A closer look at generic interchangeability in narrow. The theoretical insensitivity of pharmacokinetics was confirmed when the reference drug, synthroid, was compared to a generic candidate. The publication, approved drug products with therapeutic equivalence evaluations the list, commonly known as the orange book, identifies. Patients need a precise dose of levothyroxine sodium. The fda has approved several brand names for levothyroxine which include tirosint, levot, levothroid, levoxyl, synthroid, and unithroid. A tirosint manufactured by ibsa institut biochimique sa, pambio. Fdas approved drug products with therapeutic equivalence evaluations orange book identifies drug products approved on the basis of. How is generic liothyroninelevothyroxine equivalent to. See full prescribing information for complete boxed warning.
The 25th edition of the orange book will be available in a downloadable pdf format. Fda drug info rounds pharmacists discuss how to search the electronic orange book for generic equivalents, patents, and exclusivity. According to the orange book, products listed with a codes are therapeutically equivalent to other pharmaceutically equivalent products. That rulemaking, says abbott, should establish procedures for 1 fda s assignment of te ratings to drugs that are the subject of 505b2 drugs and 2 fda s public listing of such ratings in the orange book. This emedtv resource describes how levothyroxine works, explains what you should know before taking the drug, and lists possible side effects. Our new crystalgraphics chart and diagram slides for powerpoint is a collection of over impressively designed datadriven chart and editable diagram s guaranteed to impress any audience. The october 2004 supplement to the fda orange book now lists generic equivalents to each brandname levothyroxine product. Synthroid has a long history of problems, says fda in.
The food and drug administration fda has issued letters to all new drug application nda and abbreviated new drug application anda holders requiring that they. Thyroxine products joint position statement american. On july 28, 2004, therapeutic ratings for levothyroxine sodium products were updated in the orange book. The electronic availability of the orange book brings this valuable tool to the web for healthcare professionals. Fda cder orange book staff office of generic drugs 7620 standish place rockville, md 208552773 1. Levothyroxine and fda bioequivalence ratings mdedge family. Levothyroxine and liothyronine tablets fda prescribing. The fda, generics and differentiating authorized from. Most pharmacists already know that the orange book, created in 1980 and now in its 28th edition, is an fda publication that lists many drug products and contains indications as to whether generic versions of medications are considered to be equivalent to the drugs manufactured by the innovator company and most often marketed with brand names. The fda defines narrow therapeutic range ntr drug products as containing certain drug substances subject to therapeutic drug concentration or pharmacodynamic monitoring, andor where product labeling indicates a narrow therapeutic range designation.
Levothyroxine sodium powder dissolution peform the test with an accurately weighed quantity of levothyroxine sodium powder, equivalent to about 0. Synthroid cannot be generally recognized as safe and effective because it is of no fixed composition iii. Drug name active ingredients strength dosage formroute marketing status te code rld rs. The orange book has long been a reliable resource for information about fdaapproved drugs. Approved drug products containing levothyroxine sodium listed in the fda orange book. Last week, just before the new orange book print and electronic versions made its debut, we opined see our previous post here that changes to the orange book preface would likely be made. Thyroid hormones, including synthroid should not be used for the treatment of obesity or for weight loss. Do not use oral thyroid hormone drug products to treat myxedema coma. The publication approved drug products with therapeutic equivalence evaluations commonly known as the orange book identifies drug products approved on the basis of safety and effectiveness by the food and drug administration fda under the federal food, drug, and cosmetic act the act and related patent and exclusivity information. The orange book has long been a reliable resource for information about fda approved drugs. They contain both tetraiodothyronine sodium t4 levothyroxine and triiodothyronine sodium t3 liothyronine providing 38 mcg levothyroxine t4 and 9 mcg liothyronine t3 per grain of thyroid. Unapproved levothyroxine products hit in fda action medscape. It is created by ehealthme based on reports from food and drug administration fda, and is updated regularly. In order to inform manufacturers, consumers, and healthcare practitioners of approved drugs and bioequivalence status, fda maintains the publication approved drug products with therapeutic equivalence evaluations orange book, which lists all approved drugs and their bioequivalence status.
Some noteworthy changes to the 2017 orange book preface. Initiate synthroid at less than the full replacement dose because of the increased risk of cardiac adverse reactions, including atrial fibrillation. List of approved drug products containing levothyroxine sodium in the fda orange book on approved drug products containing levothyroxine sodium listed in the fda orange book. Levothyroxine sodium mylan tablets have been determined to be therapeutically equivalent to corresponding strengths of unithroid jerome stevens tablets. In the middle of image, you will see orange book te code. Apr 15, 2020 fda is penalizing companies that filed late for approval of levothyroxine sodium products by forcing reductions in distribution over the next 2 years. Synthroid levothyroxine sodium tablets, for oral use. The orange book is published annually and the 2015 edition is 35th edition of orange book. Jun 19, 2014 the fda publishes therapeutic equivalence evaluations for approved prescription drug products in approved drug products with therapeutic equivalence evaluations, commonly known as the orange book. Lovenox and levothyroxine thyroid drug interactions a study. For me at least, based on facts here, for desiccated thyroid, i will dispense any of these names. T3 enters the cell and binds to nuclear thyroid hormone receptors. On march 23, 2020, fda removed from the orange book the listings for biological products that have been approved in applications under section 505 of the. Dec 08, 2004 the fda orange book should reflect this by changing levot, synthroid, and levoxyl from bx to ab and adding the levothyroxine preparation sandoz to its ab listings.
Karst last week, just before the new orange book print and electronic versions made its debut, we opined see our previous post here that changes to the orange book preface would likely be made. Levothyroxine sodium product information food and drug. A new molecular entity is considered an active moiety that has not. Fda has the authority to declare synthroid a new drug ii. In 1938, a bill was passed to revise the 1906 food and drugs act. Levothyroxine sodium is the sodium salt of levothyroxine, a synthetic levoisomer of thyroxine t4 that is similar to the endogenous hormone produced by the thyroid gland.
Fda cder orange book staff office of generic drugs. Levothyroxine sodium is singled out in the preface to the fda orange book as a special situation with respect to therapeutic equivalence evaluation and related codes. Levothyroxine sodium monohydrate c15h12i4nnao5 pubchem. Currently approved levothyroxine preparations should be considered therapeutically inequivalent unless equivalency has been established and noted in the fda s approved drug products with therapeutic equivalency evaluations orange book. Citizen petition requests rulemaking process for 505b2. Because there are multiple reference listed drugs for levothyroxine sodium. The publication, approved drug products with therapeutic equivalence evaluations the list, commonly known as the orange book, identifies drug products approved on the basis of safety and. They contain both tetraiodothyronine sodium t4 levothyroxine and triiodothyronine sodium t3 liothyronine providing 38 mcg levothyroxine t4 and 9 mcg liothyronine t3 per grain of thyroid or per 65 mg of the labeled amount of thyroid. The fda now is making a distinction between the designation of an rld the drug upon which an anda may be based and a reference standard the drug that fda expects the firm to use for establishing bioequivalence. Applicant holders are requested to inform the fda orange book staff obs of any changes or corrections. They contain both tetraiodothyronine sodium t4 levothyroxine and liothyronine sodium t3 liothyronine providing 38 mcg levothyroxine t4 and 9 mcg liothyronine t3 per grain of thyroid or per 60 mg of the labeled amount of thyroid. Np thyroid 90 fda prescription drug recalls, side effects. Due to the long halflife, peak therapeutic effects may not be attained for 46 weeks.
The result is a confusing patchwork of drugs that are bioequivalent to some formulations, but not to others. Start studying orange book, pmda 1987, medical devices, hipaa law. Fda provides the following explanation and chart of therapeutic equivalence evaluations for levothyroxine sodium drug products. Approved drug products food and drug administration. An ab rating by the food and drug administration in its orange book publication does not change the application of the nti rule as noted above. At a minimum, fdas new regulations should characterize fdas assignment and listing of te ratings for 505b2. Levothyroxine sodium uses, dmf, dossier, manufacturer. What is special about the situation with levothyroxine sodium. Levothyroxine mylan previously was ab to unithroid, as noted above.
Approved drug products with therapeutic equivalence. Drug name active ingredients strength dosage formroute marketing status rld te code application no. Worell, sandoz introduces levothyroxine sodium tablets, usp, a bioequivalent alternative product to synthroid. The 24th edition of the orange book will be the last paper version. Levoxyl, levothroid, unithroid levothyroxine yuvafem estradiol vaginal tablet not only do generic. Available by prescription, levothyroxine can treat an underactive thyroid and other thyroid problems.
The publication approved drug products with therapeutic equivalence evaluations commonly known as the orange book identifies drug products approved on the basis of safety and. Levothyroxine and fda bioequivalence ratings mdedge. Chart and diagram slides for powerpoint beautifully designed chart and diagram s for powerpoint with visually stunning graphics and animation effects. Generic substitution of narrow therapeutic index drugs. The fdas role in generic substitution is through its evaluation of the therapeutic equivalency of drug products. Applicant holders are requested to inform the fda orange book.
The fda orange book should reflect this by changing levot, synthroid, and levoxyl from bx to ab and adding the levothyroxine preparation sandoz to its ab listings. They contain both tetraiodothyronine sodium t4 levothyroxine and liothyronine sodium t3 liothyronine providing 38 mcg levothyroxine t4 and 9 mcg liothyronine t3 per grain of thyroid or per 60 mg of the labeled. Orange book, pmda 1987, medical devices, hipaa law. The food and drug administration fda has issued letters to all new drug application nda and abbreviated new drug application anda holders requiring that they change the specifications for their products so that all levothyroxine sodium products approved for use in humans will meet a 95% to 105% potency specification throughout their labeled. To date, only seven of 28 possible pairs 25% have been declared bioequivalent these receive an ab rating in the fdas orange book, as illustrated in the table below levothyroxine is mylans version. As we know, all drug products approved for safety or efficacy are cited in the orange book and are considered listed drugs.
Notably, the fda does not dictate which drug products may be. The fda s role in generic substitution is through its evaluation of the therapeutic equivalency of drug products. Food and drug administration 10903 new hampshire avenue silver spring, md 20993 1888infofda 18884636332 contact fda. Levothyroxine sodium fda orange book approved drug. I think i has to be approved to be in the orange book. Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease. Levothyroxine and liothyronine thyroid tablets, usp for oral use is a natural preparation derived from porcine thyroid glands. This federal food drug and cosmetic act required that drugs be shown to meet certain safety requirements prior to their being marketed. Fda orange book the official name of fda s orange book is approved drug products with therapeutic equivalence evaluations. Levothyroxine bioequivalence, therapeutic equivalence, and.
Fda publishes this list as part of the approved drug products with therapeutic equivalence evaluations, which is known generally as the orange book. In addition, the orange book contains therapeutic equivalence. Product number the fda assigned number to identify the application products. Fdas orange book and ab ratings of pharmaceutical drug. Easy to read fda package insert, drug facts, dosage and administration, and adverse effects for synthroid levothyroxine. Levothyroxine sodium mylan tablets have been determined to be therapeutically equivalent to. In peripheral tissues, levothyroxine is deiodinated by 5deiodinase to form triiodothyronine t3. Testimony on levothyroxine sodium synthroid therapeutic. Levothyroxine qualifies as an nti drug under this statute which means that pharmacists need to get the documented consent of the prescriber and the patient before switching manufacturers on refills.
Approved levothyroxine sodium oral preparations 157 should be considered therapeutically inequivalent unless equivalence has been established and noted in the fdas approved drug products with therapeutic equivalence evaluations orange book. Levothyroxine bioequivalence, therapeutic equivalence, and generic levothyroxine substitution powerpoint ppt presentation. Now that the print version of the orange book is available, weve had a chance to peruse those preface and patent and exclusivity information addendum revisions. Np thyroid thyroid tablets, usp for oral use is a natural preparation derived from porcine thyroid glands. Reference listed drug, reference standard, basis of. That rulemaking, says abbott, should establish procedures for 1 fdas assignment of te ratings to drugs that are the subject of 505b2 drugs and 2 fdas public listing of such ratings in the orange book. There is no drug interactions reported by people who take lovenox and levothyroxine thyroid together yet. The fda, generics and differentiating authorized from branded types. The electronic availability of the orange book brings this valuable tool to the web for healthcare. Levothyroxine bioequivalence, therapeutic equivalence, and generic levothyroxine substitution 1. All the components of the paper orange book are and have been available on the internet since 1997. Worell, sandoz introduces levothyroxine sodium tablets, usp, a bioequivalent alternative product to synthroid and levoxyl. Most states follow orange book ratings for generic equivalent. Levoxyl levothyroxine sodium tablet description c h i n.
Pharmacokinetics and comparative bioavailability of a. Noranco, switzerland 150g capsule was selected as the reference product because it is the reference listed drug for levothyroxine capsules as per the orange book. Many of these products have been given a threecharacter code ab1, ab2, or ab3. Originally this book was published in october 1980 with orange cover and thus the name orange book. Nov 17, 2017 levothyroxine and liothyronine thyroid tablets, usp for oral use is a natural preparation derived from porcine thyroid glands. Drugs coded with a threecharacter code are considered therapeutically equivalent only to other drugs coded with the same threecharacter code. Jun 18, 2009 in texas, the texas board of pharmacy was given the authority to create a list of nti drugs, but to date the board has not added any drug to such a list. My state does not follow the orange book, so ab rating isnt squired to sub westminster pharmas product. Levoxyl levothyroxine sodium tablet king pharmaceuticals, inc.
Under fda regulations, drugs are removed from the list if the agency withdraws or suspends approval of the drugs nda or anda for reasons of safety or effectiveness or if fda determines. The generic was recognized as therapeutically equivalent, given the ab2 designation, and was advertised as interchangeable c. Orange book cumulative supplement 03 march 2020 fda. In texas, the texas board of pharmacy was given the authority to create a list of nti drugs, but to date the board has not added any drug to such a list.
1072 623 700 211 93 655 201 718 1271 731 316 249 1401 361 413 1051 1265 880 347 671 773 1268 548 943 1522 286 1265 395 492 63 937 430 497 415 186 766 848