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Pimecrolimus (SDZ ASM 981), an ascomycin derivative, is a nonsteroid, has anti-inflammatory activity, and has demonstrated efficacy in reducing symptoms of atopic dermatitis in adult and pediatric patients when applied topically. Compared with vehicle, topical pimecrolimus 1.0% cream was significantly more effective at reducing symptoms of atopic dermatitis, as measured by the Eczema Area and Severity Index (EASI), in infants aged 3 to 23 months, children aged 2 to 17 years, and adults. The median reductions from baseline in the total EASI score in adults after treatment with pimecrolimus 1.0% or corresponding vehicle twice daily for 3 weeks were 47 and 0%, respectively. In infants and children, treatment with pimecrolimus 1.0% twice daily for 6 weeks resulted in significant decreases in mean EASI scores compared with vehicle. The severity of pruritus was significantly reduced in patients of all age groups after topical treatment with pimecrolimus 1.0% cream. Compared with vehicle, the incidence of eczematous flares was also reduced by intermittent long-term use of topical pimecrolimus 1.0% in adults, children and infants. Sixty-one percent of children treated with pimecrolimus for 1 year completed the first 6 months of treatment without experiencing a flare, compared with 35% of patients who received vehicle. Furthermore, the use of topical corticosteroids for the treatment of uncontrolled flares in adults, children and infants was lower in the pimecrolimus groups than in the vehicle groups. Topical pimecrolimus 1.0% cream is well tolerated in atopic dermatitis patients of all age groups. There were no clinically relevant systemic adverse events reported from any of the studies in patients with atopic dermatitis. The most frequently reported adverse events pertained to application site reactions, such as burning and a feeling of warmth. In conclusion, topical pimecrolimus 1.0% cream has shown efficacy in the treatment of mild to moderate atopic dermatitis in infants, children and adults. Although tolerability data concerning infants and children have not yet been published in full, the drug appears to be well tolerated in all age groups, and there have been no reports of clinically relevant systemic adverse events. Furthermore, pimecrolimus has shown no potential for skin atrophy, a problem commonly associated with treatment with topical corticosteroids. Topical pimecrolimus 1.0% provides a promising and well tolerated treatment option in the management of infants, children and adults with mild to moderate atopic dermatitis. [ABSTRACT FROM AUTHOR]

Pimecrolimus (SDZ ASM 981), an ascomycin derivative, is a nonsteroid, has anti-inflammatory activity, and has demonstrated efficacy in reducing symptoms of atopic dermatitis in adult and paediatric patients when applied topically. Compared with vehicle, topical pimecrolimus 1.0% cream was significantly more effective at reducing symptoms of atopic dermatitis, as measured by the Eczema Area and Severity Index (EASI), in infants aged 3 to 23 months, children aged 2 to 17 years and adults. The median reductions from baseline in the total EASI score in adults after treatment with pimecrolimus 1.0% or corresponding vehicle twice daily for 3 weeks were 47 and 0%, respectively. In infants and children, treatment with pimecrolimus 1.0% twice daily for 6 weeks resulted in significant decreases in mean EASI scores compared with vehicle. The severity of pruritus was significantly reduced in patients of all age groups after topical treatment with pimecrolimus 1.0% cream. Compared with vehicle, the incidence of eczematous flares was also reduced by intermittent long-term use of topical pimecrolimus 1.0% in adults, children and infants. Sixty percent of children treated with pimecrolimus for 1 year completed the first 6 months of treatment without experiencing a flare, compared with 35% of patients who received vehicle. Furthermore, the use of topical corticosteroids for the treatment of uncontrolled flares in adults, children and infants was lower in the pimecrolimus groups than in the vehicle groups. Topical pimecrolimus 1.0% cream is well tolerated in atopic dermatitis patients of all age groups. There were no clinically relevant systemic adverse events reported from any of the studies in patients with atopic dermatitis. The most frequently reported adverse events pertained to application site reactions, such as burning and a feeling of warmth. In conclusion, topical pimecrolimus 1.0% cream has shown efficacy in the treatment of mild to moderate atopic dermatitis in infants, children and adults. Although tolerability data concerning infants and children have not yet been published in full, the drug appears to be well tolerated in all age groups, and there have been no reports of clinically relevant systemic adverse events. Furthermore, pimecrolimus 1.0% cream has shown no potential for skin atrophy, a problem commonly associated with treatment with topical corticosteroids. Pimecrolimus 1.0% cream provides a promising and well tolerated treatment option in the management of infants, children and adults with mild to moderate atopic dermatitis. [ABSTRACT FROM AUTHOR]

Lansoprazole is an inhibitor of gastric acid secretion and also exhibits antibacterial activity against Helicobacter pylori in vitro. Current therapy for peptic ulcer disease focuses on the eradication of H. pylori infection with maintenance therapy indicated in those patients who are not cured of H. pylori and those with ulcers resistant to healing. Lansoprazole 30mg combined with amoxicillin 1g, clarithromycin 250 or 500mg, or metronidazole 400mg twice daily was associated with eradication rates ranging from 71 to 94%, and ulcer healing rates were generally >80% in well designed studies. In addition, it was as effective as omeprazole- or rabeprazole-based regimens which included these antimicrobial agents. Maintenance therapy with lansoprazole 30 mg/day was significantly more effective than either placebo or ranitidine in preventing ulcer relapse. Importantly, preliminary data suggest that lansoprazole-based eradication therapy is effective in children and the elderly. In the short-term treatment of patients with gastro-oesophageal reflux disease (GORD), lansoprazole 15, 30 or 60 mg/day was significantly more effective than placebo, ranitidine 300 mg/day or cisapride 40 mg/day and similar in efficacy to pantoprazole 40 mg/day in terms of healing of oesophagitis. Lansoprazole 30 mg/day, omeprazole 20 mg/day and pantoprazole 40 mg/day all provided similar symptom relief in these patients. In patients with healed oesophagitis, 12-month maintenance therapy with lansoprazole 15 or 30 mg/day prevented recurrence and was similar to or more effective than omeprazole 10 or 20 mg/day. Available data in patients with NSAID-related disorders or acid-related dyspepsia suggest that lansoprazole is effective in these patients in terms of the prevention of NSAID-related gastrointestinal complications, ulcer healing and symptom relief. Meta-analytic data and postmarketing surveillance in >30 000 patients indicate that lansoprazole is well tolerated both as monotherapy and in combination with antimicrobial agents. After lansoprazole monotherapy commonly reported adverse events included dose-dependent diarrhoea, nausea/vomiting, headache and abdominal pain. After short-term treatment in patients with peptic ulcer, GORD, dyspepsia and gastritis the incidence of adverse events associated with lansoprazole was generally ≤5%. Similar adverse events were seen in long-term trials, although the incidence was generally higher (≤10%). When lansoprazole was administered in combination with amoxicillin, clarithromycin or metronidazole adverse events included diarrhoea, headache and taste disturbance. In conclusion, lansoprazole-based triple therapy is an effective treatment option for the eradication of H. pylori infection in patients with peptic ulcer disease. Preliminary data suggest it may have an important role in the management of this infection in children and the elderly. In the short-term management of GORD, lansoprazole monotherapy offers a more effective alternative to histamine H-receptor antagonists and initial data indicate that it is an effective short-term treatment option in children and adolescents. In adults lansoprazole maintenance therapy is also an established treatment option for the long-term management of this chronic disease. Lansoprazole has a role in the treatment and prevention of NSAID-related ulcers and the treatment of acid-related dyspepsia; however, further studies are needed to confirm its place in these indications. Lansoprazole has emerged as a useful and well tolerated treatment option in the management of acid-related disorders. [ABSTRACT FROM AUTHOR]

▴ Rasburicase (recombinant urate oxidase) is a uricolytic agent which has been developed for the prevention and treatment of chemotherapy-induced hyperuricaemia at a dosage of 0.15 or 0.2 mg/kg/day in patients with haematological malignancies. ▴ Significant reductions from baseline in plasma uric acid levels were seen in 3 noncomparative and 1 randomised comparative trial of rasburicase in patients with, or at high risk of, hyperuricaemia. ▴ A multicentre, nonblind, randomised trial found that patients who received intravenous rasburicase 0.2 mg/kg/day experienced an average 2.6-fold less exposure to uric acid than those who received oral allopurinol 10 mg/kg/day. ▴ There was no evidence of renal insufficiency in 3 noncomparative trials which monitored creatinine levels to assess renal function during chemotherapy and rasburicase treatment. ▴ Rasburicase was generally well tolerated in clinical trials, with skin rashes reported in ≈2% of patients. Bronchospasm, nausea and vomiting, and haemolysis occurred less frequently. In all cases the patients had also received chemotherapy prior to the adverse event. [ABSTRACT FROM AUTHOR]

Reviparin (reviparin sodium) is a low molecular weight heparin (LMWH) that catalyses the inactivation of factors Xa and IIa by binding to antithrombin, which ultimately leads to the inhibition of the clotting cascade. It is administered subcutaneously. Reviparin 7000 to 12 600 anti-XaIU/day was found to be as effective as intravenous unfractionated heparin in preventing the clinical recurrence of acute deep vein thrombosis (DVT) and/or pulmonary embolism in 1 large randomised, multicentre trial (COLUMBUS) and was significantly more effective than intravenous unfractionated heparin in the prevention of recurrent venous thromboembolism in another large randomised, multicentre trial (CORTES). Reviparin has also been compared with unfractionated heparin in children with established DVT. However, the trial was under-powered and no conclusion could be made regarding comparative efficacy. As prophylaxis, reviparin 1750 anti-XaIU once daily was as effective as unfractionated heparin 5000IU twice daily in 1311 patients undergoing abdominal surgery and, in a once daily dosage of 4200 anti-XaIU, was as effective as subcutaneous enoxaparin sodium 40 mg/day or acenocoumarol in patients undergoing hip replacement surgery. Reviparin 1750 anti-XaIU also effectively prevented DVT, compared with no treatment, in patients undergoing knee arthroscopy. It was also more effective than placebo in patients with brace immobilisation of the lower extremity. Reviparin was compared with ‘standard care’ in children with central venous lines. However, the trial was too small to make conclusions regarding its efficacy. Comparative data indicate that reviparin is at least as well tolerated as heparin and enoxaparin sodium. However, in a large (n = 1279) trial there were significantly fewer major bleeding episodes in patients receiving reviparin than in patients given the oral anticoagulant acenocoumarol. The most commonly reported adverse events in therapeutic trials have been intraoperative blood loss and postoperative bleeding complications such as wound haematoma, bruising and injection site haemorrhage. Reviparin was also well tolerated in 2 studies in children aged ≤16 years. Conclusion: Reviparin has shown efficacy in the treatment of established DVT and in the prevention of postoperative DVT after moderate and high risk surgery and was as effective as enoxaparin sodium or acenocoumarol in patients undergoing hip replacement surgery. As an effective and well tolerated antithrombotic agent, reviparin is likely to assume a significant role in the treatment and prevention of DVT, as it appears to have a preferable tolerability profile to subcutaneous heparin after moderate risk surgery and is at least as effective as intravenous heparin in the treatment of established DVT. [ABSTRACT FROM AUTHOR]

▴ Current evidence suggests that the addition of the long acting inhaled β-agonist formoterol to low or moderate doses of the inhaled corticosteroid budesonide is effective in improving lung function and reducing the incidence of asthma exacerbations. ▴ Concurrent use of budesonide with formoterol does not result in any untoward interaction that affects the pharmacodynamic or pharmacokinetic profiles of the individual drugs, or their adverse effect profiles. ▴ The administration of combined budesonide/ formoterol is effective in improving morning and evening peak expiratory flow rates in adults with persistent asthma. Control of asthma symptoms is also significantly improved. ▴ In children aged 4 to 17 years, combined budesonide/ formoterol is effective in increasing both morning and evening peak expiratory flow rates and significantly improving forced expiratory volume in 1 second (FEV). ▴ The most commonly encountered adverse effects in clinical trials with combination budesonide/ formoterol therapy have been respiratory infection, pharyngitis and coughing. No adverse effects on pulse rate, blood pressure or serum potassium have been reported with combination therapy. [ABSTRACT FROM AUTHOR]

The long-acting β-agonist salmeterol and the corticosteroid fluticasone propionate are available as a combination inhalation device for the treatment of persistent asthma. Well designed studies in adults, adolescents and children aged ≥4 years, demonstrate that combined salmeterol/fluticasone propionate 50/100, 50/250 and 50/500µg administered via a dry powder inhaler (DPI) is clinically equivalent to concurrent delivery of the same dosages of the 2 drugs via separate DPIs. In adults and adolescents, combined salmeterol/fluticasone 50/100 and 50/250µg twice daily produced rapid improvements in lung function that were consistently greater than those in patients receiving monotherapy twice daily salmeterol 50µg, fluticasone propionate 100 or 250µg or placebo in 2 well designed studies. Recipients of the combination had a significantly greater probability of completing 12 weeks of treatment than patients receiving monotherapy or placebo. The combination also produced significant improvements between baseline and end-point in all secondary outcome variables (morning and evening peak expiratory flow, daytime symptom scores, days and nights without asthma symptoms and requirements for as-needed β-agonists) and health-related quality of life (QOL). Combination therapy was superior to monotherapy with salmeterol and placebo for all outcomes in both studies, and was superior to fluticasone propionate 100µg for all but 1 outcome (nights without awakenings) in 1 study. Similar results were obtained in patients who had previously been using short acting β-agonists alone. Combined twice daily salmeterol/fluticasone propionate 50/100 and 50/250µg produced greater improvements in lung function than inhaled budesonide at higher dosages than fluticasone propionate in the combination. Combined salmeterol/fluticasone propionate 50/250µg produced similar improvements in lung function to concurrent budesonide 800µg plus formoterol 12µg when given twice daily for 12 weeks. In another 12-week trial, combined salmeterol/fluticasone propionate 50/100µg was more effective than oral montelukast 10 mg/day plus fluticasone propionate 100µg twice daily in patients with suboptimally controlled asthma. Salmeterol/fluticasone is more cost effective than monotherapy with fluticasone propionate or budesonide. The most frequent adverse events associated with salmeterol/fluticasone propionate are headache, throat irritation, hoarseness and candidiasis. Conclusion: Combined salmeterol/fluticasone propionate is as effective as the 2 drugs given concurrently via separate inhalers and significantly more effective than either drug given alone at the same nominal dosage. The combination is also significantly more effective than montelukast plus fluticasone propionate or monotherapy with inhaled budesonide. Furthermore, the combination is more cost effective than inhaled corticosteroid monotherapy. [ABSTRACT FROM AUTHOR]

Budesonide, a topically active corticosteroid, has a broad spectrum of clinically significant local anti-inflammatory effects in patients with inflammatory lung diseases including persistent asthma. In infants and young children with persistent asthma, day- and night-time symptom scores, and the number of days in which β-agonist bronchodilators were required, were significantly lower during randomised, double-blind treatment with budesonide inhalation suspension 0.5 to 2 mg/day than placebo in 3 multicentre trials. Significantly fewer children discontinued therapy with budesonide inhalation suspension than with placebo because of worsening asthma symptoms in a study that included children who were receiving inhaled corticosteroids at baseline. Recent evidence indicates that budesonide inhalation suspension is significantly more effective than nebulised sodium cromoglycate in improving control of asthma in young children with persistent asthma. At a dosage of 2 mg/day, budesonide inhalation suspension significantly reduced the number of asthma exacerbations and requirements for systemic corticosteroids in preschool children with severe persistent asthma. In children with acute asthma or wheezing, the preparation was as effective as, or more effective than oral prednisolone in improving symptoms. In children with croup, single 2 or 4mg dosages of budesonide inhalation suspension were significantly more effective than placebo and as effective as oral dexamethasone 0.6 mg/kg or nebulised L-epinephrine (adrenaline) 4mg in alleviating croup symptoms and preventing or reducing the duration of hospitalisation. Early initiation of therapy with budesonide inhalation suspension 1 mg/day appears to reduce the need for mechanical ventilation and decrease overall corticosteroid usage in preterm very low birthweight infants at risk for chronic lung disease. In adults with persistent asthma, budesonide inhalation suspension ≤8 mg/day has been compared with inhaled budesonide 1.6 mg/day and fluticasone propionate 2 mg/day administered by metered dose inhaler. Greater improvements in asthma control occurred in patients during treatment with budesonide inhalation suspension than with budesonide via metered dose inhaler, whereas fluticasone propionate produced greater increases in morning peak expiratory flow rates than nebulised budesonide. Several small studies suggest that the preparation has an oral corticosteroid-sparing effect in adults with persistent asthma and that it may be as effective as oral corticosteroids during acute exacerbations of asthma or chronic obstructive pulmonary disease. The frequency of adverse events was similar in children receiving budesonide inhalation suspension 0.25 to 2 mg/day or placebo in 12-week studies. During treatment with budesonide inhalation suspension 0.5 to 1 mg/day in 3 nonblind 52-week studies, growth velocity in children was generally unaffected; however, a small but statistically significant decrease in growth velocity was detected in children who were not using inhaled corticosteroids prior to the introduction of budesonide inhalation suspension. Hypothalamic-pituitary-adrenal axis function was not affected by short (12 weeks) or long (52 weeks) term treatment with nebulised budesonide. In conclusion, budesonide inhalation suspension is the most widely available nebulised corticosteroid, and in the US is the only inhaled corticosteroid indicated in children aged ≥1 year with persistent asthma. The preparation is suitable for use in infants, children and adults with persistent asthma and in infants and children with croup. [ABSTRACT FROM AUTHOR]

Montelukast is a cysteinyl leukotriene receptor antagonist used to treat persistent asthma in patients aged ≥6 years. The drug has a rapid onset of action. Improvements in lung function and reductions in as-needed β-agonist usage are apparent within 1 day of initiating montelukast treatment in adults and adolescents (aged ≥15 years treated with 10 mg/day) or children (aged 6 to 14 years treated with 5 mg/day) with persistent asthma as shown in clinical trials. In two 12-week, multicentre, randomised, double-blind studies in adults and adolescents aged ≥15 years with persistent asthma [forced expiratory volume in 1 second (FEV) = 50 to 85% predicted] there was significantly (p ≤ 0.05) greater improvement in FEV, symptom scores, peak expiratory flow (PEF), as-needed β-agonist use, peripheral eosinophil counts and health-related quality of life (QOL) in patients treated with montelukast 10 mg/day than in recipients of placebo. Improvements were significantly greater in patients treated with inhaled beclomethasone 400 µg/day than in recipients of montelukast 10 mg/day in 1 of these studies. Nonetheless, 42% of montelukast recipients experienced ≥11% improvement in FEV, the median improvement in this parameter in beclomethasone-treated patients. In an 8-week multicentre, randomised, double-blind, study in children aged 6 to 14 years with persistent asthma (FEV 50 to 85% predicted), montelukast 5 mg/day produced significantly greater improvements in FEV, clinic PEF, as-needed β-agonist use, peripheral eosinophil counts, asthma exacerbations and QOL scores than placebo. The combination of montelukast 10 mg/day plus inhaled beclomethasone 200µg twice daily provided significantly better asthma control than inhaled beclomethasone 200µg twice daily in adults with poorly controlled asthma (mean FEV = 72% predicted) despite 4 weeks treatment with inhaled beclomethasone. Patients receiving the combination experienced significant improvements in FEV and morning PEF, significant reductions in daytime symptom scores, as-needed β agonist usage and night-time awakenings with asthma, and had significantly lower peripheral blood eosinophil counts after 16 weeks in this multicentre, randomised, double-blind, placebo-controlled study. Among adults (FEV ≥70%) treated with montelukast 10 mg/day for 12 weeks, inhaled corticosteroid dosages were titrated downward by 47% (vs 30% in placebo recipients), 40% of patients were tapered off of inhaled corticosteroids (vs 29%), and significantly fewer patients (16 vs 30%) experienced failed corticosteroid rescues in a multicentre, randomised, double-blind study. During clinical studies, the frequency of adverse events in montelukast-treated adults, adolescents and children was similar to that in placebo recipients. In conclusion, montelukast is well tolerated and effective in adults and children aged ≥6 years with persistent asthma including those with exercise-induced bronchoconstriction and/or aspirin sensitivity. Furthermore, montelukast has glucocorticoid sparing properties. Hence, montelukast, as monotherapy in patients with mild persistent asthma, or as an adjunct to inhaled corticosteroids is useful across a broad spectrum of patients with persistent asthma. [ABSTRACT FROM AUTHOR]