Biomedical subjects

K L Goa

Publications and source records attributed to K L Goa.

At least 37 records · Page 2Linked to original sources

PubMed2001

Rabeprazole: an update of its use in acid-related disorders.

UNLABELLED: Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion. In 8-week studies, among patients with gastro-oesophageal reflux disease (GORD), rabeprazole 20 mg/day or 10mg twice daily was as effective as omeprazole and superior to ranitidine in the healing of GORD. Symptom relief with rabeprazole was superior to that provided by placebo and ranitidine and similar to omeprazole. In long-term trials rabeprazole 10 mg/day was similar to omeprazole 20 mg/day in a 2-year study and superior to placebo in 1-year studies, in both the maintenance of healing and prevention of symptoms in patients with healed GORD. In nonerosive GORD, 4-week studies have shown rabeprazole to be more effective than placebo in relieving heartburn and various other gastrointestinal symptoms. Data among patients with Barrett's oesophagus suggest rabeprazole 20 mg/day may be more effective than placebo in maintaining healing of associated oesophagitis after 1 year of treatment. One-week triple Helicobacter pylori eradication therapy with rabeprazole plus clarithromycin and amoxicillin achieved eradication rates of > or =85%. Rabeprazole is as effective as omeprazole and lansoprazole when included as part of a triple-therapy regimen for the eradication of H. pylori. Eradication rates of >90% were achieved when rabeprazole 20 to 40 mg/day was included as part of a quadruple eradication regimen. As monotherapy for peptic ulcer healing and symptom relief, 4- to 8-week studies have shown rabeprazole 10 to 40 mg/day to be superior to placebo and ranitidine and have similar efficacy to omeprazole. Preliminary 1-year data among 16 patients with Zollinger-Ellison syndrome suggest rabeprazole 60 to 120 mg/day can resolve and prevent the recurrence of symptoms and endoscopic lesions associated with this condition. In clinical trials of up to 2 years' duration the tolerability of rabeprazole is similar to that of placebo, ranitidine and omeprazole. Common adverse events assigned to rabeprazole have been diarrhoea, headache, rhinitis, nausea, pharyngitis and abdominal pain. Histological changes and increases in serum gastrin levels were unremarkable and typical of proton pump inhibitors. No dosage adjustment is necessary in renal and mild to moderate hepatic impairment. CONCLUSION: Rabeprazole is a well tolerated proton pump inhibitor. It has proven efficacy in healing, symptom relief and prevention of relapse of peptic ulcers and GORD and can form part of effective H. pylori eradication regimens. It is an important alternative to H(2) antagonists and an additional treatment option to other proton pump inhibitors in the management of acid-related disorders.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Rivastigmine. A pharmacoeconomic review of its use in Alzheimer's disease.

UNLABELLED: Alzheimer's disease is associated with a large cost burden, of which institutionalised care constitutes a major component. Therefore, the decision to move a patient from the community to institutionalised care is associated with a significant increase in direct costs. About three-quarters of patients with Alzheimer's disease are admitted to a nursing home within 5 years of diagnosis. Unpaid or informal caregiver time is another large cost in Alzheimer's disease, especially for patients cared for in the community; informal care can account for up to three-quarters of healthcare costs in non-institutionalised patients. Several cholinesterase inhibitors, of which rivastigmine is one, are available for the treatment of patients with mild to moderate Alzheimer's disease. By improving cognitive function and slowing the rate of cognitive decline, cholinesterase inhibitor therapy may reduce a significant part of the economic burden of the disease by delaying the move to institutionalised care. In the absence of prospective long term data which focus on pharmacoeconomic end-points, modelling techniques have been used to extrapolate clinical data available for some cholinesterase inhibitors, including rivastigmine. Four economic analyses, based on a single model of cognitive decline, have been performed with rivastigmine from the perspective of the provider or society. All show that rivastigmine therapy (excluding drug-related costs) is associated with cost savings in patients with mild to moderate Alzheimer's disease by delaying the time to institutionalisation. If the acquisition cost of the drug was factored in, the cost savings completely or partially offset treatment costs. The magnitude of the cost savings increased as the time horizon increased (up to 2 years). The largest savings were realised in patients with mild disease over a 2-year time-frame, suggesting that treatment should be initiated early from an economic viewpoint. Pharmacoeonomic data comparing different cholinesterase inhibitors are, as yet, unavailable. CONCLUSION: Pharmacoeconomic analyses, based on modelled data excluding drug costs, indicate that rivastigmine completely or partially offsets the costs of treatment by delaying cognitive decline and the time to institutionalisation in patients with mild to moderate Alzheimer's disease. From a societal perspective, cost savings are realised if the drug is introduced early in the disease. Additional benefits offered by rivastigmine on behavioural symptoms, which may reduce caregiver burden, have yet to be investigated from a pharmacoeconomic perspective.

Activities of Daily Living↗

PubMed2001

Efavirenz: a pharmacoeconomic review of its use in HIV infection.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of patients with HIV infection. Both US and British treatment guidelines for HIV infection recommend NNRTI- or protease inhibitor-based combinations [i.e. with nucleoside reverse transcriptase inhibitors (NRTIs)] as first-line treatmentoptions in the management of HIV disease. Results of a pivotal randomised study (DMP 266-006) comparing efavirenz- versus indinavir-based triple combination therapy in patients with HIV infection (the majority of whom were antiretroviral therapy-naive) showed the efavirenz-based regimen was better tolerated and had greater success in achieving reductions in viral load below the limit of detection. These and other clinical data were incorporated into economic models in 2 analyses, one conducted in the US and the other in Canada. The US analysis examined long term clinical and economic outcomes predicted on the basis of response (viral load and CD4+ cell counts), tolerability and willingness to adhere to therapy. The efavirenz-based regimen was the dominant treatment strategy as it was predicted to improve survival and reduce direct medical costs in the US healthcare system. Compared with the indinavir-containing regimen, survival was increased by 11% (absolute difference) and cumulative costs were reduced by $US10,326 per patient (1998 discounted costs) at 5 years after starting treatment with efavirenz-based therapy. The Canadian analysis was conducted from the perspective of the Ontario healthcare system. This study did not consider differences in clinical efficacy between treatment groups, costs of study medication or outcomes beyond 1 year--all factors that would have favoured the efavirenz-based regimen. Of the 2 treatment options, the efavirenz-based regimen was associated with 7.4% lower average annual medical care costs, primarily because of greater costs associated with adverse clinical events with the indinavir-based regimen. In conclusion, current treatment guidelines for HIV infection recognise efavirenz-based combination regimens as a first-line treatment option. A pivotal comparative clinical trial (DMP 266-006) showed a significantly greater virological response to efavirenz- than indinavir-based triple combination therapy, and the efavirenz-based regimen was better tolerated. These clinical data are supported by pharmacoeconomic analyses conducted in the US and Canada, both of which showed lower medical care costs with the efavirenz-based regimen. The US analysis also predicted long term health benefits, such as improved survival, with efavirenz- versus indinavir-based triple combination therapy. These results must be weighed against the inherent difficulties of predicting long term treatment failure rates from short term data, and the limited number of pharmacoeconomic analyses conducted with efavirenz to date.

Alkynes↗

PubMed2001

Oxcarbazepine: an update of its efficacy in the management of epilepsy.

UNLABELLED: Oxcarbazepine (10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide) is a 10-keto analogue of carbamazepine with anticonvulsant activity. In newly diagnosed adult patients, oxcarbazepine monotherapy is as effective as phenytoin and vaiproic acid at reducing generalised tonic-clonic and partial seizure frequency. Furthermore, oxcarbazepine 2400 mg/day as monotherapy has also proved effective in the treatment of refractory partial seizures in adult patients. Oxcarbazepine 600, 1200 and 2400 mg/day as adjunctive therapy significantly reduced seizure frequency compared with placebo in 692 patients with refractory partial seizures. The efficacy of oxcarbazepine monotherapy is similar to that of phenytoin in the treatment of children and adolescents with newly diagnosed partial or generalised tonic-clonic seizures. Additionally, adjunctive therapy with oxcarbazepine was significantly more effective than placebo at reducing seizure frequency in children and adolescents with refractory partial seizures. The most commonly reported adverse events associated with oxcarbazepine monotherapy and/or adjunctive therapy in adults and/or children are somnolence, dizziness, headache, nausea and vomiting. Oxcarbazepine monotherapy is better tolerated than phenytoin (in both adults and children) and valproic acid (in adults), and although 75 to 90% of adult patients in 5 recent monotherapy studies reported adverse events while receiving oxcarbazepine, <8% withdrew from treatment because of them. Acute hyponatraemia, although usually asymptomatic, develops in 2.7% of patients treated with oxcarbazepine. Adverse events most likely to resolve upon switching to oxcarbazepine therapy from treatment with carbamazepine are undetermined skin reactions (rashes, pruritus, eczema), allergic reactions and a combination of malaise, dizziness and headache. Although oxcarbazepine does have a clinically significant interaction with some drugs (e.g. phenytoin and oral contraceptives), it has a lower propensity for interactions than older antiepileptic drugs (AEDs) because its major metabolic pathway is mediated by noninducible enzymes. CONCLUSION: Oxcarbazepine as monotherapy is a viable alternative to established AEDs in the treatment of partial and generalised tonic-clonic seizures in adults and children. Furthermore, it is also effective as adjunctive therapy in the treatment of refractory partial seizures in both age groups. In addition, the drug is tolerated better than the older, established AEDs, and has a lower potential for drug interactions. These attributes make oxcarbazepine an effective component in the initial treatment of newly diagnosed partial and generalised tonic-clonic seizures, and also as an adjunct for medically intractable partial seizures in both adults and children.

Adult↗

PubMed2001

Frovatriptan.

black triangle Frovatriptan, a new serotonin receptor agonist developed for the acute treatment of migraine, has high affinity for serotonin 5-HT1B and 5-HT1D receptor subtypes and is a potent stimulator of contraction in human basilar arteries. black triangle A long terminal elimination half-life (approximately 26 hours) is a distinctive pharmacokinetic feature of frovatriptan which appears to be independent of dose, age, gender and renal function. black triangle A single oral dose of frovatriptan 2.5mg was effective in the acute treatment of migraine providing meaningful relief within 2 hours to approximately twice as many recipients as placebo in clinical trials. black triangle Consistent relief of migraine symptoms was achieved in patients who treated a number of consecutive attacks with frovatriptan and the incidence of 24-hour migraine recurrence was reduced. black triangle Frovatriptan was well tolerated in clinical trials, with the overall incidence of adverse events occurring with frovatriptan 2.5mg only slightly higher than that reported with placebo. Mild to moderate fatigue, nausea and paraesthesia were the most commonly reported drug-related adverse events.

Animals↗

PubMed2001

Calcipotriol ointment. A review of its use in the management of psoriasis.

UNLABELLED: Calcipotriol, a vitamin D3 analog, acts not only to inhibit cell proliferation and enhance cell differentiation in the skin of patients with psoriasis, but also appears to have effects on immunologic markers that are thought to play a role in the etiology of the disease. In several well designed, short term studies in adults, calcipotriol ointment 50 micrograms/g twice daily provided similar or superior efficacy to several other antipsoriatic agents in adult patients with mild to moderate psoriasis. In patients with nonscalp psoriasis, the drug provided superior efficacy to twice daily placebo (vehicle ointment), twice daily fluocinonide 500 micrograms/g, once daily tacalcitol 4 micrograms/g and twice daily coal tar 5% plus allantoin 2% and hydrocortisone 0.5%. Furthermore, calcipotriol therapy generally provided superior efficacy to twice daily betamethasone valerate 1 to 1.2 mg/g or once daily dithranol 1 to 20 mg/g, and similar efficacy to twice daily betamethasone dipropionate plus salicylic acid or once daily maxacalcitol 6 to 50 micrograms/g. Limited data indicated that calcipotriol ointment 50 micrograms/g also improved overall disease severity in children. In combination with other antipsoriatic agents [acitretin, cyclosporine, betamethasone valerate, halobetasol (ulobetasol)], ultraviolet B or psoralen ultraviolet A (PUVA) phototherapy, calcipotriol ointment 50 micrograms/g twice daily improved the beneficial effects of these drugs on overall disease severity in adult patients with moderate to severe psoriasis. Furthermore, in separate trials, calcipotriol combination therapy reduced the dosage of acitretin required to achieve clearance of psoriasis and the duration of PUVA and dosage of UVA phototherapy, potentially improving the benefit/risk ratio for these other antipsoriatic treatments. Calcipotriol was generally well tolerated in short and long term studies in adult patients, with the majority of adverse events being mild to moderate in intensity and transient. The most common adverse events associated with calcipotriol therapy were dermatologic in nature and included lesional or perilesional irritations, face and scalp irritations, worsening of psoriasis and miscellaneous dermatologic events. Notably, there have been very few reports of patients developing hypercalcemia or hypercalciuria during calcipotriol therapy, with most occurring in patients who exceeded the recommended dosage of 100 g/week. Although data in children are limited, the drug was well tolerated with the nature and incidence of adverse effects similar to those observed in adult patients. CONCLUSIONS: Extensive clinical experience, along with several short and long term clinical trials, has shown calcipotriol ointment to be an effective and well tolerated topical agent in adult patients with psoriasis. In addition, calcipotriol ointment proved beneficial in combination with other topical, phototherapy or systemic antipsoriatic treatments, reducing the dosage and/or duration of some of these treatments and potentially improving their benefit/risk ratio. Calcipotriol ointment is valuable as a first- or second-line therapy option for the management of mild to moderate psoriasis and in combination with other antipsoriatic agents for more severe psoriasis.

Administration, Topical↗

PubMed2001

Tenecteplase: a review of its pharmacology and therapeutic efficacy in patients with acute myocardial infarction.

UNLABELLED: Tenecteplase is a triple combination mutant variant of alteplase with high fibrin specificity and resistance to plasminogen activator inhibitor-1. The reduced rate of systemic clearance of the drug relative to alteplase allows tenecteplase to be given by rapid bolus injection to patients with acute myocardial infarction (AMI) with ST segment elevation. The efficacy of tenecteplase in AMI has been demonstrated in a phase I dose-ranging trial [Thrombolysis in Myocardial Infarction (TIMI) 10A], a nonblind phase II comparison with alteplase (TIMI 10B), and a randomized double-blind phase III comparison with alteplase in 16 949 patients [the second Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) trial]. Patients also received aspirin and intravenous heparin in all trials. In TIMI 10A and 10B, TIMI grade 3 coronary flow was achieved after 90 minutes in 54.3 to 65.8% of patients receiving tenecteplase 30, 40 or 50 mg; in TIMI 10B, grade 3 flow was reported in 62.7% patients receiving alteplase (</=100mg by front-loaded infusion over 90 minutes). Thirty-day mortality was similar with bodyweight-adjusted intravenous bolus doses of tenecteplase 30 to 50mg and front-loaded 90-minute infusion of alteplase in ASSENT-2 (approximately 6.2%). Rates of reinfarction and cardiogenic shock were also similar between groups, although mortality was reduced with tenecteplase in patients receiving treatment more than 4 hours after onset of symptoms (7 vs 9.2%; p = 0.018). Preliminary data show maintenance of the similarity between groups over 1 year (approximate 10.2% mortality in both groups), with loss of statistical significance between groups in patients treated late. ASSENT-2 showed the risks of intracranial hemorrhage (0.93%) and stroke (all causes) [1.78%] with tenecteplase to be similar to those with alteplase (0.94 and 1.66%, respectively). The rate of noncerebral bleeding was lower with tenecteplase than with alteplase (26.43 vs 28.95%; p = 0.0003). No causal link has been demonstrated between tenecteplase and allergic reactions in patients. CONCLUSIONS: Bolus tenecteplase is an effective thrombolytic agent, suitable for first-line use in patients with AMI with ST segment elevation. Results to date show overall efficacy and tolerability profiles similar to those of alteplase, with comparable mortality after 1 year's follow-up. The apparent advantages of tenecteplase (reduced mortality in patients receiving late treatment and reduced incidence of noncerebral bleeding complications) in ASSENT-2 are of interest and merit further attention. The full implications of the availability of bolus administration and its potential clinical advantages over the currently widely used infusion regimens, together with the effect on outcomes of addition of tenecteplase to platelet glycoprotein IIb/IIIa inhibition, are currently under investigation.

Acute Disease↗

PubMed2000

Verteporfin.

Verteporfin, a benzoporphyrin derivative monoacid ring A, is a photosensitising drug for photodynamic therapy (PDT) activated by low-intensity, nonheat-generating light of 689nm wavelength. Activation generates cytotoxic oxygen free radicals. The specificity and uptake of verteporfin for target cells with a high expression of low density lipoprotein (LDL) receptors, such as tumour and neovascular endothelial cells, is enhanced by the use of a liposomal formulation and its rapid uptake by plasma LDL. Verteporfin therapy (at light doses < 150 J/cm) selectively damages neovascular endothelial cells leading to thrombus formation and specific occlusion of choroidal neovascular vessels in subfoveal lesions in patients with age-related macular degeneration (AMD). Repeated applications of verteporfin therapy 6 mg/m2 improved or maintained visual acuity in the majority of patients with some classic subfoveal choroidal neovascularisation (CNV) secondary to AMD at 1 year's follow-up in 2 large multicentre, placebo-controlled, double-blind trials. Furthermore. in a subgroup of these patients with predominantly classic CNV secondary to AMD, there was a significantly more marked visual acuity (VA) benefit with 67.3% of verteporfin-treated eyes experiencing less than a 15-letter loss of VA versus 39.3% with placebo treatment. Multiple applications of verteporfin therapy were well tolerated in patients with subfoveal CNV secondary to AMD. The most common adverse events were visual disturbances, injection site reactions, photosensitivity reactions and infusion-related back pain.

Animals↗

PubMed2000

Extended-release oxybutynin.

Extended-release oxybutynin (Ditropan XL) uses an osmotic system (OROS) to deliver a controlled amount of oxybutynin chloride into the gastrointestinal tract over a 24-hour period when taken once daily. Oxybutynin binds to M3 muscarinic receptors on the detrusor muscle of the bladder, preventing acetylcholinergic activation and relaxing the muscle. Mean peak plasma concentrations are lower with extended-release oxybutynin 15mg once daily than with conventional immediate-release oxybutynin 5mg taken 3 times daily. Relative bioavailabilities of parent drug and metabolite N-desethoxybutynin are 153 and 69%, respectively, for extended-release oxybutynin when compared with immediate-release oxybutynin. In short (< or =6 weeks) randomised, double-blind clinical trials of patients with detrusor instability, extended-release oxybutynin 5 to 30mg once daily significantly reduced the mean weekly number of urge incontinence episodes by 84 to 90%. Extended-release oxybutynin had similar efficacy to immediate-release oxybutynin. Adverse events reported by patients taking extended-release oxybutynin were dose-related anticholinergic effects, most frequently dry mouth, somnolence, constipation, blurred vision and dizziness. A large noncomparative study demonstrated that approximately two thirds of the patients prescribed extended-release oxybutynin for detrusor instability were still taking the medication 6 months later.

Aged↗

PubMed2000

Docetaxel: a review of its use in non-small cell lung cancer.

Docetaxel, a semisynthetic member of the taxoid class of antineoplastic agents, is effective in the treatment of patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). In noncomparative trials in patients with NSCLC, docetaxel 75 or 100 mg/m2 produced objective response rates of 20 to 38% and 14 to 25% as a first-line or second-line monotherapy, respectively. In Japan, docetaxel 60 mg/m2 produced objective response rates of 19 to 25% in previously untreated patients. Docetaxel 100 or 75 mg/m2 produced significantly higher response rates than either vinorelbine or ifosfamide in previously treated patients; patients treated with docetaxel 75 mg/m2 had an improved 1-year survival rate compared with those who received vinorelbine or ifosfamide. Docetaxel monotherapy in chemotherapy-naive patients produced survival rates that are similar to those reported for most platinum-containing standard combinations such as cisplatin plus vinorelbine. Combination of docetaxel with one other antineoplastic resulted in objective response rates of 20 to 54% in chemotherapy-naive patients; triple chemotherapy combinations produced responses in 51 and 60% of patients. Promising results from a few small studies and one large phase II study have also indicated a potential role for docetaxel as neoadjuvant therapy. The main dose-limiting adverse event associated with docetaxel is neutropenia, and fluid retention is common in many patients. The tolerability profile is generally acceptable in the majority of patients, although extra care has to be taken in patients with impaired liver function to minimise the risk of severe or febrile neutropenia. Conclusions. Docetaxel is generally well tolerated by patients receiving treatment for locally advanced and metastatic NSCLC, and produces response and survival rates equivalent to many current standard treatment options. Comparative studies have shown that docetaxel monotherapy provides significant survival benefits over best supportive care or treatment with vinorelbine or ifosfamide. Response and 1-year survival rates with docetaxel monotherapy are particularly encouraging in patients refractory or resistant to cisplatin or carboplatin, for whom treatment options are few. Neoadjuvant docetaxel has produced improved survival compared with local treatment alone. Combinations of docetaxel with other antineoplastic agents have produced relatively high response and 1-year survival rates; however, further comparative studies are required to confirm these benefits. In the meantime, docetaxel is a welcome addition to the options available for patients with advanced NSCLC.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Dexmedetomidine.

Dexmedetomidine is a potent alpha2-adrenoceptor agonist with 8 times higher affinity for the alpha2-adrenoceptor than clonidine. Dexmedetomidine has shown sedative, analgesic and anxiolytic effects after intravenous administration to healthy volunteers or postsurgical patients in the intensive care unit. Dexmedetomidine produced a predictable haemodynamic decline (dose-dependently decreased arterial blood pressure and heart rate) in postsurgical patients coinciding with reductions in plasma catecholamines. In phase III clinical trials, dexmedetomidine 0.2 to 0.7 microg/kg/h produced clinically effective sedation and significantly reduced the analgesic requirements of postsurgical ventilated intensive care unit patients. There was no clinically apparent respiratory depression after cessation of assisted ventilation. Dexmedetomidine produced rapid and stable sedation in postsurgical ventilated patients while maintaining a high degree of patient rousability and anxiety reduction. Dexmedetomidine was well tolerated in phase III studies. The most frequently observed adverse events were hypotension, bradycardia and nausea.

Adrenergic alpha-Agonists↗

PubMed2000

Adjuvanted Lyme disease vaccine: a review of its use in the management of Lyme disease.

UNLABELLED: Lyme disease is a potentially serious infection which is caused by the spirochaete Borrelia burgdorferi and is endemic in certain areas of North America, Europe and Asia. Lyme disease vaccine (LYMErix) is an adjuvanted formulation of the outer surface protein A (OspA) of the causative spirochaete. It acts by inducing high titres of anti-OspA antibodies (anti-OspA), which must be present in vaccinated individuals before exposure to B. burgdorferi to provide protection against Lyme disease. Lyme disease vaccine efficacy against Lyme disease was 80% for definite and asymptomatic cases and 76% for definite cases at year 2 using the recommended dosage regimen [30 microg at months 0, 1 and 12 (0, 1, 12 schedule)] in a randomised, double-blind, multicentre trial in 10,936 enrolled adult volunteers who resided in areas of the US endemic for Lyme disease. On the basis of an anti-OspA correlate of protection, Lyme disease vaccine 30 microg was equally effective when administered by a shorter schedule (0, 1, 6 schedule); > or = 90% of adult volunteers developed protective anti-OspA titres with this or the 0, 1, 12 schedule. Although published data are fewer, a 0, 1, 2 schedule has also shown promise in adults. In addition, virtually all children (aged 2 to 15 years) given Lyme disease vaccine 30 microg developed protective anti-OspA titres, but published data are also limited and results of a large paediatric trial are awaited with interest. Long term protection against Lyme disease appears to be possible with Lyme disease vaccine. Although anti-OspA titres decline rapidly after completion of the recommended schedule, booster doses of 30 microg of the vaccine induced protective anti-OspA titres in > or = 96% of adult volunteers when administered 12 and/or 24 months later. Lyme disease vaccine 30 microg is well tolerated: most vaccination-related adverse events were transient and mild or moderate in severity in clinical trials. The most common spontaneously reported adverse event was pain at the injection site in 24% of vaccine recipients (vs 7.6% of the placebo group). The incidence of spontaneously reported, early nonspecific systemic adverse events was <4% but was higher with the vaccine than with placebo for some events (e.g. myalgias, fever and chills but not arthralgia). There appeared to be no association between the vaccine and the incidence of arthritis or any late systemic adverse events. The tolerability profile of Lyme disease vaccine did not appear to vary with the schedule of administration, nor to differ between adults and children. CONCLUSIONS: Lyme disease vaccine, an adjuvanted formulation of OspA, protects most adults against Lyme disease when administered by the recommended 0, 1, 12 schedule before disease exposure, and is well tolerated. The optimal schedule(s) of administration, duration of protection against Lyme disease, long term tolerability in adults and potential role in children are not fully defined for this vaccine. Lyme disease vaccine is indicated in North America for active immunisation of adults at moderate to high risk of contracting Lyme disease.

Adult↗

PubMed2000

Alosetron.

Alosetron is a potent and highly selective serotonin 5-HT3 receptor antagonist which has been evaluated for the management of irritable bowel syndrome (IBS). It blocked the fast 5HT3-mediated depolarisation of guinea-pig myenteric and submucosal neurons in vitro, with half-maximal inhibition at approximately 55 nmol/L. Alosetron attenuated the visceral nociceptive effect of rectal distension in conscious or anaesthetised dogs. It increased the compliance of the colon to distension in patients with IBS and delayed colonic transit in patients with IBS or carcinoid diarrhoea and in healthy volunteers. A single dose of alosetron 4 mg increased in vivo fluid absorption in normal human small intestine. In clinical trials in patients with IBS, alosetron 1 mg twice daily was effective in relieving abdominal pain and discomfort. Alosetron was most effective in female patients and particularly in those with diarrhoea-predominant IBS. In patients with IBS and healthy volunteers who received alosetron, the most common adverse event was constipation.

Adult↗

PubMed2000

Lenograstim: an update of its pharmacological properties and use in chemotherapy-induced neutropenia and related clinical settings.

UNLABELLED: Lenograstim is the glycosylated recombinant form of human granulocyte colony stimulating factor. The drug is used to reduce the risk of life-threatening infection in patients with neutropenia, particularly after cytotoxic chemotherapy. Lenograstim accelerates neutrophil recovery significantly after chemotherapy, with beneficial effects on clinical end-points such as incidence of laboratory-confirmed infection and length of hospital stay. Chemotherapy dose intensity has also been increased in patients receiving lenograstim, notably those with breast or small cell lung cancer, although improvements in tumour response and survival have not been demonstrated. Lenograstim also assists neutrophil recovery in patients undergoing bone marrow transplantation, and stimulates the production of peripheral blood stem cells (PBSCs) for autologous transfusion after aggressive chemotherapy. Lenograstim also mobilises CD34+ cells more efficiently in unit dose terms than filgrastim and has been used successfully to mobilise PBSCs from healthy donors for allogeneic transplantation. Randomised trials have shown increases in rates of disease remission after lenograstim therapy in patients with acute myeloid leukaemia, with no evidence of stimulation of malignant blasts. The drug has also shown potential in the mobilisation of nonmalignant PBSCs for autotransplantation in patients with chronic myeloid leukaemia. Other studies show efficacy of lenograstim in patients with acute lymphoblastic leukaemia, aplastic anaemia, in children with severe chronic neutropenia and in the reversal of neutropenia related to antiviral therapy in patients with AIDS, although data are not extensive. Cost analyses of lenograstim have been carried out from a hospital perspective, although results have been inconclusive. Cost-effectiveness or cost-benefit data are lacking at present. Lenograstim is well tolerated, with bone pain and injection site reactions being reported most frequently in clinical trials. CONCLUSIONS: Lenograstim has been confirmed as a valuable adjunct to minimise the haematological toxicity of myelosuppressive chemotherapy in patients with malignant disease. The drug also enhances neutrophil recovery in patients undergoing stem cell rescue, and assists PBSC mobilisation. Data indicate clinical benefit with lenograstim in myeloid disorders, with no evidence of malignant blast cell proliferation. Further studies are required to assess more fully the pharmacoeconomic implications of the use of lenograstim and other recombinant growth factors, to provide more data on the efficacy of the drug in the management of disease-related neutropenia, and to clarify fully its position relative to filgrastim.

Adjuvants, Immunologic↗

PubMed2000

Zolpidem: an update of its pharmacology, therapeutic efficacy and tolerability in the treatment of insomnia.

UNLABELLED: Zolpidem is an imidazopyridine agent that is indicated for the short term (< or = 4 weeks) treatment of insomnia (recommended dosage 10 mg/day in adults and 5 or 10 mg/day in the elderly or patients with hepatic impairment). Data have shown that the hypnotic efficacy of zolpidem is generally comparable to that of the benzodiazepines flunitrazepam, flurazepam, nitrazepam, temazepam and triazolam as well as nonbenzodiazepine hypnotic agents such as zopiclone and trazodone in the treatment of elderly and adult patients with insomnia. The comparative efficacy of a recently available nonbenzodiazepine hypnotic zaleplon and zolpidem has yet to be established. There was no evidence of tolerance developing to the hypnotic effects of zolpidem in a number of studies of up to 6 months' duration. However, tolerance has been described in a few patients taking the drug at high dosages for periods of up to several years. Zolpidem is well tolerated in patients with insomnia and the most common adverse events are generally nausea, dizziness and drowsiness. Although zolpidem produced some psychomotor and memory impairment over the first few hours after administration, it had few next-day effects (including effects on daytime well-being and morning coordination). In this respect, it was comparable or superior to flunitrazepam and flurazepam and comparable to other benzodiazepines in patients with insomnia. Zolpidem appears to have a low potential for abuse. CONCLUSIONS: Zolpidem is effective and well tolerated in patients with insomnia, including the elderly. Studies have shown that zolpidem generally has similar efficacy to other hypnotics including benzodiazepines and zopiclone. Zolpidem appears to have minimal next-day effects on cognition and psychomotor performance when administered at bedtime. In addition, there is little evidence of tolerance to the hypnotic effects of zolpidem, or rebound insomnia or withdrawal symptoms after discontinuation of the drug when it is given as recommended (10 mg/day for < 1 month) or over longer periods.

Animals↗

PubMed2000

Celecoxib: a review of its use in osteoarthritis, rheumatoid arthritis and acute pain.

UNLABELLED: Celecoxib is a cyclo-oxygenase (COX) inhibitor that exhibits relative in vitro and ex vivo selectivity for COX-2 over COX-1. Results of randomised double-blind multicentre studies indicate that celecoxib is superior to placebo and has similar efficacy as conventional nonsteroidal anti-inflammatory drugs (NSAIDs) in improving the signs and symptoms of osteoarthritis and rheumatoid arthritis. Analgesic efficacy and improvements in functional status are apparent within 2 weeks of starting therapy and are maintained throughout treatment. Available data suggest that celecoxib has analgesic efficacy in patients with postsurgical dental pain, although this is yet to be confirmed. In patients with osteoarthritis of the knee, celecoxib 100 and 200 mg and naproxen 500 mg twice daily were similarly efficacious and superior to placebo. Once and twice daily celecoxib dosage regimens provided comparable efficacy. Improvements in physical function paralleled those in pain relief. Celecoxib also has efficacy in treating the signs and symptoms of osteoarthritis of the hip. The effects of celecoxib were not diminished in elderly patients with osteoarthritis of the hip or knee. All dosages of celecoxib (100 to 400 mg twice daily) and naproxen 500 mg twice daily produced significant anti-inflammatory and analgesic effects in patients with active rheumatoid arthritis. In patients with stable rheumatoid arthritis, celecoxib 200 mg twice daily showed sustained symptomatic improvements similar to those of twice daily slow-release diclofenac 75 mg over a 24-week period. Celecoxib was well tolerated in clinical trials. Upper gastrointestinal complications occurred in significantly fewer patients treated with twice daily celecoxib 25 to 400 mg than in those receiving comparator NSAIDs. There was no evidence of a dose relationship in endoscopic ulcer development and incidences in celecoxib and placebo recipients were lower than in those receiving twice daily naproxen 500 mg or ibuprofen 800 mg 3 times daily. CONCLUSIONS: Celecoxib is the first COX-2 specific inhibitor approved for use in osteoarthritis and rheumatoid arthritis. Celecoxib produces significant improvements in pain and inflammation and these effects are maintained during treatment for up 24 weeks in clinical trials. Studies indicate that celecoxib has similar efficacy to conventional NSAIDs in relieving pain and improving functional status, but is associated with a lower incidence of upper gastrointestinal ulceration and complications. This promising gastrointestinal safety profile, together with sustained symptomatic relief, places celecoxib as a useful alternative for the treatment of osteoarthritis and rheumatoid arthritis, particularly in patients at high risk of developing gastrointestinal events. Although data are encouraging, its place in acute pain states remains to be established.

Acute Disease↗

PubMed2000

Desirudin: a review of its use in the management of thrombotic disorders.

UNLABELLED: Desirudin, a recombinant hirudin used in the prevention and management of thromboembolic disease, is a thrombin inhibitor which binds directly and with high affinity to clot-bound and fluid phase thrombin. As a prophylaxis in patients undergoing hip replacement surgery, desirudin was significantly more effective in reducing the incidence of deep vein thrombosis (DVT) than either unfractionated or low molecular weight heparin. However, results in patients with acute coronary syndromes are less conclusive. A significant reduction with desirudin compared with heparin in the incidence of death or non-fatal (re)infarction at 24 hours in patients with acute myocardial infarction (MI) was reported in the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) IIb trial but not in the TIMI (Thrombolysis and Thrombin Inhibition in Myocardial Infarction) 9B trial. Despite the early reduction shown in GUSTO IIb, desirudin was not associated with an improved long term clinical benefit at 30 days compared with heparin. Similar results were seen in patients with unstable angina/non-Q-wave MI enrolled in the GUSTO IIb trial. In addition, desirudin and heparin showed similar efficacy in preventing restenosis 30 weeks after coronary angioplasty for unstable angina, despite desirudin being associated with a significant reduction in the rate of cardiac events within the first 96 hours. Desirudin is as well tolerated as heparin with a similar incidence of moderate and severe bleeding, intracranial haemorrhage or stroke reported when trialled in the prevention of DVT associated with hip replacement surgery or the treatment of acute coronary syndromes. However, in the GUSTO IIb trial a significantly higher incidence of transfusions was observed in patients with unstable angina/non-Q-wave MI. CONCLUSIONS: Desirudin is clearly more effective than heparin in the prevention of DVT in patients undergoing elective hip replacement, although cost factors may influence its ultimate place in therapy. In the treatment of acute coronary syndromes the role of desirudin is less certain; however, it may be useful for patients in whom heparin therapy is not a viable option.

Angina Pectoris↗

PubMed2000

Nicorandil. An updated review of its use in ischaemic heart disease with emphasis on its cardioprotective effects.

Nicorandil is a drug with both nitrate-like and ATP-sensitive potassium-channel (K+ ATP) activating properties. By virtue of this dual mechanism of action, the drug acts as a balanced coronary and peripheral vasodilator and reduces both preload and afterload. The K+ ATP channel has been shown to be involved in the phenomenon of myocardial preconditioning, and studies in animal models of ischaemia-reperfusion-induced myocardial stunning or infarction indicate that nicorandil has cardio-protective effects. Studies in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) have shown that the administration of nicorandil reduces ST-segment elevation during ischaemia. Nicorandil significantly improved the results of exercise tolerance tests versus baseline in patients with stable effort angina pectoris in early noncomparative trials. The drug also improved the results of exercise tolerance tests relative to placebo in early randomised, double-blind, placebo-controlled trials. In randomised, double-blind comparative studies in patients with angina pectoris, nicorandil has demonstrated equivalent efficacy, as measured by exercise tolerance testing, to isosorbide di- and mononitrate, metoprolol, propranolol, atenolol, diltiazem, amlodipine and nifedipine. The effects of nicorandil on various aspects of myocardial recovery from ischaemic damage caused by acute myocardial infarction have been investigated in the short term. Regional left ventricular (LV) wall motion, a marker of myocardial function, was significantly improved in nicorandil recipients relative to control. The main adverse event associated with nicorandil as treatment for angina pectoris is headache. This can be minimised by commencing nicorandil at a low dose in patients prone to headache. There have been infrequent case reports of mouth ulcers in patients receiving nicorandil; causality has not been conclusively established, but product prescribing information indicates that an alternative treatment should be considered if persistent aphthous or severe mouth ulceration occurs. Thus, nicorandil remains a useful background therapy for patients with angina pectoris. The drug has also demonstrated potential cardioprotective effects when used as part of an intervention strategy directly after acute myocardial infarction in high-risk patients. Further large scale longer term studies of nicorandil in this latter indication are awaited with interest.

Angina Pectoris↗