While holding an active item that grants passive bonuses in the secondary slot, swapping the main slot item with a pedestal item may remove the bonuses. If this happens, you can swap the bonus-granting item to the pedestal and pick it up again to regain them.
The swap key must be pressed twice if playing as The Forgotten.
Kamikaze!: The cooldown before the player can use Kamikaze! again is eliminated when switching items. Depending on how fast the player can push the buttons, Kamikaze! can be used multiple times during Isaac's invincibility frames.
Mom's Box: If a trinket is picked up while Mom's Box is in the active slot, swapping between active items will not remove the doubled trinket effect.
A Pony / White Pony: Will continue to grant flight and the speed bonus while held in the secondary slot.
Removing Schoolbag using D100, D4, or through being granted the effect from Metronome and using it again, does not cause the second active item to be removed or dropped into a pedestal; Isaac will still be able to hold his second active item until he picks up another active item, which will then remove the second slot and delete the active item contained.
Bug!
Re-rolling by Dice Room removes the primary active item but the second one remains unchanged, allowing another active item to be picked up. Picking up another active item after this will result in the previous bug; the second slot is removed and the active item contained is deleted.
Bug!
As of V1.06.J168, the item inside the Schoolbag has a minor graphical glitch when picking up a third active item. For a single frame as the pickup animation ends, the item's "charged glow" status and number of bars will match the item that Isaac is picking up.
Bug!
When Isaac's Tears is in the first active item slot, the secondary item does not charge upon clearing rooms.
(page 5, column 9, row 3)
The Nail, may deactivate if switched with an item in the secondary slot.
? Card does not activate both active items.
Silver Dollar, 
Forget Me Now, or a 5-pip Dice Room.
Kamikaze!: The cooldown before the player can use Kamikaze! again is eliminated when switching items. Depending on how fast the player can push the buttons, Kamikaze! can be used multiple times during Isaac's invincibility frames.
Mom's Box: If a trinket is picked up while Mom's Box is in the active slot, swapping between active items will not remove the doubled trinket effect.
A Pony / 
White Pony: Will continue to grant flight and the speed bonus while held in the secondary slot.
My Little Unicorn / 
The Gamekid / 
Unicorn Stump: Switching items breaks the invincibility effect. This does not apply to other sources of invincibility.
Bug!
D100, 
D4, or through being granted the effect from 
Metronome and using it again, does not cause the second active item to be removed or dropped into a pedestal; Isaac will still be able to hold his second active item until he picks up another active item, which will then remove the second slot and delete the active item contained.
Isaac's Tears is in the first active item slot, the secondary item does not charge upon clearing rooms.
Schoolbag 
The Binding of Isaac: Rebirth 
Achievements
Attributes
Bosses
Cards and Runes
Challenges
Chapters
Characters
Co-op
Items
Monsters
Objects
Pickups
Pills
Rooms
Seeds
Transformations
Trinkets
