Chelsea defender Ampadu, 18, left the field with a knee injury as Wales were defeated 4-1 by Spain in a friendly.
20-year-old Mepham, however, missed the game with Spain to gain fitness ready for the Ireland game, but has returned to club side Brentford and will not feature in Dublin.
Gwion Edwards and Kieron Freeman, both uncapped, have been called up to Ryan Giggs' squad.
Wales currently sit second in their Nations League group behind leaders Denmark.