Safety profile of methotrexate used off-label in ectopic pregnancy: an active monitoring study based on a Chinese hospital pharmacovigilance system.

OBJECTIVE: Methotrexate (MTX) is characterized as first-line therapy although its indication of ectopic pregnancy is off-label use. We aimed to conduct a retrospective cohort study to investigate the incidence, characteristics of adverse drug reactions (ADRs) of MTX, provide valuable insights for medical workers. METHODS: Basing on China Hospital Pharmacovigilance System (CHPS), a retrospective analysis was performed to evaluate the safety of MTX (n = 672). An active monitoring model was set to detect ADR signals from the hospital information system. Frequency, Common Terminology Criteria for Adverse Events (CTCAE) grade proportion and association of dose exposure with ADRs were presented as outcomes. RESULTS: The total incidence of ADRs was 54.0%. Anaemia (37.6%) was the most frequent ADR, followed by hepatic function abnormal (11.3%), hyperuricemia (6.1%), neutropenia (4.6%), leukopenia (4.0%), and dyslipidaemia (2.5%). For the composition of all ADRs, CTCAE grade one, two and three dominated for 86.3%, 12.1% and 1.6%, respectively. The severity of hepatic function abnormal was more serious in the two-dose exposed group (p = .021), while other types of ADRs had no statistical or clinical differences. Logistic regression analysis showed the incidence of any ADRs (OR 1.87 [1.31-2.64]; p = .001), hepatic function abnormal (OR 2.75 [1.69-4.48]; p < .001), dyslipidaemia (OR 5.15 [1.87-14.13]; p = .001) were significantly higher in the two-dose exposed group. After adjusted, the positive associations were still maintained. CONCLUSIONS: MTX is quite safe in ectopic pregnancy, despite its mild to moderate hematotoxicity, hepatotoxicity and nephrotoxicity. Taking CHPS can present the accurate denominator of the incidence of adverse drug reactions into account, our study advocates that it may have great potential to be used as an active monitoring tool for off-label drug use risk management.

[Method and significance of ultrasonographic assessment of the uterine weight before pelvic floor reconstruction].

OBJECTIVE: To investigate the accuracy of ultrasonographic assessment of the total uterine weight and the feasibility of using this method in the pelvic floor reconstruction. METHODS: Firstly, 81 cases with hysterectomy due to benign uterine diseases or uterine prolapse were studied. The preoperative dimensions and gravities of corpus uteri and cervix were calculated by formulas, and were then compared with the postoperative measurements. Subsequently, 46 cases with pelvic floor reconstruction and preserved the uterus were subjected to retrospectively analysis of uterine measurement parameters. RESULTS: There were no statistically differences between the preoperative and postoperative diameters of corpus uteri and cervix (P > 0.05), and no statistically differences between the weight of corpus uteri and cervix estimated by the formulas [(87 ± 55), (32 ± 6) g] and the true weight [(88 ± 57), (33 ± 6) g; P > 0.05]. In 46 cases that underwent the pelvic floor reconstruction by transvaginal mesh repair and preserved the uterus, 42 cases were successful treated and the average weight of total uterus was (49 ± 13) g (95%CI: 39.90-49.88 g); the 4 relapsed cases were treated with hysterectomy and the weight of total uterus were 85.24, 82.69, 92.67 and 120.06 g which were consistent with the weights estimated by the formulas (87.36, 82.00, 90.88, 123.12 g; all P > 0.05). CONCLUSIONS: The uterine weight might be a significant factor for uterus preservation in pelvic floor reconstruction, while ultrasonographic assessment can accurately estimate the uterine weight preoperatively. All these raised the feasibility of assessing uterine weight preoperatively in pelvic floor reconstruction.