ROME (AP) — Twenty-year-old Danish player Holger Rune recorded his second victory over Novak Djokovic in little more than six months, beating the 22-time Grand Slam champion 6-2, 4-6, 6-2 Wednesday to reach the Italian Open semifinals.

Rune, who also defeated Djokovic in the Paris Masters final in November, gave the Serb fits with his rapid court coverage. He made his opponent hit extra balls on points that Djokovic thought he had already finished off.

The 35-year-old Djokovic didn’t appear at his best physically early on and called for a trainer after holding for a 2-1 lead in the second set. It wasn’t immediately clear what the issue was but it appeared that Djokovic swallowed a pill that the trainer gave him.

Djokovic recently returned after three weeks off because of a lingering issue with his surgically repaired right elbow. He’s preparing for the French Open, which starts in 11 days.

Rune, meanwhile, is boosting his credentials as a Grand Slam contender after a solid season on clay that included a runner-up finish in the Monte Carlo Masters, a title in Munich, and now a semifinal spot in Rome in his first main draw appearance.

Djokovic stormed out to a 5-2 lead in the second but Rune rallied back, winning a 34-shot rally with a sublime backhand drop-shot winner to set up a key break.

Rune also called for a trainer late in the second set to have his right leg treated, shortly before the match was suspended because of rain with Rune serving to stay in the set at 4-5, 0-30.

After a suspension of more than an hour, Djokovic won two straight points to break Rune’s serve and take the second set.

Rune then broke Djokovic’s serve twice early in the third.

Djokovic has won the Italian Open six times, including last year, and failed to reach the final only once in eight previous editions — when he was beaten by Rafael Nadal in the semifinals in 2018.

Nadal, who holds the record of 10 titles in Rome, is not playing as he remains hampered by a nagging hip injury, leaving his status for Roland Garros in question.

With Djokovic out of the draw, an 18-year streak of either him or Nadal playing in the Rome final ends.

Djokovic will also lose the No. 1 ranking to Carlos Alcaraz, another 20-year-old player, next week — even though Alcaraz was beaten by 135th-ranked Hungarian qualifier Fabian Marozsan in the third round on Monday.

Rune’s semifinal opponent will be either Casper Ruud or Francisco Cerundolo, who were scheduled to play later.

In the women’s quarterfinals, two-time defending champion Iga Swiatek was up against Wimbledon champion Elena Rybakina and 2017 French Open champion Jelena Ostapenko was facing Paula Badosa.

Rune, who is known for his fiery behavior, got into a heated exchange with the chair umpire about a disputed call during the second set. When the umpire refused to change the call despite Rune saying that the mark on the clay showed that Djokovic’s shot was out, he lost his cool.

“Do you get punished when you make mistakes? You don’t. So please respect the player,” Rune said to the umpire, Mohamed Lahyani. “It’s an absolute joke.”

As Rune’s coach, Patrick Mouratoglou, motioned from the stands for his player to calm down, Rune then said to nobody in particular, “It’s always the umpire who makes me look like the bad guy.”

Early in the third, Djokovic grew frustrated with Lahyani because of the way he was announcing the score between Italian and English, and when the service shot clock started.

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Andrew Dampf is at https://twitter.com/AndrewDampf

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AP Tennis: https://apnews.com/hub/tennis and https://twitter.com/AP_Sports