should therefore be used with caution in patients with congestive heart failure or severe renal insufficiency, and in clinical conditions where there is sodium retention with oedema. • Serum potassium should be monitored during therapy since renal excretion of phenylacetylglutamine may induce a urinary loss of potassium. General considerations • Even on therapy, acute hyperammonaemic encephalopathy may occur in a number of patients. • PHEBURANE oral solution is not recommended for the management of acute hyperammonaemia, which is a medical emergency. Excipients with known effect PHEBURANE 350 mg/mL oral solution • This medicinal product contains 124 mg (5.4 mmol) sodium per g dose of sodium phenylbutyrate, equivalent to 6.2% of the WHO recommended maximum daily intake of 2 g sodium for an adult. The maximum daily dose of this medicinal product contains 2.5 g sodium , equivalent to 125% of the WHO recommended maximum daily intake of 2 g of sodium for an adult. PHEBURANE oral solution is considered high in sodium. This should be particularly taken into account for those on a low salt diet. • This medicinal product contains 5.7 mg aspartame per g dose of sodium phenylbutyrate. Aspartame is a source of phenylalanine. It may be harmful for persons who have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly. Neither non-clinical nor clinical data are available to assess aspartame (E951) use in infants below 12 weeks of age. Blackcurrant flavour topping The blackcurrant flavour topping contains 26.55 mg propylene glycol per drop. If your baby is less than 4 weeks old, talk to your doctor or pharmacist before giving them this flavour topping in particular if the baby is given other medicines that contain propylene glycol or alcohol.