Leitlinien & Arzneimittelsicherheit

HOS-096606 · has-adverse-reaction-information · PDF-Seite 15

Summary of the safety profile The current safety profile of Velphoro is based on a total of 778 patients on haemodialysis and 57 patients on peritoneal dialysis, who received sucroferric oxyhydroxide treatment of up to 55 weeks. In these clinical trials, approximately 43% of the patients experienced at least one adverse reaction during Velphoro treatment, and 0.36% of the adverse reactions were reported as serious. The majority of the adverse reactions reported from trials were gastrointestinal disorders, with the most frequently reported adverse reactions being diarrhoea and discoloured faeces (very common). The vast majority of these gastrointestinal disorders occurred early during treatment and abated with time with continued dosing. No dose-dependent trends were observed in the adverse reaction profile of Velphoro. Tabulated list of adverse reactions Adverse reactions reported from the use of Velphoro at doses from 250 mg iron/day to 3,000 mg iron/day in these patients (n=835) are listed in Table 2. 15 The reporting rate is classified as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100). Table 2 Adverse reactions detected in clinical trials System organ class Very common Common Uncommon Metabolism and Hypercalcaemia nutrition disorders Hypocalcaemia Nervous system Headache disorders Respiratory, thoracic Dyspnoea and mediastinal disorders Gastrointestinal Diarrhoea* Nausea Abdominal distension disorders Faeces discoloured Constipation Gastritis Vomiting Abdominal discomfort Dyspepsia Dysphagia Abdominal pain Gastro-oesophageal Flatulence reflux disease (GORD) Tooth discolouration Tongue discolouration Skin and subcutane

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096600 · has-adverse-reaction-information · PDF-Seite 5

Summary of the safety profile The current safety profile of Velphoro is based on a total of 778 patients on haemodialysis and 57 patients on peritoneal dialysis, who received sucroferric oxyhydroxide treatment of up to 55 weeks. In these clinical trials, approximately 43% of the patients experienced at least one adverse reaction during Velphoro treatment, and 0.36% of the adverse reactions were reported as serious. The majority of the adverse reactions reported from trials were gastrointestinal disorders, with the most frequently reported adverse reactions being diarrhoea and discoloured faeces (very common). The vast majority of these gastrointestinal disorders occurred early during treatment and abated with time with continued dosing. No dose-dependent trends were observed in the adverse reaction profile of Velphoro. 5 Tabulated list of adverse reactions Adverse reactions reported from the use of Velphoro at doses from 250 mg iron/day to 3,000 mg iron/day in these patients (n=835) are listed in Table 2. The reporting rate is classified as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100). Table 2 Adverse reactions detected in clinical trials System organ class Very common Common Uncommon Metabolism and Hypercalcaemia nutrition disorders Hypocalcaemia Nervous system Headache disorders Respiratory, thoracic Dyspnoea and mediastinal disorders Gastrointestinal Diarrhoea* Nausea Abdominal distension disorders Faeces discoloured Constipation Gastritis Vomiting Abdominal discomfort Dyspepsia Dysphagia Abdominal pain Gastro-oesophageal Flatulence reflux disease (GORD) Tooth discolouration Tongue discolouration Skin and subcutaneous

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096596 · has-contraindication-information · PDF-Seite 4

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Haemochromatosis and any other iron accumulation disorders.

HOS-096602 · has-contraindication-information · PDF-Seite 14

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Haemochromatosis and any other iron accumulation disorders.

HOS-096595 · has-indication-information · PDF-Seite 2

Velphoro is indicated for the control of serum phosphorus levels in adult chronic kidney disease (CKD) patients on haemodialysis (HD) or peritoneal dialysis (PD). Velphoro is indicated for the control of serum phosphorus levels in paediatric patients 2 years of age and older with CKD stages 4-5 (defined by a glomerular filtration rate <30 mL/min/1.73 m²) or with CKD on dialysis. Velphoro should be used within the context of a multiple therapeutic approach, which could include calcium supplement, 1,25­dihydroxy vitamin D3 or one of its analogues, or calcimimetics to control the development of renal bone disease.

HOS-096601 · has-indication-information · PDF-Seite 12

Velphoro is indicated for the control of serum phosphorus levels in adult chronic kidney disease (CKD) patients on haemodialysis (HD) or peritoneal dialysis (PD). Velphoro is indicated for the control of serum phosphorus levels in paediatric patients 2 years of age and older with CKD stages 4-5 (defined by a glomerular filtration rate <30 mL/min/1.73 m²) or with CKD on dialysis. Velphoro should be used within the context of a multiple therapeutic approach, which could include calcium supplement, 1,25­dihydroxy vitamin D3 or one of its analogues, or calcimimetics to control the development of renal bone disease.

HOS-096604 · has-interaction-information · PDF-Seite 14

Velphoro is almost not absorbed from the gastrointestinal tract. Although the potential for interactions with medicinal products seems low, for concomitant treatment with medicinal products with a narrow therapeutic window, the clinical effect and adverse events should be monitored, on initiation or dose- adjustment of either Velphoro or the concomitant medicinal product, or the physician should consider measuring blood levels. When administering any medicinal product that is already known to interact with iron (like alendronate and doxycycline) or has the potential to interact with sucroferric oxyhydroxide based only on in vitro studies like levothyroxine, the medicinal product should be administered at least one hour before or two hours after Velphoro. In vitro and in vivo studies suggest that bioavailability of vadadustat and roxadustat may be reduced when taken concomitantly with phosphate binders including Velphoro. In order to minimize potential interactions with Velphoro, vadadustat and roxadustat should be administered at least one hour before or two hours after Velphoro. In vitro studies with the following active substances did not show any relevant interaction: acetylsalicylic acid, cephalexin, cinacalcet, ciprofloxacin, clopidogrel, enalapril, hydrochlorothiazide, metformin, metoprolol, nifedipine, pioglitazone and quinidine. Interaction studies have only been performed in healthy volunteers. They have been conducted in healthy human male and female subjects with losartan, furosemide, digoxin, warfarin, and omeprazole. Concomitant administration of Velphoro did not affect the bioavailability of these medicinal products as measured by the area under the curve (AUC). 14 Data from clinical studies have shown that sucroferric oxyhydroxide does not affect the lipid lowering effects of HMG-CoA reductase inhibitors (e.g., atorvastatin and simvastatin). In addition, post-hoc analyses from clinical studies demonstrated no impact of Velphoro on iPTH lowering effect of oral Vitamin D analogues. Vitamin D and 1,25­dihydroxy Vitamin D levels remained unchanged. Velphoro does not affect guaiac based (Haemoccult) or immunological based (iColo Rectal and Hexagon Obti) faecal occult blood tests.

HOS-096598 · has-interaction-information · PDF-Seite 4

Velphoro is almost not absorbed from the gastrointestinal tract. Although the potential for interactions with medicinal products seems low, for concomitant treatment with medicinal products with a narrow therapeutic window, the clinical effect and adverse events should be monitored, on initiation or dose- adjustment of either Velphoro or the concomitant medicinal product, or the physician should consider measuring blood levels. When administering any medicinal product that is already known to interact with iron (like alendronate and doxycycline) or has the potential to interact with sucroferric oxyhydroxide based only on in vitro studies like levothyroxine, the medicinal product should be administered at least one hour before or two hours after Velphoro. In vitro and in vivo studies suggest that bioavailability of vadadustat and roxadustat may be reduced when taken concomitantly with phosphate binders including Velphoro. In order to minimize potential interactions with Velphoro, vadadustat and roxadustat should be administered at least one hour before or two hours after Velphoro. In vitro studies with the following active substances did not show any relevant interaction: acetylsalicylic acid, cephalexin, cinacalcet, ciprofloxacin, clopidogrel, enalapril, hydrochlorothiazide, metformin, metoprolol, nifedipine, pioglitazone and quinidine. 4 Interaction studies have only been performed in healthy volunteers. They have been conducted in healthy human male and female subjects with losartan, furosemide, digoxin, warfarin, and omeprazole. Concomitant administration of Velphoro did not affect the bioavailability of these medicinal products as measured by the area under the curve (AUC). Data from clinical studies have shown that sucroferric oxyhydroxide does not affect the lipid lowering effects of HMG-CoA reductase inhibitors (e.g., atorvastatin and simvastatin). In addition, post-hoc analyses from clinical studies demonstrated no impact of Velphoro on iPTH lowering effect of oral Vitamin D analogues. Vitamin D and 1,25­dihydroxy Vitamin D levels remained unchanged. Velphoro does not affect guaiac based (Haemoccult) or immunological based (iColo Rectal and Hexagon Obti) faecal occult blood tests.

HOS-096605 · has-pregnancy-information · PDF-Seite 15

Pregnancy There are no available clinical data from the use of sucroferric oxyhydroxide on exposed human pregnancies. Reproductive and developmental toxicity studies in animals revealed no risk with respect to pregnancy, embryonic/foetal development, parturition or postnatal development (see section 5.3). Sucroferric oxyhydroxide should only be used by pregnant women if clearly needed following careful assessment of benefit/risk. Breast-feeding There are no available clinical data from the use of Velphoro in breast-feeding women. Since absorption of iron from this medicinal product is minimal (see section 5.2), excretion of iron from sucroferric oxyhydroxide in breast milk is unlikely. A decision on whether to continue breast-feeding or to continue therapy with sucroferric oxyhydroxide should be made taking into account the benefit of breast-feeding to the child and the benefit of Velphoro therapy to the mother. Fertility There are no data on the effect of Velphoro on fertility in humans. In animal studies, there were no adverse effects on mating performance, fertility, and litter parameters following treatment with sucroferric oxyhydroxide (see section 5.3).

HOS-096599 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no available clinical data from the use of sucroferric oxyhydroxide on exposed human pregnancies. Reproductive and developmental toxicity studies in animals revealed no risk with respect to pregnancy, embryonic/foetal development, parturition or postnatal development (see section 5.3). Sucroferric oxyhydroxide should only be used by pregnant women if clearly needed following careful assessment of benefit/risk. Breast-feeding There are no available clinical data from the use of Velphoro in breast-feeding women. Since absorption of iron from this medicinal product is minimal (see section 5.2), excretion of iron from sucroferric oxyhydroxide in breast milk is unlikely. A decision on whether to continue breast-feeding or to continue therapy with sucroferric oxyhydroxide should be made taking into account the benefit of breast-feeding to the child and the benefit of Velphoro therapy to the mother. Fertility There are no data on the effect of Velphoro on fertility in humans. In animal studies, there were no adverse effects on mating performance, fertility, and litter parameters following treatment with sucroferric oxyhydroxide (see section 5.3).

HOS-096603 · has-warning-information · PDF-Seite 14

Peritonitis, gastric and hepatic disorders and gastrointestinal surgery Patients with a recent history of peritonitis (within the last 3 months), significant gastric or hepatic disorders and patients with major gastrointestinal surgery have not been included in clinical studies with Velphoro. Velphoro treatment should only be used in these patients following careful assessment of benefit/risk. Discoloured stool Sucroferric oxyhydroxide can cause discoloured (black) stool. Discoloured (black) stool may visually mask gastrointestinal bleeding (see section 4.5). Information about sucrose and starches (carbohydrates) Velphoro contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose- galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product. It may be harmful to the teeth. Velphoro contains potato starch and pregelatinised maize starch. Patients with diabetes should take notice that one sachet of Velphoro oral powder is equivalent to approximately 0.7 g of carbohydrates (equivalent to 0.056 bread units).

HOS-096597 · has-warning-information · PDF-Seite 4

Peritonitis, gastric and hepatic disorders and gastrointestinal surgery Patients with a recent history of peritonitis (within the last 3 months), significant gastric or hepatic disorders and patients with major gastrointestinal surgery have not been included in clinical studies with Velphoro. Velphoro treatment should only be used in these patients following careful assessment of benefit/risk. Discoloured stool Sucroferric oxyhydroxide can cause discoloured (black) stool. Discoloured (black) stool may visually mask gastrointestinal bleeding (see section 4.5). Information about sucrose and starches (carbohydrates) Velphoro contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose- galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product. It may be harmful to the teeth. Velphoro contains potato starch and pregelatinised maize starch. Patients with diabetes should take notice that one tablet of Velphoro is equivalent to approximately 1.4 g of carbohydrates (equivalent to 0.116 bread units).