By O. Kalesch. Otterbein College. 2018.
The 7 ICSs currently available include: beclomethasone dipropionate generic dostinex 0.5 mg line women's health issues forum, budesonide dostinex 0.5 mg free shipping menstruation 3 days only, ciclesonide, flunisolide, fluticasone propionate, mometasone furoate, and triamcinolone acetonide. Table 2 lists the trade names, manufacturers, available formulations, and age indications for controller medications for persistent asthma. Although it is not approved for the treatment of asthma and thus is not ® included in Table 2, tiotropium (Spiriva ) was included in this report to determine if there is any published evidence for its use in people with asthma. Dulera (mometasone/formoterol), now approved for treatment of asthma in people >12 years, is not included in this report because it was approved after our cutoff date for the inclusion of new medications. Controller medications for asthma 10 of 369 Final Update 1 Report Drug Effectiveness Review Project 1, 5-10 Table 2. Long-term controller medication class, trade names, manufacturers, formulations, and indications Dosage Approved indication Medication class Generic name Trade name Manufacturer form/device Strength in US and Canada 40 mcg/puff a ® 50 mcg/puff Asthma (age ≥ 5) QVAR Ivax HFA Beclomethasone 80 mcg/puff a dipropionate 100 mcg/puff ®b 42 mcg/puff Asthma (age ≥ 5) Vanceril Schering MDI 84 mcg/puff Pulmicort 90 mcg/dose ®c AstraZeneca DPI Flexhaler 180 mcg/dose Asthma (age ≥ 6) 100 mcg/dose Pulmicort ®a AstraZeneca DPI 200 mcg/dose Turbuhaler 400 mcg/dose Budesonide 0. Long-term controller medication class, trade names, manufacturers, formulations, and indications Dosage Approved indication Medication class Generic name Trade name Manufacturer form/device Strength in US and Canada 100 mcg/dose 250 mcg/dose a 500 mcg/dose Asmanex 110 mcg/dose Asthma (age ≥ 4) Mometasone furoate ®c Schering DPI Twisthaler 220 mcg/dose Triamcinolone ®b MDI – with spacer Asthma (age ≥ 6) Azmacort Abbot 75 mcg/dose acetonide mouthpiece Leukotriene Tablets 10 mg ® Asthma (age ≥ 1) modifiers Montelukast Singulair Merck Chewable tablets 4 mg, 5 mg Granules 4 mg/packet Leukotriene Asthma (age ≥ 5 yrs in c receptor ® 10 mg Zafirlukast Accolate AstraZeneca Tablets US); (age ≥ 12 yrs in antagonists 20 mg Canada) ®c Tablets Zyflo 600 mg Asthma (age ≥ 12 yrs) 5-lipoxygenase Zileuton ®c Critical Therapeutics Extended release Zyflo CR 600 mg Inhibitor tablets ®c Not approved for Arformoterol Brovana Sunovion Inhalation solution 15 mcg/2ml asthma (COPD only) ®c Asthma (age ≥ 5 yrs) Foradil Aerolizer Schering DPI 12 mcg/capsule Novartis ®a Foradil Pharmaceuticals DPI 12 mcg/capsule Asthma (age > 6 yrs) Formoterol fumarate/ Canada Inc. Long-Acting Beta- Eformoterol 2 Agonists Oxeze 6 mcg/capsule Asthma (age ≥ 6 yrs) ®a AstraZeneca (Canada) DPI Turbuhaler 12 mcg/capsule ®f 6 mcg/puff Oxis Turbohaler Astra Pharmaceuticals DPI Asthma (age ≥ 6 yrs) 12 mcg/puff ® Serevent Diskus GlaxoSmithKline DPI 50 mcg/blister Asthma (age ≥ 4 yrs) Salmeterol xinafoate Serevent Asthma (age ≥ 4 yrs) ®a GlaxoSmithKline DPI 50 mcg/blister Diskhaler Genentech (US) Powder for 202. Long-term controller medication class, trade names, manufacturers, formulations, and indications Dosage Approved indication Medication class Generic name Trade name Manufacturer form/device Strength in US and Canada 100mcg/50mcg ® GlaxoSmith Asthma (age ≥ 4 yrs) Advair Diskus DPI 250mcg/50mcg Kline 500mcg/50mcg Fluticasone 45mcg/21mcg ®c GlaxoSmith Asthma (age ≥ 12 yrs) propionate/ Advair HFA HFA 115mcg/21mcg Kline Salmeterol xinafoate 230mcg/21mcg 50 mcg/25 mcg ®a GlaxoSmith Asthma (age ≥ 12 yrs) Advair HFA 125mcg/25mcg Combination Kline g 250mcg/25mcg products ®c 80mcg/4. Note: Unless otherwise noted, the products are available in both the US and Canada a This product is available in Canada only. Controller medications for asthma 13 of 369 Final Update 1 Report Drug Effectiveness Review Project Inhaled corticosteroids are delivered through a variety of devices including metered dose inhalers (MDIs), dry powder inhalers (DPIs), or nebulizers. In the past, MDI products contained chlorofluorocarbons (CFCs) which were found to be detrimental to the ozone and have now been banned from use. They were replaced with alternative administration devices including hydrofluoroalkane propellant (HFA) MDIs and dry powder inhalers. The ICSs often have different kinetic and side effect profiles with similar numerical doses depending on the delivery 1 device and the product. Since there are not enough head-to-head trials comparing all of the various ICSs, determining equivalency among products is sometimes difficult. Table 3 lists 1 comparative dosing of the available products based on the recently updated NAEPP guidelines. Long-Acting Beta-2 Agonists (LABAs) are agents used in combination with ICSs to obtain control in persistent asthma. The mechanism of action of these agents is through 1, 5 relaxation of airway smooth muscles to reverse bronchoconstriction. In contrast to short-acting beta-2 agonists, which are used for quick relief of acute symptoms due to their quick onset and short-duration of action, LABAs provide long-acting bronchodilation for 12 hours allowing for 1 twice daily administration. The NAEPP expert panel advocates the use of LABAs as the 1 preferred adjunct therapy with ICSs in individuals ≥ 12 years old for persistent asthma. In 1, 5 addition, LABAs are useful in the prevention of exercise-induced bronchospasm (EIB). These agents are not recommended nor approved for relief of acute asthma symptoms or for use as 1 monotherapy for persistent asthma. Currently there are two available LABAs: formoterol (formerly known as eformoterol in the UK) and salmeterol. Arformoterol is available in the US but is currently approved only for COPD (Table 2). The main clinical difference in the two 1 available agents is that formoterol has a quicker onset of action than salmeterol. The leukotriene modifiers are another class of controller medications used in the treatment of asthma and are comprised of two classes of medications: leukotriene receptor antagonists (montelukast and zafirlukast) and 5-lipoxygenase inhibitors (zileuton) (Table 2). Leukotrienes cause contraction of smooth muscles, mucous secretion, and inflammation 1, 5 contributing to asthma symptoms. The leukotriene receptor antagonists (LTRAs) bind to cell 1 receptors to prevent these actions from occurring. Montelukast is approved for children ≥ 1 year old and zafirlukast for children ≥ 5 years old in the United States and ≥ 12 years old in Canada.
Efficacy and Effectiveness What is the comparative efficacy and effectiveness of controller medications used to treat outpatients with persistent asthma? Inhaled Corticosteroids Summary of findings 22-24 We found 3 systematic reviews with meta-analyses and 48 head-to-head RCTs (47 25-71 31 order dostinex 0.25mg on-line breast cancer yoga mat, publications) (Table 7) cheap 0.5 mg dostinex amex menstruation hormone levels. Seven of the head-to-head RCTs included children < 12 (Table 8). Overall, efficacy studies provide moderate evidence that ICSs do not differ in their ability to control asthma symptoms, prevent exacerbations, and reduce the need for additional rescue medication at equipotent doses administered through comparable delivery devices (Appendix H, Table H-1). Relatively few studies reported exacerbations, healthcare utilization (hospitalizations, emergency visits), or quality of life outcomes. Long-term data beyond 12 weeks is lacking for most of the comparisons. In children, head-to-head trials support the conclusion that ICSs do not differ in their impact on health outcomes, but data was only available for 5 comparisons (3 systematic reviews and 7 RCTs): beclomethasone compared with budesonide, beclomethasone compared with fluticasone, budesonide compared with ciclesonide, budesonide compared with fluticasone, and ciclesonide compared with fluticasone. We conducted meta-analyses for comparisons within this section when sufficient data were available and a recent meta-analysis was not already published. There were often too few trials comparing equipotent ICS doses reporting similar outcomes measures to allow quantitative synthesis. Detailed Assessment Description of Studies Of the included studies (Table 7), one systematic review with meta-analysis and two RCTs compared beclomethasone with budesonide; two systematic reviews with meta-analyses and eleven RCTs compared beclomethasone with fluticasone; two RCTs compared beclomethasone with mometasone; two RCTs compared beclomethasone with triamcinolone; five RCTs compared budesonide with ciclesonide; one RCT compared budesonide with flunisolide; one meta-analysis and eight RCTs compared budesonide with fluticasone; two RCTs compared budesonide with mometasone; one RCT compared budesonide with triamcinolone; eight RCTs compared ciclesonide with fluticasone; one RCT compared flunisolide with fluticasone; three RCTs compared fluticasone with mometasone; three RCTs compared fluticasone with triamcinolone. Based on National Asthma Education and Prevention Program equipotent dose estimates (Table 3), 36 head-to-head RCTs (75%) included equipotent comparisons for some arms (seven 36, 38, 39, 43, 48, 52, of these had multiple arms, with both equipotent and non-equipotent comparisons) 59 43, 45, 46, 49, 51, 54, 55, 58, 60, 66 and 12 RCTs (25%) compared only non-equipotent doses. Of the 36 head-to-head trials that compared equivalent doses, 10 compared high dose to high dose, 16 compared medium dose to medium dose, 10 compared low dose to low dose. The most commonly used delivery devices were MDIs and DPIs; 19 studies (40%) compared MDI to Controller medications for asthma 28 of 369 Final Update 1 Report Drug Effectiveness Review Project MDI; 12 studies (25%) compared DPI to DPI; 15 studies (31%) compared MDI to DPI; one 36 study (2%) compared both MDI to MDI and MDI to DPI; one study (2%) compared both DPI 27 to DPI and MDI to DPI. Study Populations The 48 head-to-head RCTs included a total of 19,071 patients. Most studies were conducted in 31, 34, 44, 46, 62, 68, 69 adult populations. Seven studies were conducted primarily in pediatric populations. Ten studies (21%) were conducted in the United States, 15 (31%) in Europe, one in Canada, one in Japan, and 19 (40%) were other multinational combinations often including Europe, Canada, or the US. Asthma severity ranged from mild persistent to severe persistent: nine studies (19%) were conducted in patients with mild to moderate persistent asthma, nine (19%) in patients with mild to severe persistent asthma, 11 (23%) in patients with moderate persistent asthma, eight (17%) in patients with moderate to severe persistent asthma, and five (10%) in patients with severe persistent asthma. Six studies did not report the severity or it was unable to be determined. Smoking status was not reported for 15 studies (31%), including six studies in pediatric populations. Among the others, 16 studies (33%) excluded individuals with a recent or current history of smoking and 17 (35%) allowed participants to smoke. Among the studies that allowed and reported smoking status, 2% to 34% of participants were current smokers. Other asthma medications were often allowed if maintained at a constant dose; all trials allowed the use of a short-acting beta-agonist. Most trials enrolled patients who were currently being treated with ICS. Methodologic Quality The overall quality of the head-to-head trials included in our review was rated fair to good. The method of randomization and allocation concealment was rarely reported. Sponsorship Of the 48 head-to-head trials, 40 (83%) were funded by pharmaceutical companies; 4 trials (8%) did not report the source of funding but at least one author had a primary affiliation with a pharmaceutical company, and 4 studies (8%) did not report funding sources. Beclomethasone compared with budesonide 22 27, 28 One good systematic review and two fair head-to-head RCTs comparing beclomethasone (BDP) to budesonide (BUD) met our inclusion criteria. Twelve studies (50%) had treatment periods of between two and four weeks, 10 studies (42%) had treatment periods of between six and 12 weeks.
Microbicides dostinex 0.5mg with amex women's health clinic pacific fair, lubricants buy generic dostinex 0.25 mg on line menstruation taboos, diaphragms Microbicides are chemical agents, mostly of topical application, in the form of gels that kill or immobilize HIV and other diseases. Heterogenic mechanisms are being examined, among them are agents that inhibit docking to the target cell or antivi- ral agents. Microbicides will need to be inexpensive, easy to apply non-toxic, and effective against other STDs, as these increase the risk of HIV transmission. The CAPRISA trial (see below) led to a revival in this field of research. Classical microbicides: Up to now, there is no product that has delivered convinc- ing protective effects in clinical studies. Prevention of HIV infection 265 nonoxynol-9 (Van Damme 2002) or cellulose sulfate (van Damme 2008). PRO 2000, which initially seemed promising (Abdool Karim 2011), had no effect (McCormack 2010). Application of diaphragms and/or lubricants in addition to condoms had no protective effect, as one randomized study showed (Padian 2007). Antiretroviral microbicides: A breakthrough in research of microbicides was achieved in 2010 in the CAPRISA trial, a double-blind study in which 889 HIV-neg- ative women in South Africa used 1% tenofovir gel (Abdol Karim 2010). Compared to placebo, HIV incidence was reduced from 9. Transmission risk for women applying the gel regularly was reduced by 54% and safety and tolerabil- ity were pretty good (Sokal 2013). According to newer estimations (Williams 2011), over 20 years, the use of tenofovir gel in South Africa could avert up to 2 million new infections and 1 million AIDS deaths. Even with low rates of gel use, it is highly cost-effective and compares favorably with other control methods. This first success (“proof of concept”) has led to a focus on antiretroviral agents in the research of microbicides, such as tenofovir and even the more experimental NNRTIs dapivirine and MIV-150, as well as maraviroc and raltegravir (Review: Mertenskötter 2011). PrEP (Pre-exposure Prophylaxis) PrEP is an oral prophylactic antiretroviral treatment. It is a novel strategy to stem the spread of HIV with ARVs (mainly used: TDF or TDF+FTC) in at-risk HIV-negative populations such as MSM, female sex workers or injecting drug users. In contrast to PEP (post-exposure prophylaxis, see chapter on PEP), PrEP attempts to prevent trans- mission before the exposure occurs. The impetus for the development of PrEP was the successful use of prophylaxis for mother-to-infant transmission, as well as animal studies. However, early studies were regarded with skepticism. Pressured by activists and others, a study with Cambodian sex workers was interrupted in 2004 and others in Cameroon and Nigeria in 2005 (Cohen 2004, Sing 2005). Researchers were accused of not providing sufficient information to the participants and of discontinuing treat- ment once the study was over. A breakthrough was seen with PrEP at the end of 2010. In the iPrEx Study, 2499 MSM from six countries received either TDF+FTC or placebo. Apart from slightly more cases of nausea and weight loss in the active arm, there were no differences. Of note, only in 3/34 patients of those infected in the active group was tenofovir or FTC detected in plasma. Protective effects were also proven in the Partners PrEP trial, a large trial involving 5000 heterosexual couples in Kenyia and Uganda, and the TDF2 trial (Thigpen 2011, Baeten 2012+2014). In the Partners PrEP trial, the placebo arm was stopped in July 2011 and the subjects re-randomized to tenofovir or TDF+FTC. In the Bangkok Tenofovir Study, daily oral TDF reduced the risk of HIV infection in people who inject drugs. Among 2413 par- ticipants, 1204 on TDF and 1209 on placebo, 17 and 33 participants became infected (incidence of 0. These results, however, have not been without their setbacks. In the FEM-PrEP Trial on African woman, 35 infections in the placebo arm were observed compared to 33 with TDF+FTC.