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* STOXX down 0.5 percent
* Italian index hits 6-week lows on political, bank worries
* British midcaps Essentra, Mitie slump after warnings
* Aixtron falls as U.S. regulator opposes China takeover
* Losses limited by rebound in miners, energy stocks
By Danilo Masoni
MILAN, Nov 21 (Reuters) - European shares fell on Monday, weighed down by losses among pharmaceuticals and financials and by worries that next month's Italian referendum on constitutional reform could create political instability.
The pan-European STOXX 600 fell 0.5 percent by 1000 GMT. Italy's blue chip index fell 1 percent after hitting its lowest point since end-September as investors priced in a possible rejection of Prime Minister Matteo Renzi's reform plan.
Investors are concerned that if Renzi loses the referendum, as the latest polls predict, the Italian government would fall into a serious crisis, threatening to destabilise the whole continent ahead of a string of national elections next year.
"The growing focus on political risk is contributing to Italian assets' difficulties," said JCI Capital portfolio manager Alessandro Balsotti, who noted how continued uncertainty over multi-billion-euro capital increases at UniCredit and Monte dei Paschi di Siena had also been weighing.
Among the biggest weights on the STOXX were Swiss-listed heavyweight drug makers Novartis and Roche, which fell 1.4 and 0.6 percent respectively; and big banks Lloyds and UBS, both down more than 1 percent.
German chip designer Aixtron fell more than 6 percent after a U.S. regulator moved to stop a planned Chinese takeover. The move raised concerns the deal would not go through.
"It is totally unclear whether the acquisition by Chinese investors will take place," said DZ Bank analyst Harald Schnitzer, who has a sell rating on the stock.
But BCP Millennium rose more than 3 percent after agreeing on a stake sale to Chinese conglomerate Fosun in a deal that would help the Portuguese lender to beef up its balance sheet.
UK midcaps were also on the backfoot after Essentra and Mitie warned over their outlook, raising concerns over the impact of Brexit on domestic UK companies. Essentra fell 19 percent and Mitie slumped 10 percent.
Gains in mining and energy stocks helped limit the broader market losses, as the sectors benefited from rising metal prices and hopes OPEC was moving closer to reaching an agreement to cut output when it meets next week.
Markus Huber of stockbrokers City of London Markets said concerns over the Italian vote on Dec. 4 as well as the likelihood that the U.S. Federal Reserve will raise rates next month kept investors cautious, even though broader sentiment remained positive.
"At this stage more good economic data will be needed to tempt traders to increase their risk exposure further," he said. (Reporting by Danilo Masoni; Editing by Mark Trevelyan)