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Biomedical subjects

Greg L Plosker

Publications and source records attributed to Greg L Plosker.

At least 37 records · Page 2Linked to original sources
PubMed2006

Zolpidem extended-release.

Zolpidem extended-release, or controlled-release (CR), is a new formulation of zolpidem, a nonbenzodiazepine hypnotic. It is indicated in the US for the treatment of insomnia, characterised by difficulties with sleep onset and/or sleep maintenance. Zolpidem CR is a dual-layered tablet; one layer releases zolpidem immediately and a second layer provides a slower release of additional zolpidem for maintenance of plasma zolpidem concentrations. Efficacy of zolpidem CR was assessed in two 3-week, randomised, double-blind, placebo-controlled, phase III polysomnography trials in younger adult (aged 18-64 years) or elderly (aged > or =65 years) patients with primary insomnia. Patients received nightly zolpidem CR (12.5mg in younger adult and 6.25mg in elderly patients). Efficacy was assessed objectively on nights 1, 2, 15 and 16. Patients who received zolpidem CR had significantly improved objective latency to persistent sleep, wake time after sleep onset and sleep efficiency on assessment nights compared with placebo recipients. In subjective assessments of sleep quality on day 2 and nights 15 and 22, significantly more zolpidem CR than placebo recipients gave favourable responses on a Patient Global Impression scale in the study in younger adult patients. In the other study, significantly more elderly patients in the zolpidem CR group rated their sleep as improved compared with the placebo group. Zolpidem CR was generally well tolerated and appears to have a tolerability profile similar to that of the original formulation of zolpidem.

Adolescent↗
PubMed2006

Retigabine: in partial seizures.

Retigabine has anticonvulsant properties that appear to be primarily mediated by opening neuronal voltage-gated potassium channels. This action has been shown in neuronal KCNQ2/3 and KCNQ3/5 potassium channels. In addition to this unique action, retigabine also potentiates GABA-evoked currents in cortical neurons at high concentrations. When used as adjunctive therapy in patients with partial seizures, retigabine 600-1200 mg/day (200-400 mg three times daily) was associated with significant linear dose-dependent reductions in monthly seizure frequency compared with placebo in a large 16-week randomised phase II trial. Median monthly seizure frequency decreased from baseline by up to 35% among patients in the retigabine treatment arms compared with 13% in the placebo group. Retigabine 1200 mg/day was also significantly more effective than retigabine 600 mg/day. Responder rates, defined as the proportion of patients with > or = 50% reduction in seizure frequency, were significantly higher among patients in the retigabine 900 and 1200 mg/day groups than in those who received placebo. CNS-related adverse events were the most commonly reported treatment-emergent adverse events associated with retigabine in clinical trials. Across all three retigabine groups in the large phase II trial, somnolence (20.3%), dizziness (14.6%), confusion (12.3%) and speech disorder (11.3%) were the most frequent CNS-related adverse events.

Animals↗
PubMed2006

Galantamine extended release.

Galantamine inhibits acetylcholinesterase (AChE) to slow acetylcholine hydrolysis, and may also modulate presynaptic nicotinic receptor activation, thereby increasing neurotransmitter concentrations in the synaptic cleft.black triangle Once-daily galantamine extended release (ER) 24 mg and twice-daily galantamine immediate release (IR) 12 mg are bioequivalent in terms of the area under the plasma concentration-time curve from time 0 to 24 hours and steady-state minimum plasma concentration.black triangle Primary endpoints indicated a significantly greater effect of galantamine ER on cognitive performance than placebo, with efficacy similar to galantamine IR, in a randomised, double-blind trial. While galantamine ER did not show a significant effect on the coprimary endpoint of global change, neither did galantamine IR in this study. Exploratory post hoc analyses of global change correcting for study centre and prognostic factors associated with response (baseline Mini-Mental State Examination, Alzheimer's Disease Assessment Scale cognitive score, prior cholinomimetic use) indicated nominal significance in the galantamine ER treatment arm. Secondary endpoints indicated an improvement in activities of daily living and memory- and nonmemory-dependent measures of cognitive performance, but not in measures of behaviour or dichotomised rating of global change. Adverse events occurred in similar proportions of galantamine ER, galantamine IR and placebo recipients.

Alzheimer Disease↗
PubMed2006

Escitalopram: a review of its use in the management of anxiety disorders.

Escitalopram (Cipralex, Lexapro, Seroplex, Sipralexa), the therapeutically active S-enantiomer of racemic citalopram (RS-citalopram), is a potent and highly selective serotonin reuptake inhibitor. It is effective and generally well tolerated in the treatment of moderate to severe generalised anxiety disorder (GAD) or social anxiety disorder (SAD), panic disorder (with or without agoraphobia) as well as obsessive-compulsive disorder (OCD). Moreover, escitalopram is at least as effective as paroxetine for the treatment of GAD, SAD or OCD and appears to achieve a more rapid response than racemic citalopram in the management of panic disorder. Generally, it has a more favourable tolerability profile than paroxetine in terms of fewer discontinuation symptoms. In addition, a favourable pharmacokinetic profile permits once-daily administration of the drug. Additional comparative studies are required to definitively position escitalopram with respect to other SSRIs and venlafaxine. Nevertheless, available clinical data indicate that escitalopram is an effective first-line treatment option for the management of GAD, SAD, panic disorder and OCD.

Animals↗
PubMed2006

Spotlight on pioglitazone in type 2 diabetes mellitus.

Pioglitazone (Actos(trade mark)) is an antihyperglycemic agent that, in the presence of insulin resistance, increases hepatic and peripheral insulin sensitivity, thereby inhibiting hepatic gluconeogenesis and increasing peripheral and splanchnic glucose uptake. Pioglitazone is generally well tolerated, weight gain and edema are the most common emergent adverse events, and there are no known drug interactions between pioglitazone and other drugs. In clinical trials in patients with type 2 diabetes mellitus, pioglitazone as monotherapy, or in combination with metformin, repaglinide, insulin, or a sulfonylurea, induced both long- and short-term improvements in glycemic control and serum lipid profiles. Pioglitazone was also effective in reducing some measures of cardiovascular risk and arteriosclerosis. Pioglitazone thus offers an effective treatment option for the management of patients with type 2 diabetes.

Blood Glucose↗
PubMed2006

Spotlight on Trastuzumab in the management of HER2-positive metastatic and early-stage breast cancer.

Trastuzumab (Herceptin) is a humanized monoclonal antibody used in the treatment of breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2), which is associated with clinically aggressive disease and a poor prognosis. The addition of intravenous trastuzumab to first-line chemotherapy improved the time to disease progression, objective response rate, duration of response, and overall survival in randomized, multicenter trials in women with HER2-positive metastatic breast cancer. As such, trastuzumab has become the standard of care in this setting, despite its high acquisition cost and potential for cardiac events, and is licensed for use in combination with paclitaxel (Europe and the US) or docetaxel (Europe). In addition, trastuzumab monotherapy is approved for use in patients with HER2-positive metastatic breast cancer who have previously received chemotherapy for their metastatic disease. Recent data from large phase III trials with trastuzumab in the adjuvant setting revealed significant improvements in disease-free and overall survival. Thus, trastuzumab is also rapidly becoming a standard component of adjuvant therapy for patients with HER2-positive early-stage breast cancer.

Antibodies, Monoclonal↗
PubMed2005

Rasagiline.

Rasagiline is a second-generation potent, irreversible and selective inhibitor of monoamine-oxidase type B (MAO-B), which has been evaluated for the treatment of Parkinson's disease. Rasagiline also possesses neuroprotective properties that are independent of its MAO inhibitory activity. Unlike selegiline, rasagiline has no amphetamine-like metabolites and its major metabolite, 1-(R)-aminoindan, has demonstrated favourable pharmacological activity in experimental studies. Rasagiline has shown significant beneficial effects as monotherapy in the treatment of early Parkinson's disease. Monotherapy with rasagiline 1 or 2 mg once daily significantly attenuated the worsening of symptoms, compared with placebo, in patients with early Parkinson's disease in a randomised, double-blind trial (n = 404). Furthermore, patients treated with rasagiline for 12 months had less functional decline than patients whose treatment was delayed for 6 months (n = 371). In patients with moderate-to-advanced disease receiving background therapy with levodopa and additional anti-parkinsonian medications (n = 1159), rasagiline 0.5 or 1 mg once daily reduced the daily 'off' time by 0.49-0.94 hours relative to that in placebo recipients in two randomised, double-blind trials. The efficacy of rasagiline 1 mg once daily was similar to entacapone 200 mg administered with each levodopa dose. Rasagiline was generally well tolerated in clinical trials as both monotherapy and when administered with other antiparkinsonian drugs. Adverse events with rasagiline were generally similar in frequency to those seen in placebo or entacapone recipients.

Biological Availability↗
PubMed2005

Desmopressin: in adults with nocturia.

Desmopressin, a synthetic antidiuretic hormone analogue, is the only drug currently approved for the treatment of nocturia associated with nocturnal polyuria or multiple sclerosis (MS). Compared with vasopressin, desmopressin has a longer lasting and more potent antidiuretic effect and is devoid of vasopressor and uterotonic effects. In two large, randomised, double-blind phase III trials in adults with nocturia associated with nocturnal polyuria, 3 weeks of oral desmopressin therapy was significantly more effective than placebo in reducing the mean number of nocturnal voids and in normalising the rate of nocturnal urine production. Beneficial effects of desmopressin on nocturia were maintained and increased in patients completing 10 or 12 months of further treatment in a nonblind extension of short-term trials. In randomised, double-blind trials in MS patients with nocturia, nasal desmopressin reduced the mean number of nocturnal voiding episodes by 31-54%. In both patient populations, desmopressin increased the initial sleep period or mean maximum period of uninterrupted sleep by approximately 2 hours, an outcome significantly greater than that achieved with placebo. In trials of < or =6 weeks duration in adults with nocturia, desmopressin was generally well tolerated. Most desmopressin-related adverse events were transient and mild or moderate in severity. Clinically significant hyponatraemia was reported in approximately 5% and required withdrawal from studies in < or =3% of patients.

Adult↗
PubMed2005

Atorvastatin: a review of its use in the primary prevention of cardiovascular events in patients with type 2 diabetes mellitus.

Atorvastatin (Lipitor) is an HMG-CoA reductase inhibitor with well documented lipid-lowering effects. It has recently been evaluated for the primary prevention of major cardiovascular events in patients with type 2 diabetes mellitus without elevated serum low-density lipoprotein (LDL)-cholesterol levels. Atorvastatin 10mg daily for 4 years was effective at reducing the risk of a first major cardiovascular event, including stroke, in a large, placebo-controlled, multicentre trial in patients with type 2 diabetes and at least one other coronary heart disease (CHD) risk factor, but without markedly elevated LDL-cholesterol levels. In this trial, known as CARDS (the Collaborative AtoRvastatin Diabetes Study), atorvastatin had a similar tolerability profile to that of placebo. Thus, atorvastatin has a potential role in the primary prevention of cardiovascular events in diabetic patients at risk of CHD, irrespective of pre-treatment LDL-cholesterol levels.

Atorvastatin↗
PubMed2005

Tenofovir disoproxil fumarate: a review of its use in the management of HIV infection.

Tenofovir disoproxil fumarate (tenofovir DF; Viread), an ester prodrug of the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir, is indicated in combination with other antiretroviral agents in the treatment of HIV infection. As a component of an antiretroviral regimen, oral tenofovir DF 300 mg once daily effectively reduces viral load in patients with HIV infection who are treatment-experienced with baseline NRTI resistance mutations or treatment-naive. Tenofovir DF provides a simple and convenient once-daily dosage regimen, and is generally well tolerated and able to produce sustained suppression of viral replication.

Adenine↗
PubMed2005

Peginterferon alpha-2a (40KD) plus ribavirin: a review of its use in the management of patients with chronic hepatitis C and persistently 'normal' ALT levels.

Combination therapy with subcutaneous peginterferon alpha-2a (40KD) [Pegasys] plus oral ribavirin (Copegus) has been evaluated previously in patients with chronic hepatitis C and elevated ALT levels. A recent randomised, nonblind, multicentre trial examined the efficacy of this combination therapy in the treatment of patients with persistently 'normal' ALT levels. These trial results showed that combination therapy with peginterferon alpha-2a (40KD) plus ribavirin is effective in patients with chronic hepatitis C and persistently normal ALT levels. Overall, a sustained virological response occurred in over 50% of patients who received combination therapy for 48 weeks, albeit with a low daily dosage of ribavirin. The tolerability profile of combination therapy in patients with persistently normal ALT levels is similar to that seen in patients with elevated ALT levels. The decision as to whether or not treatment should be initiated in patients with chronic hepatitis C and persistently normal ALT levels should be made on an individual basis. If a decision is made to treat, combination therapy with peginterferon alpha-2a (40KD) plus ribavirin can be considered a first-line treatment option.

Alanine Transaminase↗
PubMed2005

Sulfasalazine: a review of its use in the management of rheumatoid arthritis.

Sulfasalazine (salazosulfapyridine) [Azulfidine, Salazopyrin] is a well established disease-modifying antirheumatic drug (DMARD) used in the treatment of patients with rheumatoid arthritis. Clinical trials with sulfasalazine have used an array of measures of disease activity, such as the number of tender and swollen joints, Ritchie articular index (RAI) and erythrocyte sedimentation rate (ESR). In randomised, double-blind, placebo-controlled trials, sulfasalazine was associated with statistically significant benefits for various measures of disease activity, according to results of individual trials and/or meta-analysis. Sulfasalazine was associated with broadly similar efficacy to that of various other DMARDs in several randomised, double-blind, comparative trials. Promising results have also been demonstrated with sulfasalazine in combination with other DMARDs (e.g. methotrexate and hydroxychloroquine) in patients with early rheumatoid arthritis and in those with more established disease. Sulfasalazine was generally well tolerated in clinical trials, the most frequently reported adverse effects being adverse gastrointestinal effects, headache, dizziness and rash; myelosuppression can also occur. Sulfasalazine has a relatively short lag time until its onset of action and is often considered to be among the more efficacious traditional DMARDs. Based on considerations of safety, convenience and cost, many rheumatologists (particularly outside of the US) select sulfasalazine as initial therapy, although preferred first-line treatment options vary between countries.

Antirheumatic Agents↗
PubMed2005

Ramipril/felodipine extended-release fixed-dose combination: a review of its use in the management of essential hypertension.

Ramipril/felodipine extended release (ER) [Triapin and Triapin Mite, Unimax] is a once-daily fixed-dose combination of the ACE inhibitor ramipril and the ER formulation of the dihydropyridine calcium channel antagonist felodipine. It is indicated in adult patients with essential hypertension whose blood pressure (BP) is inadequately controlled with ramipril or felodipine monotherapy. In this patient population, commercially available fixed-dose combinations (i.e. 2.5 mg/2.5 mg and 5 mg/5 mg) of ramipril and felodipine ER are more effective at controlling hypertension than the individual components used as monotherapy at the same dosages. Likewise, the 5 mg/5 mg combination is as effective as felodipine ER 10 mg, and more effective than ramipril 10 mg administered as monotherapy. The addition of low-dose ramipril plus felodipine ER (fixed-dose or combination of individual components) to the existing antihypertensive regimen also appears to provide adequate BP control and renal protection in hypertensive patients with non-diabetic chronic renal disease. In these patients, the low-dose combination of ramipril and felodipine ER was as effective as standard-dose felodipine ER, but more effective than standard-dose ramipril, in providing diastolic BP (DBP) control, and as effective as standard-dose ramipril, but more effective than standard-dose felodipine ER, in slowing the rate of regression of glomerular filtration. The ramipril/felodipine ER combination is as well tolerated as ramipril or felodipine ER monotherapy administered at the same dosages, and is better tolerated than felodipine ER monotherapy given at twice the dosage used in the combination. Overall, ramipril/felodipine ER appears to be an effective option for the treatment of adults with essential hypertension that is poorly controlled with monotherapy. In addition, a fixed, low-dose combination of ramipril/felodipine ER is a potential alternative to monotherapy for the initial management of essential hypertension.

Antihypertensive Agents↗
PubMed2005

Doxazosin gastrointestinal therapeutic system: a review of its use in benign prostatic hyperplasia.

Doxazosin, a well established treatment in patients with bothersome lower urinary tract symptoms from benign prostatic hyperplasia (BPH), is available in a new controlled-release formulation, doxazosin gastrointestinal therapeutic system (GITS). Doxazosin GITS (Cardura XL, Cardular PP Uro, Diblocin PP Uro) has an altered pharmacokinetic profile, which allows a higher initial dosage to be used than with the standard formulation and less titration steps to reach a clinically effective dosage. In two large, double-blind, randomised studies (one was placebo-controlled) in patients with BPH, doxazosin GITS (4-8 mg once daily) was as effective as the standard formulation (2-8 mg once daily), and both were more effective than placebo, after 13 weeks' treatment in improving symptom scores, health-related quality of life (HR-QOL), and maximum urinary flow rate (Qmax). Doxazosin GITS was at least as well tolerated as the standard formulation of doxazosin in clinical studies in patients with BPH.

Adrenergic alpha-Antagonists↗
PubMed2005

Octocog alfa, plasma/albumin-free method.

Octocog alfa, plasma/albumin-free method (octocog alfa-PFM) is a recombinant, human, full length, coagulation factor VIII that has been produced without the addition of human- or animal-derived plasma proteins, thereby virtually eliminating the risk of transmission of blood-borne pathogens. Octocog alfa-PFM is structurally and functionally very similar to a previously marketed, albumin-containing formulation of the same recombinant factor VIII. The haemostatic efficacy of octocog alfa-PFM was rated excellent or good in the acute treatment of most breakthrough bleeding episodes in adolescents or adults with moderately severe or severe haemophilia A who were receiving prophylaxis with octocog alfa-PFM and who had been previously treated with factor VIII. Most bleeding episodes resolved after one or two infusions of octocog alfa-PFM. Efficacy was similar regardless of the cause or site of the bleeding episode. Similar excellent or good haemostatic efficacy was observed with octocog alfa-PFM in previously treated children aged <6 years with haemophilia A and during perioperative use in patients with haemophilia A undergoing surgical or invasive dental procedures. Octocog alfa-PFM was well tolerated during clinical development and in the 15-month post-marketing period. There were very few adverse events and serious events were rare. The risk for developing inhibitors (antibodies) to factor VIII was very low.

Adolescent↗
PubMed2005

Goserelin: a review of its use in the treatment of early breast cancer in premenopausal and perimenopausal women.

Goserelin (Zoladex), a gonadotropin-releasing hormone analogue, reduces plasma/serum estrogen levels in pre- or perimenopausal women (to postmenopausal levels), and is indicated in hormone receptor-positive early breast cancer in this population group. Adjuvant goserelin monotherapy has similar efficacy to adjuvant chemotherapy in pre- or perimenopausal women with early, hormone receptor-positive breast cancer. Furthermore, the addition of goserelin to adjuvant chemotherapy appeared to offer an advantage over chemotherapy alone in younger patients. Fewer patients remained amenorrheic after goserelin therapy than after chemotherapy. Complete endocrine blockade provided by the addition of tamoxifen to therapy including goserelin appears to improve outcomes. Thus, goserelin offers a valuable addition to the currently available options for treating pre- or perimenopausal women with hormone therapy-responsive early breast cancer, particularly for women wishing to regain ovarian function after treatment.

Antineoplastic Agents, Hormonal↗
PubMed2005

Memantine: a pharmacoeconomic review of its use in moderate-to-severe Alzheimer's disease.

Memantine (Ebixa, Namenda, Axura) is an uncompetitive NMDA receptor antagonist used in the management of patients with moderate-to-severe Alzheimer's disease. It is currently the only drug approved for use in these more advanced stages of the disease. Significant reductions in functional and cognitive decline have been demonstrated with memantine relative to placebo in randomised, double-blind trials in this patient population. Clinical trial and postmarketing surveillance data indicate that the drug is generally well tolerated. Two fully published modelled cost-effectiveness analyses of memantine in moderate-to-severe Alzheimer's disease have been conducted in the UK and Finland, in which patient progression was simulated through health states related to dependency, residential setting and cognitive function. Although the specific costs included in the analyses varied, as did the study perspective and geographical location, results of the base-case analyses consistently showed that memantine was dominant over no pharmacological treatment. In the UK and Finnish analyses, memantine increased the duration of independence by 1.3 and 4.1 months, respectively, and the time to institutionalisation by 0.8 and 1 month. Mean total per-patient costs were reduced by 1963 pounds over 2 years (2003 costs) in the UK analysis and by 1687 eurossover 5 years (2001 costs) in the Finnish analysis. Memantine was also associated with a small gain in quality-adjusted life expectancy in the UK model. In sensitivity analyses, memantine remained dominant for almost all plausible changes to key variables. Memantine reduced total societal costs by $1090 per patient per month (1999 costs) compared with no pharmacological treatment over 28 weeks in a resource utilisation and cost analysis conducted alongside a pivotal US trial in patients with moderate-to-severe Alzheimer's disease. Results were primarily driven by reductions in total caregiver costs, which included the opportunity cost of time spent in caregiving tasks, and in direct nonmedical costs, which included the cost of care in a nursing home or similar institution.In conclusion, in patients with moderate-to-severe Alzheimer's disease, memantine is associated with significant reductions in functional and cognitive decline compared with no pharmacological treatment. Available pharmacoeconomic data from Europe and the US, despite some inherent limitations, support the use of memantine as a cost-effective treatment in this patient population, although definitive conclusions are not feasible because of limited data.

Alzheimer Disease↗