De Guzman has a groin problem which kept him out of Swansea's game at Southampton on Sunday, while PSV Eindhoven's Stijn Schaars misses out with a knee injury.
That has led to Louis van Gaal drafting in 23-year-old Fer, whose last appearance for Holland came just over a year ago when he was a substitute in the 2-0 win over Turkey.
Paris St Germain right-back Gregory van der Wiel has also pulled out of the Holland squad after being forced out of training on Monday with a knee injury.
Augsburg defender Paul Verhaegh, 30, has been drafted in as his replacement and could be in line to make his second appearance for his country.
Holland, who have already qualified for the 2014 World Cup, face Hungary in Amsterdam on Friday before completing their campaign with a trip to Turkey on Tuesday.