Kidney Disease Medication
Mircera (methoxy polyethylene glycol-epoetin beta)
BOXED WARNING ... edited
WARNINGS: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS, AND TUMOR PROGRESSION OR RECURRENCE
Chronic Kidney Disease [see Warnings and Precautions (5.1)]
- In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL.
- No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks.
- Use the lowest Mircera dose sufficient to reduce the need for red blood cell (RBC) transfusions. Cancer [see Warnings and Precautions (5.2)]
- Mircera is not indicated and is not recommended for the treatment of anemia due to cancer chemotherapy. A dose-ranging study of Mircera was terminated early because of more deaths among patients receiving Mircera than another ESA.
- ESAs have shown shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers.
- Uncontrolled hypertension [see Warnings and Precautions (5.3)]
- Pure red cell aplasia (PRCA) that begins after treatment with Mircera or other erythropoietin protein drugs [see Warnings and Precautions (5.6)]
- History of serious or severe allergic reactions to Mircera (e.g. anaphylactic reactions, angioedema, bronchospasm, skin rash, and urticaria).
Significant edits to the following sections...
5.1 Increased Mortality, Myocardial Infarction, Stroke, and Thromboembolism
5.2 Increased Mortality and/or Increased Risk of Tumor Progression or Recurrence in
5.3 Hypertension
5.4 Seizures
5.6 Pure Red Cell Aplasia
5.7 Serious Allergic Reactions
5.8 Dialysis Management
5.9 Laboratory Monitoring
Source : FDA (Oct 2014)
Samsca (Tolvaptan): Drug Safety Communication - FDA Limits Duration and Usage Due To Possible Liver Injury Leading to Organ Transplant or Death
ISSUE: FDA has determined that the drug Samsca (tolvaptan) should not be used for longer than 30 days and should not be used in patients with underlying liver disease because it can cause liver injury, potentially leading to liver transplant or death. FDA has worked with the manufacturer to revise the Samsca drug label to include new limitations.
BACKGROUND: Samsca is a selective vasopression V2-receptor antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia, including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH). An increased risk of liver injury was observed in recent large clinical trials evaluating Samsca for a new use in patients with autosomal dominant polycystic kidney disease (ADPKD).
RECOMMENDATION: Samsca treatment should be stopped if the patient develops signs of liver disease. Treatment duration should be limited to 30 days or less, and use should be avoided in patients with underlying liver disease, including cirrhosis. Patients should be aware that Samsca may cause liver problems, including life-threatening liver failure, and should contact their health care professional to discuss any questions or concerns about Samsca.
Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of this product to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:
Source : FDA
Samsca (tolvaptan): Drug Warning - Potential Risk of Liver Injury
ISSUE: Otsuka and FDA notified healthcare professionals of significant liver injury associated with the use of Samsca. In a double-blind, 3-year, placebo-controlled trial in about 1400 patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and its open-label extension trial, 3 patients treated with the drug developed significant increases in serum alanine aminotransferase (ALT) with concomitant, clinically significant increases in serum total bilirubin. In the trials the maximum daily dose of Samsca administered (90 mg in the morning and 30 mg in the afternoon) was higher than the maximum 60 mg daily dose approved for the treatment of hyponatremia.
Most of the liver enzyme abnormalities were observed during the first 18 months of therapy. Following discontinuation of treatment, all 3 patients improved. An external panel of liver experts assessed these 3 cases as being either probably or highly likely to be caused by tolvaptan. These findings indicate that Samsca (tolvaptan) has the potential to cause irreversible and potentially fatal liver injury. These data are not adequate to exclude the possibility that patients receiving Samsca for its indicated use of clinically significant hypervolemic and euvolemic hyponatremia are at a potential increased risk for irreversible and potentially fatal liver injury.
BACKGROUND: Samsca is a selective vasopressin V2-receptor antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia. Samsca is not approved for the treatment of ADPKD.
RECOMMENDATION: Healthcare providers should perform liver tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice. If hepatic injury is suspected, Samsca should be promptly discontinued, appropriate treatment should be instituted, and investigations should be performed to determine probable cause. Samsca should not be re-initiated in patients unless the cause for the observed liver injury is definitively established to be unrelated to treatment with Samsca.
Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of this product to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:
Source : FDA
Study Questions Safety and Effectiveness of Common Kidney Disease Drugs
Longest placebo-controlled trial of phosphate binders conducted to date challenges the drugs’ utility
Highlights
• Phosphate binders, drugs commonly prescribed to patients with chronic kidney disease, may not be as effective as previously thought.
• Phosphate binders may have negative effects on cardiovascular health.
• Additional studies are needed on the safety and effectiveness of these drugs.
60 million people globally have chronic kidney disease.
Newswise — Washington, DC (July 19, 2012) — Drugs commonly prescribed to patients with chronic kidney disease (CKD) may not be as strongly effective as once thought, and may cause unexpected harm to blood vessels, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings indicate that additional studies on the drugs, called phosphate binders, are needed.
Higher blood levels of phosphorus that are still within the normal range have been linked with heart problems, kidney disease, and premature death. Because the kidneys get rid of excess phosphorus by excreting it through the urine, patients with CKD often have elevated blood phosphorus levels.
Drugs called phosphate binders can lower blood phosphorus levels, and while they are approved only for patients with kidney failure, they are often prescribed off-label to patients with CKD. Geoffrey Block, MD (Denver Nephrology) and his colleagues evaluated the effects of these drugs (calcium acetate, lanthanum carbonate, sevelamer carbonate) in patients with moderate to advanced CKD and normal or near normal blood phosphorus levels.
The study included 148 patients who were randomized to receive one of the three phosphate binders or a placebo. The investigators examined patients after three, six, and nine months of treatment. The study is the longest placebo-controlled trial of phosphate binders in patients with CKD conducted to date.
Treatment with phosphate binders significantly lowered patients’ urinary phosphorus levels, moderately lowered their blood phosphorus levels, and slowed progression of a parathyroid disorder that is a common complication of CKD, while treatment with placebo did not. Despite these positive effects, phosphate binders did not have any effect on the blood levels of a hormone that regulates phosphate excretion in the urine, and the drugs caused calcium build-up in blood vessels, which can lead to heart problems. Heart disease is the leading cause of death in patients with CKD.
These findings call into question the safety and effectiveness of phosphate binders in patients with CKD.
“While we continue to believe that serum, or blood, phosphorus is a key component of the increased cardiovascular risk associated with kidney disease, our results suggest the use of the currently approved phosphate binding drugs does not result in substantial reductions in serum phosphorus and may be associated with harm in this population,” said Dr. Block. “Future clinical trials should be conducted in all populations with adequate placebo controls and should address alternative or complementary methods to reduce serum phosphorus,” he added.
Source : Newswise
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Erythropoiesis-Stimulating Agents (ESAs) In Chronic Kidney Disease: Drug Safety Communication - Modified Dosing Recommendations
Epoetin alfa (marketed as Epogen and Procrit) and darbepoetin alfa (marketed as Aranesp)
FDA notified healthcare professionals that new, modified recommendations for more conservative dosing of Erythropoiesis-Stimulating Agents (ESAs) in patients with chronic kidney disease (CKD) have been approved to improve the safe use of these drugs. FDA has made these recommendations because of data showing increased risks of cardiovascular events with ESAs in this patient population. The new dosing recommendations are based on clinical trials showing that using ESAs to target a hemoglobin level of greater than 11 g/dL in patients with CKD provides no additional benefit than lower target levels, and increases the risk of experiencing serious adverse cardiovascular events, such as heart attack or stroke.BACKGROUND: ESAs treat certain types of anemia by stimulating the bone marrow to produce red blood cells and by decreasing the need for blood transfusions. The manufacturer has revised the Boxed Warning, Warnings and Precautions, and Dosage and Administration sections of the labels for the ESAs to include this new information.
RECOMMENDATION: Healthcare professionals should weigh the possible benefits of using ESAs to decrease the need for red blood cell transfusions in CKD patients against the increased risks for serious cardiovascular events, and should inform their patients of the current understanding of potential risks and benefits. Therapy should be individualized to the patient and the lowest possible ESA dose given to reduce the need for transfusions.
Source : FDA
Link to Source
SEE ALSO
FDA Drug Safety Communication: Erythropoiesis-Stimulating Agents (ESAs): Procrit, Epogen and Aranesp