Michele A. Faulkner

Impact of Pharmacy Counseling on Compliance and Effectiveness of Combination Lipid-Lowering Therapy in Patients Undergoing Coronary Artery Revascularization: A Randomized, Controlled Trial

This randomized, controlled trial evaluated the impact of personalized follow‐up on compliance rates in high‐risk patients receiving combination lipid‐lowering therapy over 2 years. A random sample of 30 patients 7–30 days after cardiac surgery had baseline fasting low‐density lipoprotein levels higher than 130 mg/dl. All patients received lovastatin 20 mg/day and colestipol 5 g twice/day. Weekly telephone contact was made with each patient for 12 weeks. Short‐ and long‐term compliance was assessed by pill and packet counts and refill records. Compliance and lipid profile results were significantly better in the intervention group (p<0.05) up to 2 years after the start of therapy than in the control group for all parameters except high‐density lipoprotein. However this effect was not apparent during the first 12 weeks of therapy. Short‐term telephone follow‐up favorably affected compliance and lipid profile results up to 2 years after start of therapy.

The economic impact of chronic obstructive pulmonary disease

The cost burden associated with chronic bronchitis and emphysema, collectively known as chronic obstructive pulmonary disease (COPD), is large. The disease impacts not only on patients but caregivers and society as well. An estimated 16 million people in the US are currently diagnosed with COPD, the majority having chronic bronchitis. Mortality associated with this disease is on the upswing, as is its prevalence in the female population and the elderly. It is currently the fourth most common cause of death both in the US and worldwide. To date, the only proven cost-effective therapies for the disease are the cessation or prevention of smoking, which is the single most common cause of COPD, and vaccination to prevent influenza and pneumococcal infection. Hospitalisation and associated costs represent the greatest healthcare expenditures for people with the disease. Long-term oxygen therapy is also among the most costly interventions in terms of total money spent on direct medical costs for COPD treatment, although it is probably cost-effective because of its positive impact on rates of mortality. In fact, oxygen therapy is the only intervention to date that has been shown to decrease death rates due to COPD. Appropriate treatment with medication has the potential to decrease resource utilisation but does not appear to affect death rates. Similarly, pulmonary rehabilitation programs appear to benefit patients in terms of quality of life; however, long-term cost-effectiveness and effects on mortality have yet to be elucidated. Indirect costs also contribute a substantial part of the economic burden of the disease but are significantly harder to quantify.

Vigabatrin: a comprehensive review of drug properties including clinical updates following recent FDA approval

Background: Vigabatrin (Sabril®) was approved in the USA in mid-2009 for the adjunctive treatment of refractory complex partial seizures and as treatment of infantile spasms. Vigabatrins more than 30-year history of research and development is condensed into a clinically relevant review pertaining to this 2009 approval. Methods/discussion: A review of the scientific literature was conducted with special focus given to the drug molecule, its mechanism of action, its effects on living systems (e.g., pharmacokinetic, pharmacologic and toxicologic), and its anticipated role among antiepileptic drugs in the USA. Conclusions: The recent approval of vigabatrin makes a significant addition to antiepileptic drug options. The FDA implemented a Risk Evaluation and Mitigation Strategy to control for the possibility of severe adverse drug events.

Risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis

Introduction: Multiple sclerosis (MS) is an autoimmune disorder that is characterized by inflammatory processes that lead to the destruction of myelin. Recently, several medications for MS that possess immune suppressing characteristics have been developed. As a consequence, cases of progressive multifocal leukoencephalopathy (PML) have been identified in MS patients. PML is potentially fatal, and specific strategies to minimize risk must be undertaken during therapy. Areas covered: A Medline search was performed to gather information about medications used to treat MS to assess the risk of PML with each. Specific risk factors for infection development are discussed and monitoring approaches are outlined. Expert opinion: Several medications have been associated with PML in MS patients, including natalizumab, fingolimod and dimethyl fumarate. Alemtuzumab and rituximab have been linked to cases of PML in other disease states. Consideration must be given to balancing efficacy with the potential for serious side effects, including PML. The severity of MS presentation may justify the use of a higher-risk medication at the outset. Increased diligence in obtaining MRIs and antibody status is essential as data demonstrate early identification of PML results in better outcomes. Lymphopenia and antibody index also appear to be reasonable factors to consider when choosing therapy.

Safety profile of two novel antiepileptic agents approved for the treatment of refractory partial seizures: ezogabine (retigabine) and perampanel

Introduction: Complex-partial seizures are frequently resistant to antiepileptic therapy. Two new medications with mechanisms of action novel within the antiepileptic class have recently received approval for the adjunctive treatment of partial (focal) seizures. Areas covered: A Medline search was conducted to identify preclinical and clinical studies of ezogabine and perampanel. This was supplemented with additional articles obtained from online sources and information provided by the FDA and the manufacturers. The focus of this review is on the safety profiles of ezogabine (retigabine), a novel antiepileptic that targets voltage-gated potassium channels, and perampanel, a noncompetitive α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate glutamate receptor antagonist. Expert opinion: Central nervous system effects are predominant within the adverse event profiles of both ezogabine and perampanel. In addition, ezogabine exerts its inhibitory effects on potassium channels in the urogenital tract potentially resulting in urinary retention and related outcomes. Recent reports of blue discoloration of the skin and in the retinas of long-term ezogabine users have surfaced. Both drugs have demonstrated the ability to induce neuropsychiatric symptoms. Though both are welcome additions to the antiepileptic drug class, additional monitoring, appropriate counseling, and careful selection of patients are warranted to minimize adverse events.

Safety overview of FDA-approved medications for the treatment of the motor symptoms of Parkinson's disease

Introduction: Parkinson’s disease (PD) is among the most common of the neurodegenerative disorders. Treatment is primarily focused on correcting neurotransmitter imbalances. Several classes of medication are available for this purpose. Areas covered: A Medline search was performed to gather information about the safety of the medications approved for the treatment of the motor symptoms of PD. This was supplemented with additional articles obtained from online sources and information provided by the FDA and the manufacturers. The focus of this review is the side-effect and safety profiles of carbidopa/levodopa, dopamine agonists, selective monoamine oxidase inhibitors, catechol-o-methyltransferase inhibitors, anticholinergics and amantadine. Expert opinion: Though serious side-effects may occur, as a group, the medications used for the treatment of PD motor symptoms tend to produce side-effects that are mild to moderate in nature, and that primarily reflect the focus on dopaminergic therapies. Care plans for Parkinson’s patients should be approached based on the needs of the individual as disease presentation, lifestyle, level of disability, concurrent disease states and the presence of non-motor symptoms make each case unique. Patients and caregivers must have realistic expectations about the use of PD medications.

Pharmacologic Treatment of Chronic Obstructive Pulmonary Disease: Past, Present, and Future

Pharmacologic treatment of chronic obstructive pulmonary disease (COPD) has evolved considerably during the past several decades. Initial treatment of the disease was accomplished primarily through antibiotics, mucolytic agents, and nonselective sympathomimetic agents. Up‐to‐date treatment guidelines stratified according to strength of evidence are published in the National Heart, Lung, and Blood Institute‐World Health Organization workshop report on the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Current drug therapy for stable COPD focuses primarily on bronchodilation through inhaled β2‐agonists and anticholinergic agents, immunization, and elimination of smoking as a risk factor. Although many pharmacologic agents are available to treat COPD, no drug has demonstrated effectiveness in halting progression of the disease. Rather, the goal of drug therapy at this time is to maintain control of symptoms and prevent COPD exacerbations. Compared with asthma, research into treatment for COPD has been minimal. However, a long‐acting anticholinergic agent, tiotropium, has received approval status by the United States Food and Drug Administration. The drug has been shown to improve spirometric parameters, quality of life, and utilization of health care resources. In addition, several new targets for the treatment of COPD are being studied, and a few agents, including some that theoretically may slow functional decline in patients with COPD, are in development.

Amlodipine/benazepril: fixed dose combination therapy for hypertension

Myocardial infarction, stroke, heart failure and end-stage renal disease have all been linked to inadequate control of blood pressure. Despite overwhelming evidence that uncontrolled hypertension is responsible for a sizeable number of adverse health-related outcomes, control of the disease remains considerably suboptimal. Available data demonstrate that in order to achieve adequate blood pressure control, a large number of patients require therapy with more than one medication. Fixed dose combination antihypertensive therapy has many advantages over other treatment options. Positive effects on blood pressure control, rates of adherence, adverse effects and cost have been identified. Amlodipine/benazepril (Lotrel®, Novartis) is a fixed dose combination product indicated for the treatment of hypertension. Although not currently recommended as first-line therapy, studies confirm that this combination of a long-acting calcium antagonist and an angiotensin-converting enzyme (ACE) inhibitor possesses substantial blood pressure lowering capabilities. Whereas adverse events tend to become more frequent with increasing doses of antihypertensive monotherapy, the rate of adverse events attributed to amlodipine/benazepril in clinical trials often correlates with rates ascribed to placebo. Amlodipine/benazepril is capable of sustaining blood pressure control over a 24 h period and appears to be minimally affected by an occasional dose omission. Unlike the older calcium antagonists, amlodipine is unlikely to cause alterations in myocardial contractility. Additionally, the amlodipine/benazepril combination product costs less than the same therapy administered as the individual components. It is, therefore, reasonable to consider therapy with amlodipine/benazepril in appropriate patients after an adequate trial of antihypertensive monotherapy.

Refractory status epilepticus

Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED), i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs) and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits.

Perampanel: a new agent for adjunctive treatment of partial seizures.

PURPOSE The pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of perampanel are reviewed. SUMMARY Perampanel, a first-in-class antiepileptic agent, was recently approved for use as adjunctive therapy for the treatment of resistant partial seizures in patients 12 years of age and older. It acts as a selective, noncompetitive antagonist at postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors. Perampanel exhibits linear pharmacokinetics and has a half-life of approximately 105 hours. The drug is rapidly and nearly completely absorbed after oral administration, achieving its maximum serum concentration in approximately 1 hour. Its bioavailability is nearly complete. Several efficacy studies have consistently demonstrated the utility of perampanel as adjunctive therapy for the treatment of refractory partial seizures with or without secondary generalization. Drug interactions have been noted with agents that induce cytochrome P-450 hepatic enzymes, including other antiepileptics, and alterations in perampanel dosing may be necessary when these medications are used concurrently. Adverse effects associated with perampanel use are primarily related to the central nervous system, and slow dosage adjustment and bedtime administration are recommended to maximize patient tolerance. The drugs labeling includes a boxed warning about the possible induction of serious adverse psychiatric and behavioral reactions that necessitate close monitoring. Perampanel is not recommended for individuals with severe liver disease or severely compromised kidney function, including those undergoing hemodialysis. CONCLUSION Perampanel is a novel antiepileptic agent specifically designed to exhibit selective noncompetitive antagonist activity at AMPA receptors. Perampanel has consistently demonstrated the ability to control treatment-refractory partial seizures in many patients.