Background Bullous pemphigoid has been associated to dipeptidase-4 inhibitors. Objectives Addressing the potential Bullous pemphigoid-dipeptidase-4 inhibitors association based on pharmacovigilance data currently available in Spain in order to obtain a composite disproportionality estimator from all the data generated by the case-non case studies conducted to this date. Setting The Spanish Pharmacovigilance System for Human Use Drugs database. Method Case-non case study based on the Spanish Pharmacovigilance System for Human Use Drugs notifications submitted between 2007 and 2018 (n = 169,280), using the Medical Dictionary for Regulatory Activities term (Preferred Term) 'pemphigoid' for sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin (n = 1952). As negative control, we used acetaminophen, while furosemide was the positive control. A pooled reported odds ratio analysis in the French, Japanese, and Spanish national pharmacovigilance databases was performed. On The Spanish Pharmacovigilance System for Human Use Drugs, we conducted a bullous pemphigoid-metformin association analysis within the period 1982-2018. Main outcome measure Adverse reaction cases in pharmacovigilance databases and the disproportionality through the reporting odds ratio. Results Within The Spanish Pharmacovigilance System for Human Use Drugs, we found 45 cases of bullous pemphigoid in dipeptidase-4 inhibitors patients. Median age was 77 years (range 72-82). The median latency period was 7 months (range 0.23-86). The Bullous pemphigoid-dipeptidase-4 inhibitors association was established with a reporting odd ratio = 70.0 (95% confidence intervals 49.1-10.1). In the combined analysis of the three aforementioned pharmacovigilance databases, the pooled reporting odd ratio was 81.0 (95% confidence intervals 69.5-94.4). Conclusion The composite estimator for the three national pharmacovigilance databases yields clear evidence of a Bullous pemphigoid-dipeptidase-4 inhibitors association, which was statistically significant for both the pharmacological class as a whole and each of the dipeptidase-4 inhibitors agents under investigation. Metformin's role in the incidence of bullous pemphigoid appeared casual rather than causal. No differences between Caucasian and Asian populations were noted.

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Background Thromboembolic events (TEs) are known to be a severe complication for COVID-19. They are associated with a systemic inflammatory response syndrome with coagulation cascade activation. Objective The aim of this study was to determine a potential association between the COVID-19 pandemic and the increment of the risk of suspected TEs in women on systemic hormonal contraceptives (SHCs). Patients and MethodsThis study utilised a case/non-case approach in the Spanish Pharmacovigilance Database, which includes more than 290,000 cases of suspected adverse drug reactions (ADRs). The reporting odds ratio (ROR) was calculated during an initial pandemic period in 2020 compared with a pre-pandemic period in 2019 and an additional control period in 2018. Results While there was a decreased number of ADR notifications for any medications and for any type of ADR in patients on SHCs during the pandemic period, the TE ROR for all SHCs was higher in the 2020 pandemic period ] relative to the pre-pandemic period in 2019 [ROR = 6.3 (3.2-12.5)] and the additional control period in 2018 [ROR = 4.6. (2.1-9.9)]. In contrast, ROR for progestogen-only contraceptives was lower during the pandemic as compared with the two control periods. ConclusionThe reported disproportionality of TEs in women on SHCs rose during the pandemic period. This suggests a potential interaction of the drug (SHC) with COVID-19, which led to an increased risk of TEs in women exposed to both factors. This should be taken into consideration in the context of the COVID-19 pandemic.

A 55-year-old woman developed an atraumatic sternum fracture during treatment with alendronate for osteoporosis. The woman received alendronate 70 mg in combination with cholecalciferol 5600 IU once weekly, as well as nonsteroidal anti-inflammatory drugs. After 4 years of treatment, following a dorsal flexion with no direct thoracic trauma, the patient suffered a fracture of the sternum, with an X-ray revealing sternal body fracture. This fracture was seen to be transverse, noncomminuted and without displacement. Magnetic resonance imaging was carried out to rule out the presence of either a pathological fracture or a fracture resulting from osteoporotic fragility, and showed a triple sternal fracture involving the body, as well as the upper and lower manubrium of the sternum. This fracture presented the features of an atypical femur fracture, except for the location. The alendronate and cholecalciferol combination was discontinued and denosumab was prescribed. After the withdrawal of alendronate, the patient showed clinical improvement, with a decrease in pain, and is currently having routine checkups. The causality algorithm of the Spanish Pharmacovigilance System shows a score of 5, indicating a possible relationship between the patient’s sternum fracture and her use of the suspect drug (Naranjo scale 6 = probable).