In this episode, we “deep dive” into diltiazem, describing its most important drug facts, pharmacology and medicinal chemistry, pharmaceutics, AB compatibility, and important medication safety issues.

Key Concepts

1. Diltiazem is a non-dihydropyridine calcium channel blocker (CCB). This type of CCB reduces both heart rate and blood pressure whereas dihydropyridine CCBs only reduce blood pressure.
2. Diltiazem has numerous dosage forms (IV, immediate release tablets, and extended-release products). Extended-release products are always dosed once or twice daily. Historically there were a significant number of extended-release capsules with a variety of brand names and AB-compatibility. Today, only a few branded products still exist in the US market (Cardizem CD, Cartia XT, Cardizem LA, Tiazac, Taztia XT).
3. The FDA Orange Book describes “AB” compatibility, which outlines whether one formulation is therapeutically equivalent to another formulation. Depending on state law, pharmacists can use AB compatibility codes to automatically substitute formulations without notifying the prescriber.
4. The numerous dosage forms of diltiazem is a medication safety issue. Remember that immediate release diltiazem is always dosed TID/QID (3-4 times per day) whereas extended-release formulations are always dosed once daily. A twice-daily extended-release product was previously on the market but has since been discontinued.

In this episode, the hosts of the HelixTalk reflect back on the history and making of HelixTalk to commemorate the 150th episode. We review each of our three favorite episodes and with a brief reflection on the episode content. We have come a long way from where we began and it is all thanks to the wonderful listeners and contributors who have a common thing in mind: a quest and thirst for knowledge!

Links to Previous Episodes:

1. #50 - Three shocking recommendations from CHEST 2016 that will blow your mind (https://www.rosalindfranklin.edu/academics/college-of-pharmacy/helixtalk/helixtalk-episode-50--three-shocking-recommendations-from-chest-2016-that-will-blow-your-mind/)
2. #29, 30, and 31 - Therapeutic Drug Monitoring (https://www.rosalindfranklin.edu/academics/college-of-pharmacy/helixtalk/helixtalk-episode-29--therapeutic-drug-monitoring-i/, https://www.rosalindfranklin.edu/academics/college-of-pharmacy/helixtalk/helixtalk-episode-30--therapeutic-drug-monitoring-ii/, https://www.rosalindfranklin.edu/academics/college-of-pharmacy/helixtalk/helixtalk-episode-31--therapeutic-drug-monitoring-iii/)
3. #111 - The Basics of Immune Checkpoint Inhibitors for Non-Oncology Healthcare Providers (https://www.rosalindfranklin.edu/academics/college-of-pharmacy/helixtalk/helixtalk-episode-111-the-basics-of-immune-checkpoint-inhibitors-for-non-oncology-healthcare-providers/)
4. #51 - Pharmacists to the rescue! (https://www.rosalindfranklin.edu/academics/college-of-pharmacy/helixtalk/helixtalk-episode-51--pharmacists-to-the-rescue/)
5. #124 - The ABCs of EUAs: Understanding FDA Emergency Use Authorizations (https://www.rosalindfranklin.edu/academics/college-of-pharmacy/helixtalk/helixtalk-episode-124-the-abcs-of-euas-understanding-fda-emergency-use-authorizations/)
6. #123 - Dr. Rosalind Franklin: Beyond Photo 51 (https://www.rosalindfranklin.edu/academics/college-of-pharmacy/helixtalk/helixtalk-episode-123-dr-rosalind-franklin-beyond-photo-51/)
7. #137 - It’s Time for PBM Reform: How PBMs Have Hurt Pharmacies and Increased Drug Costs (https://www.rosalindfranklin.edu/academics/college-of-pharmacy/helixtalk/helixtalk-episode-137-it-s-time-for-pbm-reform-how-pbms-have-hurt-pharmacies-and-increased-drug-costs/)

In this episode, we will cover a complete overview of definition, diagnosis, treatment and monitoring of iron deficiency anemia (IDA).

Key Concepts

1. Iron-deficiency anemia (IDA) is the most common type of nutritional anemia. The most common risk factors are insufficient dietary intake, malabsorption, and increased requirement states like pregnancy or blood loss.
2. Serum ferritin serves as the most confirmatory lab test for diagnosis of IDA. A low serum ferritin level usually indicates the presence of IDA. Other iron studies and CBC can be helpful in diagnosing IDA as well. 
3. Generally oral iron therapy is a well-accessible, inexpensive, safe, and effective approach for IDA treatment. Almost all PO options are equally effective and safe. Gastrointestinal adverse effects are common and can sometimes limit further dosing. 
4. Intravenous iron therapy is generally reserved for patients who are refractory or intolerant to PO treatment, have malabsorption of PO iron therapy, or have other health conditions such as chronic kidney disease, cancer, upcoming surgery, etc. Available IV options are equally effective and selection of an agent depends on insurance coverage, formulary inclusion, patient preference for test dose, frequency of dosing, etc. 

In this episode, we interview Hetal Patel, PharmD and RFUMS COP Alumni, regarding her career path that eventually led her to open Lebanon Family Pharmacy in TN in 2021. We discuss the challenges and opportunities of starting a new independent pharmacy and what the future of independent pharmacy looks like.

Key Concepts

1. Starting a new, independent pharmacy requires substantial planning 8 to 12 months before the pharmacy’s doors even open. New pharmacy owners need to consider a variety of factors such as location, type of building, a business plan with financial analysis, a variety of building and pharmacy inspections, paperwork and government approvals, and so much more.
2. PSAOs (pharmacy services administrative organizations) can be helpful, especially for new pharmacy owners, to serve as a liaison between the pharmacy and PBMs (pharmacy benefit managers) to negotiate reimbursement contracts. As owners gain more experience, there may be financial advantages to not using PSAOs and negotiating with PBMs directly.
3. Companies like “Health Mart” have a franchise-like model to provide products, services, documentation, policies and procedures, and more to independent pharmacies. These companies reduce the workload associated with running a pharmacy so that the pharmacy owners can focus their time and attention on the business itself and providing exceptional customer service.
4. There are a number of challenges to independent pharmacies – some of these challenges involve PBMs (DIR fees and MAC pricing) as well as unrestricted dispensaries in primary care clinics.

References

• Lebanon Family Pharmacy. https://lebanonfamilypharmacy.com/

In this episode, we review new updates and key concepts from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. This guideline is newly published (April 2022) and is a full update of the 2013 guidelines and the 2017 focused update for heart failure.

Key Concepts

1. Heart failure is classified as HFrEF (heart failure with reduced ejection fraction <= 40%), HFimpEF (with improved ejection fraction – was <=40% but is now > 40%), HFmrEF (ejection fraction 41% to 49% with increased LV filling pressures), and HFpEF (preserved ejection fraction >= 50% with increased LV filling pressures). Most drug therapy recommendations are similar for HFrEF, HFimpEF, and HFmrEF whereas HFpEF therapies are different.
2. The 2022 AHA/ACC/HFSA heart failure guidelines now recommend SGLT2 inhibitors, such as dapagliflozin and empagliflozin, in patients with HFrEF, HFmrEF, and HFpEF.
3. The 2022 AHA/ACC/HFSA heart failure guidelines continue to prefer ARNi, such as sacubitril/valsartan (Entresto), over ACE inhibitors and ARBs in patients with HFrEF. Based on the PARAGON-HF trial, ARNi is also recommended in those with HFpEF albeit with a weak recommendation.
4. Avoiding excessive dietary sodium is reasonable to reduce congestive symptoms in patients with heart failure; however, guidelines do not recommend a specific maximum intake nor does data support clinical outcome benefit with dietary sodium restriction.

References

• Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published online ahead of print, 2022 Apr 1]. Circulation. 2022;101161CIR0000000000001063. doi:10.1161/CIR.0000000000001063. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063
• Ezekowitz JA, Colin-Ramirez E, Ross H, et al. Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial. Lancet. 2022;399(10333):1391-1400. doi:10.1016/S0140-6736(22)00369-5

In this episode, we discuss six newer antibiotics that target multidrug resistant gram negative bacteria with Dr. Christie Bertram, PharmD, BCIDP. We review common resistance mechanisms, particularly to carbapenems, and highlight the current role in therapy for the following antibiotics: ceftolozane/tazobactam (Zerbaxa®), ceftazidime/avibactam (Avycaz®), meropenem/vaborbactam (Vabomere®), imipenem/cilastatin/relebactam (Recarbrio®), cefiderocol (Fetroja®), and eravacycline (Xerava®).

Key Concepts

1. Ceftolozane/tazobactam (Zerbaxa®) is primarily used for multidrug resistant Pseudomonas; it does not cover carbapenemase-producing organisms and (despite the tazobactam) needs metronidazole for intra-abdominal anaerobic coverage.
2. Ceftazidime/avibactam (Avycaz®) is primarily used to cover CRE (Carbapenem-resistant Enterobacterales) but also has activity for many other gram negatives except Acinetobacter.
3. Meropenem/vaborbactam (Vabomere®) has similar coverage to Avycaz® but may provide coverage for certain KPCs (Klebsiella pneumoniae carbapenemase). Vaborbactam does not restore activity for meropenem-resistant Pseudomonas.
4. Imipenem/cilastatin/relebactam (Recarbrio®) has similar coverage to Avycaz® and Vabomere®; true niche in therapy is not yet well defined.
5. Cefiderocol (Fetroja®) uses a unique mechanism to enter gram negative bacteria and has a broad spectrum of activity against carbapenemase-producing bacteria and many other multidrug resistant gram negatives. It has no gram positive activity.
6. Eravacycline (Xerava®) is a tigecycline-like tetracycline with a broad spectrum of activity against carbapenemase-producing gram negative, gram positive, an anaerobic bacteria EXCEPT it lacks coverage for Pseudomonas.

References

• Yusuf E, Bax HI, Verkaik NJ, van Westreenen M. An Update on Eight "New" Antibiotics against Multidrug-Resistant Gram-Negative Bacteria. J Clin Med. 2021;10(5):1068. Published 2021 Mar 4. doi:10.3390/jcm10051068
• CDC Antibiotic Resistance Threats in the United States, 2019 report. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf

In this episode, we bring in two guests to discuss the impact of professional advocacy and resulting professional advancements in the state of Illinois. These guests were the front-line agents of advocacy which resulted in pharmacists' ability to prescribe hormonal contraceptives for patients in Illinois (HB 135). We take a deep dive into their efforts to make this change possible, how it will impact patient care, and its implications on possibilities for further advancement of the pharmacy profession all the while highlighting the importance of professional advocacy.

In this episode, we interview Dr. Danyelle Martin, a Medical Science Liaison (MSL) at Moderna, in order to learn more about the what, how, and future of mRNA-based therapeutics, and what impact it can have on healthcare and healthcare professionals in general.

Key Concepts

1. Moderna has a “Research Engine” proprietary service that takes an mRNA idea from a web-based digital designer, to a digital ordering system, and finally to a production facility where mRNA constructs are synthesized and quality tested.
2. Pharmaceutics play a big role in the formulation of mRNA particles. Lipid nanoparticles (LNPs) play an important role for stability and delivery of mRNA cargo. After LNPs and mRNA are co-formulated, the product is purified, filtered, frozen, and subjected to a series of good manufacturing practice (GMP) tests to ensure product quality.
3. COVID-19 vaccines are a small glimpse into the potential future of mRNA-based therapeutics. Moderna’s pipeline includes mRNA vaccines for other viruses (including RSV, influenza, Zika and CMV) as well as therapeutics for non-viral diseases (including a personalized cancer vaccine and a VEGF-A mRNA molecule for myocardial ischemia).

In this episode, we review the diagnostic criteria and treatment strategy of hypothyroidism including the controversy surrounding brand versus generic levothyroxine and non-levothyroxine thyroid drugs.

Key Concepts

1. The most common cause of hypothyroidism is autoimmune thyroiditis - the body attacks the thyroid gland cells. Typically in hypothyroidism, TSH levels will be high and thyroid hormone levels (T3 and T4) will be normal or low.
2. Levothyroxine is the drug of choice to treat hypothyroidism. Doses should start low (to avoid cardiovascular side effects) and then be titrated up based on TSH levels.
3. All other thyroid hormone formulations (including Thyroid USP, Armour Thyroid, liothyronine, etc.) are NOT recommended for use in hypothyroidism. These are not FDA approved medications and there is no data showing these products are more effective than levothyroxine.
4. Generic formulations of levothyroxine are as effective and safe as brand-name Synthroid®. Although several levothyroxine formulations are AB compatible and can be interchanged by a pharmacist, patients should be maintained on the same formulation whenever possible.

References

• Dong BJ, Hauck WW, Gambertoglio JG, et al. Bioequivalence of generic and brand-name levothyroxine products in the treatment of hypothyroidism. JAMA. 1997;277(15):1205-1213.
• Rennie D. Thyroid storm. JAMA. 1997;277(15):1238-1243.
• American Thyroid Association. https://www.thyroid.org/

In this episode, we will build up on our previous Weight loss Pharmacotherapy Episode, episode #13 to discuss updates in guidelines, prevention of obesity from comorbidity standpoint, and new treatment agents for weight-loss with a particular focus on Contrave (naltrexone/bupropion), Saxenda (liraglutide), and Wegovy (semaglutide).