PHYSIONEAL Risk Management Plan 2016 MAY 13

Transcription

1 VI.2 Elements for a Public Summary VI.2.1 Overview of Disease Epidemiology In Europe, it is estimated that more than 10% of people are affected by kidney disease. The number of patients with end-stage kidney disease is estimated to continue to rise at a rate of 5% to 8% each year in developed countries. People with chronic (long-term) kidney disease are at high risk for end-stage kidney disease. For other conditions requiring peritoneal dialysis, it is estimated up to 66% may suffer from severe water retention and up to 75% from electrolyte imbalances. Peritoneal dialysis may also be a useful method of removing toxins for certain types of drug intoxication when appropriate.

2 Overall, peritoneal dialysis solutions are essential for patients with chronic kidney failure and other conditions requiring removal of excessive water and toxins from the body. Without treatment to remove water and different types of waste from the blood, patients with kidney failure can die. Peritoneal dialysis is a well-known treatment for end-stage kidney disease, especially for long-term treatment. VI.2.2 Summary of Treatment Benefits A kidney transplant is the best treatment for end-stage kidney disease, but kidney transplants are not always possible and may not happen right away. Instead of a kidney transplant, or while a person waits for a kidney transplant, a person can be placed on PD to help them live. The goals of PD therapy are to maintain the condition of the peritoneum, which is the belly s protective and filtering layer, for as long as possible and to maintain adequate exchange of waste and fluids, which helps to keep patients on PD long term, in order prevent serious outcomes, including death, due to end-stage kidney disease. PD solutions containing glucose (sugar) have been commonly used for the last 35 years. is a type of PD solution that has glucose in it. also contains an element called bicarbonate at the same level as normally found in the body, ph (the amount of acid/base in the body) at the same level as normally found in the body, and it has less amounts of parts of sugars (called glucose degradation products) than other glucose-based PD solutions. may also be used with other PD medicines for PD treatment. helps to keep the amount of acid in the body at a normal level. Clinical studies with showed that some patients with pain when a PD solution is administered experienced less pain with ; however, there are no data available which indicate that complications are reduced overall. Based on the evidence of clinical studies in approximately 377 patients, has been shown to be safe and efficacious. VI.2.3 Unknowns Relating to Treatment Benefits No studies of have been performed in children. The benefits of have to be balanced versus the risks of side effects in patients younger than 18 years of age. 40 in the Clear-Flex container is not recommended in children requiring a fill volume of less than 1600 ml. In addition, no information was available for patients during pregnancy or when breastfeeding; therefore, caution should also be utilized when used in such circumstances.

3 In clinical studies conducted using, there were no important differences in baseline characteristics across studies. The mean values for age, height, and weight were approximately the same in each study. There were no upper age limits in any studies and elderly patients were included. VI.2.4 Summary of Safety Concerns Table 41. Important Identified Risks Risk What is Known Preventability Higher than normal bicarbonate levels in the blood (Metabolic alkalosis) Higher than normal blood sugar (Hyperglycemia) Peritonitis (Aseptic peritonitis) Higher than normal levels of lactic acid in the blood (Lactic acidosis) The belly's protective and filtering layer becomes thick and Patients who already have bicarbonate levels of 30 mmol/l or higher usually have higher levels of bicarbonate levels while using. Diabetic patients and patients with pre-existing hyperglycemia are at higher risk for development of hyperglycemia or worsened hyperglycemia due to the glucose content of. Patients can get aseptic peritonitis with any kind of peritoneal dialysis treatment. Patients with certain abdominal conditions may be at increased risk for aseptic peritonitis. can cause the blood to have higher levels of acid in it than it should. How EPS happens is not known. Patients can get EPS with any The label for includes warning statements about the risk of metabolic alkalosis in patients with bicarbonate levels above 30 mmol/l. The label for instructs the doctor to consider the risk of metabolic alkalosis against the benefits of in patients with higher levels of bicarbonate in their blood. The label has of higher than normal blood sugar. In patients with diabetes, blood sugar levels should be monitored and any blood sugar medication the patient may be taking, including insulin, should be adjusted. Peritoneal dialysis should be done with caution in patients with certain abdominal conditions. The label has of peritonitis. should be used with caution in patients who already have higher than normal levels of lactic acid in the blood or who have conditions that increase the risk of lactic acidosis. The label has of lactic acidosis. It is difficult to detect EPS at an early stage. Patients who are

4 Table 41. Important Identified Risks Risk What is Known Preventability hard and as a result does not allow for the flow of the PD solution. EPS causes inflammation in the abdomen (belly) and thickening of the intestines that may be associated with abdominal pain, abdominal distension, or vomiting. (Encapsulating peritoneal sclerosis (EPS)) kind of peritoneal dialysis treatment. suspected of having EPS should switch to hemodialysis therapy. The label has of EPS. Giving with the wrong glucose concentration can result in the removal of too much water, not enough fluid in the body, and the loss of protein from the blood (Severe dehydration, excessive water removal (hypovolemia) and protein loss due to administration of incorrect concentration of glucose (medication error)) Lower than normal levels of potassium in the blood (Hypokalemia) There are potential risks associated with giving with the wrong glucose concentration, such as the removal of too much water during the peritoneal dialysis treatment which can result in not enough fluid in the body and loss of protein from the blood. can cause the blood to have lower levels of potassium in it than it should. An identification system has been adopted to distinguish the different glucose concentrations for : - The colored band on the carton label - The number of notches on the carton label - The colored pull ring cap on the bag - The number of notches on the pull ring cap with 1.36% glucose is identified with the yellow color and 1 notch; 2.27% glucose is identified with the green color and two notches; and 3.86% glucose is identified with the orange color and three notches. Blood potassium levels should be monitored periodically. Potassium may be added to the solution to prevent severe hypokalemia, only under the direction of a physician. The label has of hypokalemia.

5 Table 42. Important Potential Risks Risk The parathyroid glands make too much of a hormone called parathyroid hormone because the calcium levels in the blood are too low (Worsened secondary hyperparathyroidism) Not activating the bag properly, causing the patient to receive unmixed solution from only the small chamber of the bag. Infusion of this unmixed solution can cause the blood sodium level to be too high and the body s ph level to be too high. (Hypernatremia and severe metabolic alkalosis due to misinfusion (specific to Clear-Flex)) What is Known (Including Reason Why it is Considered a Potential Risk) 40 is made with less calcium than 35. In patients who have secondary hyperparathyroidism, a condition characterized by low calcium levels in the blood, using 40 may keep the calcium levels in the blood low, which may make the secondary hyperparathyroidism worse. Clear-Flex bags have two chambers. When the long seal between chambers is not properly activated, the two solution chambers are not mixed and only the small chamber is administered. The Clear-Flex containers have been re-designed with a SafetyMoon seal to prevent mis-infusion. Table 43. Missing Information Risk Lack of studies in children younger than 18 years of age (Lack of clinical data on safety in pediatric patients) Lack of data in pregnant or breastfeeding women (Lack of data in pregnant or lactating females) Lack of data on interactions with other medicinal products What is Known No studies have been performed in children. The benefits of have to be balanced versus the risks of side effects in patients younger than 18 years of age. 40 in the Clear-Flex container is not recommended in children requiring a fill volume of less than 1600 ml. There are no adequate data from the use of in pregnant or breastfeeding women. Physicians should carefully consider the potential risks and benefits for each specific patient before prescribing. No interaction studies have been conducted with. When prescribing, physicians should consider the potential interaction between the dialysis treatment and therapy directed at other existing illnesses.

6 VI.2.5 Summary of Risk Minimization Measures by Safety Concern All medicines have a summary of product characteristics (SmPC) which provides physicians, pharmacists, and other healthcare professionals with details on how to use the medicine, the risks, and recommendations for minimizing them. An abbreviated version of this in lay language is provided in the form of the package leaflet. The measures in these documents are known as routine risk minimization measures. The summary of product characteristics and the package leaflet for are available in the public domain. This medicine has no additional risk minimization measures. VI.2.6 Planned Post-Authorization Development Plan There are no planned post-authorization studies or activities for. Studies which are a Condition of the Marketing Authorization There are no studies which are a condition of the marketing authorization. VI.2.7 Summary of Changes to the Risk Management Plan Over Time Major Changes to the Risk Management Plan Over Time Table 44. Major Changes to the Risk Management Plan Over Time Version Date Safety Concerns Comment 1 22 JUN 2007 Mis-infusion None 2 12 NOV 2007 Identified risks: 1. Metabolic alkalosis 2. Mis-infusion 3 08 JUL 2009 Identified risks: 1. Metabolic alkalosis 2. Mis-infusion Metabolic alkalosis was added as a safety concern. None 4 22 FEB 2013 Hyperglycemia identified risk. Lactic acidosis, especially in patients with elevated lactate levels or with conditions known to increase the risk of lactic acidosis Medication error: Administration of incorrect glucose concentration potential risk. potential risk.

7 Table 44. Major Changes to the Risk Management Plan Over Time Version Date Safety Concerns Comment Worsened secondary hyperparathyroidism Encapsulating peritoneal sclerosis (EPS) potential risk. potential risk. 11 JUN 2013 Aseptic peritonitis identified risk at the request of the Danish Authorities. Lactic acidosis, especially in patients with elevated lactate levels or with conditions known to increase the risk of lactic acidosis Encapsulating peritoneal sclerosis (EPS) Medication error: Administration of incorrect glucose concentration Hypokalemia 5 13 MAY 2016 Mis-infusion (specific to Clear- Flex) Lactic acidosis, especially in patients with elevated lactate levels or with conditions Amended from an important potential risk to an important identified risk at the request of the Danish Authorities. Amended from an important potential risk to an important identified risk at the request of the Danish Authorities. Amended from an important potential risk to an important identified risk at the request of the Danish Authorities. identified risk. Amended from an important identified risk to an important potential risk. Risk wording revised to Hypernatremia and severe metabolic alkalosis due to misinfusion (specific to Clear- Flex) in order to more clearly describe the risk to the patient. Re-worded to simply Lactic acidosis.

8 Table 44. Major Changes to the Risk Management Plan Over Time Version Date Safety Concerns Comment known to increase the risk of lactic acidosis Lack of data in pregnant or lactating females Added as missing information. Lack of data on interactions with other medicinal products Medication error: Administration of incorrect glucose concentration Risk wording revised to Severe dehydration, excessive water removal (hypovolemia) and protein loss due to administration of incorrect concentration of glucose (medication error) in order to more clearly describe the risk to the patient.