(Adds details, FDA comments, byline)

By Susan Heavey

WASHINGTON, March 1 (Reuters) - The U.S. Food and Drug Administration has ordered 20 companies including Novartis AG's <NOVN.VX> <NVS.N> Sandoz unit to stop marketing several unapproved headache drugs, the agency said on Thursday.

The FDA sent warning letters to eight manufacturers, which also included Ivax Pharmaceuticals Inc., recently acquired by Teva Pharmaceutical Industries Ltd. <TEVA.O>.

Twelve distributors also were warned.

Like other approved products for migraine and other headaches, the drugs contain the active ingredient ergotamine tartrate. But they have been manufactured and distributed without undergoing review by the FDA, the agency said.

"Because these drugs don't have approval ... we don't know if they're safe and effective," said Deborah Autor, who oversees compliance issues at the FDA.

The unapproved ergotamine tartrate drugs do not carry necessary cautions against their use in patients also taking drugs that inhibit the metabolic enzyme CYP 3A4 found on labels for similar approved headache drugs, the agency said.

Such inhibitors can include certain antibiotics, antifungal treatments and protease inhibitors.

Representatives for Novartis and Teva did not return calls seeking comment.

FDA officials said the goal was to get the unapproved drugs off the market but that manufacturers could later seek approval to sell them.

The action on Thursday is part of a larger effort to reign in a number of unapproved drugs that have made it onto the U.S. market without FDA approval due to legal quirks, they said.

"Doctors and patients often do not realize that not all drugs that are available on the market are backed by FDA approval," Autor said in a separate statement.

She added that fewer than 2 percent of prescription medications are unapproved.

"Drugs that skirt the approval process may be unsafe, may not work, and in our experience, often have inadequate labeling," she said.

Ergotamine medications approved by the FDA to treat headaches include Sandoz's Cafergot as well as products from privately held Rosedale Therapeutics, Mikart and West-Ward and G & W Labs, according to the agency.

The FDA posted the letters, dated Feb. 26, on its Web site at http://www.accessdata.fda.gov/scripts/wlcfm/date.cfm?MONTH=2&YEAR=2007

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