Use Of New Drugs Research Articles

NICE puts brakes on its planned overhaul of drugs evaluation processes

England’s health technology body will not push ahead with its proposed introduction of value-based assessments — including burden of illness and societal impact — in the evaluation of new drugs for use by the NHS.

Diffusion of antipsychotics in the US And French markets, 1998-2008.

Second-generation antipsychotics captured most of the U.S. antipsychotic market shortly after their introduction. Little is known about how second-generation antipsychotics have diffused in other countries with different health systems. The study objective was to describe trends in antipsychotic use in the United States and France from 1998 to 2008. Pharmaceutical policies in France and the United States are briefly described, followed by descriptive data on quarterly prescriptions for oral antipsychotics dispensed between January 1998 and September 2008. Data are from Xponent for the United States and the GERS database for France. Trends in the use of first- versus second-generation antipsychotics and in ingredient formulations of second-generation antipsychotics used are reported. Between 1998 and 2008, total antipsychotic use in the United States increased by 78%. Total use in France was consistently higher despite a 9% decrease during the period. By 2008, second-generation antipsychotics represented 86% of the antipsychotics sold in the U.S. market, versus only 40% of the French market. However, average annual growth rates in use of second-generation antipsychotics were similar in the two countries. In France, use of all but one second-generation antipsychotic steadily increased, whereas in the United States trends in the use of newer drugs varied substantially by drug. For example, use of olanzapine decreased after 2003, but use of quetiapine increased. These results highlight markedly divergent trends in the diffusion of new antipsychotics in France and the United States. Some differences may be explained by differences in health systems; others may reflect physicians' preferences and norms of practice.

Parasitic Infections in Solid Organ Transplantation

Parasitic Infections in Solid Organ Transplantation

The Effect of Pharmaceutical Innovation on Longevity: Patient Level Evidence from the 1996-2002 Medical Expenditure Panel Survey and Linked Mortality Public-use Files.

This study uses patient-level data to analyze the effect of technological change embodied in pharmaceuticals on the longevity of elderly Americans. Previous patient-level studies could not control for important patient attributes such as education, income, and race; they did not provide estimates of the effect of using newer drugs on life expectancy, or of the overall cost-effectiveness of new drugs relative to old drugs; and they were not based on nationally representative samples of individuals. Our data, primarily derived from the Medical Expenditure Panel Survey and the Linked Mortality Public-use Files, enable us to overcome those limitations. We investigate the effect of the vintage (year of U.S. Food and Drug Administration approval) of the prescription drugs used by an individual on his or her survival and medical expenditure, controlling for a number of demographic characteristics and indicators and determinants of health status. When we control only for age, sex, and interview year, we estimate that a 1-year increase in drug vintage increases life expectancy by 0.52%. Controlling for a much more extensive set of other attributes (the mean year the person started taking his or her medications, and dummy variables for activity limitations, race, education, family income as a percent of the poverty line, insurance coverage, Census region, body mass index, smoking, and more than 100 medical conditions) has virtually no effect on the estimate of the effect of drug vintage on life expectancy. Between 1996 and 2003, the mean vintage of prescription drugs increased by 6.6 years. This is estimated to have increased the life expectancy of elderly Americans by 0.41-0.47 years. This suggests that not less than two-thirds of the 0.6-year increase in the life expectancy of elderly Americans during 1996-2003 was due to the increase in drug vintage. The 1996-2003 increase in drug vintage is also estimated to have increased annual drug expenditure per elderly American by $207, and annual total medical expenditure per elderly American by $218. This implies that the incremental cost-effectiveness ratio (cost per life-year gained) of pharmaceutical innovation was about $12,900. This estimate of the cost per life-year gained from the use of newer drugs is a small fraction of leading economists' estimates of the value of (willingness to pay for) an additional year of life. It is also consistent with estimates from clinical trials.

Fulminant hepatic failure in association with quetiapine: a case report.

IntroductionFulminant hepatic failure is a serious disease with significant mortality and morbidity. Identifying the exact cause of hepatic failure and predicting prognosis is of paramount importance in managing such patients. Drug-induced liver injury is a common but challenging entity to treat. The use of newer drugs and medications with previously unknown hepatotoxicity add to the challenges faced by treating physicians. Quetiapine is an antipsychotic that has rarely been linked to acute liver injury. In the present work we describe a case of fulminant hepatic failure secondary to use of quetiapine.Case presentationA 59-year-old Caucasian woman with known Parkinson’s disease was being treated with quetiapine for hallucinations. She was referred to our hospital with yellow discoloration of the sclera and later on developed clinical features suggestive of hepatic encephalopathy. A diagnosis of fulminant hepatic failure was made following her admission to the intensive care unit. Her condition improved after discontinuing the drug and providing the standard supportive treatment.ConclusionsOur findings in the present report emphasize the importance of keeping an open mind in cases of fulminant hepatic failure. As drug-induced hepatotoxicity is the most common cause of fulminant hepatic failure in many parts of the world, consideration should be given to the medication(s) patients receive as the potential cause and a review of this list should be part of the clinical care given.

Stephen G Holtzman

Stephen G Holtzman

Update in New Medications for Primary Care

Each year, the FDA approves dozens of new drugs for use in clinical practice. Clinicians must wade through a staggering amount of evidence to determine which drugs will be important new additions to their practice. Many of the new drugs relate to specialty practices, such as chemotherapeutic agents and immune-based therapies. A fraction of the newly approved drugs are potentially relevant for primary care clinicians. Most of these drugs are “me too” drugs that are a new drug within an existing class of medications. For example, the FDA may approve a new beta-blocker or a new proton-pump inhibitor. When these types of new drugs are as effective and safe as existing drugs, they are welcome primarily when their cost to patients and health plans is lower than that of currently available drugs. However, a small number of drugs each year are novel and relevant for primary care practice. These are drugs that work through a completely new mechanism compared to existing therapies and have the potential to represent an addition to our pharmacologic armamentarium. It is challenging for busy clinicians to determine which new drugs meet this requirement and to receive balanced information regarding efficacy, safety, side effects, and cost of these new medications. In addition, each year, new practice guidelines and systematic reviews provide guidance regarding optimal use and sequence of existing medications for common clinical problems in primary care. In this paper, we provide a balanced presentation of some of the most important new drugs in primary care, followed by important updates in pharmacologic management of common conditions seen in primary care. In preparation of the New Drugs section of this paper, we reviewed the FDA database of new drugs1 approved from January 1, 2006 through March 1, 2008. We excluded drugs that were (1) used exclusively in inpatient settings, (2) parenteral agents, (3) prescribed only by subspecialty providers, or (4) new formulations or combinations of existing medications. From the remaining drugs, we identified those that work by a novel mechanism and represent the first drug in a new class of medications. From this list, we selected those drugs that, in our opinion, had the most relevance and potential to change primary care practice. For the update in Management of Common Conditions section of this paper, we reviewed the following medical journals from January 1, 2006 through April 7, 2008: New England Journal of Medicine, Annals of Internal Medicine, ACP Journal Club, JAMA, Journal Watch, and Hypertension. We identified new practice guidelines and systemic reviews on the pharmacologic management of common and important medical problems managed in the office by general internists and offer our own recommendations for pharmacologic management of these conditions.

Ranolazin – ein ergänzendes Antianginosum

Ranolazine is a new drug for use in patients with stable angina pectoris. Unlike other antianginal drugs ranolazine does not alter heart rate or systemic blood pressure. Inhibition of the persistent or late sodium current (I(Na,late)) by ranolazine reduces [Na(+) ](i)-dependent Ca(2+) overload and the effects of ischaemia. Moreover, ranolazine holds potential promise to be effective in treatment of atrial fibrillation and diastolic heart failure.

Perioperative pharmacology in elderly patients

Populations across the world are getting older and requiring more surgery. Elderly patients present unique challenges to the anesthesiologist and anesthesia-care team. This review addresses some concerns when caring for an elderly patient. Specifically, we discuss postoperative cognitive decline (POCD) and postoperative delirium, perioperative beta-blockade and use of newer drugs, as well as older drugs. POCD has emerged as a new concern for anesthesiologists and their older patients. Several recent studies indicate that POCD is common after noncardiac surgery, with an incidence approaching 30-40% at discharge, although this incidence declines at 3 months. Some data suggest that POCD imparts risk for death. However, there is conflicting evidence. With regard to beta-blocker therapy, there has been growing concern about widespread use of beta-blocker therapy in the perioperative period, especially because such therapy might increase the risk for stroke. Elderly patients require focused diligent care. They are particularly sensitive to the many drugs that are administered in the perioperative period. Recent data suggest that POCD is a real concern, but it is unclear what, if anything, can be done to prevent this complication. Beta-blocker therapy is beneficial in select patients but its widespread use cannot be supported.

Diagnostic and Therapeutic Advances in Hepatology: A New Feature in the Journal

The recent explosion of diagnostic and therapeutic modalities has provided much hope for our patients with liver disease and the treating hepatologist alike. However, it has also posed a challenge as many of the newer advances were not even on the drawing board during the training of the hepatologist looking after these patients. Moreover, even when the hepatologist receives information regarding the newer drugs or devices, it has often been through pharmaceutical-sponsored dinner meetings or symposia where a somewhat biased presentation may be made. As recently as the late 1970s, therapy was restricted to the three L's — lactulose, lactone (spironolactone), and Lasix for patients with cirrhosis. Steroids and azathioprine were used only by the few hepatologists who were familiar with treatment of autoimmune hepatitis. Physicians looking after patients with liver disease required only a limited knowledge of pharmacology to manage their patients with liver disease. In the early 1980s, beta blockers were more widely used for prophylaxis against variceal bleeding, and vasopressin was increasingly used in the control of acute esophageal variceal hemorrhage. Chenodeoxycholic acid and ursodeoxycholic acid were subsequently introduced for dissolution of gallstones, but ursodeoxycholic acid is now mainly used for primary biliary cirrhosis. Technology for imaging of the liver was also limited, with gray scale ultrasound, poor quality nuclear scans, and invasive procedures such as spleno-porto-venograms being utilized to visualize the liver and its vasculature. Subsequently, agents were introduced for immunosuppression following liver transplantation, and there was an explosion of imaging technology including ultrasound, Doppler sonography, computer tomography and positron emission tomography (PET) scans, and magnetic resonance imaging. In the last decade several agents have been introduced for treatment of hepatitis B and hepatitis C and, more recently, for palliative therapy of hepatocellular carcinoma. The current unmet need is finding a simple modality for educating the hepatologist in the proper use of newer drugs, devices or techniques. Beginning in this issue of HEPATOLOGY, we have introduced a new section termed “Diagnostic and Therapeutic Advances in Hepatology”. This section will feature on an intermittent basis and deal mainly with agents that have been recently added to the therapeutic and diagnostic armamentarium of the hepatologist. The section will typically be authored by an expert in the field who has had only limited ties with the particular drug or device company. The format to be followed will be standardized, very practical, and patient-based. For new drugs, the discussant will cover the pharmacology of the drug, including its mechanism of action, the adverse effect profile and, most important of all, how the drug is to be used, including monitoring and dose adjustments. Since it is anticipated that there will be not only several new drugs introduced for treatment of liver disease in the future, but also newer devices (artificial and bioartificial liver support systems), as well as newer imaging modalities (such as ultrasound and MR Elastography), new devices will also be discussed. We are confident that this section will be a step in the right direction in providing the practicing hepatologist with expert and unbiased advice regarding newer advances in the field.

Parasitic Infections in Solid Organ Transplant Recipients

Parasitic Infections in Solid Organ Transplant Recipients

Predictors of successful genotype-guided antiretroviral therapy in treatment-experienced individuals over calendar years: A cohort study

Background The continuous development of new drugs for use in triple-drug combination antiretroviral therapy (cART) has dramatically decreased morbidity and mortality in HIV-1 infected individuals. However, increasing drug resistance could be associated with a poor outcome. Objectives To determine the efficacy of resistance genotype-guided antiretroviral regimens in combination antiretroviral therapy (cART)-failing patients over calendar years and its predictors. Study design Patients, with an available resistance genotype performed between 1999 and 2008, who failed a highly active antiretroviral therapy (HAART) regimen, changed therapy within 6 months from genotype and maintained the same salvage regimen, were selected from a clinical cohort database. Virologic efficacy was analyzed using time-to virologic suppression (VS, HIV-1 RNA < 50 copies/ml). Results In 270 sequences analyzed from 212 patients, after a median follow-up of 23 weeks, there were 160 patients with VS (59.3%). Mean regimens’ genotypic sensitivity score (GSS) increased from 1.86 (SD ± 0.92) in 1999–2001, to 2.29 (SD ± 0.96) in 2005–2008 ( p = 0.001 for trend). VS was achieved in 39% of those patients genotyped in 1999–2001, and increased to 69% for patients with genotyping performed between 2005 and 2008 ( p < 0.001). More recent calendar year, younger age and less use of suboptimal therapy were predictors of more effective HAART regimens but only more recent calendar year maintained a trend toward significance in a multivariable model. More recent genotyping calendar year, younger age, lower number of HAART regimens experienced, lower HIV-1 RNA and higher GSS independently conveyed and increased the probability of VS. Conclusions Resistance-guided salvage antiretroviral therapy was more effective during more recent calendar years, independent from other measurable confounders, including the GSS of the employed regimen. Convenience and tolerability of newer agents should account for the observed effect.

Pediatric migraine.

Migraine is the most common cause of acute recurrent headaches in children. The pathophysiological concepts have evolved from a purely vascular etiology to a neuroinflammatory process. Clinical evaluation is the mainstay of diagnosis and should also include family history. Investigations help to rule out secondary causes. The role of new drugs in treatment of migraine is discussed and trials are quoted from literature. Indications for starting prophylaxis should be evaluated based on frequency of attacks and influence on quality of life. For management of acute attacks of migraine both acetaminophen and ibuprofen are recommended for use in children. Many drugs like antiepileptic drugs (AED), calcium channel blockers, and antidepressants have been used for prophylaxis of migraine in children. The data for use of newer drugs for migraine in children is limited, though AEDs are emerging a popular choice. Biofeedback and other nonmedicinal therapies are being used with promising results.

Update in New Medications for Primary Care

Each year, the FDA approves dozens of new drugs for use in clinical practice. Clinicians must wade through a staggering amount of evidence to determine which drugs will be important new additions to their practice. Many of the new drugs relate to specialty practices, such as chemotherapeutic agents and immune-based therapies. A fraction of the newly approved drugs are potentially relevant for primary care clinicians. Most of these drugs are “me too” drugs that are a new drug within an existing class of medications. For example, the FDA may approve a new beta-blocker or a new proton-pump inhibitor. When these types of new drugs are as effective and safe as existing drugs, they are welcome primarily when their cost to patients and health plans is lower than that of currently available drugs. However, a small number of drugs each year are novel and relevant for primary care practice. These are drugs that work through a completely new mechanism compared to existing therapies and have the potential to represent an addition to our pharmacologic armamentarium. It is challenging for busy clinicians to determine which new drugs meet this requirement and to receive balanced information regarding efficacy, safety, side effects, and cost of these new medications. In addition, each year, new practice guidelines and systematic reviews provide guidance regarding optimal use and sequence of existing medications for common clinical problems in primary care. In this paper, we provide a balanced presentation of some of the most important new drugs in primary care, followed by important updates in pharmacologic management of common conditions seen in primary care. In preparation of the New Drugs section of this paper, we reviewed the FDA database of new drugs1 approved from January 1, 2006 through March 1, 2008. We excluded drugs that were (1) used exclusively in inpatient settings, (2) parenteral agents, (3) prescribed only by subspecialty providers, or (4) new formulations or combinations of existing medications. From the remaining drugs, we identified those that work by a novel mechanism and represent the first drug in a new class of medications. From this list, we selected those drugs that, in our opinion, had the most relevance and potential to change primary care practice. For the update in Management of Common Conditions section of this paper, we reviewed the following medical journals from January 1, 2006 through April 7, 2008: New England Journal of Medicine, Annals of Internal Medicine, ACP Journal Club, JAMA, Journal Watch, and Hypertension. We identified new practice guidelines and systemic reviews on the pharmacologic management of common and important medical problems managed in the office by general internists and offer our own recommendations for pharmacologic management of these conditions.

The Need to Reform Current Drug Registration Processes to Improve Access to Essential Medicines in Developing Countries

A new or improved regulatory pathway is necessary to facilitate access to medicines developed specifically for developing countries. The main focus of the US Food and Drug Administration (FDA) and European Medicines Agency (EMEA) is the registration of new drugs for use in the US and European markets and drugs that have been developed or tested domestically, not the registration of drugs intended for use in developing countries. Furthermore, the FDA and EMEA processes are time consuming and do not consider benefits or risks beyond their domestic contexts. This complicates drug registration throughout the world, as many countries approve medicines on the basis that they have been licensed and used in the US or Europe. Because of the technical complexity of the registration process, coupled with the insufficient capacity of many regulatory authorities in developing countries, access to new medicines is almost always delayed.

Management of narcolepsy

Background: Narcolepsy is a rare chronic sleep disorder classically characterized by excessive daytime sleepiness. Other symptoms of the disease, including cataplexy, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep, may follow later. The disease can be incapacitating and frequently results in impaired psychosocial interaction. In the absence of a cure for narcolepsy, medical therapy is directed at symptom control. Objectives: The aim of this study was to review the current approach to the treatment of narcolepsy. Methods: A search of three bibliographic databases (MEDLINE/PubMed, EMBASE and the Cochrane Library Database) was conducted from 1966 to January 2008 using the National Library of Medicine MeSH search terms narcolepsy and cataplexy. Relevant studies, case reports, review articles, editorials, short communications and chapters from selected textbooks were then extracted and manually cross-referenced. Results/conclusions: Traditionally, stimulants have been used to improve the symptoms of excessive daytime sleepiness. However, the treatment of narcolepsy has evolved recently with the widespread use of newer drugs, including modafinil for daytime sleepiness, newer antidepressants for cataplexy and γ-hydroxybutyrate (sodium oxybate) for both excessive daytime sleepiness and cataplexy.

Retapamulin (Altabax)

In Brief In 2007, the FDA approved several new drugs for use in primary care. From new antibiotics to innovative contraception methods, nurse practitioners need to be aware of the latest medications now available.

Novel Augmentation Therapy with Cilostazol for the Geriatric Major Depressive Disorder Patient with Deep White Matter Hyperintensities on T2-Weighted Brain MRI: A Case Report

In our search of a new augmentation therapy for geriatric patients with intractable depression, we administered cilostazol, an antiplatelet agent, in addition to conventional antidepressants to a patient with persistent major depressive disorder showing deep white matter hyperintensities on a T2-weighted magnetic resonance image and evaluated cerebral blood flow before and after the administration of cilostazol by 99m Tc-ethyl-cysteinate dimer single photon emission computed tomography. This patient showed improvements of depressive symptoms as well as an increase in cerebral blood flow. These findings suggest a potential efficacy of cilostazol as a new drug for use in augmentation therapy for depressed patients with deep white matter hyperintensities.

Venous thromboembolism in cervical cancer

Venous thromboembolism (VTE) is common in malignant disease and is associated with substantial morbidity and mortality. Recently, VTE has received increased attention as a result of the use of newer drugs, such as erythropoietin-stimulating agents or antiangiogenic drugs, which increase the risk of this condition. Several reviews have been published on VTE in cancer, but none have specifically focused on cervical cancer. In this review, we focus on the incidence of VTE, patient, tumour, and treatment-related risk factors for VTE, and treatment and prevention of VTE in the setting of cervical cancer.

Amazonian ethnobotany and the search for new drugs.

Tropical rain forests offer enormous prospects for the discovery of new drugs for use in Western medicine. The Amazon supports 80,000 species of higher plants and a diverse Indian population. Focusing attention on those plants used as medicines by indigenous peoples is the most efficient way of identifying the plants that contain bioactive compounds. There is an urgent need for more ethnobotanists and ethnopharmacologists to be trained to document as much information as possible before it and the plants are lost through destruction of the rain forest and acculturation of the indigenous peoples. Ethnobotanical studies have identified plants documented by early travellers; these include Paullinia yoco and Ilex guayusa which are used as stimulants and have been shown to be rich in caffeine. Studies of the hallucinogen prepared from Banisterioposis caapi have shown that the native people know which plants to add to the mixture to lengthen and intensify the intoxication produced by the beta-carboline alkaloids in the plant. Three major snuffs are used in the Amazonia; the plants from which they are derived have been identified. One of the snuffs also has antifungal and curare-like activities; chemical analysis on the active principles has not been done. Several plants are considered as prime candidates for scientific study as sources of useful chemicals for medicine or industry. These include some used to prepare teas or other infusions for treatment of various symptoms of senile dementia.