The Coppa holders have several players out injured, including Brazilian playmaker Hernanes, while the team's leading scorers Antonio Candreva and Miroslav Klose are unavailable with the flu.
Only two players that featured in Saturday's 1-1 draw against Juventus are expected to be included in Lazio's starting XI.
"I am forced to make a turnover," Reja said in Tuesday's press conference. "It's a necessity.
"We have no alternatives up front, we have (Balde) Keita and (Brayan) Perea.
"More than ever, our starting line up will be determined by our doctor.
"I want to include players that are physically well."
Despite the absences, Reja remains upbeat about his team's chances.
Lazio are unbeaten in 2014 travel to Naples having ended Juve's 12-match winning run in Serie A at the weekend.
The 1-1 result in Rome followed their 3-2 triumph at Udinese and lifted Lazio to 10th place.
"We have a 50 percent chance to go through," Reja said. "It will all depend on the will and mentality my team displays on the pitch.
"I don't know if we will play the right game as we have done in our last two matches but I do know we have chances to go through despite our absences.
"I know whoever goes on the pitch will make life difficult for Napoli."
Victory on Wednesday would see Lazio face city rivals Roma in the semi-finals of the competition.
"We first have to go through before we can think of anything else," Reja said. "We have to focus only on Wednesday's match."
Napoli last won the Coppa back in the 2011-12 campaign and are determined to lift the Cup this season.
"The Coppa Italia is one of our aims this season," Napoli coach Rafa Benitez said. "My players have prepared well for the game.
"It's an important test for us and we have the advantage of playing at home.
"Although we are confident, we cannot forget that Lazio are unbeaten under Reja."
Benitez's men will look to bounce back from Saturday's 1-1 draw to Chievo that followed their 2-2 result at Bologna.
Their latest league setbacks have seen Napoli, who are third in the standings, drop six points behind second-place Roma and just three clear of Fiorentina.
Napoli will be bolstered by the return of Pepe Reina in goal.
The Spanish goalkeeper has fully recovered from a muscular injury and will start.