Liverpool manager Jurgen Klopp says it is "necessity" for clubs to have five substitutes per match in the Premier League, while Manchester City boss Pep Guardiola has labelled the current three sub limit a "disaster".
Klopp and Guardiola renewed their calls for the rules to be changed after Liverpool defender Trent Alexander-Arnold suffered a suspected calf injury during Sunday's 1-1 draw at the Etihad.
The Liverpool manager has rejected claims that reintroducing the five substitutes rule, which was briefly used last season after Project Restart, could favour the 'big six' and insists player welfare should be the priority this season.
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"All the teams have to understand why it's so helpful. It's not an advantage, it's a necessity. 100 per cent," said Klopp.
"In all other countries it happens and here we make a bit more fun of the competition by having only three subs. That is really incredible, so we have to talk again."
Alexander-Arnold will have a scan on Monday and is expected to withdraw from the England squad for their games against the Republic of Ireland, Belgium and Iceland later this month.
Klopp believes the Football Association should take action over the substitutes rule, or risk having more international players ruled out through injury.
"In my understanding it is a lack of leadership," Klopp added. "It is the only big league where you have only three subs. Surprise.
"The FA has to be involved. Tonight we lost Trent Alexander-Arnold. I'm pretty sure Gareth Southgate is not fine [with that].
"If we continue like this and hopefully we can play the Euros in the summer… if they happen, let's see who will be part of that."
Manchester City have used all three of their substitutes twice this season and only two clubs have made fewer total substitutions, but manager Guardiola says he fully agrees with Klopp that the limit must be increased.
"All around the world it's five substitutions, but here we believe we are more special people," said Guardiola.
"We don't protect the players, and that's why it's a disaster. In this calendar, especially. I will demand, if the people allow, we have to come back to five substitutions. If not, it's difficult to sustain it."
The Professional Footballers' Association (PFA) has confirmed it remains in support of allowing clubs to use five substitutes.
"We told the Premier League we would support such a move on health and safety grounds for our members before the first vote and our position has not changed," a PFA statement read.
'PL could vote to change rule mid-season'
Sky Sports News reporter Rebecca Williams says the five substitutes rule could be reintroduced mid-season if enough Premier League clubs vote in favour of the change.
"If you look across Europe, the likes of the Bundesliga, La Liga, Serie A and Ligue 1, they've all voted to bring in five substitutes this season, as have the MLS in the United States.
"This is because the fixture list is a lot more congested because of the impact coronavirus has had. Clearly it would benefit the bigger teams with the bigger budgets, perhaps more than those at the bottom of the Premier League table.
"A lot of people have asked me whether a change can be brought in midway through the season. It is possible - any club can bring forward a proposal and ask other clubs if they want to vote on it.
"But it is worth pointing out that they've already voted on it twice so far this season and we're only in November. Both times it hasn't got the required 14 votes to push it through.
"So I think it's unlikely at this stage and at the last Premier League shareholders' meeting, it wasn't brought up at all."
Moyes: I've changed my mind over five subs
West Ham manager David Moyes had previously been in favour of only using three substitutes but he admits he would now prefer the option of being able to have up to five replacements.
"I recommended to our board that we would vote for three subs and not more. I've got to say, my mind has changed now is because of player welfare," said Moyes, speaking after Saturday's 1-0 win over Fulham.
"I don't think I expected so many injuries. So many games in such a small period of time, whether it be that you're an international player or in the Champions League or the Europa League, has meant that the programme has been so congested.
"There has been no parties willing to give up any games, whether it be the Carabao Cup or any other cup competition. Nobody has been willing to give anything up.
"That's why now I would consider the change if it was there, that we could have more subs."
Roy Keane believes Manchester City lack the firepower needed to win the Premier League this season, after their 1-1 draw with Liverpool.
Pep Guardiola's side were a distant second to the Reds last season and eight games into the 2020/21 campaign they already trail Liverpool by five points, sitting 11th in the table, six off early leaders Leicester City.
Interestingly, Man City have scored 17 goals fewer than they had at the same stage of last season, and Keane believes with Sergio Aguero struggling with injuries, they aren't able to make their dominance count in matches - and criticised them for not investing in a striker in the summer.
"I know there were other positions they wanted to fill, a centre-half I suppose was a priority. They've got nobody but themselves to blame for being short on strikers. You have to have strength in depth - particularly if you're expected to challenge for all the major trophies. I don't see City winning the league this year."