The easiest way - is to create a constant variable that will stop the autoresponder from firing again as long as this variable exists.
But it is also desirable that this variable be deleted after some time, so I suggest using the switch "-u300" (300 seconds), to set the time for auto deletion of the variable.

For example:
Code
on *:TEXT:*Hello*:#:{
  if (!%no_reply1) {
    .timerAUTOREPLY1 1 $rand(2,5) msg $chan $+($nick,$chr(44)) Hi dude!
    set -u300 %no_reply1 $true
  }
}

Ideally, this would be better done with hash tables instead of variables.

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