But the Manchester United defender, who earned his first call-up under manager Hodgson for the double header and was due to join up with the squad today, insisted he wants to continue his international career.
Hodgson, who met Ferdinand in London yesterday, said: "I'm disappointed Rio will not be available, but due to the detailed pre-planned training and medical programme he must follow it's not possible."
Tottenham defender Steven Caulker, originally in the Under-21 squad, has been called up as a replacement.
Hodgson added: "I was pleased that Rio called and asked to meet with me. It was important to hear from him personally about the way he must manage his body between games.
"This is not to say he cannot play back-to-back games - he can and has proven so. He's out this time due to particular pre-planned details already in place for his programme.
"I must place on record how I was impressed with his commitment to playing for England and I look forward to hopefully selecting him for squads in the future."
The last of Ferdinand's 81 England caps came in a UEFA EURO 2012 qualifier at home to Switzerland in June 2011.
The 34-year-old said: "It was important for me to be able to speak with Roy face to face and explain the situation, and one thing I made clear was that my passion and commitment to represent my country is as strong as ever.
"It is disappointing that I won't be able to play a part in the upcoming games but I told Roy that I want to continue to be available for England and I look forward to working with him in the future."
England travel to face San Marino on Friday before heading on to Montenegro, the Group H leaders, for a crucial clash the following Tuesday.