Generic Clopidogrel: Has Substitution for Brand Name Plavix® Been Effective?

BACKGROUND: Following the expiration of brand name exclusivity of Plavix® in 2012, generic clopidogrel bisulfate was approved. As a widely prescribed medication with significant inter-patient pharmacokinetic and pharmacodynamic variability, data regarding the impact of switching to generic clopidogrel bisulfate on patients is needed. OBJECTIVE: The objective of this study was to determine whether generic clopidogrel bisulfate is as efficacious as Plavix® for the inhibition of platelet aggregation. METHODS: Patients treated with Plavix® monotherapy (n = 254) or generic clopidogrel bisulfate monotherapy (n = 185) were included in this retrospective review. Confounding factors previously found to affect clopidogrel responsiveness (diabetes, female sex, and smoking) were assessed, as well as medications classified as substrates, inducers, and inhibitors of enzymes involved in clopidogrel metabolism. Whole blood impedance aggregometry was used to measure platelet aggregation in response to adenosine diphosphate. Patients were tested after ≥2 weeks of treatment and designated as non-responders if aggregation response exceeded sensitivity thresholds of 6 ohms of impedance. RESULTS: The introduction of generic clopidogrel bisulfate was associated with a decrease in antiplatelet resistance (44% to 31%, p < 0.01) and decreased mean ohms of resistance (5.06 ± 4.55 to 3.32 ± 4.03, p < 0.01). Prior to analysis of secondary outcomes, 217 patients were eliminated due to antiplatelet usage for longer than 3 years (n = 123 for Plavix® and n = 118 for clopidogrel). There was no statistically significant finding in prevalence of secondary events. CONCLUSION: Resistance rates to the antiplatelet, clopidogrel are significantly lower since the switch to generic formulations. Further investigation into the impact of variability between clopidogrel bisulfate formulations is needed.

Ropinirole in Bipolar Disorder: Rate of Manic Switching and Change in Disease Severity.

PURPOSE: To determine the effects of ropinirole on manic switching and disease severity in bipolar disorder. DESIGN AND METHODS: A cross-sectional survey was conducted in 23 bipolar depressed patients using ropinirole combination therapy (Young Mania Rating Scale [YMRS], Bipolar Inventory of Symptoms Scale [BISS]). Retrospective Clinical Global Impression of Change (CGI-C) and CGI-S (Severity) were captured via chart review. FINDINGS: One patient (4.3%) experienced induction of mania (YMRS). All patients responded or partially responded to ropinirole (CGIs). YMRS and BISS mania scores were correlated. PRACTICE IMPLICATIONS: Ropinirole has a low rate of manic switching and significantly reduces bipolar depression severity.

Treatment options for multiple sclerosis: current and emerging therapies.

Multiple sclerosis is a chronic autoimmune disease affecting the central nervous system, more specifically, the myelin sheath covering of nerve fibers in the brain and spinal cord. This disease requires lifelong disease-modifying therapy, and all of the currently available first-line disease-modifying agents are parenteral formulations only. To date, eight drugs have entered or completed phases II and III clinical trials, four of which are oral drugs. These include five immunomodulators--cladribine, fingolimod, laquinimod, teriflunomide, and dimethyl fumarate--and three monoclonal antibodies--alemtuzumab, daclizumab, and rituximab. Although comparing these new drugs with available therapies is difficult, they do show promise as potential first-line agents for the treatment of multiple sclerosis. This marks a new frontier in the treatment of this disease, as the advent of new oral drugs will lead to increased patient compliance and contribute to longer sustained symptom-free periods and less marked disability.

Prevalence of platelet nonresponsiveness to aspirin in patients treated for secondary stroke prophylaxis and in patients with recurrent ischemic events.

To determine the prevalence of platelet nonresponsiveness to aspirin treatment for secondary stroke prophylaxis, the authors studied consecutive patients during a 29-month period. Information regarding their ischemic events, risk factors, and medications was collected. Platelet aggregation in response to collagen and arachidonic acid was used to determine platelet responsiveness to aspirin. A total of 653 patients were evaluated. Of these, 129 patients (20%) were determined to be nonresponsive to aspirin based on continued platelet aggregation in response to collagen, arachidonic acid, or both. A total of 87 (13%) of the 653 patients were clinical aspirin failures (ie, presented with new focal cerebral ischemic symptoms while taking aspirin). Of the patients with new cerebral ischemic symptoms, 57 (66%) were determined to be platelet nonresponsive to aspirin. The odds ratio for platelet nonresponsiveness to aspirin in patients who suffered a recurrent ischemic event while taking aspirin was 14.25 (95% confidence interval: 8.5-23.7; P < .5). Continued platelet aggregation despite aspirin treatment occurred in 20% of ambulatory patients treated for secondary stroke prophylaxis. The prevalence of nonresponsiveness to aspirin was statistically higher in those patients who suffered recurrent cerebral ischemia while taking aspirin (P < .5) compared with patients who remained without new ischemic symptoms.

Effects of ibuprofen on the magnitude and duration of aspirin's inhibition of platelet aggregation: clinical consequences in stroke prophylaxis.

This study was designed to measure the magnitude and duration of inhibition of platelet aggregation following doses of aspirin or ibuprofen alone or taken in combination in a group of healthy volunteers. Ten normal volunteer subjects underwent 3 randomized treatment sessions: aspirin 325 mg alone, ibuprofen 400 mg alone, and ibuprofen 400 mg, followed by dosing with aspirin 325 mg 2 hours thereafter. In addition, a confirmatory study was performed in patients. Over 27 months, a cohort of patients treated with aspirin for secondary stroke prophylaxis while concomitantly taking a nonsteroidal anti-inflammatory drug (NSAID) was identified. A significant reduction was found in both the magnitude and duration of aspirin's inhibitory effect on platelet aggregation when ibuprofen was given prior to aspirin administration in normal volunteer subjects. During a 27-month period, a cohort of 28 patients took regular daily doses of ibuprofen or naproxen. Of these 28 patients, 18 returned for follow-up testing in the absence of this pharmacodynamic interaction. None of these 18 patients demonstrated inhibition of platelet aggregation while on both NSAID and aspirin; however, all showed inhibition of aggregation following discontinuation of the NSAID. Notably, 13 of these 18 patients (72%) had experienced a recurrent ischemic episode while taking aspirin and NSAIDs concomitantly. These data suggest that ibuprofen prevents the irreversible inhibition of platelet aggregation produced by aspirin needed for secondary stroke prophylaxis, and this interaction can have clinical consequences for patients taking aspirin.

Comparative efficacy of zolpidem and temazepam in transient insomnia.

This study compared hypnotic effects of zolpidem 10 mg, temazepam 15 mg and placebo in healthy adults. Two factors expected to promote insomnia, the 'first night effect' and a 2-hour phase advance, were combined in a single night laboratory-based double-blinded protocol. This was a multi-center study, with data collected in 13 sleep laboratories. Subjects with normal sleep histories and without prior sleep laboratory experience were randomly assigned to treatment groups. Medications were administered 15 min before lights out, with polysomnographic monitoring for 7.5 h. Subjective questionnaires and performance tests, digit symbol substitution test (DSST) and symbol copying test (SCT), were administered at study entry and after arising. 630 subjects completed the study and provided data analyzed using repeated measures ANOVAs. Neither agent significantly reduced objective sleep latency relative to placebo. Zolpidem reduced awakenings and wake after sleep onset (WASO); temazepam did not. Both agents improved sleep efficiency and most subjective sleep measures relative to placebo, with zolpidem superior for five of six subjective outcome measures compared to temazepam. SCT, morning sleepiness and morning concentration were not altered by any treatment. Zolpidem significantly reduced morning DSST performance; temazepam did not. Zolpidem 10 mg provided greater subjective hypnotic efficacy than temazepam 15 mg in this model of transient insomnia, with reduced polysomnographic awakenings and WASO. Impairment of DSST was seen with zolpidem but not temazepam. Copyright 2001 John Wiley & Sons, Ltd.