Bulletin Today
The National Institutes of Health (NIH) has estimated that insomnia and obstructive sleep apnea (OSA) are two of the most common sleep disorders in the U.S. population and are even more prevalent in military and veteran populations. As a result, the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) have developed a joint clinical practice guideline for assessing and managing patients with chronic insomnia disorder and OSA. A synopsis of the guideline was published in Annals of Internal Medicine in early March.
Using a systematic, evidence-based approach, a work group established by the VA and DoD identified 41 recommendations related to diagnosis and treatment of OSA and chronic insomnia disorder. The group also developed clinical practice algorithms to assist clinicians in assessing and managing patients with chronic insomnia disorder and OSA.
The work group recommended positive airway pressure (PAP) therapy for OSA, with other options available for patients who do benefit from PAP. It recommended cognitive behavioral therapy for treatment of chronic insomnia disorder, while identifying several other treatment options. Finally, the work group recommended against use of benzodiazepines or trazodone; melatonin; herbal products such as valerian, kava, chamomile; and antihistamines and antipsychotics for treatment of chronic insomnia disorder.
The group plans future research to compare the relative benefits of different approaches.
FDA removes ranitidine from the market
In the latest step of an investigation that began with a voluntary recall in September, FDA announced on April 1, 2020, that it is now requiring manufacturers to remove all prescription and OTC ranitidine drugs from the market immediately.
The agency said that ranitidine should no longer be prescribed or available for OTC use, and those taking OTC ranitidine should discontinue use immediately.
FDA has determined that N-Nitrosodimethylamine (NDMA)—a probable human carcinogen found in some ranitidine products—can increase over time and, when stored at higher than room temperatures, may rise above the acceptable daily intake limit.
Further testing revealed that the older a ranitidine product is, or the longer the length of time since it was manufactured, the greater the level of NDMA it could contain.
Patients currently prescribed ranitidine should speak with their prescriber about other treatment options before stopping the medication. To date, FDA’s testing has not found NDMA in famotidine (Pepcid), cimetidine (Tagamet), esomeprazole (Nexium), lansoprazole (Prevacid) or omeprazole (Prilosec).
In light of the COVID-19 pandemic, the agency recommends patients not take their medicines to a drug take-back location but follow the specific disposal instructions in the medication guide or package insert to safely dispose of these medications at home.
Know the risks of DTE
Some patients with hypothyroidism seem to prefer use of desiccated thyroid extract (DTE) as a thyroid hormone replacement formulation over the clinically recommended levothyroxine (LT4) treatment, despite its unpredictable response and potential adverse effects.
In a recent study published in Medicina, Toloza and colleagues at the Mayo Clinic and the University of Arkansas for Medical Sciences analyzed patient-reported information from patient online forums. They found that the majority of patients reported feeling better when using DTE rather than the standard LT4 therapy.
DTE, made from desiccated pig thyroid glands, is not approved by FDA (its use predates the agency), though it is sold legally by prescription. DTE is used by an estimated 10% to 29% of patients with hypothyroidism, despite concerns about the risk for hyperthyroidism-associated adverse effects.
In the study, the researchers qualitatively evaluated almost 700 online posts from three popular online hypothyroidism forums. They found that patients had many reasons for switching from a previous therapy to DTE, including lack of improvement in hypothyroidism-related symptoms (58%) and the development of adverse effects (22%).
The majority of patients described DTE as moderately to majorly effective overall (81%) and more effective than the previous therapy (77%). One-fifth of patients described adverse effects related to use of DTE, including tremors, insomnia, hair loss, rash, and biochemical adverse events, such as hyperthyroidism and high glucose readings.
The researchers concluded that individualized treatment is needed in treating hypothyroidism, and that the reasons behind DTE preference should be investigated further.
Groups file amicus briefs in PBM Supreme Court case
Health advocacy organizations, employers, and retailers were among the groups that filed amicus curiae briefs in the Rutledge v Pharmaceutical Care Management Association (PCMA) suit. The case, which will affect states’ ability to regulate certain PBM practices, is set to be heard by the U.S. Supreme Court.
PCMA argues that Act 900, the Arkansas law that sought to regulate PBM practices in the state, is preempted by the Employee Retirement and Income Security Act (ERISA) of 1974. PCMA contends, therefore, that states cannot regulate PBMs.
The groups that submitted amicus briefs supporting the Arkansas law included the Community Oncology Alliance and six other cancer and hematology groups, the National Association of Chain Drug Stores, the National Association of Specialty Pharmacy, Alliance for Transparent and Affordable Prescriptions, AIDS Healthcare Foundation, American Medical Association, state-level retail trade associations, and the National Council of Insurance Legislators. APhA and other groups filed a brief in February.
Groups siding with PBMs included J.B. Hunt Transport Services Inc., which said Arkansas’s Act 900 would negatively affect employees who fill prescriptions across many state lines while on the road; American’s Health Insurance Plans, which said Act 900 is preempted by federal law and threatens predictable and uniform plans between states; the Society for Human Resource Management, which said uniformity across states controls administrative costs and leverages employer plans’ purchasing power; the Academy of Managed Care Pharmacy, which said maximum allowable cost (MAC) lists incentivize pharmacies to dispense lower-priced drugs; and the Employers Health Purchasing Corporation, which said MAC pricing holds pharmacies accountable in their drug procurement procedures.
AARP filed a brief supporting neither party; its brief, however, does ask the Court to reverse a circuit court’s ruling against Arkansas’s PBM regulation law.
Oral arguments in the case, initially scheduled for April, have been postponed to the Supreme Court’s October session.
Metformin before surgery
A recent study published in JAMA Surgery found a link between metformin prescriptions provided to patients with type 2 diabetes before a major surgical procedure and reduced risk-adjusted mortality and readmission after the operation. The researchers, led by Matthew Neal, MD, at the University of Pittsburgh, conducted a retrospective analysis of patients from a multicenter, single health care system in Pennsylvania. The study included more than 5,400 adults with diabetes matched by propensity score who underwent a major operation with hospital admission from January 1, 2010, to January 1, 2016, at 15 community and academic hospitals within the system.
Neal and colleagues found that preoperative metformin prescriptions were associated with a reduced hazard for 90-day mortality and hazard of readmission, with mortality as a competing risk at both 30 and 90 days. The results also suggested that metformin prescriptions were associated with a reduction in preoperative inflammation, as measured through mean neutrophil to leukocyte ratio.
The researchers noted several limitations to the study and suggested that further research is needed to confirm their results.
Warfarin may pose risks for patients with AF and ESRD
Warfarin remains a commonly used anticoagulant for patients with atrial fibrillation (AF), who are at increased risk of thrombus formation and subsequent cardioembolic ischemic stroke. Patients with end-stage renal disease (ESRD) also have a higher risk of ischemic stroke and bleeding events, as well as a higher incidence of AF compared with the general population. But a systematic review and meta-analysis published recently in JAMA Network Open found that warfarin may pose risks for patients with both conditions.
Randhawa and colleagues at Michigan State University assessed 15 studies involving 47,480 patients with both AF and ESRD. They found that 10,445 of the patients studied were taking warfarin. With a mean follow-up period of 2.6 years, warfarin use was associated with no significant change for the risk of ischemic stroke but a significantly higher risk of hemorrhagic stroke. The drug made no significant difference in the risk of major bleeding and overall mortality.
The researchers concluded that although these results are retrospective and observational, anticoagulants other than warfarin should be investigated for use in patients with AF and ESRD. These include non–vitamin K antagonist oral anticoagulants, antithrombotics or antiplatelets with or without warfarin, and left atrial appendage occlusion devices.