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COX-2 Selective NSAIDs (cox-2 + selective_nsaid)
Selected AbstractsKetorolac in the Era of Cyclo-Oxygenase-2 Selective Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Efficacy, Side Effects, and Regulatory IssuesPAIN MEDICINE, Issue 4 2001Alex Macario MD Objective., The recent introduction of oral COX-2 selective NSAIDs with potential for perioperative use, and the ongoing development of intravenous formulations, stimulated a systemic review of efficacy, side effects, and regulatory issues related to ketorolac for management of postoperative analgesia. Design.,To examine the opioid dose sparing effect of ketorolac, we compiled published, randomized controlled trials of ketorolac versus placebo, with opioids given for breakthrough pain, published in English-language journals from 1986,2001. Odds ratios were computed to assess whether the use of ketorolac reduced the incidence of opioid side effects or improved the quality of analgesia. Results., Depending on the type of surgery, ketorolac reduced opioid dose by a mean of 36% (range 0% to 73%). Seventy percent of patients in control groups experienced moderate-severe pain 1 hour postoperatively, while 36% of the control patients had moderate to severe pain 24 hours postoperatively. Analgesia was improved in patients receiving ketorolac in combination with opioids. However, we did not find a concomitant reduction in opioid side effects (e.g., nausea, vomiting). This may be due to studies having inadequate (to small) sample sizes to detect differences in the incidence of opioid related side effects. The risk for adverse events with ketorolac increases with high doses, with prolonged therapy (>5 days), or invulnerable patients (e.g. the elderly). The incidence of serious adverse events has declined since dosage guidelines were revised. Conclusions., Ketorolac should be administered at the lowest dose necessary. Analgesics that provide effective analgesia with minimal adverse effects are needed. [source] Onset of acute myocardial infarction after use of non-steroidal anti-inflammatory drugs,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2008Tarek A. Hammad MD Abstract Purpose To examine the association between cyclooxygenase-2 (COX-2) selective and traditional nonsteroidal anti-inflammatory drugs (NSAIDs) and incident acute myocardial infarction (AMI), and to address unanswered questions regarding the contour of risk over time. Methods A cohort of new NSAID users aged 40,84 years was followed for the occurrence of first AMI. Data were collected within the General Practice Research Database (GPRD) from 1 January 1997 to 31 December 2004. Results The study population included 1185 AMI events (889 probable and 296 possible) from a cohort of 283,136 patients. After adjustment for demographic and cardiovascular risk factors, the hazard ratio (HR) for AMI was significantly increased for both coxib (2.11, 95% confidence interval (CI) 1.04,4.26) and non-coxib (2.24, 95%CI 1.13,4.42) COX-2 selective NSAIDs when compared to remote exposure to NSAIDs, but was not increased for traditional NSAIDs. Stratifying exposure into the first month of use versus use beyond 1 month, the risk of AMI was increased during the first month of COX-2 selective NSAIDs use, but not later (3.43, 95%CI 1.66,7.07 and 1.88, 95%CI 0.82,4.31, respectively p -value for interaction,=,0.6). Conclusions The results suggest that the use of coxib and non-coxib COX-2 selective NSAIDs was associated with an elevated risk of AMI within the first month of exposure. Recent past exposure to NSAID was not associated with a similar increase in risk. Copyright © 2008 John Wiley & Sons, Ltd. [source] Latest news and product developmentsPRESCRIBER, Issue 13-14 2008Article first published online: 29 JUL 200 NSAIDs stroke risk NSAIDs have been linked with an increased risk of stroke in an epidemiological study from The Netherlands (Arch Intern Med 2008;168: 1219-24). Nine years' follow-up of 7636 older persons (mean age 70) identified 807 strokes. The risk of stroke was significantly increased for current use of nonselective NSAIDs (hazard ratio 1.72 for all strokes) and COX-2 selective NSAIDs (HR 2.75 for all strokes; HR 4.54 for ischaemic stroke). Increased risk was found for several individual NSAIDs but was statistically significant only for naproxen (HR 2.63) and the withdrawn rofecoxib (HR 3.38). HPV vaccine chosen The DoH has chosen GlaxoSmithKline's Cervarix HPV vaccine for the national immunisation campaign beginning in September. Cervarix is a bivalent vaccine conferring immunity against HPV16 and 18, which account for 70 per cent of cervical cancers worldwide. Its competitor, Gardasil, is a quadrivalent vaccine additionally protecting against HPV6 and 11, which cause 90 per cent of genital warts. The procurement process assessed the vaccines against ,a wide range of criteria such as their scientific qualities and cost effectiveness'. The DoH has not revealed what it will pay for Cervarix. Melatonin for insomnia Lundbeck has introduced melatonin (Circadin) as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 or over. The dose is 2mg once daily two hours before bed-time and after food for three weeks. A course costs £10.77. Fesoterodine launched Pfizer has introduced feso-terodine (Toviaz), a prodrug for tolterodine (Detrusitol), for the treatment of symptoms of overactive bladder. Treatment is initiated at a dose of 4mg per day and increased to 8mg per day according to response. The full therapeutic effect may not occur until after two to eight weeks; treatment should be re-evaluated after eight weeks. A month's treatment at either dose costs £29.03, the same as sustained-release tolterodine (Detrusitol XL). Intensive glycaemic control for T2D? Two large trials of intensive glycaemic control in patients with type 2 diabetes have conflicting implications for clinical practice. The ACCORD study (N Engl J Med 2008;358:2545-9) found that treating patients at high CVD risk to a target HbA1c of <6.0 per cent was associated with a 22 per cent increased risk of death and no reduction in macrovascular end-points compared with a target of 7.0-7.9 per cent. The ADVANCE study compared treating to a standard (HbA1c 7.3 per cent) or low (HBA1c 6.5 per cent) target. More intensive glycaemic control significantly reduced microvascular end-points, primarily due to a reduction in nephropathy. There was no difference in the risk of retinopathy or macrovascular end-points. Nicorandil as ulcer cause The potassium-channel activator nicorandil (Ikorel) may be associated with gastro-intestinal ulceration but is frequently overlooked as a possible cause, warns the MHRA in its latest Drug Safety Update (2008;1:Issue 11). Ulceration may affect any portion of the gastro-intestinal tract from the mouth to the perianal area, and it is frequently severe and may cause perforation. Ulcers due to nicorandil are refractory to treatment and only resolve on withdrawal of the drug. Withdrawal should be carried out under the supervision of a cardiologist. , This issue of Drug Safety Update also includes an overview of safety issues with natalizumab (Tysabri) for multiple sclerosis. Atypical antipsychotics diabetes risk ,small' The excess risk of diabetes due to treatment with an atypical antipsychotic is small compared with older anti-psychotics, say UK researchers (Br J Psychiatry 2008;192:406-11). Their meta-analysis of 11 studies found that, compared with the use of first-generation antipsychotics in patients with schizophrenia, the over-all increased risk of diabetes with atypicals was 32 per cent. Risperidone was associated with lowest excess risk (16 per cent), followed by quetiapine (Seroquel) and olanzapine (Zyprexa; 28 per cent) then clozapine (39 per cent). Most studies had method-ological limitations. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 10 2008Article first published online: 3 JUN 200 Glitazones more than double fracture risk An analysis of the UK General Practice Research Database has found that both glitazones increase the risk of fracture more than two-fold (Arch Intern Med 2008;168:820-5). Compared with nonusers, the odds ratio for fracture (mostly hip and wrist) was 2.59 for pioglitazone and 2.38 for rosiglitazone. The risk increased with dose but was unrelated to age and sex. Reduce antipsychotics in dementia patients Antipsychotics should be prescribed for patients with dementia only as a last resort at times of severe distress or critical need, the All-Party Parliamentary Group on Dementia has concluded. Its inquiry (available at www.alzheimers.org.uk) found that antipsychotics are being prescribed for patients with mild behavioural symptoms and for prolonged periods despite the limited benefits they offer and the risk of serious adverse effects such as stroke. Contributory factors include lack of training for staff, inadequate leadership and exclusion of family and friends from decisions about treatment. High-dose atorvastatin in chronic kidney disease High-dose atorvastatin (Lipitor) reduces cardiovascular events in patients with chronic kidney disease (CKD) more than a low dose , despite similar reductions in LDL-C (J Am Coll Cardiol 2008;51:1448-54). A post hoc subgroup analysis of the Treating-to-New-Targets study involving 10 001 patients with CHD, with or without CKD, found that atorvastatin 10 and 80mg per day reduced LDLC and triglycerides to similar levels; there was no change in HDL-C. After a median follow-up of five years, the incidence of cardiovascular events in patients with CKD was 9.3 per cent at 80mg per day and 13.4 per cent at 10mg per day (number needed to treat to prevent one event, NNT, 24). In patients with no CKD, the corresponding figures were 7.9 vs 9.2 per cent (NNT 74). There was no difference in all-cause mortality; adverse events were more frequent at the higher dose. COX-2 NSAIDs not more cost-effective An economic analysis of COX-2 selective NSAIDs has concluded that they are not more cost effective than older agents plus a proton pump inhibitor (PPI) in the treatment of osteoarthritis and rheumatoid arthritis (Health Technology Assessment 2008;12:No. 11). The analysis concluded that selective and nonselective NSAIDs were similarly effective but selective agents were associated with a lower risk of upper GI events and a higher risk of cardiovascular events. However, the available evidence includes only low numbers of events and further studies are needed. Compared with ibuprofen or diclofenac plus a PPI, the COX-2 selective NSAIDs look ,generally unattractive from a cost effectiveness point of view', even in high-risk patients with a history of peptic ulcer. There were insufficient data to allow a reliable comparison within the COX-2s. Naftidrofuryl helps intermittent claudication Naftidrofuryl increases pain-free walking distance (PFWD) in patients with intermittent claudication, a new Cochrane review has shown (Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD001368. DOI: 10.1002/ 14651858.CD001368.pub3; also see page 49 in this issue). The meta-analysis of six trials involving a total of 1083 patients found that, compared with placebo, naftidrofuryl increased PFWD by over a third with a proportion successfully treated of 20 per cent (NNT 4.5). Coversyl Arginine To clarify any confusion following our recent news item (Perindopril brand switch, 19 April issue, page 12), Servier has asked us to reiterate that the new formulations Coversyl Arginine 2.5, 5 and 10mg are equivalent to 2, 4 and 8mg of the discontinued Coversyl formulation. Coversyl Arginine contains perindopril arginine, a salt that offers greater stability and a longer shelf-life. Prescriptions for the Coversyl brand of perindopril must in future be written as Coversyl Arginine in its revised strengths. Coversyl Plus has also been replaced by Coversyl Arginine Plus and the same revised dosages apply. Generic formulations of perindopril remain unaffected. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 4 2008Article first published online: 20 MAR 200 Suicide warning for all antidepressants All antidepressants are to include a warning of the risk of suicide in their product information, the MHRA says. The requirement formerly applied only to SSRIs but, following a US review of safety data, the Agency says the risk is similar for all classes of antidepressants. Patients at increased risk include young people with psychiatric morbidity and those with a history of suicidal ideation. Patients are at increased risk of suicide until remission occurs, and clinical experience shows that the risk is increased during the early stages of recovery. Confusion over type 2 diabetes management Contradictory findings have been reported from two studies of intensive management of type 2 diabetes. The STENO-2 study (N Engl J Med 2008;358:580-91) found that tight control of blood glucose, blood pressure and lipids plus low-dose aspirin in 160 patients with type 2 diabetes and microalbuminuria significantly reduced all-cause mortality, cardiovascular events, cardiovascular death and microvascular complications by 40-60 per cent. The US National Heart, Blood and Lung Institute has announced the end of the intensive treatment arm of the ACCORD study (unpublished). This study was comparing intensive lowering of blood glucose below currently recommended levels (target HbA1C <6 per cent) with conventional management in adults with type 2 diabetes at especially high risk for heart attack and stroke. Although mortality was reduced in both arms compared with other populations, intensive treatment was associated with increased mortality equivalent to three deaths per 1000 patients per year over four years. Another antibiotics campaign The Government has launched another campaign to promote public awareness that antibiotics are not appropriate for viral infections causing coughs, colds and sore throats. Get Well Soon , Without Antibiotics is supported by a national advertising campaign and leaflets and posters encouraging the public to ask advice rather than demand a prescription. Details are available at www.dh.gov.uk. Episenta: once-daily sodium valproate Following a launch to specialists last year, a new once-daily modified-release formulation of sodium valproate is being promoted more widely to GPs. Episenta is licensed for the treatment of all forms of epilepsy and is formulated as modified-release capsules of 150mg and 300mg and sachets of modified-release granules of 500mg and 1000mg. The dose may be administered once or twice daily. Patients may be switched from enteric-coated tablets of valproate to the same dose given as Episenta. Episenta costs £5.70 or £10.90 for 100 × 150mg or 300mg capsules, and £18 or £35.50 for 100 × 500mg or 1000mg sachets. Latest NICE agenda The Department of Health has referred a new batch of topics for appraisal by NICE. Six of seven technology appraisals are for cancer drugs; the last is for dabigatran etexilate for venous thromboembolism. There will be four new clinical guidelines: autism spectrum disorders, hypertension in pregnancy, bed-wetting in children and severe mental illness with substance abuse. Two combined public health and clinical guidelines will address alcohol misuse. Varenicline vs NRT Varenicline (Champix) offers slightly greater smoking cessation rates than nicotine replacement therapy (NRT) in the long term and better symptom improvement, an international study has shown (Thorax 2008; published online:10.1136/ thx.2007.090647). A total of 746 smokers were randomised to treatment with varenicline 1mg twice daily for 12 weeks or transdermal NRT (21mg reducing to 7mg per day) for 10 weeks. Continuous abstinence rates for the last four weeks of treatment were 56 vs 43 per cent. The corresponding rates for one year were 26 and 20 per cent. Varenicline was associated with greater reductions in cravings, withdrawal symptoms and smoking satisfaction, but more nausea (37 vs 10 per cent). Adverse reactions class effect of statins The MHRA has identified several adverse effects that it says are class effects of the statins (Drug Safety Update 2008;1:Issue 7). Following a review of clinical trials and spontaneous reports, it is now apparent that any statin may be associated with sleep disturbance, depression, memory loss and sexual dysfunction; interstitial lung disease has been reported rarely. Product information is being updated to include the new information. Depression, including suicidal ideation, has also been associated with varenicline (Champix), the MHRA says; affected patients should stop treatment immediately. The combination of transdermal nicotine replacement therapy (NRT) and varenicline appears to be associated with a higher incidence of nausea, headache, vomiting, dizziness, dyspepsia and fatigue than NRT alone. The MHRA has also announced that, following the suspension of marketing authorisation for carisoprodol (Carisoma), it is considering a phased withdrawal of the closely-related meprobamate , the main active metabolite of carisoprodol. Following a successful pilot study, the public are being encouraged to report adverse reactions on yellow cards; the MHRA notes that health professionals provide more complete reports but patients include more information about quality of life. The scheme will be promoted via community pharmacies throughout the UK from February 2008. Cochrane: evidence on back pain interventions The latest release of Cochrane reviews includes three meta-analyses assessing interventions for back pain. Overall, NSAIDs were found to be effective as short-term treatment for acute or chronic back pain but the effect size was small. They were comparable with paracetamol but associated with more adverse effects; COX-2 selective NSAIDs were similarly effective, with slightly fewer adverse effects. There was no evidence that antidepressants reduced back pain but intensive individual patient education (lasting 2.5 hours) was effective for acute and subacute back pain and comparable with manipulation and physiotherapy; its effects on chronic pain were unclear. Copyright © 2008 Wiley Interface Ltd [source] | ||||||||||