Castrogiovanni, who wins his 94th cap, takes over from Sergio Parisse for the game at the Stadio Olimpico in Rome.
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Parisse is serving a 40-day ban – 10 days of which were suspended – after being sent off playing for his club Stade Francais in a French Top 14 game against Bordeaux-Begles last weekend.
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Castrogiovanni, who skippered his country in last season’s Six Nations game against Scotland, takes over the leadership reins, with Manoa Vosawai packing down at number eight instead of Parisse.
Kristopher Burton takes over from Luciano Orquera at fly-half while Edoardo Gori starts ahead of Tobias Botes to form a new half-back combination.
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Ratu Manoa Vosawai starts at number eight in the place of suspended skipper Sergio Parisse.
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In the second row, Antonio Pavanello takes over from Quintin Geldenhuys.
Italy: 15 Andrea Masi, 14 Giovambattista Venditti, 13 Tommaso Benvenuti, 12 Gonzalo Canale, 11 Luke McLean, 10 Kristopher Burton, 9 Edoardo Gori, 8 Ratu Manoa Vosawai, 7 Simone Favaro, 6 Alessandro Zanni, 5 Francesco Minto, 4 Antonio Pavanello, 3 Martin Castrogiovanni, 2 Leonardo Ghiraldini (c) 1 Andrea Lo Cicero.
Replacements: 16 Davide Giazzon, 17 Alberto De Marchi, 18 Lorenzo Cittadini, 19 Quintin Geldenhuys, 20 Paul Derbyshire, 21 Tobias Botes, 22 Luciano Orquera , 23 Gonzalo Garcia.
