Book of Shadows' quality is treated as 2 for the purposes of Bag of Crafting.
Synergies
4.5 Volt: With sufficient damage, the Book of Shadows can be kept active indefinitely.
Book of Virtues: Spawns shielded wisps in the middle ring. The wisps have 1 health, but will not be damaged by blocking projectiles, and can only be destroyed on contact with enemies. When Book of Shadows is active, wisps are immune to all damage, allowing for easy melee kills.
Car Battery: Doubles the duration of invulnerability.
Cube of Meat and most other orbitals: Highly effective with Book of Shadows, as Isaac can run into enemies with an active shield to deal massive amounts of damage.
Razor Blade: Can be used at no cost while the Book of Shadows shield is present, allowing damage to be significantly increased for the room.
Interactions
Blood Oath: If the book is used just before the knife stabs Isaac, he will not lose any health, nor gain any stat upgrades associated with the item.
This item belongs to the 
Bookworm set. Collecting three items from this set will transform Isaac into Bookworm.
Blood Donation Machines, 
Devil Beggars, 
Hell Game, and 
Confessional.
Book of Shadows' quality is treated as 2 for the purposes of 
Bag of Crafting.
4.5 Volt: With sufficient damage, the Book of Shadows can be kept active indefinitely.
Book of Virtues: Spawns shielded wisps in the middle ring. The wisps have 1 health, but will not be damaged by blocking projectiles, and can only be destroyed on contact with enemies. When Book of Shadows is active, wisps are immune to all damage, allowing for easy melee kills.
Car Battery: Doubles the duration of invulnerability.
Cube of Meat and most other orbitals: Highly effective with Book of Shadows, as Isaac can run into enemies with an active shield to deal massive amounts of damage.
Razor Blade: Can be used at no cost while the Book of Shadows shield is present, allowing damage to be significantly increased for the room.
Blood Oath: If the book is used just before the knife stabs Isaac, he will not lose any health, nor gain any stat upgrades associated with the item.
Blood Rights/
IV Bag/
3DS The icon of Book of Shadows as seen on the lower 3DS screen.
Books 
The Binding of Isaac: Rebirth
