Third division Lotte had already shocked Bundesliga Werder Bremen in the first round.

Despite seeing defender Tim Wendel sent off on 79 minutes for a second yellow card, Lotte held on to a 2-2 draw after extra-time in the second round clash.

Leverkusen were booed by their own fans while director of sport Rudi Voeller was left fuming.

"This can't be surpassed in terms of stupidity," he said.

Kevin Volland's two goals for Leverkusen were cancelled out by an own goal from Roberto Hilbert and Kevin Freiberger's equaliser for Lotte in the 106th minute.

In the shoot-out, Chile's Charles Aranguiz, Volland and Austria's Julian Baumgartlinger, all of whom are internationals, missed penalties for Leverkusen.

It has been a worrying dip in for for Bayer, who are away to Tottenham Hotspur in the Champions League week next but are winless in their last four matches.

"This is the most difficult situation since I joined the club," admitted striker Stefan Kiessling, who has spent the last decade at Bayer.

They crashed 3-0 at home to Hoffenheim on Saturday in the Bundesliga, and the pressure is ratcheting up on coach Roger Schmidt.

The embarrassing defeat comes just 24 hours after Schmidt was banned for two games by the German FA for verbally abusing a rival coach.

Schmidt had to watch the nightmare unfold from the team bus while serving his ban, which saw him excluded from the playing area.

Freiburg were another Bundesliga club to crash out on penalties when they lost 4-3 at home to second-division Sandhausen following a 3-3 draw.

On Wednesday, holders Bayern Munich are in action when they host Augsburg in an all-Bundesliga match.

Injury-hit Borussia Dortmund, last season's losing finalists, are waiting on the fitness of star striker Pierre-Emerick Aubameyang ahead of hosting second division Union Berlin.