It’s a legit question, I believe. Every time i’m ill, every time I take a drugs box out of our medicines cabinet, it seems that I always open it on the wrong side. That’s just what you don’t want on that particular moment. You’re miserable enough.
So a ‘What’s the upside?’ arrow indication like they do on courier packages should be obliged. You could state that for educational purposes (you cannot take drugs without reading the manual), the upside always keeps the manual. First time user? Open the box from the upside. In other occasions, you would open the downside because that’s where you are. Or vice versa. Depending on what behavioral therapists and psychologists say.