Hyperparathyroidism, Secondary

Pictured: Amgen's office in Tampa, Florida/iStock, JHVEPhoto The FDA on Friday updated the label of Amgen’s osteoporosis medicine Prolia (denosumab) to include a boxed warning for the risk of hypocalcemia, or severely low calcium levels, when used to treat patients with chronic kidney disease. According to the regulator, Prolia’s hypocalcemia risk is much higher in chronic kidney disease (CKD) patients who also have mineral and bone disorder (MBD), which could lead to serious harm including hospitalization, various life-threatening events and death. Severe hypocalcemia may come without symptoms or may manifest as confusion, seizures, fainting and uncontrolled muscle spasms, among other signs. Per the adjusted label, prescribers should first evaluate patients for the presence of CKD-MBD. Patients with this condition who nevertheless require Prolia treatment should be “supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD.” The FDA found that the risk of severe hypocalcemia was highest in patients with advanced CKD, including those who were dependent on dialysis and those with concurrent MBD. The adverse event typically developed within two to 10 weeks after Prolia injection, though its risk peaked at weeks two through five. Despite these risks, the FDA has told patients to not stop taking Prolia without consulting their doctors, as doing so might aggravate the risk of bone fractures “including in the spine.” A boxed warning is the FDA’s most serious precautionary signal for drugs. It signals to prescribers that there is “an adverse reaction so serious in proportion to the potential benefit from the drug … that it is essential that it be considered in assessing the risks and benefits of using the drug,” according to an October 2011 guidance document. These risks include fatal or life-threatening events, or adverse reactions that could result in permanent disability. In the case of Prolia, a review by the Centers for Medicare and Medicaid Services flagged a “significant increase” in the risk of severe hypocalcemia in patients treated with Amgen’s drug versus other bisphosphonate-based osteoporosis therapies. The FDA’s Adverse Event Report System also identified 25 cases of severe hypocalcemia from July 2010 through May 2021. An Amgen spokesperson In a statement to Fierce Pharma said that safety is of the “utmost importance” to the company and that it remains “confident” in the benefit/risk pro Prolia. A monoclonal antibody, Prolia binds and blocks the RANK protein which in turn suppresses the action of osteoclasts, bone cells that normally degrade bone to promote repair and remodeling. In many bone diseases, like osteoporosis, osteoclasts often play a pathologic role. Prolia was first approved in 2010 for postmenopausal women with osteoporosis who are at a high risk of fracture. The therapy has since been approved for other indications, such as improving bone mass in men with osteoporosis, including those undergoing androgen deprivation therapy. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

January 19, 2024 Audience: Patient, Health Professional, Endocrinology, Nephrology, Pharmacy January 19, 20204 -- Based on a completed FDA review of available information, FDA has concluded that the osteoporosis medicine Prolia ( denosumab ) increases the risk of severe hypocalcemia, very low blood calcium levels, in patients with advanced chronic kidney disease (CKD), particularly patients on dialysis. Severe hypocalcemia appears to be more common in patients with CKD who also have a condition known as mineral and bone disorder (CKD-MBD). In patients with advanced CKD taking Prolia, severe hypocalcemia resulted in serious harm, including hospitalization, life-threatening events, and death. As a result, the FDA is revising the Prolia prescribing information to include a new Boxed Warning, FDA’s most prominent warning, communicating this increased risk. Severe hypocalcemia can be asymptomatic or may present with symptoms that include confusion; seizures; irregular heart rhythm; fainting; face twitching; uncontrolled muscle spasms; or weakness, tingling, or numbness in parts of the body. FDA is adding a Boxed Warning to the Prolia prescribing information about the significant risk of developing severe hypocalcemia in patients with advanced CKD. This warning and new labeling contains information to help reduce this risk, including appropriate patient selection for Prolia treatment, increased monitoring of blood calcium levels, and other strategies. The FDA is adding this updated information to the patient Medication Guide and the Prolia Risk Evaluation and Mitigation Strategy (REMS) , a drug safety program required by FDA. BACKGROUND: Prolia is a monoclonal antibody initially developed for the treatment of osteoporosis in postmenopausal women at increased risk of fracture or who are refractory to or cannot tolerate other therapies. Prolia was later approved to increase bone mass in men with osteoporosis; to treat men with high risk for fracture receiving androgen deprivation therapy for prostate cancer; to treat women at high risk for fracture receiving aromatase inhibitor therapy for breast cancer; and, to treat men and women with glucocorticoid-induced osteoporosis. Prolia works by blocking a protein called RANK (receptor activator of nuclear factor kappa beta) and helps prevent bone cells called osteoclasts from breaking down bone in the body. Prolia may lower the calcium levels in your blood, and it is administered as a subcutaneous injection under the skin by a health care professional once every 6 months. Common side effects of Prolia include back pain, muscle pain, and pain in the arms or legs. RECOMMENDATIONS: Patients For patients considering Prolia for osteoporosis treatment, talk to your health care professional about your kidney function and the risk of severe hypocalcemia. Whether Prolia treatment is appropriate for patients with advanced CKD should be determined by a health care professional with expertise in the diagnosis and management of CKD-MBD, including renal osteodystrophy. For patients already taking Prolia for osteoporosis, maintain adequate calcium and vitamin D intake while receiving this medicine. Since your health care professional administers Prolia by subcutaneous injection every 6 months, you should discuss with them if you are at increased risk, and if so, whether continuing this treatment is best for you. If discontinuation of Prolia treatment is recommended, your health care professional may advise other measures to monitor for and minimize the risk of rebound fractures. For patients with advanced kidney disease, especially those on dialysis treated with Prolia, frequent monitoring of calcium in the blood, especially for the first 2 to 10 weeks after each Prolia injection, is recommended. Talk to your health care professional about specific instructions for the dose and type of calcium and vitamin D supplements that may be needed. Do not stop taking Prolia without talking with your health care professional as your risk of bone fracture, including in the spine, is increased after stopping, skipping, or delaying Prolia. Tell your health care professional if you develop symptoms suggestive of hypocalcemia such as confusion; seizures; irregular heart rhythm; fainting; face twitching; uncontrolled muscle spasms; or weakness, tingling, or numbness in parts of the body. Health Care Professionals It is important that the appropriateness of Prolia treatment in patients with advanced CKD be determined by a health care professional with expertise in the diagnosis and management of CKD-MBD including renal osteodystrophy, a complication that weakens bone. Treating bone disease in patients with advanced and dialysis-dependent CKD is challenging because of the difficulty in diagnosing and confirming the underlying altered bone metabolism responsible for the low bone mass and increased fracture risk, and the complex benefit-risk considerations of approved osteoporosis treatments in this population. Before prescribing Prolia, health care professionals should assess their patients’ kidney function. For patients with advanced CKD, particularly those on dialysis, health care professionals should consider the risk of severe hypocalcemia with Prolia in the context of other available treatments for osteoporosis. If Prolia is still being considered for these patients, for initial or continued use, check their calcium blood levels and assess them for evidence of CKD-MBD. Treatment with Prolia in patients with advanced CKD, including those on dialysis, and particularly patients with diagnosed CKD-MBD should involve a health care provider with expertise in the diagnosis and management of CKD-MBD. Proper management of CKD-MBD, correction of hypocalcemia, and supplementation with calcium and activated vitamin D prior to Prolia treatment is expected to decrease the risk of developing severe hypocalcemia and any associated complications. Following Prolia administration, close monitoring of blood calcium levels and prompt management of hypocalcemia is essential to prevent complications such as seizures or arrhythmias. Advise patients to promptly report symptoms that could be consistent with hypocalcemia. RELATED INFORMATION: Hypocalcemia Osteoporosis The FDA’s Drug Review Process: Ensuring Drugs Are Safe and Effective Think It Through: Managing the Benefits and Risks of Medicines Health professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program: Complete and submit the report online . Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on form, or submit by fax to 1-800-FDA-0178. Source: FDA More news resources FDA Medwatch Drug Alerts Daily MedNews News for Health Professionals New Drug Approvals New Drug Applications Drug Shortages Clinical Trial Results Generic Drug Approvals Subscribe to our newsletter Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

SHANGHAI, Dec. 26, 2023 /PRNewswire/ -- Jemincare, a leading pharmaceutical company from China, announced that its wholly owned subsidiary company, Shanghai Jemincare Pharmaceutical Co., Ltd., recently received 6 approvals of clinical trials for its innovative drugs in the field of cancer, kidney and anti-infectious diseases, including 4 approvals from National Medical Products Administration (NMPA) and 2 approvals from the U.S. Food & Drug Administration (FDA). Continue Reading On December 20, NMPA has approved a clinical trial for JMKX003801 to treat serious infection caused by Gram-negative bacteria. Drug resistance of antibiotics, especially carbapenem resistance, in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa has risen year by year. Preclinical studies on its mechanism show that JMKX003801 can overcome carbapenem resistance with very broad antibacterial spectrum. On December 12, NMPA has approved a clinical trial for JMKX003142 to treat renal edema. There are about 120 million patients of chronic kidney disease (CKD) in China. The rise of proteinuria during the late stage of CKD will cause edema. Research has shown that JMKX003142 can improve patients' quality of life with minor side effects as a novel diuretic drug. On November 28, NMPA has approved a clinical trial for JMKX003948 to treat renal cell carcinoma. In China, the number of newly diagnosed patients suffered from renal cell carcinoma is around 60 to 80 thousand each year. Since the failure of TKI and/or PD-1 immunotherapy, there is no other drug with new mechanism. Preclinical studies indicate that JMKX003948 show significant effect in animal models with a different mechanism of action. On December 12, FDA has approved a clinical trial for JMKX000197 to treat BCG-unresponsive non-muscle-invasive bladder cancer, and earlier on October 19, NMPA has approved the clinical trial. Bladder cancer is the most common malignant tumor in bladder system and the number of newly diagnosed patients with bladder tumor is around 80 thousand each year in China. Preclinical studies indicate that JMKX000197 can regulate the immune system and show significant anti-tumor effect in BCG-unresponsive animal models. Earlier on November 9, FDA has approved a clinical trial for JMKX003002 to treat hyperphosphatemia in end-stage kidney disease patients on dialysis. There are about 120 million patients of CKD in China and CKD causes hyperphosphatemia and CKD-mineral and bone disorder. As a novel drug to reduce phosphorus, JMKX003002 is expected to reduce phosphorus with a long-lasting effect and better oral compliance to improve the patients' quality of life. About Jemincare Jiangxi Jemincare Group Co., Ltd. is a leading pharmaceutical company from China. Founded in 1999, Jemincare is mainly engaged in pharmaceutical industry. The company is dedicated to the development, manufacturing and commercialization of therapeutics in its strategic fields including oncology, nephrology, cerebro-cardiovascular, anti-infection, analgesic, respiratory and Pediatrics. Shanghai Jemincare Pharmaceutical Co., Ltd is the R&D center of Jiangxi Jemincare Group Co., Ltd. Shanghai Jemincare has developed a strong team with more than 600 scientists comprised by 3 innovative research institute, Innovative Small Molecule Research Institute, Innovative Biologics Research Institute and Innovative Technologies Research Institute. The 6 innovative drug programs were developed by Innovative Small Molecule Research Institute which had more than 10 programs entering IND stage and 17 programs entering clinical stage. For more information, please visit SOURCE Jemincare