There was also a bunch of dropcap discussion in these three topics (Oldest -> Recent):
https://www.mobileread.com/forums/sho...d.php?t=228236
https://www.mobileread.com/forums/sho...d.php?t=229512
https://www.mobileread.com/forums/sho...d.php?t=237323
There were SOME solutions, that might work in most cases... although you can't rely on it working everywhere. A bunch of devices are notorious for breaking (as was brought up, larger/smaller font size, different fonts, changing margins/line-spacing, etc. etc.).
Overall, I would probably say stay away. Go with a Raised Cap instead (which is what we settled on doing over at work as an ok "middle ground"). Although even THAT breaks on some devices (the Nook Touch (?) has a bug where it messes up the line spacing when there is a raised cap).