The way the US military works, throwing rolls of toilet paper at the drone from the deck of the shop is likely more expensive than the drone said toilet paper is hurling towards.
Depends on the target, some large ISR drones totally need big 20mm rounds but you scale the system down to machine guns and shotguns and build out integrated air defence systems with electronic actively scanning radar and sensors to detect and track the threats to kill
They need something in the realm of a big automatic shotgun.