Unithroid Becomes First Levothyroxine Tablet to Gain FDA Approval
An NDA for Unithroid tablets, manufactured by Bohemia, N.Y.-based Jerome Stevens Pharmaceuticals Inc., was approved Aug. 20 by FDA. As of Aug. 14, 2001, FDA will consider any oral levothyroxine sodium product that has not been similarly sanctioned an "unapproved drug," subject to regulatory action.
Unithroid tablets were found to be equivalent to a levothyroxine sodium solution prepared in accordance with the current United States Pharmacopeia method. The product is available in 11 dosage strengths ranging from 25 mcg to 300 mcg. Stability studies performed by the manufacturer supported an initial 18-month expiration date, which may be extended after additional study.
Manufacturers first started marketing levothyroxine sodium products in the United States in the 1950s, before FDA required a prescription drug product have an approved NDA. FDA has acknowledged that with proper manufacturing, storage, and prescribing, levothyroxine sodium is a safe and effective treatment for hypothyroidism.
However, FDA has found that some formulations of the drug have inconsistent potency levels and are not uniformly stable until the expiration date. Levothyroxine recalls are common, said FDA. Concerns about adverse events prompted the agency to set a deadline by which all manufacturers of oral levothyroxine sodium products must have their NDA approved in order to continuing marketing those products.
Literature references supporting levothyroxine's safety and effectiveness can be submitted with the NDA, since FDA does not require new clinical studies of the drug. However, manufacturers must complete bioavailability and stability studies and submit the results with each NDA.
Ronald Steinlauf, vice president of Jerome Stevens Pharmaceuticals, while "very excited" about Unithroid's approval by FDA, said he expects a "long battle and challenge ahead." Although FDA approval is a big step, success of the product will depend on "educating physicians, pharmacists, and patients" about Unithroid.
Unithroid, said Steinlauf, has been marketed since 1990 under the names levothyroxine and Thyrox. The company changed the name to Unithroid to obtain FDA approval of the NDA.
FDA reviews all proposed drug brand names to determine whether products with similar names exist and could possibly lead health care providers to mistakenly prescribe or dispense the incorrect drug. The agency found no currently marketed drugs with names dangerously similar to Unithroid.
In 1997, Knoll Pharmaceutical Company, maker of Synthroid, settled a series of class action lawsuits alleging the company delayed publication of research comparing the bioavailability of four levothyroxine products including Synthroid. The research eventually appeared in the American Journal of Therapeutics and the Journal of the American Medical Association (JAMA). Unithroid was not one of the products examined in the study that, when interpreted by the JAMA authors, found the four products bioequivalent.
Knoll has questioned FDA's recommended bioavailability testing procedures, and Jones Pharma Inc., the maker of one of the products tested in the disputed research, has agreed with some of Knoll's statements. Both companies have communicated their concerns to FDA.