Monday, March 27, 2023
Will these new drug approvals from 2011 affect your practice in 2012?
These selected FDA alerts from 2011 may help keep your patients safe in 2012.
The following examples are new device and product approvals and alerts from 2011.
Authors
Joanna M. Pangilinan, PharmD, Freelance medical writer/clinical editor, Medscape from WebMD
Laurie Scudder, DNP, NP, Clinical Editor, Medscape from WebMD
Reviewers
Henry R. Black, MD, Clinical Professor of Internal Medicine; Director of Hypertension Research, New York University School of Medicine, NYU Center for the Prevention of Cardiovascular Disease, New York, New York
Désirée Lie, MD, MSEd, Clinical Professor, Family Medicine, University of California, Orange; Director, Division of Faculty Development, UCI Medical Center, Orange, California
Jennifer L. Athay, PharmD, Director of Student Affairs, American Association of Colleges of Pharmacy, Alexandria, Virginia
Laurie Briceland, PharmD, Professor of Pharmacy, Albany College of Pharmacy and Health Sciences, Albany, New York
Joseph T. DiPiro, PharmD, Executive Dean; Professor, College of Pharmacy, University of South Carolina and the Medical University of South Carolina, Charleston, South Carolina
Katherine K. Knapp, PhD, Professor; Dean, Touro University California College of Pharmacy, Vallejo, California
Reviewers cont.
Stanley Lloyd, PharmD, Prestige Clinical Instructor of Pharmacy Practice, College of Pharmacy, University of Toledo, Toledo, Ohio; Pharmacist, Express Scripts, Inc., Mason, Ohio
Mary Lynn McPherson, PharmD, BCPE, CPE, CDE, Professor, Vice Chair, Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, Maryland; Consultant Pharmacist, Hospice and Palliative Care, Millersville, Maryland
2011's Most Important Drug News for Primary Care
What was the most important drug news for primary care this past year? US Food and Drug Administration (FDA) news and alerts with significant patient safety implications -- black box warnings, dosage instructions, adverse event warnings along with news related to drugs indicated for major disease states, such as obesity, diabetes, and cardiovascular disease, and important information in the area of health promotion and disease prevention. Finally, major news in the management of cancer, HIV, and other diseases frequently comanaged by PCPs and specialists are included.
Labeling changes to glitazones were made in 2011. Rosiglitazone (Avandia®; GlaxoSmithKline; Research Triangle Park, North Carolina) and all rosiglitazone-containing products now include information regarding a possible increased risk for heart attacks. A risk evaluation and mitigation strategy (REMS) requires that all rosiglitazone products be available through a restricted access and distribution system. Pioglitazone (Actos®; Takeda Pharmaceutical Company Limited; Osaka, Japan) and all pioglitazone-containing medicines now include information regarding a possible increased risk for bladder cancer associated with use for more than 1 year.
The strength of prescription acetaminophen products was limited to 325 mg per dose. Note: Over-the-counter products were not affected by this change. Based on this news, prescription products containing acetaminophen are to include a black box warning with information about risk for severe liver injury with use and an addition to the warning section regarding risk for severe allergic reactions with use.
The FDA has also issued a warning to parents about potential confusion stemming from the recent introduction of a new 160 mg/5 mL strength of acetaminophen marketed for use in infants and young children. Acetaminophen strengths of 80 mg/mL and 80 mg/0.8mL are still in stores and families' medicine cabinets with the potential for both under- and over-dosing.
Adverse effects of proton pump inhibitors (PPIs) were clarified in March with an FDA warning to healthcare professionals that prolonged use of prescription PPIs -- usually longer than 1 year-- may result in hypomagnesemia. Additionally, the FDA reported that risk for fracture and osteoporosis is unlikely with OTC PPIs due to low-dose and short-term indications for use. Clinicians should consider risk for fracture and osteoporosis if recommending off-label use of OTC PPIs. Prescription-strength PPIs continue to carry a warning about these adverse effects.
The FDA approved rivaroxaban (Xarelto®; Janssen Pharmaceuticals, Inc.; Titusville, New Jersey), an oral factor Xa inhibitor, for prevention of deep venous thrombosis after knee or hip replacement surgery as well as to prevent stroke and systemic embolism in patients with nonvalvular atrial fibrillation.
Changes and clarifications were made regarding common drugs used for hyperlipidemia. In June, the FDA warned that simvastatin 80 mg (Zocor®; Merck Sharp & Dohme Ltd.; Cramlington, Northumberland, United Kingdom; also available as generics) should not be used in new patients or in patients already taking lower doses due to risk for myopathy. Dose limitations are recommended for certain drug combinations. Recently, the recommended dose for use with amiodarone was raised to 20 mg from the 10 mg originally recommended in June. In November, the FDA warned that fenofibric acid (Trilipix®; Abbott Laboratories; North Chicago, Illinois) may not reduce risk for heart attack or stroke. Further trial investigation is required to evaluate fenofibric acid use in patients with high risk for cardiovascular disease who are taking statins. Finally, a generic version of atorvastatin was approved in December.
2011 brought new therapies for type 2 diabetes. Linagliptin (Tradjenta™; Eli Lilly and Company; Indianapolis, Indiana; and Boehringer Ingelheim Pharmaceuticals; Ridgefield, Connecticut), a dipeptidyl peptidase-4 inhibitor, was approved on May 2 to improve blood glucose control in adults with type 2 diabetes. The glucagon-like peptide-1 receptor agonist exenatide (Byetta®; Amylin Pharmaceuticals, Inc.; San Diego, California, and Eli Lilly and Company; Indianapolis, Indiana) received expanded approval as an adjunct to insulin glargine, with or without metformin and/or thiazolidinedione therapy, in patients with type 2 diabetes not controlled on insulin glargine alone.
On June 9, the FDA warned that an increased risk for high-grade prostate cancer is associated with use of 5-alpha reductase inhibitors (5-ARIs). These agents, including finasteride and dutasteride, are marketed for benign prostatic hypertrophy. Healthcare professionals are urged to evaluate patients for urologic conditions prior to initiating therapy and to evaluate patients who have any increase in prostate-specific antigen while on therapy. Label warnings reflecting this risk for a more serious form of prostate cancer have been added to all 5-ARI products.
Several vaccines were approved for expanded use this year. Previously licensed for patients between 10 and 64 years of age, Tdap (tetanus toxoid/reduced diphtheria/acellular pertussis; Boostrix®; GlaxoSmithKline Biologicals; Rixensart, Belgium; and Novartis Vaccines and Diagnostics GmbH; Marburg, Germany) was approved on July 8 for adults 65 years and older. Menactra® (Sanofi Pasteur Inc.; Swiftwater, Pennsylvania) was approved in children as young as 9 months for prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y, and W-135. Menactra was already approved for patients ages 2 through 55 years. The live zoster vaccine, Zostavax® (Merck Sharp & Dohme Corp.; Whitehouse Station, New Jersey), was approved for patients 50-59 years of age. Zostavax was previously approved for patients 60 years and older.
New agents were approved for chronic obstructive pulmonary disease (COPD). On July 1, the FDA approved indacaterol inhalation powder (Arcapta™ Neohaler™; Novartis Pharma Stein AG; Stein, Switzerland), a once-daily, long-acting beta-2 adrenergic agonist (LABA) for treatment of COPD in adults. On March 1, once-daily, oral roflumilast (Daliresp™; Forest Pharmaceuticals, Inc.; St. Louis, Missouri) was approved to decrease the frequency of COPD exacerbations. Roflumilast is the first in a new class of drugs for COPD called phosphodiesterase type 4 inhibitors.
There were also several notable drug approvals for cardiovascular disease in 2011. The antiplatelet agent ticagrelor (Brilinta®; AstraZeneca; Wilmington, Delaware) was approved after a protracted process. The approval comes with a boxed warning stating that use of ticagrelor with aspirin doses above 100 mg/day decreases the effectiveness of the medication. In December, the combination of azilsartan medoxomil and chlorthalidone (Edarbyclor®; Takeda Pharmaceutical Company Limited; Osaka, Japan) was approved for the treatment of hypertension. The new combination is the first fixed-dose therapy in the United States to combine an angiotensin II receptor blocker with the diuretic chlorthalidone.
Drug Safety Communications were issued regarding varenicline (Chantix®; Pfizer Ireland Pharmaceuticals; Dublin, Ireland). On July 22, the FDA reported labeling changes for varenicline with updated information on use in patients with stable cardiovascular disease and COPD, as well as alternative directions for use. In October, updated results of an ongoing safety review of varenicline and risk for neuropsychiatric adverse events were issued. Clinicians should continue to follow labeling recommendations and monitor patients for neuropsychiatric adverse events when prescribing varenicline.
Warnings regarding use of several medications during pregnancy were issued this year. Notably, the FDA warned that long-term, high-dose fluconazole (Diflucan®; Pfizer Inc.; New York, New York; also available as generics) may be associated with birth defects. A possible increased risk for cognitive delay in children born to mothers who have taken valproate sodium, valproic acid, or divalproex sodium was announced. Topiramate (Topamax®; Janssen Ortho, LLC; Gurabo, Puerto Rico; also available as generics) may increase the risk for cleft palate and/or cleft lip in infants. Finally, healthcare professionals were informed that the pregnancy section for all antipsychotic drugs will contain more and consistent information on extrapyramidal signs and withdrawal symptoms in newborns born to mothers taking these agents during the third trimester of pregnancy.
According to a September Drug Safety Communication, ECG changes, including QT interval prolongation and torsade de pointes, have been reported in patients receiving ondansetron (Zofran®; GlaxoSmithKline; Research Triangle Park, North Carolina; also available as generics). Patients with congenital long QT syndrome should not receive ondansetron. ECG monitoring is recommended in the following situations: patients with electrolyte abnormalities, congestive heart failure, bradyarrhythmias, or patients receiving other drugs that cause QT interval prolongation. Labeling is being revised to reflect the findings of this ongoing safety review.
Another Drug Safety Communication warned that citalopram (Celexa®; Forest Laboratories, Inc.; St. Louis, Missouri; also available as generics), should not be given in doses larger than 40 mg daily. Labeling will be revised to reflect this new maximum dose that was previously up to 60 mg daily. Higher-dose citalopram has been associated with QT interval prolongation; citalopram should not be used in patients with congenital long QT syndrome. Patients with congestive heart failure, bradyarrhythmias, or predisposition to hypokalemia or hypomagnesemia are at higher risk for torsade de pointes. A maximum dose of 20 mg daily is recommended in the following situations: age greater than 60 years, hepatic impairment, CYP 2C19 poor metabolizers, and use of concomitant cimetidine.
A Drug Safety Communication issued in July warned that coadministration of the antibiotic linezolid (Zyvox®; Pfizer Inc.; New York, New York) or the medicinal dye methylene blue (various) with serotonergic agents should be avoided. These combinations could result in serotonin syndrome, a serious condition characterized by confusion, hyperactivity, memory problems and other mental changes, fever, shaking, chills, diarrhea, trouble with coordination, and, rarely, death. Both linezolid and methylene blue are thought to inhibit the action of monoamine oxidase A. The initial communication warned about use of all psychiatric drugs with serotonergic activity, but that was clarified in October to specifically indicate selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors.
Advances in hepatitis C infection therapy came this year in the form of 2 oral protease inhibitors both approved in May. Boceprevir (Victrelis™; Schering Corporation; Whitehouse Station, New Jersey) and telaprevir (Incivek®; Vertex Pharmaceuticals Incorporated; Cambridge, Massachusetts) are indicated for the adult treatment of chronic hepatitis C genotype 1 infection in combination with peginterferon alfa and ribavirin, in patients with compensated liver disease, including cirrhosis, who are treatment-naive or who have been previously treated with interferon-based treatment.
2011 brought many advances for melanoma management. Ipilimumab (Yervoy™; Bristol-Myers Squibb Company; Princeton, New Jersey), a monoclonal antibody directed against the cytotoxic T-lymphocyte antigen, was approved for treatment of unresectable or metastatic melanoma, and a REMS was approved shortly afterwards. On August 17, vemurafenib (ZelborafTM; Hoffman La-Roche Ltd; Basel, Switzerland) was approved for metastatic or unresectable melanomas with V600E mutations in the BRAF gene, as determined by an FDA-approved diagnostic test. Peginterferon alfa-2b (Sylatron™; Schering Corporation; Kenilworth, New Jersey) was approved on April 4 to treat melanoma with nodal involvement after surgical resection.
On May 20, the FDA approved rilpivirine (Edurant™; Janssen-Cilag S.p.A.; Latina, Italy), a once-daily nonnucleoside reverse transcriptase inhibitor, for treatment of HIV infection in treatment-naive adults. On August 10, the once-daily, triple-drug combination Complera™ (emtricitabine/rilpivirine/tenofovir disoproxil fumarate; Gilead Sciences, Inc.; Foster City, California) was approved for HIV infection in treatment-naive adults. Both emtricitabine and tenofovir are nucleoside reverse transcriptase inhibitors.
Will these new drug approvals from 2011 affect your practice in 2012?
These selected FDA alerts from 2011 may help keep your patients safe in 2012.
The following examples are new device and product approvals and alerts from 2011.
