Kirk E. Evoy

Abuse and Misuse of Pregabalin and Gabapentin

BackgroundGabapentinoid (pregabalin and gabapentin) abuse is increasingly being reported.ObjectiveTo assess the extent of gabapentinoid abuse, characteristics of typical abusers, patterns of abuse, and potential harms in order to bring this trend to providers’ attention.MethodsA systematic review of MEDLINE, Cochrane Library, ClinicalTrials.gov, and US FDA data, indexed through 28 July 2016, utilizing the following searches: pregabalin OR gabapentin OR gabapentinoid AND one of the following: abuse, misuse, overdose, or substance-related disorders[MESH], was conducted. Additional studies were identified through review of references. English-language epidemiological studies, clinical studies, and case reports/series of gabapentinoid abuse/misuse/overdose were included. The authors reached consensus regarding study inclusion after full-text review. The body of literature was assessed for bias qualitatively.ResultsFifty-nine studies were included in this systematic review (24 epidemiological, three clinical abuse liability, 16 abuse/misuse/dependence case reports/series, 17 acute overdose case reports/series—one included both an epidemiological study and case series and was included in both counts). Analysis of these studies indicates increasing numbers of patients are self-administering higher than recommended doses to achieve euphoric highs. In the general population, a 1.6% prevalence of gabapentinoid abuse was observed, whereas prevalence ranged from 3% to 68% among opioid abusers. An international adverse event database identified 11,940 reports of gabapentinoid abuse from 2004–2015, with >75% reported since 2012. Risk factors include a history of substance abuse, particularly opioids, and psychiatric co-morbidities. While effects of excessively high doses are generally non-lethal, gabapentinoids are increasingly being identified in post-mortem toxicology analyses.ConclusionEvidence suggests gabapentinoids possess potential for abuse, particularly in individuals with a history of opioid abuse, and reports of such abuse are increasingly being documented. Prescribers should be aware of high-risk populations and monitor for signs of abuse.

Suvorexant A Dual Orexin Receptor Antagonist for the Treatment of Sleep Onset and Sleep Maintenance Insomnia

Objective: To review the efficacy, safety, and pharmacology data available for suvorexant and determine its role in therapy as compared with other agents available for the treatment of insomnia. Data Sources: A PubMed search using the terms suvorexant and MK-4305 (the original name given to suvorexant during early trials) was conducted in December 2014 to identify initial literature sources. No time frame was used for exclusion of older trials. Study Selection and Data Extraction: Animal studies and trials written in a language other than English were excluded. Abstracts of the remaining trials were evaluated for determination of relevance to this review. References from these studies along with suvorexant prescriber information were used to identify additional literature. Data Synthesis: Three randomized, double-blind, placebo-controlled clinical trials were identified showing suvorexant to be safe, effective, and tolerable for the treatment of insomnia. After 4 weeks of therapy, relative to placebo, the 10- and 20-mg doses improved subjective total sleep time (22.3 and 49.9 minutes, respectively), wake after sleep onset (−21.4 and −28.1 minutes), and latency to persistent sleep (−2.3 and −22.3 minutes). Conclusion: Suvorexant is the first dual orexin receptor antagonist approved for the treatment of insomnia. Clinical trials have shown that it is relatively safe and effective for the treatment of both sleep onset and sleep maintenance at doses of 20 mg or less. Higher doses were studied but not approved because of concerns for next-day somnolence and effects on driving. Further studies are needed to assess this medication in patients with a history of addiction, because they were excluded from clinical trials, as well as to compare suvorexant with other insomnia medications available because no head-to-head studies have yet been conducted. However, its novel mechanism of action and theoretically lower addiction liability make suvorexant an appealing new option.OBJECTIVE To review the efficacy, safety, and pharmacology data available for suvorexant and determine its role in therapy as compared with other agents available for the treatment of insomnia. DATA SOURCES A PubMed search using the terms suvorexant and MK-4305 (the original name given to suvorexant during early trials) was conducted in December 2014 to identify initial literature sources. No time frame was used for exclusion of older trials. STUDY SELECTION AND DATA EXTRACTION Animal studies and trials written in a language other than English were excluded. Abstracts of the remaining trials were evaluated for determination of relevance to this review. References from these studies along with suvorexant prescriber information were used to identify additional literature. DATA SYNTHESIS Three randomized, double-blind, placebo-controlled clinical trials were identified showing suvorexant to be safe, effective, and tolerable for the treatment of insomnia. After 4 weeks of therapy, relative to placebo, the 10- and 20-mg doses improved subjective total sleep time (22.3 and 49.9 minutes, respectively), wake after sleep onset (-21.4 and -28.1 minutes), and latency to persistent sleep (-2.3 and -22.3 minutes). CONCLUSION Suvorexant is the first dual orexin receptor antagonist approved for the treatment of insomnia. Clinical trials have shown that it is relatively safe and effective for the treatment of both sleep onset and sleep maintenance at doses of 20 mg or less. Higher doses were studied but not approved because of concerns for next-day somnolence and effects on driving. Further studies are needed to assess this medication in patients with a history of addiction, because they were excluded from clinical trials, as well as to compare suvorexant with other insomnia medications available because no head-to-head studies have yet been conducted. However, its novel mechanism of action and theoretically lower addiction liability make suvorexant an appealing new option.

Aflibercept: Newly Approved for the Treatment of Macular Edema Following Central Retinal Vein Occlusion

OBJECTIVE: To review the pharmacology, efficacy, and safety data available for aflibercept and compare the drug to other therapeutic options for treatment of macular edema following central retinal vein occlusion (CRVO) to determine its likely role in therapy. DATA SOURCES: A PubMed search using the terms aflibercept and VEGF trap-eye was conducted to identify initial literature sources. No timeframe was used for exclusion of older trials. All trials referenced were published between January 1995 and December 2012. STUDY SELECTION AND DATA EXTRACTION: Trials pertaining to oncologic use were excluded, as were studies conducted in animals and those written in a language other than English. Abstracts of the remaining trials were evaluated for determination of relevance to this review. Additional information sources were obtained via Internet and PubMed following a review of references. DATA SYNTHESIS: While previous Phase 1, 2, and 3 trials for other indications (age-related macular degeneration and diabetic macular edema) have shown intravitreal injections of aflibercept to be safe and well tolerated in many patients, preliminary results from the ongoing COPERNICUS and GALILEO trials proved the efficacy of this medication in treating macular edema secondary to CRVO. Of the combined 358 patients studied in COPERNICUS and GALILEO, 56% and 60%, respectively, of the patients receiving aflibercept 2 mg monthly achieved at least a 15-letter improvement in best-corrected visual acuity (BCVA) from baseline over 6 months compared with just 12% and 22% in the control group (p < 0.01 for both). Additionally, in COPERNICUS and GALILEO, patients achieved a 21.3- and 14.7-letter improvement, respectively, in BCVA compared with placebo (p < 0.01 for both). CONCLUSIONS: In September 2012, aflibercept became the second vascular endothelial growth factor (VEGF) inhibitor approved for treatment of macular edema secondary to CRVO. While efficacy and safety appear similar to other anti-VEGF treatments, the higher potency, binding affinity, and duration of action make aflibercept an appealing new option.

Combination bupropion SR and varenicline for smoking cessation: a systematic review

ABSTRACT Background: Tobacco is the leading cause of preventable death in the world. Current cessation medications include nicotine replacement therapy (NRT), varenicline, and bupropion, while combination therapy primarily entails NRT with either varenicline or bupropion. However, recent studies have examined varenicline and bupropion in combination. Objectives: A systematic review assessing the efficacy and safety of combination varenicline and bupropion was conducted. Methods: PubMed and Clinicaltrials.gov were searched using terms: “varenicline combination”, “bupropion combination”, “bupropion AND varenicline”, and “bupropion AND varenicline combination smoking cessation”, yielding four studies including 1193 total patients. Results: Combination therapy yielded greater efficacy than varenicline monotherapy in two randomized controlled trials and one retrospective outcomes study. One single-arm Phase II trial provided additional efficacy and safety data. Of the prospective trials, one displayed a greater 4-week smoking abstinence for weeks 8–11 with combination (39.8%) versus monotherapy (25.9%) (OR = 1.89; 95% CI = 1.07–3.35). The other demonstrated greater prolonged abstinence (continuous abstinence from week 2) at 12 weeks (OR = 1.49; 95% CI = 1.05–2.12) and 26 weeks (OR = 1.52; 95% CI = 1.04–2.22), though results were not significant at 52 weeks in this study. The retrospective study displayed higher success rates (continuous abstinence rates at 52 weeks) with combination varenicline and bupropion (55.0%; compared to varenicline monotherapy (32.1%), p < 0.001). Subgroup analyses suggest that this combination may be more beneficial in males and patients with higher baseline nicotine dependence. Conclusion: To the authors’ knowledge, this is the first review conducted to compile current literature on this novel pharmacotherapy combination for smoking cessation. Combination bupropion SR and varenicline displayed greater efficacy in smoking cessation than varenicline monotherapy, though further safety analysis is warranted to rule out additive psychiatric adverse effects.

Ranibizumab: The First Vascular Endothelial Growth Factor Inhibitor Approved for the Treatment of Diabetic Macular Edema

OBJECTIVE: To review the pharmacology, efficacy, and safety data available for ranibizumab and compare the drug to other therapeutic options for diabetic macular edema (DME) to determine its likely role in therapy. DATA SOURCES: A PubMed search was initially used to identify all trials pertaining to the use of ranibizumab for DME. This search was conducted in February 2013 without a time frame for exclusion of older trials (all references included were published between January 1987 and February 2013). Following a review of the references of these articles, additional sources were obtained from PubMed, the manufacturers website, and clinicaltrials.gov. STUDY SELECTION AND DATA EXTRACTION: Trials conducted in animals and those written in a language other than English were excluded. Abstracts of remaining trials were reviewed for determination of relevance to this review. Preference was given to randomized controlled trials. Additional information sources were obtained from a review of references as deemed necessary by the authors. DATA SYNTHESIS: Six Phase 2 or 3 randomized controlled trials studying the effects of ranibizumab in patients with DME were identified. Within these trials, ranibizumab consistently produced significantly greater gains in mean best corrected visual acuity than focal/grid laser photocoagulation or sham (7.4-12.5 letter improvement with ranibizumab vs 0.5-3 letters following focal/grid laser photocoagulation monotherapy) with a favorable safety and tolerability profile. Ranibizumab was also studied in combination with focal/grid laser photocoagulation, showing no additional gains in vision versus ranibizumab monotherapy. CONCLUSIONS: The identified trials provide support for the safety and efficacy of ranibizumab in the treatment of vision loss due to DME and present a strong case for the shift to first-line treatment with vascular endothelial growth factor inhibitors from focal/grid laser photocoagulation, the standard of care since the Early Treatment Diabetic Retinopathy Study of 1985.

Predictors of gabapentin overuse with or without concomitant opioids ina commercially-insured US population

Research suggests the medical consequences of gabapentin overuse depend on whether gabapentin is abused alone or with opioids to potentiate an opioid “high.” The objective of this study was to assess predictors of gabapentin overuse with or without concomitant opioids.

Implementing mentoring into a pharmacy teaching and learning curriculum

Recent recommendations for standardization of postgraduate pharmacy experiences in education include the implementation of a mentoring program.[1][1],[2][2] The Indiana Pharmacy Teaching Certificate (IPTeC) program emphasizes the importance of the mentor–mentee relationship in developing

Gabapentin for Off-Label Use: Evidence-Based or Cause for Concern?

Gabapentin is widely used in the United States for a number of off-label indications, often as an alternative to opioid therapy. Increasing evidence has emerged suggesting that gabapentin may not be as benign as once thought and may be associated with substance abuse in concert with opioids. With concerns for safety mounting, it is prudent to examine the efficacy of gabapentin across its many uses to understand the risk-benefit balance. Reviews on off-label indications such as migraine, fibromyalgia, mental illness, and substance dependence have found modest to no effect on relevant clinical outcomes. This high-quality evidence has often been overshadowed by uncontrolled studies and limited case reports. Furthermore, the involvement of gabapentin in questionable marketing schemes further calls its use into question. Overall, clinicians should exercise rigorous appraisal of the available evidence for a given indication, and researchers should conduct larger, higher-quality studies to better assess the efficacy of gabapentin for many of its off-label uses.

A cautionary tale for the physician: case report and review of food-dependent exercise-induced anaphylaxis

Food-dependent exercise-induced anaphylaxis (FDEIA) is a rare subset of anaphylaxis that only occurs when a patient consumes the causative food (or in some cases non-specific food intake) within four to six hours prior to physical exercise. It may be triggered by a variety of foods, but most commonly wheat, shellfish, and peanuts, and is treated similarly to general anaphylaxis [1,2]. Though various case reports have described this phenomenon, FDEIA is rare and thought to be underdiagnosed as lack of familiarity with the condition likely results in many practitioners failing to include FDEIA in their differential diagnosis of patients presenting with anaphylaxis. With the publication of this case, we hope to raise awareness of physicians who may encounter such patients during exercise or athletic activities.

Volunteering as medical staff at a diabetes summer camp as a component of a pharmacy residency program

A number of summer camps across the country have been developed specifically for children with diabetes, most of whom would not be able to attend a traditional summer camp due to the extensive medical attention and scheduling considerations required to continually maintain appropriate glycemic control. These camps rely on the service of various medical practitioners to ensure the safety of the children. In addition to providing an important service to the campers, volunteering at such camps offers both personal and professional rewards for the practitioners. Furthermore, such experiences provide tremendous learning opportunities for medical trainees. However, while a limited number of articles were identified discussing the experience of nurses, physicians, and pharmacy students volunteering at diabetes camps, no such accounts from the perspective of pharmacy residents were found in the medical literature. This educational case report briefly describes the recent experience of ambulatory care pharmacy residents serving as diabetes camp medical staff.