Estudio de casos de eventos adversos y problemas relacionados con Denosumab reportados en Bogotá D. C. 2012-2017
Barbosa Amaya, Ana Milena | 2018
The objective of this work is to characterize the adverse events of Denosumab that have been reported during the years 2012 to 2017 in the pharmacovigilance program of the district health secretary in Bogotá, Colombia.
There is a varied group of pharmaceutical alternatives approved to treat osteoporosis, these contemplate medicines for prevention and treatment. Currently in Colombia are approved: Bisphosphonates (Alendronate, Etidronate, Risedronate), Calcium as a supplement, alone or in combination with vitamin D, selective modulator of estrogen receptors (Raloxifene) and a parathyroid hormone analogue (Teriparatide), among others. These drugs reduce the risk of fracture by different mechanisms of action in patients who have suffered fractures due to fragility and / or diagnosis of osteoporosis. Pharmacotherapy can also reduce the risk of fracture in patients with low bone mass, without previous fractures.
Currently there is great concern about its safety with long-term use, for this reason several associations worldwide such as: the American Society for Bone and Mineral Research, the National Osteoporosis of the United Kingdom Group of Guides and the European Menopause and Andropause Society have published about the balance risk benefit and the use of drugs such as bisphosphonates.
The drug of interest in this review is denosumab. Denosumab is a human monoclonal IgG2 antibody, it has high affinity and specificity for the human receptor activator of nuclear factor kappa-B ligand (RANKL), the main regulator of osteoclastic bone resorption. Denosumab binds to RANKL, which prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. This acts to inhibit the formation, function and survival of osteoclasts, thus decreasing bone resorption. Denosumab is an effective and safe treatment option for osteoporosis, with current data of up to 8 years of continuous use that show a continuous improvement in bone density with a sustained reduction in fracture risk. There is a greater theoretical risk of infection with the inhibition of RANKL. Future considerations include the safety of prolonged treatment beyond 8 years, and the risk of efficacy / fracture after discontinuation or non-adherence, given the characteristic pharmacodynamic profile of denosumab.
Denosumab is the first and so far the only RANKL inhibitor approved for the treatment of osteoporosis. It is extremely effective in reducing bone turnover and has reversible effects on interruption. Since its approval, it has demonstrated sustained efficacy in increasing BMD and reducing the risk of fractures, with extension data now through 8 years of use. Although safety has been a concern for this agent given its novel mechanism, current post-marketing data appear favorable in this regard, showing good tolerability and safety compared to placebo and bisphosphonates.
The initial approval of the United States FDA for denosumab was in June 2010 for the indication of the treatment of osteoporosis in postmenopausal women at high risk of fracture. In September 2011, the FDA granted an additional indication for treatment to increase bone mass in men at high risk of fracture receiving androgen deprivation therapy for non-metastatic prostate cancer and to increase bone mass in women with high fracture risk receiving therapy for breast cancer. In September 2012, denosumab was approved to increase bone mass in men with osteoporosis with a high risk of fracture. A dose of 60 mg is administered every 6 months subcutaneously. Currently the drug is marketed in Colombia under its two registered trademarks: PROLIA and XGEVA, after subcutaneous administration it is evident that the bioavailability of PROLIA is 78% while that of XGEVIA is 62%.
Different adverse reactions have been detected after drug consumption, being the most important: urinary tract infection, respiratory infection, cataracts, joint pain and osteonecrosis processes.
In Colombia, there is a national pharmacovigilance program led by INVIMA (national food and drug surveillance institute) whose objective is to monitor medicines after they are being marketed to determine the safety of them, in turn. It has a district pharmacovigilance program from which 55 reports of adverse reactions produced by Denosumab were obtained in the period from 2012 to 2017.
This is an observational descriptive study of a series of cross-sectional cases. The Case Reports methodology is used. The age and sex description is made. The seriousness, the causality and the descriptors of the World Health Organization are classified. Alphabetical classification is used according to the mechanism of action of the drug. Results: A total of 55 reports were analyzed, where there are 9 medication errors and 46 adverse reactions, of these the most frequent were alterations in the skin and general. 15% of cases (n = 8) are serious events, two related to death classified as unlikely. Causality in most cases is possible with 45% (n = 25). The age of the patients ranges from 50 to 88 years, the most frequent sex is female with 89% (n = 49)
It is concluded that 84% of the cases analyzed, n = 46 correspond to ADR derived from the administration of denosumab, it is important to mention that information about the safety of the drug is scarce since it has been on the market for less than 10 years. which makes this characterization of great importance in the quantification of new adverse reactions.