For DNA replication and cellular division to occur, topoisomerase I is required. It is an enzyme that creates and helps repair strands of DNA. In cancer cells, it has been shown that there is an increased activity of topoisomerases. This is why topoisomerase inhibitor medications have been used in many cancer therapies. Mainly topoisomerase I is responsible for relaxing supercoiled double strands of DNA, which then allows for replication to occur. The most common topoisomerase I inhibitor medications are irinotecan and topotecan.

In 1996, irinotecan and topotecan were approved for use in the United States. Camptothecin is another topoisomerase I inhibitor, and irinotecan and topotecan were originally derived from it. Camptothecin was isolated from the Camptotheca acuminata, which is a Chinese tree. Since its discovery and use, there have been fewer toxic analogues made.

Depending on the drug, indications can vary. Commonly, they are used in advanced colorectal, ovarian, and small-cell lung cancer. There are multiple regimens, and dose administration is dependent on the specific regimen cycle it is being used for. Irinotecan has been used with other therapies, such as 5-fluorouracil (5-FU) and leucovorin (LV). Hepatic adjustments may be seen with irinotecan because it is metabolized by the liver. Compared to topotecan, it is renally eliminated, which may result in possible renal adjustments in patients. Moreover, dosage and administration can sometimes vary based on the regimen, body weight, and other patient-specific factors.

What are the differences and similarities between liposomal irinotecan and irinotecan?

• Liposomal form of irinotecan has a lipid bilayer
• SN-38 is an active metabolite of both medications
• The lipid bilayer prolongs irinotecan half-life, and it prevents it from converting to its active metabolite quicker
• The liposomal form is used for treatment in patients with metastatic adenocarcinoma of the pancreas
• These are not interchangeable medications

There are many chemotherapeutic medications that have extensive side effect profiles or adverse reactions associated with them. It is important to distinguish that there are acute and delayed adverse reactions. To overcome these acute and delayed adverse reactions, patients are pre-medicated. For example, the most notable toxicity seen with irinotecan is diarrhea, which is usually delayed. To overcome this, some patients will receive loperamide. Another example associated with irinotecan is its acute cholinergic syndrome, which can be treated with atropine. Overall, not all patients will be pre-medicated with the same regimens because there are patient-specific factors to account for prior to selecting treatments that mitigate and prevent adverse effects seen with these chemotherapeutic medications. The noticeable toxicities in topoisomerase I inhibitors are typically hematologic and gastrointestinal.

Irinotecan and topotecan have been used for a long time. It is important to notice that even though these medications are in the same drug class, they are not interchangeable. These medications are utilized for many different cancer types, such as advanced colorectal, ovarian, and small-cell lung cancer. Overall, staying up to date with new findings and the most current literature is important to ensure that patients receive the best-individualized therapy.

Dagmara Zajac

RxPharmacist Team

References:

1. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Topoisomerase Inhibitors. [Updated 2020 Sep 12]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548372/
2. Topoisomerase inhibitor. Topoisomerase Inhibitor – an overview | ScienceDirect Topics. https://www.sciencedirect.com/topics/neuroscience/topoisomerase-inhibitor#:~:text=Topoisomerase%20I%20inhibitors%20include%20irinotecan,etoposide%2C%20doxorubicin%2C%20and%20epirubicin. Accessed December 13, 2022.
3. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Irinotecan. [Updated 2018 Apr 27]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548037/
4. CAMPTOSAR®Dosage and Administration (irinotecan hcl). CAMPTOSAR® Dosage and Administration (irinotecan HCl) | Pfizer Medical Information – US. https://www.pfizermedicalinformation.com/en-us/camptosar/dosage-admin. Accessed December 13, 2022.
5. Baker DE, Levien TL. Irinotecan Liposome Injection. Hosp Pharm. 2017;52(2):144-150. doi:10.1310/hpj5202-144
6. HYCAMTIN® (topotecan) for injection, for intravenous use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020671s023lbl.pdf. Accessed December 13, 2022.

Pseudomonas aeruginosa is a type of bacteria that causes a variety of different infections. In 2012, there were roughly 46,000 individuals hospitalized due to multidrug-resistant Pseudomonas aeruginosa. Similarly in 2017, there were roughly 32,600 hospitalizations due to infections caused by this bacterium, and roughly 2,700 deaths occurred. It has been shown that between 2012 and 2017, the infections of multidrug-resistant Pseudomonas aeruginosa infections have been decreasing due to the continued efforts to prescribe the correct antibiotics.

Pseudomonas aeruginosa is an aerobic, gram-negative, non-sporing forming rod. It can be found in freshwater and the environment. Anyone can acquire this type of infection, but more commonly, it does affect individuals with weakened immune systems or those in hospital settings. The most common risk factors for patients in the hospital setting are catheters, surgery, and breathing machines. Individuals that are commonly infected are patients with cystic fibrosis, AIDS, neutropenia, burns, cancer, and organ transplantation. Overall, these bacteria can spread through contaminated surfaces, equipment, or by touching contaminated hands.

Antibiotics are used to treat these types of infections. This type of bacteria is affected by antibiotic resistance. Most commonly, patients are started on a broad-spectrum antibiotic. Local antibiograms should be used to determine the correct empiric therapy. If a patient has one or more risk factors for multi-drug resistant organisms, septic shock, respiratory failure with mechanical ventilation, or intensive care unit admissions, they may require double pseudomonal coverage. The drug classes commonly used are carbapenems, cephalosporins, aminoglycosides, fluoroquinolones, and others.

The specimen is sent off to the laboratory to confirm the exact type of bacteria that is growing. After that, the specific bacteria will be tested against all the antibiotics to determine which antibiotic it is susceptible. Next, narrowing down the antibiotic for the patient will ensure coverage of only that specific bacterium that is growing. Once the results come back, the antibiotic selection will be made based on the susceptibilities, the area where the bacteria are growing, and other patient-specific factors.

For this type of infection, it is important to make sure that the patient not only receives the appropriate antibiotic, but also the appropriate duration and dosage form as well. Oral and IV antibiotics selection is usually dependent on the infection itself and the site of infection. Patients might be required to be on extended courses of antibiotics to ensure that all the bacteria are killed. Sometimes, antibiotics are not the only form of action needed to get rid of the infection. If the infection is deep, patients may be required to take extended intravenous (IV) antibiotics and undergo surgical debridement. This is when interprofessional healthcare teams are important to select the appropriate treatments to make sure that the infection will be gone entirely.

Pseudomonas aeruginosa can cause serious types of infections. It most commonly affects patients in the hospital setting or immunocompromised patients. There are various antibiotics that can be used to treat these types of infections. Due to multidrug resistance seen with these bacteria, it is important to send off the specimen to the laboratory to ensure that physicians or other healthcare professionals can narrow the antibiotic that is susceptible so that it can get to the site of action. Sometimes in certain cases, antibiotics may not be the only form of treatment used for patients to get rid of these infections, which is why interprofessional teams in these situations are very beneficial in considering all specific factors to ensure patients receive the best care possible.

Dagmara Zajac
RxPharmacist Team

References:

1. Wilson MG, Pandey S. Pseudomonas Aeruginosa. [Updated 2022 Aug 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557831/
2. Pseudomonas aeruginosa infection. Centers for Disease Control and Prevention. https://www.cdc.gov/hai/organisms/pseudomonas.html. Published November 13, 2019. Accessed December 10, 2022.
3. 2019 antibiotic resistance threats report. Centers for Disease Control and Prevention. https://www.cdc.gov/drugresistance/biggest-threats.html. Published November 23, 2021. Accessed December 10, 2022.

Antibiotics are commonly prescribed. In 2021, there were 211.1 million oral antibiotic prescriptions given by healthcare professionals in the outpatient setting. In other terms, that is an estimated 636 oral antibiotic prescriptions per 1000 individuals. To compare this to previous year’s statistics, in 2020, there were 201.9 million oral antibiotic prescriptions given by healthcare professionals in the outpatient setting, meaning 613 oral antibiotic prescriptions per 1000 individuals. Clearly, this shows that the number of antibiotic prescriptions keeps increasing.

According to the Centers for Disease Control (CDC), about 30 % of antibiotics are prescribed unnecessarily in the outpatient setting (See Figure 1). With that being said, it is crucial to discuss and understand the issue of antimicrobial resistance. Due to increased unnecessary prescribing of antibiotics, antimicrobial resistance is on the rise and it has become a serious matter and threat to not just local health, but also global public health. Since the pharmaceutical industry isn’t providing new drugs on the market to make up for the increase in antibiotic resistance, then what has been done to address this growing problem? One answer to that question is antibiotic stewardship programs. 

According to CDC 2021 annual report, the top 5 most common oral antibiotic classes prescribed in the United States were:

Due to antimicrobial resistance, antibiotics lose their effectiveness in fighting off infections. This has led to other implications, such as prolonged hospital stays, increased costs, treatment failures, and much more. On average, patients will be in the hospital for 13 days due to antimicrobial resistance. Therefore, multidrug resistance (MDR) has become a significant challenge in healthcare and has worsened the antimicrobial resistance issue. For example, globally, 500,000 new cases of MDR tuberculosis are diagnosed yearly. On top of everything, it has been shown that the COVID-19 pandemic has set to increase the threat of antimicrobial resistance as well. Overall, pharmaceutical companies have drifted away from this drug development area, which is why there has been a decrease in new antibiotic development for many years.

Antibiotic stewardship programs aim to help this growing problem by improving the use of antibiotics. Physicians and pharmacists have led the majority of antibiotic stewardship programs. These programs ensure that clinicians prescribe antibiotics only when it is necessary, prescribe antibiotics that cover the necessary infection, and do not expose patients to unnecessary antibiotics. To be in accordance with the Centers for Medicare and Medicaid Services, the Joint Commission made it a requirement for hospital settings to have antibiotic stewardship programs implemented. This is a huge win in reducing inappropriate antibiotic use. Antibiotic stewardship programs can be found in various settings, such as hospital settings, outpatient settings, nursing homes, and resource-limited settings. The CDC website has a page with core elements designated to each antibiotic stewardship program setting to understand that each program may differ depending on its location.

Antibiotic resistance has been on the uptrend for quite a while. It is important to know why antibiotics must be carefully prescribed. Antibiotic stewardship programs are one way that this growing problem is being addressed. Hopefully, we will see that antibiotic stewardship efforts have decreased the issue of antibiotic resistance over time.

References:

1. Majumder MAA, Rahman S, Cohall D, et al. Antimicrobial Stewardship: Fighting Antimicrobial Resistance and Protecting Global Public Health. Infect Drug Resist. 2020;13:4713-4738. Published 2020 Dec 29. doi:10.2147/IDR.S290835
2. Barlam TF. The state of antibiotic stewardship programs in 2021: The perspective of an experienced steward. Antimicrob Steward Healthc Epidemiol. 2021;1(1):e20. Published 2021 Aug 5. doi:10.1017/ash.2021.180
3. Measuring outpatient antibiotic prescribing. Centers for Disease Control and Prevention. https://www.cdc.gov/antibiotic-use/data/outpatient-prescribing/index.html. Published October 5, 2022. Accessed December 1, 2022.
4. Outpatient antibiotic prescriptions — United States, 2021. Centers for Disease Control and Prevention. https://www.cdc.gov/antibiotic-use/pdfs/Annual-Report-2021-H.pdf. Published October 7, 2021. Accessed December 1, 2022.
5. Outpatient Antibiotic Prescriptions – United States, 2020. Centers for Disease Control and Prevention. https://www.cdc.gov/antibiotic-use/pdfs/Annual-Report-2020-H.pdf. Published October 7, 2021. Accessed December 1, 2022.
6. Core elements of antibiotic stewardship. Centers for Disease Control and Prevention. https://www.cdc.gov/antibiotic-use/core-elements/index.html. Published April 7, 2021. Accessed December 1, 2022.

There are roughly 30 million adults on a beta blocker in the United States. Beta-blockers have been around for a very long time. This class of medications has both been used for on and off-label purposes. Over the years, their usage has evolved and has been seen in various disease states. Overall, the indications that this class of medications have been utilized in, are heart failure, glaucoma, hypertension, anxiety, migraines, and many others. This beta blocker refresher will provide you with the overview that will potentially spark your interest to dive deeper into each medication discussed.

Most common beta-blockers have been recognized for being either selective beta blockers or non-selective beta-blockers:

Depending on which specific beta-blocker a patient is prescribed, it is important to provide education on that specific drug’s adverse effects. Individuals taking non-selective beta blockers may experience some side effects that are not seen with selective beta blockers due to their mechanism of action. For example, sotalol has a risk for QT prolongation because it blocks potassium channels. The adverse effects are dependent on the specific drug, but there are overall common side effects seen within this class of medications, such as fatigue, hypotension, dizziness, and bradycardia. The less common side effects that individuals should be aware of are insomnia, weight gain,  hepatotoxicity, and bronchospasm. Historically, beta-blockers have been contraindicated in patients with asthma due to their mechanism of action. Also, beta-blockers may mask the signs of hypoglycemia. Patients who have diabetes should be educated on what to do when on a beta blocker just in case they experience hypoglycemia. Beta-blockers, however, have their useful places in therapy. To illustrate, this class of medication has been utilized for its anxiolytic effect. An example is propranolol, which is often prescribed off-label for anxiety or to help with stage performance to reduce some peripheral symptoms associated with anxiety.

Other beta-blocker class pertinent details:

• Individuals should monitor their blood pressure and heart rate while on this medication.
• There are multiple formulations available on the market.
  • The most common routes of administration are oral, intravenous, or ophthalmic.
• The dosage of these medications depends on the specific drug.
  • Some of these medications come in immediate release or extended release.
  • For example, propranolol ranges from 80 mg/day to 320 mg/day, which can be split into multiple doses daily due to its half-life.
• Patients can be on this medication for an extended period of time.

Overall, this class of medication has been on the market for a long time; it is well-established compared to other classes of medications in terms of indications and side effect profiles. It is important to differentiate between selective and non-selective beta-blocker medications to understand their mechanism of action and their respective indications. A large patient population utilizes this class of medications, so it is extra important to keep up with new findings and updates. Hopefully, this refresher on beta-blockers has helped to provide you with beneficial information to continue delivering the best care in your own pharmacy setting.

Dagmara Zajac

RxPharmacist Team

References:

1. Beta-blockers: Types, uses and side effects. Cleveland Clinic. https://my.clevelandclinic.org/health/treatments/22318-beta-blockers. Accessed November 28, 2022.
2. What you should know about beta blockers. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/high-blood-pressure/in-depth/beta-blockers/art-20044522. Published August 13, 2021. Accessed November 28, 2022.
3. Oliver E, Mayor F Jr, D’Ocon P. Beta-blockers: Historical Perspective and Mechanisms of Action. Rev Esp Cardiol (Engl Ed). 2019;72(10):853-862. doi:10.1016/j.rec.2019.04.006
4. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Beta Adrenergic Blocking Agents. [Updated 2018 Jun 3]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548127/
5. Farzam K, Jan A. Beta Blockers. [Updated 2022 Jul 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532906/
6. Srinivasan AV. Propranolol: A 50-Year Historical Perspective. Ann Indian Acad Neurol. 2019;22(1):21-26. doi:10.4103/aian.AIAN_201_18

An ample drug supply is important to ensure that patients receive the medications they need. What happens if the drugs patients need are not able to be supplied for reasons that are out of our control? Drug shortages are more common than individuals think. Since 2018, there have been more than 200 ongoing drug shortages on average yearly. Pharmacists can truly help make drug shortages less of an identifiable problem. Everything that pharmacy school teaches pharmacists and pharmacy students is crucial in utilizing and strategizing the temporary or long-term solutions for these drug shortages. The figure below from the American Society of Health System Pharmacists (ASHP) website shows just how many new drug shortages are identified yearly.

Reasons for Current Drug Shortages

Drug shortages can occur for various reasons. Some of those reasons are due to manufacturing issues, the increase in demand for the product, regulatory issues, voluntary or involuntary recalls, shortage of raw materials, and economic issues. Historically, pharmacies sometimes would start to compound a product, but that is only if a product has such a solution for its shortage. For example, some chain hospitals can borrow between their sites to help relieve some of their shortages because depending on a patient population or patient volume for a given hospital, they can have a higher demand for one product over another and have the luxury to loan products between their sites.

Drug Shortages in the Workplace

Depending on certain workplaces, there can be protocols in place for what to do in case a drug becomes unavailable. Sometimes the shortage can be solved temporarily by using an alternative product, but the problem starts when there is no alternative for a given product.  For example, in an inpatient pharmacy setting in a large hospital, there can be weekly meetings in place for staff from different areas of the hospital at various administration levels to discuss drug shortages. During these drug shortage situations, it is important to have transparency between staff members. Clear communication helps create a collaborative environment which can help identify more solutions to situations. Each individual drug in shortage may need its individualized solution. Those solutions depend on the product in shortage, the facility that utilizes that product, the reason for the shortage, the return to market date, and many other factors.

Resources for Drug Shortages:

• ASHP has a whole section on its website dedicated to the drug shortage topic. It is very helpful to utilize it to stay up to date on new drug shortages. Depending on the product, it can list the reason for the shortage, and the estimated resupply dates as well. Also, ASHP has a section on the drug shortage trends that have been seen over the years. ASHP has a section on the website for resolved drug shortage items, which perhaps can be helpful to gain historical knowledge about a given product or its history with shortages.
• The Food and Drug Administration (FDA) has a whole section of its website dedicated to drug shortages. The FDA has a whole database that details breakdowns for each product on shortage in detail by the manufacturer name, shortage duration, specific NDC numbers, and anything else that might be relevant to that given product. The FDA created an app for quicker access and information regarding drug shortages as well.

Drug shortages are clearly complex and not as simple as some may think. They can be caused by various reasons. The solutions for them sometimes can be easy because there is an alternative on the market, but sometimes require a team to figure out temporary strategies and protocols such as compounding the product in pharmacies. It is important for pharmacists everywhere to have these discussions and continually educate other healthcare professionals to prepare for current and future drug shortages. Overall, drug shortages require our immediate attention and responding to the call will ensure that our patients have fewer disruptions to their treatments.

Dagmara Zajac

RxPharmacist Team

References:

1. Center for Drug Evaluation and Research. Drug shortages. U.S. Food and Drug Administration. https://www.fda.gov/drugs/drug-safety-and-availability/drug-shortages. Accessed November 23, 2022.
2. Drug Shortages Statistics. ASHP. https://www.ashp.org/drug-shortages/shortage-resources/drug-shortages-statistics?loginreturnUrl=SSOCheckOnly. Accessed November 23, 2022.
3. Drug Shortages. ASHP. https://www.ashp.org/drug-shortages?loginreturnUrl=SSOCheckOnly. Accessed November 23, 2022.
4. Ventola CL. The drug shortage crisis in the United States: causes, impact, and management strategies. P T. 2011;36(11):740-757.