Monica Shah, PharmD

Monica Shah, PharmD is a Clinical Pharmacist at RWJ Barnabas Health in New Jersey and adjunct faculty member at Ernest Mario School of Pharmacy at Rutgers University.

Germin FahimCurrently, about 29 million Americans have diabetes according to the CDC. Despite evidence that optimal glycemic control can help reduce disease progression and complications, most patients do not achieve recommended treatment goals.

 “Effective management of type 2 diabetes mellitus (T2DM) requires the use of combination therapy with different mechanisms of action,” said Germin Fahim, PharmD, BCPS, Clinical Assistant Professor at Ernest Mario School of Pharmacy and internal medicine clinical pharmacist at Monmouth Medical Center, Long Branch, N.J. The world of diabetes is rapidly evolving, and staying abreast of various treatment options enables pharmacists to provide optimal patient care.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors, unlike other available agents, decrease renal glucose reabsorption by promoting urinary glucose excretion. “This novel mechanism of action offers clinicians a different approach to individualize diabetes treatment and help patients control their blood sugar levels,” said Fahim.

The class is currently made up of 3 agents-canagliflozin (Invokana, Janssen), dapagliflozin (Farxiga, AstraZeneca), and empagliflozin (Jardiance, Boehringer Ingelheim). Fahim pointed out that additional benefits of using SGLT2 inhibitors in individuals with T2DM include significant reductions in blood pressure and body weight.

Regulatory guidance specifies the need to establish cardiovascular (CV) safety of new diabetes therapies to rule out excess CV risk. According to a study published in the 

 – involving more than 7,000 patients with T2DM – those receiving empagliflozin had significantly lower rates of death from CV events, hospitalization for heart failure, and death from any cause compared with placebo.

 As reported in previous clinical trials, genital infection was more common in the empagliflozin group than placebo.

Fahim views glucagon-like-peptide-1 (GLP-1) receptor agonists as a welcome addition to the diabetes therapy armamentarium, because they effectively lower A

, weight, and blood pressure while posing a low risk of hypoglycemia.

The long-awaited, once-daily GLP-1 agent, lixisenatide (Adlyxin, Sanofi) received FDA approval for adults with T2DM in July, 2016, based on thirteen studies with more than 5,000 patients. Additionally, in a CV outcomes trial in patients with T2DM, lixisenatide did not increase the risk of CV adverse events. The drug’s availability also paves the way for approval of a combination product that incorporates lixisenatide with Sanofi’s basal insulin, Lantus (insulin glargine 100 U/mL).

Recently liraglutide (Victoza, Novo Nordisk) demonstrated improved CV outcomes in patients with T2DM who were at high risk for CV events. Published in the 

, the study followed 9,340 high-risk adults with T2DM for 3.5 to 5 years, who received either a subcutaneous injection of liraglutide or placebo along with standard therapy.

 The primary endpoint was CV death, nonfatal myocardial infarction, or nonfatal stroke among T2DM patients. Liraglutide decreased the risk of CV death by 22% and overall heart risks by 13% compared with placebo.

Another GLP-1 analogue, semaglutide (Novo Nordisk), is currently in phase 3 development. In two studies, SUSTAIN 2 and SUSTAIN 3, presented at the 

 in New Orleans, the once-weekly GLP-1 agent showed superior improvements in glycemic control compared with sitagliptin (Januvia, Merck) or exenatide extended-release (Bydureon, AstraZeneca). In the SUSTAIN 2 trial, semaglutide demonstrated superiority by a bigger margin, with reductions in A

 of 1.3% for a 0.5-mg dose and 1.6% for a 1-mg dose compared with 0.5% with sitagliptin. In the SUSTAIN 3 trial, semaglutide lowered A

 levels by 1.5% (1-mg dose) versus 0.9% with exenatide extended-release (2-mg dose). Fahim noted that in both trials, patients in the semaglutide group also achieved significantly greater reductions in body weight (up to 6.1 kg). The most common adverse events seen were GI, such as nausea and diarrhea.

Similar to liraglutide, semaglutide has been shown to reduce the rate of CV events in T2DM patients in a study published in the 

 In this CV outcomes study, patients were followed for 2.1 years.

Fahim cautioned that while the data on GLP-1 agonists are encouraging, all agents in this class carry an FDA warning for pancreatitis and thyroid cancer. According to the October 6, 2016 issue of 

, what sets albiglutide (Tanzeum, GSK) apart from other GLP-1 agonists are more than 1,500 reports of patients having problems using the complex Tanzeum pen correctly. The ISMP newsletter advises that physicians should consider the ease of use when prescribing a GLP-agonist pen and ensure that patients know how to use the device if prescribing the Tanzeum pen.

Long-acting insulins are also effective for glycemic control in diabetic patients. The safety and efficacy of insulin degludec (Tresiba, Novo Nordisk), a long-acting insulin analog, was evaluated in three clinical trials involving 1,102 participants with type 1 and 2 diabetes. Treatment with Tresiba achieved levels of glycemic control similar to those achieved with Lantus and Levemir (insulin detemir), according to Tresiba’s package insert.

Ryzodeg 70/30 is a mixture of insulin degludec, a long-acting insulin analog, and insulin aspart, a rapid-acting human insulin analog. In clinical trials, treatment with Ryzodeg 70/30 provided reductions in A

 equivalent to those achieved with other, previously approved long-acting or pre-mixed insulin. According to the drug labels, Tresiba and Ryzodeg should not be used in individuals with diabetic ketoacidosis.

Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. 

Marso SP, Daniels GH, Brown-Frandsen KB, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. 

Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. September 16, 2016.

http://www.nejm.org/doi/full/10.1056/NEJMoa1607141#t=article

Articles

Despite evidence that optimal glycemic control can help reduce disease progression and complications, most patients do not achieve recommended treatment goals.

Update on Diabetes Therapy

Most people experiencing heart attack symptoms would immediately call 911 in order to be taken to the hospital for urgent care. Yet patients suffering a stroke or "brain attack" often do not seek immediate help, researchers say. This is of particular concern because the clot-busting drug tissue plasminogen activator (tPA, alteplase) has been shown to be most effective at limiting stroke damage the earlier it is administered - within 3 to 4.5 hours of symptom onset. 

"This delay points to a need for more awareness and education about early stroke symptoms among patients and emergency personnel," said John Galbraith Simmons, co-author of 

tPA for Stroke: The Story of a Controversial Drug

Furthermore, neurologists typically have not been trained to make decisions in emergency settings about such matters as stroke care, but more often treat conditions that develop slowly, such as Parkinson's disease.  

How can pharmacists help improve stroke care? According to Simmons, pharmacists can play a crucial role in educating patients about stroke risk factors and primary stroke prevention, such as smoking cessation and blood pressure control.  

Hospital pharmacists can actively work with a multidisciplinary team to develop treatment protocols and start appropriate therapy for select patients in a safe and timely manner. 

Independent of its clot-busting properties, a modified form of tPA exerts neuroprotective effects on brain cells when they are deprived of oxygen and glucose, a recent study reported in 

. The investigators studied the effects of modified tPA in mice by blocking a vessel supplying blood to the brain for one hour, simulating a stroke. A decrease in the volume of ischemic lesion was seen following treatment with the mutated form of tPA.  

A main implication of the study findings, the authors suggested, is that those ischemic stroke patients who currently remain untreated due to contraindications to protease-active tPA as a thrombolytic may still benefit from administration of inactive tPA as a neuroprotector. These preliminary findings, however, still need further validation in a pilot clinical trial. 

Patients suffering stroke often do not seek immediate help. Just as disturbing, lack of stroke expertise in many hospitals and skepticism among ER physicians may prevent tPA from being administered to the patients who need it most.

tPA: Still the underused clot-buster in stroke management

Automated medication management systems are a common component of the pharmacy process in healthcare facilities. The integration of such devices has been shown to improve efficiency and patient safety. However, if automated devices are not used appropriately, their maintenance and education requirements can compromise patient safety.  

Pharmacy personnel at Wake Forest Baptist Health in Winston-Salem, N.C., recently discovered bacterial contamination of the automated pharmacy robot used for intravenous medication preparation at the facility. As reported in 

Infection Control and Hospital Epidemiology

 bacteria during routine quality assurance testing of the automated device, IntelliFill i.v. (Baxa). 

, a spore-forming bacterium, is resistant to most commonly used disinfectants, including alcohol – a factor that has played a role in healthcare-associated infections.  

"To our knowledge, this is the first published report of a pharmacy robot being contaminated with 

 with resultant contamination of intravenous drug product," the article's authors write. Katarzyna Gejdel, PharmD, BCPS, pharmacy manager at Bronx-Lebanon Hospital Center, Bronx, N.Y., concurred.  

A detailed investigation revealed that the washing station and its associated tubing were the potential source of contamination, as it was the only culture-positive site.   

However, the authors report that they may never know how the organism was first introduced into the sterile environment of the robot. They have considered the possible risk of contamination from human hands during cleaning and setup. They advocate that current cleaning and maintenance requirements may need to be strengthened, since "the company's recommendations to monitor the robot's environment do not involve surface testing of the washing station, and has no defined schedule for exchanging the tubing or container." 

The report's authors point out that the contamination was identified early, and confirm that, fortunately, no patient was harmed. But they caution that "the implications of contaminated intravenous product are potentially severe, most notably life-threatening bloodstream infections." 

To prevent other users of the robot from experiencing the same problem, the authors suggest that the manufacturer should consider "establishing a formal procedure for cleaning and maintaining the washing station, with detailed recommendations to change the drain tube, container, and possibly the washing station itself." Furthermore, use of the robot in the pharmacy's clean room could further decrease the risk of contamination.  

While Gejdel acknowledges the authors' concerns, she is not convinced that additional protocols are required at this time. "We have not experienced any such problem with our automated device or seen a report where patient safety has been potentially compromised, so I think it's fair to say that the sterility assurance protocols currently provided by the manufacturer are sufficient," she says. 

Studies have shown that human-borne contamination is a principal threat to the sterility of compounded preparations and is a pivotal factor that needs to be controlled in an aseptic environment. Gejdel believes that, if used properly, the deployment of automation to remove the human element from the compounding of sterile preparations should significantly reduce the potential for microbial contamination. She advises that institutions that use automated pharmacy robots understand the limitations of technology and establish policies and procedures around competent use, quality assurance, and foreseeable complications.  

"Ultimately, the pharmacy personnel are the most important determinants of quality. Following standard operating procedures and ensuring that all staff members who use the automated device receive initial and ongoing competency education are the cornerstone for promoting patient safety," Gejdel says.  

The American Society of Health-System Pharmacists' guidelines on the safe use of automated dispensing devices (ADD) advocate that "the automated system should comply with applicable federal and state consumer protection laws and regulations, and state boards of pharmacy may have different requirements for the use of ADD in practice settings." Gedjel supports this recommendation and believes that the state board of pharmacy's involvement and legislation, where necessary, would be an added step in enhancing patient safety. 

 is a writer and hospital pharmacist in New Jersey.

Bacterial contaminants have been traced back to a robot in a Winston-Salem, N.C. health center pharmacy

Pharmacy robot linked to bacterial contamination

Long-term-care (LTC) consultant pharmacists will not be required to be independent from dispensing pharmacies, pharmaceutical manufacturers, or distributors, according to the final ruling of the Centers for Medicare and Medicaid Services (CMS). "From comments received on this issue, we now believe a more targeted and less disruptive approach is warranted," CMS stated in a fact sheet summarizing the rule.  

However, CMS would like the LTC industry to increase transparency and reduce drug overuse by adopting the following: Separation of LTC consultant contracting for dispensing and other pharmacy services; disclosure to the LTC facility of potential conflict of interest by the consultant pharmacist, or execution of a consultant pharmacist integrity agreement; and payment of fair market rates for consultant pharmacist services. 

In the rule proposed last October, CMS raised the possibility of a mandatory independent status for consultant pharmacists, noting concerns about conflict of interest, kickbacks, financial incentives, and impact on drug utilization.  

A final ruling from CMS states that "We now believe a more targeted and less disruptive approach is warranted"

Author | Monica Shah, PharmD

Articles

Update on Diabetes Therapy

tPA: Still the underused clot-buster in stroke management

Pharmacy robot linked to bacterial contamination

CMS issues final rule on status of LTC consultant pharmacists