The authors studied the effect of raltegravir on the pharmacokinetics of the antiepileptic agent lamotrigine. Twelve healthy volunteers (group A) received 400 mg raltegravir twice daily from days 1 to 5. On day 4, a single dose of 100 mg lamotrigine was administered. After a washout period, participants received a second single dose of 100 mg of lamotrigine but now without raltegravir (day 32). In group B, 12 participants received the same treatment as in group A but in reverse order. On days 4 and 32, 48-hour pharmacokinetic curves were drawn. Geometric mean ratios (+90% confidence intervals [CIs]) of lamotrigine area under the plasma concentration-time curve (AUC(0-->48)) and peak plasma concentration (C(max)) for raltegravir + lamotrigine versus lamotrigine alone were 0.99 (0.96-1.01) and 0.94 (0.89-0.99), respectively. The mean ratio of the AUC(0-->48) of lamotrigine-2N-glucuronide to lamotrigine was similar when lamotrigine was taken alone (0.35) or when taken with raltegravir (0.36). Raltegravir does not influence the glucuronidation of lamotrigine.
ObjectivesDuring COVID-19 vaccination programmes, new safety signals have emerged for vaccines, including extremely rare cases of thrombosis with thrombocytopaenia syndrome (TTS). Background event rates before and during the pandemic are essential for contextualisation of such infrequent events. In the literature, most studies do not report an overall TTS event rate. Rather, background rates are mainly reported for subtypes of thrombotic/thromboembolic diagnoses included in the TTS clinical definition mostly by anatomical location, with reported rates for TTS subtypes varying widely. The objective of this study was to report prepandemic TTS background event rates in the general population.MethodsPrepandemic background TTS rates were generated via secondary data analysis using a cohort design in the IBM Truven MarketScan (now Merative MarketScan) US health insurance claims database, from 1 January 2019 to 31 December 2019. Two algorithms were applied: thrombocytopaenia occurring±7 days (algorithm 1) or occurring 1 day prior to ≤14 days after the thrombotic/thromboembolic event (algorithm 2).ResultsThe study population derived from the MarketScan database analysis included approximately 9.8 million adults (aged ≥18 years; mean age 45 years, 52% females). Using this study population, prepandemic background TTS incidence was estimated as 9.8–11.1 per 100 000 person-years. Event rates were higher in males and increased with age. Similar patterns were observed with both algorithms.ConclusionsThis study presents an estimate of aggregate prepandemic background TTS event rates including by type of thrombosis/thromboembolism and age group. The background event rates are dependent on the precision of capturing underlying TTS events in variable data sources, and the ability of electronic health records or insurance claims databases to reflect the TTS clinical definition. Differences between reported event rates demonstrate that estimating background event rates for rare, unprecedented safety events is methodologically challenging.
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