Tiotropium/Olodaterol: A Review in COPD

This article reviews the efficacy of a new inhaler for COPD (chronic obstructive pulmonary disease) that was approved by the FDA in May 2015 and has since been out on the market. This new inhaler is named Stiolto Respimat (tiotropium/olodaterol), and it was developed by the company Boehringer Ingelheim.

For a quick review, COPD is an overarching term that describes a group of diseases that affect the lungs. People with COPD have difficulty breathing and receiving necessary airflow through their lungs. Patients who receive treatment for COPD typically use long-acting inhalers that are used to improve their chronic state of limited breathing along with “rescue” inhalers that are used to treat acute asthma attacks as needed. Some examples of common, long-acting inhalers already on the market are Advair and Symbicort, and some examples of commonly used “rescue” inhalers already on the market are albuterol inhalers sold under the brand names of Ventolin, ProAir, and Proventil.

Stiolto Respimat is a long-acting inhaler that is a combination of 2 drugs used to treat respiratory problems, which are tiotropium and olodaterol. Tiotropium (bromide) is a long-acting antimuscarinic agent (LAMA), so it works by blocking muscarinic acetylcholine receptors to dilate the bronchioles. Olodaterol is the new drug in this inhaler that has allowed Boehringer Ingelheim to patent and manufacture Stiolto Respimat. Olodaterol is an ultra long-acting beta 2-adrenoreceptor agonist (LABA) that works on beta 2 receptors in the lungs to dilate the bronchioles.

 

This article reviewed clinical trial data and compared Stiolto Respimat to the commonly used inhaler, Advair (fluticasone/salmeterol), that is also a long-acting inhaler for the treatment of COPD. The article determined that Stiolto Respimat seems to be a relatively safe inhaler that has minimal side effects when used correctly and does not have any adverse cardiovascular side effects. It was found to work more efficiently than Advair over a 24 hour period for bronchodilation and lung functioning. The article determined that the combination of tiotropium and olodaterol was more effective when used in combination compared to using the two drug components monotherapeutically. This inhaler can be used once daily, which is convenient in comparison to other long-acting inhalers that must be administered twice daily. Stiolto Respimat was also found to increase exercise capacity in COPD patients and the amount of gas they can inhale into their lungs.

In conclusion, this article has shed a positive light on Stiolto Respimat as it makes it way into the medical world through the new few years. It seems to be a great addition to current therapies for COPD, and could be a good alternative to COPD patients who are allergic to drugs in some of the other inhalers. I find it interesting how drug developers have combined drugs with different mechanism of actions in inhalers to maximize the efficacy of inhaled therapies. These newer combination therapies have been very popular in the treatment of COPD since they came out a few years ago (I’m thinking of inhalers such as Advair, Symbicort, and Ventolin). I am thinking that I want to become a community pharmacist, so I am interested in learning more about the treatment options for COPD and all of the side effects that come with these treatments.

My question posed to colleagues: How are the mechanism of action between Advair (fluticasone/salmeterol) and Stiolto Respimat (tiotropium/olodaterol) different?

Dhillon, S. Tiotropium/olodaterol: A review in COPD. Drugs. 2016;76:135-146.

 

New Drugs Used to Treat Hepatitis C

A little over two years ago two antiviral drugs were developed. Sofosbuvir and ledipasvir were combined in a formulation for an antiviral medication that is indicated in treating hepatitis C virus (HCV) genotype 1. HCV is known to exist in 6 major genotypes numbered as such. Last fall the drug was approved for treatment of HCV genotypes 4, 5, and 61.

Currently the third drug from this class is to enter the market. Daclatasvir dihydrochloride is a drug in this new class of antiviral medications which work by inhibiting Hepatitis C virus (HCV) NS5A, a protein that is required for viral replication. Only the third drug to be marketed in this class, daclatasvir is indicated alongside sofosbuvir to treat patients with chronic HCV genotype 3. This is the first proposed drug regimen used to treat HCV genotype 3 that does not contain another antiviral drug called ribavirin, a guanosine analog1.

The daclatasvir/sofosbuvir combination has shown to be effective in treating the virus as it exhibited a 98% sustained virologic response (SVR) in a 24 week trial in which the drug was administered to patients who had not been treated for the condition before. The drug has reduced effects in patients with cirrhosis of the liver (which is a common hindrance for other HCV drugs) as they showed a 58% SVR. Patients who had undergone treatment in the past had slightly different outcomes (92% in those without cirrhosis and 69% in those who did)1 Previous drug regimen had shown to have SVR rates ranging from 65-80% in patients without cirrhosis2. Thus, the effectiveness of the NS5A inhibitors may be the future of first line drug therapy in treating HCV.

References:

  1. Hussar, Daniel A., and Joellen Friedman. “Ceftazidime Pentahydrate/avibactam Sodium, Isavuconazonium Sulfate, and Daclatasvir Dihydrochloride.” J Am Pharm Assoc. 56.1 (2016): 100-03. Web.

    Journ Am Pharm Assoc. 2016; 56(1): 100-103

  2. Spach D. Treatment of HCV genoype 3. Hepatitis C Online. University of Washington, 27 Jan. 2016. Web. 9 Feb. 2016.

New Drug to Prevent Heart Failure

In the event of a myocardial infarction or another related episode concerning one’s cardiovascular health, it is common for an angiotensin converting enzyme inhibitor to be prescribed in addition to a beta adrenergic blocker, and a diuretic or aldosterone antagonist. In place of an ACE inhibitor an angiotensin II receptor blocker (ARB) may be prescribed. However, a new class of drug is being studied that may become an additional team player in the fight against cardiovascular disease.

Sacubitril is a prodrug which is converted to LBQ657 by esterases in the body. This metabolite is a neprilysin inhibitor. Neprilysin is an endopeptidase that can degrade peptides that are responsible for regulating actions in the blood vessels. This can lead to vasoconstriction and increased sodium retention. Thus, sacubitril would work to reduce vasoconstriction and sodium retention.

So far the formulation of this drug has been only in a form coupled with valsartan; it has not been administered as the single drug, sacubitril. It was administered to 8,400 patients with symptomatic heart failure and a left ventricle ejection of 40% or lower. The patients involved had been treated with an ACE inhibitor and a beta adrenergic blocker for at least 4 weeks. Many of the patients were also taking a diuretic. The rate of cardiovascular deaths for those taking sacubitril was 13.3% which was considered significantly lower than that of those taking the ACE inhibitor, enalapril, which was 16.5%.

Thus there is reason to believe that sacubitril, and other drugs from this class of neprilysin inhibitors, may account for a new model of first line drug therapy in the treatment of cardiovascular disease.

Reference

Hussar D, Abdelsayed M. Sacubitril/valsartan, ivabradine hydrochloride, alirocumab, and evolocumab. Journ Am Pharm Assoc. 2015; 55(6): 674-78.

J Am Pharm Assoc. 2016; 55(6): 674-678