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ABSTRACT: Bevacizumab (Avastin™) is a humanized monoclonal antibody directed against vascular endothelial growth factor. In patients with human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer, bevacizumab is indicated as first-line therapy in combination with paclitaxel, or in combination with capecitabine when treatment with other chemotherapy options, including taxanes or anthracyclines, is not considered appropriate. This article reviews the efficacy and tolerability of these combination therapies in the first-line treatment of patients with metastatic breast cancer, and summarizes the pharmacological properties of bevacizumab. In randomized, controlled, phase III trials in patients with predominantly HER2-negative metastatic or locally recurrent breast cancer, the addition of bevacizumab to paclitaxel or capecitabine significantly prolonged progression-free survival (PFS; investigator assessment) by a median of 5.9 and 2.9 months, respectively, relative to paclitaxel or capecitabine alone. It also significantly increased the objective response rate, but not overall survival. Independent reviews of data supported the results of the primary analyses of investigator-assessed PFS. However, as the efficacy of bevacizumab in combination with capecitabine appears to be less than that of other available options, it should be used only if treatment with other chemotherapy options are not considered appropriate. The addition of bevacizumab to paclitaxel had no significant adverse effects on health-related quality of life. Efficacy data from two routine clinical practice studies were generally consistent with those from the phase III trials. Bevacizumab had generally acceptable tolerability when administered in combination with paclitaxel or capecitabine as first-line therapy in these studies, and adverse events were consistent with the known tolerability profiles of the individual agents. The most common adverse events associated with bevacizumab combination therapy in phase III trials were sensory neuropathy and grade ≥3 hypertension, occurring more frequently with combination therapy than with chemotherapy alone. Potentially life-threatening events, such as venous thromboembolism, gastrointestinal perforation, arterial thromboembolism, haemorrhage and left ventricular dysfunction, occurred in ≤5% of patients receiving combination therapy in these trials. In conclusion, bevacizumab administered in combination with paclitaxel, or in combination with capecitabine if other chemotherapy regimens are not appropriate, may be considered as an option for the first-line treatment of patients with HER2-negative metastatic breast cancer.
Drugs 11/2011; 71(16):2213-29. · 4.23 Impact Factor
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ABSTRACT: Mirtazapine (Remeron, Zispin) is a noradrenergic and specific serotonergic antidepressant (NaSSA) that is approved in many counties for use in the treatment of major depression. Monotherapy with mirtazapine 15-45 mg/day leads to rapid and sustained improvements in depressive symptoms in patients with major depression, including the elderly. It is as effective as other antidepressants and may have a more rapid onset of action than selective serotonin reuptake inhibitors (SSRIs). Furthermore, it may also have a higher sustained remission rate than amitriptyline. Preliminary data suggest that mirtazapine may also be effective in the treatment of anxiety disorders (including post-traumatic stress disorder, panic disorder and social anxiety disorder), obsessive-compulsive disorder, undifferentiated somatoform disorder and, as add-on therapy, in schizophrenia, although large, well designed trials are needed to confirm these findings. Mirtazapine is generally well tolerated in patients with depression. In conclusion, mirtazapine is an effective antidepressant for the treatment of major depression and also has the potential to be of use in other psychiatric indications.
CNS Drugs 02/2009; 23(5):427-52. · 4.80 Impact Factor
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ABSTRACT: Atazanavir (Reyataz), a protease inhibitor (PI), is approved in many countries for use as a component of antiretroviral therapy (ART) regimens for the treatment of adult, and in some countries in paediatric, patients with HIV-1 infection. ART regimens containing ritonavir-boosted atazanavir improved virological and immunological markers in adult patients with HIV-1 infection, and had similar efficacy to regimens containing lopinavir/ritonavir in treatment-naive and treatment-experienced patients. In addition, unboosted atazanavir was noninferior to ritonavir-boosted atazanavir in treatment-naive patients. Atazanavir is administered once daily and has a low capsule burden. Atazanavir, whether unboosted or boosted, was generally well tolerated and appeared to be associated with less marked metabolic effects, including less alteration of lipid levels, than other PIs. These properties mean that boosted atazanavir, and unboosted atazanavir in patients unable to tolerate ritonavir, continues to have a role as a component of ART regimens in patients with HIV-1 infection.
Drugs 02/2009; 69(8):1107-40. · 4.23 Impact Factor
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ABSTRACT: Etoricoxib is a selective cyclo-oxygenase (COX)-2 inhibitor, approved in Europe for the symptomatic treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and acute gouty arthritis. Etoricoxib provided similar symptomatic relief to nonselective NSAIDs in patients with these conditions, and to celecoxib in patients with osteoarthritis. The drug was associated with fewer uncomplicated upper gastrointestinal (GI) adverse events than nonselective NSAIDs, and was noninferior to diclofenac in terms of the rate of thrombotic cardiovascular (CV) events. Etoricoxib may be considered as a treatment option for patients requiring NSAID therapy, particularly those at risk of upper GI events, after careful consideration of significant risk factors for CV events (including uncontrolled hypertension). As with all NSAIDs, the potential GI and CV risks of treatment with etoricoxib should be weighed against the potential benefits in individual patients, and it should be administered at the lowest effective dose for as short a duration as possible.
Drugs 02/2009; 69(11):1513-32. · 4.23 Impact Factor
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ABSTRACT: Adalimumab is a recombinant, human, IgG1 monoclonal antibody specific for tumor necrosis factor. The clinical efficacy and safety of adalimumab (40 mg administered subcutaneously every other week) in patients with moderate-to-severe chronic plaque psoriasis have been demonstrated in several randomized, double-blind clinical trials, including the pivotal trials REVEAL (n = 1212) and CHAMPION (n = 271). Based on these trials, adalimumab was significantly more effective than placebo and methotrexate at relieving the signs and symptoms of psoriasis after 16 weeks of treatment, as assessed by the percentage of patients achieving a 75% improvement from baseline in Psoriasis Area and Severity Index. Based on open-label extension studies of up to 2 years' duration, the efficacy of adalimumab was sustained over the long term. Of patients who had responded to 33 weeks of treatment with adalimumab in REVEAL, patients randomized to remain on adalimumab for an additional 19 weeks of treatment were significantly less likely to experience loss of an adequate response than patients who were transferred to placebo. Compared with placebo or methotrexate, adalimumab was associated with significantly greater improvements in dermatology-specific and general measures of health-related quality of life in patients with plaque psoriasis. Adalimumab was generally well tolerated in trials in patients with plaque psoriasis, and the adverse-event profile was similar to that associated with its use in rheumatoid arthritis.
American Journal of Clinical Dermatology 02/2009; 10(1):43-50. · 1.71 Impact Factor
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ABSTRACT: Liraglutide (Victoza) is an acylated analogue of glucagon-like peptide-1 (GLP-1) indicated for the treatment of type 2 diabetes mellitus. In phase III studies, once-daily subcutaneous liraglutide improved glycaemic control compared with placebo or active comparator in adult patients with type 2 diabetes, both as monotherapy and in combination with one or two oral antidiabetic drugs such as metformin, sulfonylureas or thiazolidinediones. Liraglutide provided significantly better glycaemic control than rosiglitazone or insulin glargine in combination trials. At appropriate dosages, liraglutide was noninferior to glimepiride with respect to glycaemic control in a combination trial, but provided significantly better control than glimepiride or glibenclamide in monotherapy trials. Liraglutide improved pancreatic beta-cell function, generally led to weight loss, and was associated with a low risk of hypoglycaemia. Liraglutide was generally well tolerated, with the most common adverse events being gastrointestinal events, such as nausea, which decreased over time. Thus, liraglutide is an effective treatment option for use in patients with type 2 diabetes mellitus.
Drugs 01/2009; 69(14):1985-2004. · 4.23 Impact Factor
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ABSTRACT: Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor VII or eptacog alfa) is structurally similar to human plasma-derived coagulation factor VIIa, but is manufactured using DNA biotechnology. Recombinant factor VIIa interacts with thrombin-activated platelets to produce a thrombin burst leading to accelerated fibrin clot formation localized to the site of vascular injury. It is approved in many countries for use as an intravenous hemostatic agent in patients with congenital hemophilia with inhibitors, and also for acquired hemophilia, factor VII deficiency, and Glanzmann thrombasthenia in some countries. Studies have shown it to be effective and generally well tolerated when used intravenously to treat bleeding episodes or provide hemostatic cover during surgery in patients with congenital hemophilia with inhibitors, acquired hemophilia, factor VII deficiency or Glanzmann thrombasthenia. Based on available data, its efficacy in terms of patient-assessed response may be similar to that of activated prothrombin complex concentrate (aPCC), but treatment with a single 270 microg/kg dose of recombinant factor VIIa might reduce the need for rescue therapy compared with aPCC. Recombinant factor VIIa is not immunogenic in patients with hemophilia, does not produce an anamnestic response in hemophilia patients with inhibitors, and has very low thrombogenicity. It is recommended in guidelines as the treatment of choice for bleeds in patients with hemophilia B with high-responding inhibitors and for patients with factor VII deficiency, and is also a first-line therapeutic option for high-responder hemophilia A patients with inhibitors and those with acquired hemophilia. Cost data from pharmacoeconomic analyses support its use in hemophilia patients with inhibitors. Thus, recombinant factor VIIa is a valuable treatment option for patients with these rare, but potentially serious, bleeding disorders.
BioDrugs 02/2008; 22(2):121-36. · 3.44 Impact Factor
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ABSTRACT: Sildenafil citrate (Revatio), an inhibitor of phosphodiesterase type 5 (PDE5), is approved for use in the US, Europe and other countries for the treatment of pulmonary arterial hypertension (PAH). Oral sildenafil 20 mg three times daily added to conventional background therapy was significantly more effective than placebo at increasing exercise capacity in patients with idiopathic PAH or PAH associated with connective tissue diseases or repaired congenital systemic-to-pulmonary shunts. Sildenafil was also associated with improvements in WHO functional class and haemodynamic parameters, and was generally well tolerated. Sildenafil provides benefits in terms of exercise capacity when added to epoprostenol; however, these findings come from a trial that did not use the approved dosage of sildenafil. In conclusion, sildenafil is an effective oral treatment option for patients with PAH.
Drugs 02/2008; 68(3):383-97. · 4.23 Impact Factor
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ABSTRACT: Irbesartan (Aprovel, Avapro, Irbetan, Karvea), an angiotensin II receptor type 1 antagonist, is approved in many countries worldwide for the treatment of hypertension. It is also approved in some regions for the treatment of nephropathy in patients with hypertension and type 2 diabetes mellitus. In adults with essential hypertension, irbesartan is effective at reducing blood pressure (BP) over a 24-hour period with once-daily administration. Irbesartan also slows the progression of renal disease in hypertensive patients with type 2 diabetes, with this effect partly independent of its BP-lowering effect. In addition, irbesartan was generally well tolerated in clinical trials. Thus, irbesartan is a useful treatment option for patients with hypertension, including those with type 2 diabetes and nephropathy.
Drugs 01/2008; 68(11):1543-69. · 4.23 Impact Factor
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ABSTRACT: Fenofibrate is a fibric acid derivative indicated for use in the treatment of primary hypercholesterolaemia, mixed dyslipidaemia and hypertriglyceridaemia in adults who have not responded to nonpharmacological measures. Its lipid-modifying effects are mediated by activation of peroxisome proliferator-activated receptor-alpha. Fenofibrate also has nonlipid (i.e. pleiotropic) effects (e.g. it reduces fibrinogen, C-reactive protein and uric acid levels and improves flow-mediated dilatation). Fenofibrate improves lipid levels (in particular triglyceride [TG] and high-density lipoprotein-cholesterol [HDL-C] levels) in patients with primary dyslipidaemia. Its lipid-lowering profile means that fenofibrate is particularly well suited for use in atherogenic dyslipidaemia (characterised by high TG levels, low HDL-C levels and small, dense low-density lipoprotein [LDL] particles), which is commonly seen in patients with the metabolic syndrome and type 2 diabetes mellitus. Indeed, fenofibrate improves the components of atherogenic dyslipidaemia in patients with these conditions, including a shift from small, dense LDL particles to larger, more buoyant LDL particles. Greater improvements in lipid levels are seen when fenofibrate is administered in combination with an HMG-CoA reductase inhibitor (statin) or in combination with ezetimibe, compared with monotherapy with these agents. In the DAIS study, fenofibrate significantly slowed the angiographic progression of focal coronary atherosclerosis in patients with type 2 diabetes. In terms of clinical outcomes, although no significant reduction in the risk of coronary events was seen with fenofibrate in the FIELD trial in patients with type 2 diabetes, treatment was associated with a significantly reduced risk of total cardiovascular disease (CVD) events, primarily through the prevention of non-fatal myocardial infarction and coronary revascularisation. Subgroup analyses revealed significant reductions in total CVD events and coronary heart disease events in patients with no previous CVD, suggesting a potential role for primary prevention with fenofibrate in patients with early type 2 diabetes. Improvements were also seen in microvascular outcomes with fenofibrate in the FIELD trial. Fenofibrate is generally well tolerated, both as monotherapy and when administered in combination with a statin. Combination therapy with fenofibrate plus a statin appears to be associated with a low risk of rhabdomyolysis; no cases of rhabdomyolysis were reported in patients receiving such therapy in the FIELD trial. Thus, fenofibrate is a valuable lipid-lowering agent, particularly in patients with atherogenic dyslipidaemia.
Drugs 02/2007; 67(1):121-53. · 4.23 Impact Factor
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ABSTRACT: Ibandronate (ibandronic acid) is a potent nitrogen-containing bisphosphonate that inhibits osteoclast-mediated bone resorption in women with postmenopausal osteoporosis. Recently, an intravenous (IV) formulation of ibandronate for intermittent injection, which circumvents the fasting and posture requirements associated with administration of oral bisphosphonates, was approved for use in this patient population. In initial placebo-controlled studies of 1 year's duration, IV ibandronate (< or =2mg once every 3 months) increased lumbar spine bone mineral density (BMD) and reduced levels of biochemical markers of bone turnover in a dose-dependent manner. Dosages < or =1mg every 3 months were found to be suboptimal in terms of fracture prevention in a 3-year trial. Subsequently, the large randomised, double-blind, noninferiority DIVA trial showed that, in terms of increasing lumbar spine BMD (primary endpoint), IV ibandronate 3mg once every 3 months and 2mg once every 2 months for 1 year were noninferior and also superior to oral ibandronate 2.5mg once daily, a regimen with proven antifracture efficacy. Median reductions from baseline in biochemical markers of bone turnover were similar for the IV and oral regimens. IV ibandronate was generally well tolerated in clinical trials. Treatment-related adverse events included musculoskeletal events and transient influenza-like symptoms, the latter mainly associated with the first dose.
Drugs 02/2006; 66(12):1593-601; discussion 1602-3. · 4.23 Impact Factor
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ABSTRACT: Nifedipine is a dihydropyridine calcium channel antagonist with predominantly vasodilatory activity. Modified-release formulations of nifedipine are effective antihypertensive and antianginal therapies and are generally well tolerated. Among the available formulations, those that produce a gradual increase in plasma nifedipine concentration, which is then sustained over a 24-hour period, are preferred, as they cause a gradual onset of vasodilatation and avoid baroreflex sympathetic activation (for example, nifedipine gastrointestinal therapeutic system [GITS] and a Japanese controlled-release formulation). Modified-release nifedipine had beneficial effects on a number of markers of vascular function, and nifedipine GITS reduced the need for coronary procedures in patients with coronary artery disease. In patients with hypertension, nifedipine GITS and nifedipine retard had beneficial effects on the overall incidence of major cardiovascular events, as did nifedipine retard in patients with concurrent hypertension and coronary artery disease.
Drugs 02/2006; 66(4):497-528. · 4.23 Impact Factor
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ABSTRACT: Everolimus (Certican) is an orally administered mammalian target of rapamycin inhibitor (proliferation signal inhibitor) derived from sirolimus (rapamycin), which is used as part of immunosuppressant therapy in kidney and heart transplantation. When evaluated as part of triple therapy with ciclosporin and corticosteroids, everolimus showed equivalent efficacy to mycophenolate mofetil after renal transplantation, and superiority to azathioprine in cardiac transplant recipients, in terms of reducing efficacy failure after transplantation. Everolimus potentiates ciclosporin-associated nephrotoxicity, and it is recommended that concentration-controlled everolimus is used with reduced-dosage ciclosporin in order to limit renal toxicity while retaining immunosuppressive efficacy. Ongoing trials with everolimus, such as the evaluation of ciclosporin-withdrawal strategies, should help clarify its optimal usage. The use of everolimus may be associated with reduced rates of cytomegalovirus (CMV) infection and of cardiac allograft vasculopathy. Available data suggest that everolimus may be cost-neutral for healthcare providers.
Drugs 02/2006; 66(4):547-70. · 4.23 Impact Factor
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Drugs & Aging 02/2006; 23(12):997-1001. · 2.67 Impact Factor
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ABSTRACT: A new formulation combining fixed doses of the nucleoside reverse transcriptase inhibitors emtricitabine (200mg) and tenofovir disoproxil fumarate (tenofovir DF; 300 mg) with the non-nucleoside reverse transcriptase inhibitor efavirenz (600 mg) represents the first once-daily, one-tablet antiretroviral regimen. Co-formulated efavirenz/emtricitabine/tenofovir DF demonstrated bioequivalence to concomitant administration of the individual agents in a pharmacokinetic trial in healthy volunteers (n = 48). Co-formulated efavirenz/emtricitabine/tenofovir DF has not been evaluated in clinical trials. However, a once-daily regimen of efavirenz, emtricitabine and tenofovir DF (administered as individual agents) was superior to once-daily efavirenz plus twice-daily co-formulated lamivudine/zidovudine in terms of virological suppression, immunological recovery and adverse events resulting in discontinuation of the study medications in a randomised, multicentre, noninferiority study in treatment-naive patients with HIV infection (n = 517). Both regimens are currently recommended as initial antiretroviral therapy. Preliminary data suggest that co-formulated efavirenz/emtricitabine/tenofovir DF, like the individual agents in combination with other antiretroviral drugs, is generally well tolerated. CNS adverse events, primarily headache and dizziness, were the most common treatment-emergent, drug-related adverse events in the pharmacokinetic study involving the co-formulation.
Drugs 02/2006; 66(11):1501-12; discussion 1513-4. · 4.23 Impact Factor
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ABSTRACT: Decitabine is a hypomethylating agent. Its action in DNA leads to the reactivation of tumour suppressor genes and the subsequent differentiation of cancer cells. In a randomised, phase III trial in patients (n = 170) with myelodysplastic syndromes (MDS), intravenous decitabine (45 mg/m(2)/day for 3 consecutive days every 6 weeks) combined with supportive care achieved a higher response rate (including eight complete and seven partial responses) than supportive care alone, which achieved no responses (17% vs 0%; p < 0.001). The median times to response and duration of response were 3.3 and 10.3 months in the phase III trial. In three phase II studies in patients (n = 29-87) with MDS treated with decitabine (40 or 50 mg/m(2)/day for 3 days every 5-6 weeks), the percentage of patients achieving a complete or partial response or an improvement ranged from 26% to 49%, and the median duration of response or improvement ranged from 4.9 to 8.3 months. The main adverse event associated with decitabine is myelosuppression.
Drugs 01/2006; 66(7):951-8. · 4.23 Impact Factor
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ABSTRACT: Metopimazine (Vogalene®) is a dopamine D2 receptor antagonist that has been used in France for many years for the prevention and treatment of nausea and vomiting. Guidelines suggest a role for dopamine receptor antagonists in the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy and as add-on therapy in refractory cases; recent data on sublingual metopimazine suggest it may have a role as an alternative to ondansetron in the prevention of delayed CINV in patients receiving moderately to highly emetogenic non-cisplatin-based chemotherapy. Trials comparing metopimazine with other drugs used in the prevention of delayed CINV would be of interest. Data also support the use of metopimazine as add-on therapy in the treatment of acute emesis in patients receiving moderately emetogenic chemotherapy who are refractory to initial therapy or unable to take corticosteroids, roles which are also suggested for dopamine receptor antagonists in guidelines, as is their potential use in rescue therapy for patients with breakthrough symptoms.
American Journal of Cancer 12/2005; 5(2):123-136.
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ABSTRACT: Lansoprazole is a proton pump inhibitor that inactivates the H(+)/K(+)-ATPase pump in parietal cells, thus inhibiting gastric acid secretion and increasing intragastric pH. In an open-label, uncontrolled trial in children aged 1-11 years with gastro-oesophageal reflux disease (GORD), treatment with lansoprazole 15 or 30 mg (depending on weight) once daily for 8-12 weeks improved symptoms compared with baseline in 76% of patients (47 of 62) based on patient diaries and healed erosive oesophagitis (confirmed endoscopically) in all 27 children who had it at baseline. In adolescents aged 12-17 years with GORD, 8 weeks' treatment with lansoprazole 15 mg (in 64 patients with non-erosive disease) or 30 mg (in 23 patients with erosive oesophagitis) once daily reduced the frequency and severity of symptoms by 63% and 69% compared with baseline, based on patient diaries. In this open-label, uncontrolled trial, 96% of evaluable patients with erosive disease (21 of 22) had mucosal healing by week 8, as confirmed by endoscopy; mucosal healing did not occur after an additional 4 weeks' treatment in one patient. Lansoprazole was generally well tolerated in children and adolescents, with the most common treatment-related adverse events being gastrointestinal events and headache.
Drugs 02/2005; 65(15):2129-35; discussion 2136-7. · 4.23 Impact Factor
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ABSTRACT: 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.
Drugs 02/2005; 65(13):1825-49. · 4.23 Impact Factor
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ABSTRACT: Gatifloxacin (Tequin) is an 8-methoxy fluoroquinolone approved in the US for use in the treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), acute sinusitis, uncomplicated and complicated urinary tract infections (UTIs), pyelonephritis, gonorrhoea and uncomplicated skin and skin structure infections. Gatifloxacin has a broad spectrum of antibacterial activity in vitro and good clinical and bacteriological efficacy in patients with indicated infections following once-daily administration by the intravenous or oral routes. It is generally well tolerated; the most common adverse events are associated with the gastrointestinal tract and CNS. Recent approvals for the use of gatifloxacin in the treatment of CAP due to multidrug-resistant Streptococcus pneumoniae (MDRSP) and in uncomplicated skin and skin structure infections extend the role of this drug in the treatment of bacterial infections in the US.
Drugs 02/2005; 65(5):695-724. · 4.23 Impact Factor
