Year in Review: Troubling New Drug Approvals of 2013

Of the 27 new drugs approved by the Food and Drug Administration (FDA), Public Citizen’s Health Research Group has identified many as dangerous or ineffective. This article reviews those drugs, as well as dangerous newly approved uses for two drugs already on the market.

New drugs approved in 2013: Do Not Use

Alogliptin
(approved January 2013)[1]

Alogliptin is the latest in a class of diabetes drugs known as incretin mimetics. The FDA approved three versions of alogliptin, each with a different brand name: NESINA, a single-drug pill containing only alogliptin; KAZANO, a combination pill containing alogliptin and the diabetes medication metformin; and OSENI, a combination pill containing alogliptin and the older diabetes drug pioglitazone.[2] Alogliptin and other incretin mimetics are associated with severe side effects, including pancreatitis[3] and possible pancreatic cancer.[4] Due to these and other safety concerns, all incretin mimetics are classified as Do Not Use drugs by Worst Pills, Best Pills.[5]

Mipomersen
(approved January 2013)

Mipomersen (KYNAMRO) was approved to treat an extremely rare, fatal genetic condition called homozygous familial hypercholesterolemia (HoFH), which causes very high blood-cholesterol levels.[6] Its approval followed closely on the heels of a similar drug, lomitapide (JUXTAPID), approved for the same disease in December 2012.[7] Public Citizen testified against mipomersen’s approval due to its liver toxicity[8] and because studies of the drug did not compare it with the current standard and life-prolonging treatment for HoFH, LDL apheresis[9] (a procedure in which a patient’s blood is passed through a specialized filter that removes LDL or “bad” cholesterol directly from the blood[10]).

Canagliflozin
(approved March 2013)

Canagliflozin (INVOKANA) was the first of a new class of medications for type 2 diabetes known as sodium-glucose co-transporter 2 (SGLT2) inhibitors.[11] (The second drug in this class, dapagliflozin [FARXIGA], was approved in January 2014.[12]) For more information on canagliflozin, see the top story in the February 2014 edition of Worst Pills, Best Pills News.

Fluticasone/Vilanterol
(approved May 2013)

The combination inhaler (BREO ELLIPTA) contains the steroid fluticasone (a drug used to suppress inflammation in the lungs) and the bronchodilator vilanterol (a drug that dilates the large airways in the lungs, known as bronchi). It was approved to treat chronic obstructive pulmonary disease (COPD).[13] Public Citizen’s Health Research Group testified before the FDA’s Pulmonary and Allergy Diseases Advisory Committee, strongly opposing approval of the combination of fluticasone and vilanterol because it did not provide any substantial benefit over vilanterol alone in improving COPD symptoms, but it did lead to an increased number of serious side effects, including bone fractures and infections such as pneumonia.[14]

Flutemetamol F18 injection
(approved October 2013)

Flutemetamol F18 injection (VIZAMYL) is the second radioactive tracer drug to be approved for use with a positron emission tomography (PET) scan of the brain to rule out a diagnosis of Alzheimer’s disease (AD), which is associated with the buildup in the brain of a substance known as beta amyloid.[15]

As acknowledged by the FDA in announcing flutemetamol F18’s approval, beta amyloid tracers used in PET imaging can only help rule out AD with a negative result.[16] However, as Public Citizen has previously noted, a positive test indicating the presence of beta amyloid is essentially useless because it cannot specifically identify a cause of the cognitive impairment, meaning patients must always be assessed for additional causes regardless of whether the imaging test is negative or positive.[17] Moreover, no clinical trial has demonstrated that PET imaging for beta amyloid changes the health outcomes of patients displaying early signs of cognitive dysfunction or of any other patient population.[18] Indeed, even if a test existed that was 100 percent accurate in diagnosing AD, it would not lead to any tangible health benefits for patients because there are currently no available therapies to reverse or substantially slow the progression of AD.[19]

Umeclidinium/Vilanterol
(approved December 2013)

This drug (ANORO ELLIPTA), an inhaled combination of two long-acting bronchodilators, umeclidinium and vilanterol, was approved as a once-daily, long-term maintenance treatment for COPD.[20] It represents the first time two different classes of long-acting bronchodilators, long-acting muscarinic antagonists and long-acting beta agonists, had been approved as a single combination drug. However, because of troubling potential cardiac risks, Public Citizen’s Health Research Group testified before the FDA’s Pulmonary and Allergy Diseases Advisory Committee that the drug should not be approved until a larger trial was conducted to further clarify the nature of this potential side effect.[21]

New indications: Do Not Use

Oxybutynin (granted over-the-counter status in January 2013)[22]

In January 2013, the FDA approved over-the-counter status for oxybutynin (OXYTROL FOR WOMEN), available by prescription since 1975[23] for overactive bladder. In so doing, the FDA ignored the advice of its own advisory committee, which in November 2013 had warned that it was too dangerous to use the drug without a physician’s supervision, especially for the elderly.[24] Because of a litany of side effects and the need to rule out potentially serious causes of symptoms similar to those of overactive bladder, Public Citizen warned consumers not to use oxybutynin without first seeing a doctor and discussing the benefits and risks of the drug (for more details, see the article about over-the-counter oxybutynin in the August 2013 issue of Worst Pills, Best Pills News).[25]

Paroxetine for menopausal symptoms (approved for this new indication in June 2013)[26]

Paroxetine has been on the market as an antidepressant (PAXIL) since 1992.[27] In March 2013, the FDA’s Advisory Committee on Reproductive Health Drugs considered an application for approval of a lower dose of the drug as a treatment for hot flashes and flushing in menopausal women.[28] Public Citizen’s Health Research Group testified that there was insufficient evidence from the pre-approval clinical trials that the drug provided meaningful benefits for menopausal symptoms,[29] but it did come with several serious risks, including seizures and possible suicidal tendencies.

In June, the FDA approved paroxetine (BRISDELLE) for the treatment of moderate to severe hot flashes.[30] The company secured approval for a 7.5 milligram (mg) dose, making it more difficult for patients to obtain this dose by simply breaking in half cheaper 10 mg or 20 mg pills of generic paroxetine.[31] A 30-day supply of BRISDELLE costs $135, compared to just $7 for 30 tablets of the 10 mg dose of generic paroxetine.[32] An article in the January 2014 issue of Worst Pills, Best Pills News advises against the use of paroxetine for treatment of hot flashes.[33]

Conclusion

There were slightly fewer new drugs approved in 2013 than in 2012, which had the highest number of approvals (39) since 1997.[34] Yet there are no indications that this small decline represents a harbinger of improved approval standards at Obama’s FDA.

With so many dangerous and ineffective drugs already slipping through the FDA’s lax approval process, it may just be a matter of time before we experience a new wave of drug safety disasters.

References

[1] Food and Drug Administration. New drugs at FDA: CDER’s new molecular entities and new therapeutic biological products of 2013. http://www.fda.gov/drugs/developmentapprovalprocess/druginnovation/default.htm. Accessed January 9, 2014.

[2] Food and Drug Administration. FDA News Release. FDA approves three new drug treatments for type 2 diabetes. Jan. 25, 2013. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm336942.htm. Accessed January 21, 2014.

[3] Takeda Pharmaceuticals America, Inc. Nesina (alogliptin) label. January 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022271s000lbl.pdf. Accessed January 9, 2014; Novo Nordisk. Victoza (liraglutide) label. April 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022341s020lbl.pdf. Accessed January 9, 2014.

[4] Public Citizen. New study underscores increased dangers of certain diabetes treatments. March 22, 2013. http://www.citizen.org/pressroom/pressroomredirect.cfm?ID=3850. Accessed January 9, 2014.

[5] Diabetes drugs linked to pancreas disease. Worst Pills Best Pills News. August 2013. /newsletters/view/864. Accessed January 9, 2014.

[6] Genzyme Corporation. Kynamro (mipomersen sodium) injection label. January 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203568s000lbl.pdf. Accessed January 9, 2014.

[7] FDA News Release. FDA approves new orphan drug for rare cholesterol disorder. Dec. 26, 2012. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333285.htm. Accessed January 9, 2014.

[8] Public Citizen. Testimony before FDA hearing on mipomersen for treatment of homozygous familial hypercholesterolemia. October 18, 2012. http://www.citizen.org/documents/2079.pdf. Accessed January 9, 2014.

[9] Public Citizen. Press Release. FDA should reject dangerous cholesterol medication, Public Citizen tells advisory committee. October 18, 2012. http://www.citizen.org/pressroom/pressroomredirect.cfm?ID=3736. Accessed January 9, 2014.

[10] University of Colorado Hospital. What is LDL apheresis? http://www.uch.edu/conditions/weight-metabolism/lipid-cholesterol/ldl-apheresis-treatment/. Accessed January 21, 2014.

[11] Food and Drug Administration. Medical Review: canagliflozin. February 8, 2013. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204042Orig1s000MedR.pdf. Accessed February 7, 2014.

[12] Food and Drug Administration. FDA News Release. FDA approves Farxiga to treat type 2 diabetes. January 8, 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm380829.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery. Accessed January 9, 2014.

[13] Food and Drug Administration. FDA News Release. FDA approves Breo Ellipta to treat chronic obstructive pulmonary disease. May 10, 2013. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm351664.htm. Accessed January 9, 2014.

[14] Public Citizen. Letter to FDA opposing approval of fluticasone furoate/vilanterol (FF/VI) for COPD. April 30, 2013. http://www.citizen.org/hrg2119. Accessed January 7, 2014.

[15] Food and Drug Administration. FDA News Release. FDA approves second brain imaging drug to help evaluate patients for Alzheimer’s disease, dementia. October 25, 2013. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm372261.htm. Accessed January 9, 2014.

[16] Ibid.

[17] Public Citizen. Letter to the Centers for Medicare and Medicaid Services. July 23, 2013. http://www.citizen.org/documents/2143.pdf. Accessed January 10, 2014.

[18] Ibid.

[19] Ibid.

[20] Food and Drug Administration. FDA News Release. FDA approves Anoro Ellipta to treat chronic obstructive pulmonary disease. Dec. 18, 2013. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm379057.htm. Accessed January 9, 2014.

[21] Public Citizen. Testimony before the FDA’s Pulmonary and Allergy Drugs Advisory Committee on umeclidinium/vilanterol (proposed trade name Anoro Ellipta) for the long-term treatment of patients with chronic obstructive pulmonary disease (COPD). September 10, 2013. http://www.citizen.org/hrg2156. Accessed February 7, 2014.

[22] Do not use over-the-counter oxybutynin without first checking with your doctor. Worst Pills, Best Pills News. August 2013. /newsletters/view/863. Accessed January 10, 2014.

[23] Ibid.

[24] Public Citizen. Press Release. Patients should beware when new drug for overactive bladder soon becomes available over-the-counter. August 1, 2013. http://www.citizen.org/pressroom/pressroomredirect.cfm?ID=3951. Accessed January 10, 2014.

[25] Do not use over-the-counter oxybutynin without first checking with your doctor. Worst Pills, Best Pills News. August 2013. /newsletters/view/863. Accessed January 10, 2014.

[26] Food and Drug Administration. FDA News Release. FDA approves the first non-hormonal treatment for hot flashes associated with menopause. June 28, 2013. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm359030.htm. Accessed January 9, 2014.

[27] Food and Drug Administration. Drugs@FDA. Paxil. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed January 10, 2014.

[28] Public Citizen. Press Release. No hot flash relief here: medications for depression, seizures and neuropathic pain should not get nod from the FDA. March 4, 2013. http://www.citizen.org/pressroom/pressroomredirect.cfm?ID=3827. Accessed January 10, 2014.

[29] Ibid.

[30] Food and Drug Administration. FDA News Release. FDA approves the first non-hormonal treatment for hot flashes associated with menopause. June 28, 2013. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm359030.htm. Accessed January 9, 2014.

[31] Paroxetine. Dosing forms & strengths. Medscape. http://reference.medscape.com/drug/paxil-brisdelle-paroxetine-342959. Accessed January 10, 2014.

[32] Paroxetine (Brisdelle) for Hot Flashes. Medical Letter. Volume 55 (Issue 1428). Oct. 28, 2013.

[33] Do not use paroxetine (BRISDELLE) for treatment of hot flashes. Worst Pills, Best Pills News. January 2014. /newsletters/view/882. Accessed January 21, 2014.

[34] U.S. FDA Drug Approvals, by year (1990-2012). Reuters. http://pdf.reuters.com/pdfnews/pdfnews.asp?i=43059c3bf0e37541&u=2012_12_31_07_46_31edc30559fb4ac58d00fe8efc81e251_PRIMARY.jpg. Accessed January 10, 2014.