HelixTalk - Rosalind Franklin University's College of Pharmacy Podcast

In this episode, we discuss the evidence, safety, and place in therapy of Auvelity® (dextromethorphan-bupropion), a newly approved antidepressant with a unique mechanism of action and interesting pharmacokinetic considerations.

Key Concepts

1. Auvelity® (bupropion-dextromethorphan) was FDA approved in 2022 for major depressive disorder (MDD). The bupropion component inhibits CYP2D6 metabolism and increases serum concentrations of dextromethorphan. The proposed mechanism of benefit in MDD is via dextromethorphan (as an NMDA antagonist) and possibly with bupropion (as a dopamine/norepinephrine reuptake inhibitor).
2. Although the bupropion component in Auvelity® is being used for its drug interaction, the dose is a therapeutic dose and carries several warnings and precautions, including the risk of seizure and hypertension.
3. In short (6-week) clinical trials, Auvelity® improved depression symptoms quickly (within 1-2 weeks), which is faster than many other antidepressants. Auvelity® is associated with dizziness, anxiety, hyperhidrosis, nausea, headache, diarrhea, and dry mouth.
4. As a CYP2D6 inhibitor, the bupropion component of Auvelity® will cause drug interactions with many other medications, including some antidepressants, antipsychotics, and opioid analgesics (among others).

References

• Iosifescu DV, Jones A, O'Gorman C, et al. Efficacy and Safety of AXS-05 (Dextromethorphan-Bupropion) in Patients With Major Depressive Disorder: A Phase 3 Randomized Clinical Trial (GEMINI). J Clin Psychiatry. 2022;83(4):21m14345. Published 2022 May 30. doi:10.4088/JCP.21m14345
• Tabuteau H, Jones A, Anderson A, Jacobson M, Iosifescu DV. Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial. Am J Psychiatry. 2022;179(7):490-499. doi:10.1176/appi.ajp.21080800
• Kotlyar M, Brauer LH, Tracy TS, et al. Inhibition of CYP2D6 activity by bupropion. J Clin Psychopharmacol. 2005;25(3):226-229. doi:10.1097/01.jcp.0000162805.46453.e3

In this episode, we highlight important changes to the 2023 GOLD Guidelines for COPD. In particular, we discuss a revision to the GOLD group classification system and the preferred initial therapies in patients with COPD.

Key Concepts

1. The newest GOLD COPD guidelines now recognize three GOLD groups – "A", "B", and "E". Group "E" (formerly groups C and D) are patients with frequent exacerbations (defined as 2 or more in the past 12 months or 1 exacerbation requiring hospitalization).
2. For group "E" patients, the preferred initial inhaler regimen is a LABA+LAMA. Triple therapy (LABA+LAMA+ICS) can be considered if blood eosinophils are elevated.
3. "Triple therapy" (LABA+LAMA+ICS) has gained traction based on the IMPACT and ETHOS trials – this regimen reduced exacerbations and mortality compared to LABA+LAMA and LABA+ICS.
4. With an exploding market of new COPD inhalers, the role of the pharmacist is even more critical to help identify affordable medications and provide patient education for proper inhaler technique.

References

• Global Strategy for Prevention, Diagnosis, and Management of COPD: 2023 Report. Global Initiative for Chronic Obstructive Lung Disease (GOLD). https://goldcopd.org/2023-gold-report-2/
• IMPACT study: Lipson DA, Barnhart F, Brealey N, et al. Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med. 2018;378(18):1671-1680. doi:10.1056/NEJMoa1713901
• ETHOS study: Rabe KF, Martinez FJ, Ferguson GT, et al. Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD. N Engl J Med. 2020;383(1):35-48. doi:10.1056/NEJMoa1916046

In this episode, we will discuss all things peripheral arterial disease – definitions, staging, clinical presentation, risk factors, goals of therapy, and guideline-directed medication therapy recommendations including the newest evidence for the use of DOACs.

Key Concepts

1. Addressing modifiable risk factors (weight loss, smoking cessation, blood pressure and blood glucose control, dyslipidemia, structured exercise program, etc.) are recommended for the treatment of PAD.
2. Single antiplatelet therapy with either aspirin 81 mg or clopidogrel 75 mg daily are recommended in patients to reduce stroke, MI and other vascular deaths in symptomatic (1A) and asymptomatic patients (IIa- C-EO).
3. Rivaroxaban 2.5 mg BID, when added to aspirin 81 mg daily, is superior to aspirin alone in preventing composite outcome of stroke, MI, and CV death in PAD patients with recent revascularization surgery for PAD but increases the risk of major bleeding.
4. In the absence of heart failure, cilostazol is effective in improving symptoms, quality of life, and increasing walking distance in patients with intermittent claudication.

References

• Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135:e686–e725. https://doi.org/10.1161/CIR.0000000000000470
• Criqui MH, Matsushita K, Aboyans V, et al. Lower Extremity Peripheral Artery Disease: Contemporary Epidemiology, Management Gaps, and Future Directions: A Scientific Statement From the American Heart Association. Circulation. 2021;144:e171–e191. https://doi.org/10.1161/CIR.0000000000001005
• Alonso-Coello P, Bellmunt S, McGorrian C, Anand SS, Guzman R, Criqui MH, Akl EA, Vandvik PO, Lansberg MG, Guyatt GH, Spencer FA. Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e669S-e690S. doi: 10.1378/chest.11-2307. PMID: 22315275; PMCID: PMC3278062.
• Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017; 377:1319-1330. https://www.nejm.org/doi/full/10.1056/nejmoa1709118
• Bonaca MP, Bauersachs RM, Anand SS, et al. Rivaroxaban in peripheral arterial disease after revascularization. N Engl J Med. 2020; 382:1994-2004. https://www.nejm.org/doi/full/10.1056/nejmoa2000052

In this episode, we review the management of a patient with hypokalemia, including both inpatient and outpatient supplementation with potassium chloride supplements and what dosage forms are available for potassium repletion.

Key Concepts

1. Most diets will provide sufficient potassium to avoid hypokalemia. Hypokalemia usually occurs due to drug therapy (such as diuretics) or GI losses from severe vomiting or diarrhea.
2. In patients with chronically low potassium, supplements are dosed to increase dietary intake of potassium by about 20-40 mEq per day. For acute repletion, 10 mEq of potassium should increase serum potassium by about 0.1 mEq/L.
3. Over-the-counter potassium (as potassium gluconate) contains a very small amount of potassium (2.5 mEq). Potassium chloride powders and liquids (like salt substitutes) taste terrible and are poorly tolerated. Most patients will replete potassium via slow-release tablets (Klor-Con or Klor-Con M) or via potassium chloride IV infusions.
4. Most IV fluids do not contain any potassium at all (or very little potassium). Patients receiving these IV fluids who are NPO will eventually become hypokalemic. Certain maintenance fluids do contain potassium – most patients will receive about 40 mEq of potassium per day with these IV fluids.

In this episode, we will define Digital Health, its categories and examples, describe how pharmacists are involved in DH practice, opportunities and limitations and future of DH. We will also discuss what implications DH has for educators, educational institutions, student pharmacists, pharmacists, and practice of pharmacy in general.

Key Concepts

1. Digital Health is currently a broad umbrella category that uses mobile health, telehealth, web-based platforms, personalized medicine, and IT to provide scalable patient care.
2. There are several focused areas within DH that would impact pharmacy practice by warranting pharmacist oversight or collaborative insights.
3. There is positive data for pharmacist-led DH interventions using mobile apps and web-based tools, but the use of telehealth modality has mixed results.
4. Pharmacists need to stay current in their knowledge and skills for utilizing DH tools in integrative and collaborative patient care.

References

• Aungst TD, Franzese C, Kim Y. Digital health implications for clinical pharmacists services: A primer on the current landscape and future concerns. J Am Coll Clin Pharm. 2020;4(4):514-524. DOI: 10.1002/jac5.1382. https://accpjournals.onlinelibrary.wiley.com/doi/abs/10.1002/jac5.1382
• American Association of Colleges of pharmacies. Digital Health Workshop - Resources. https://www.aacp.org/resource/digital-health-workshop-resources (Lists resources from Digital Therapeutics Alliance and Digital Medicine Society)
• Park T, Muzumdar J, Kim H. Digital Health Interventions by Clinical Pharmacists: A Systematic Review. Int J Environ Res Public Health. 2022 Jan 4;19(1):532. doi: 10.3390/ijerph19010532. PMID: 35010791; PMCID: PMC8744767.

In this episode, we invite Dr. Amir Ali, PharmD, BCOP to discuss with us the pathophysiology, risk factors, prevention, and treatment clinical pearls of tumor lysis syndrome TLS).

Key Concepts

1. TLS is caused by rapid cell death of cancerous cells that results in intracellular contents "spilling" into the blood – this leads to high serum uric acid, high serum potassium, high serum phosphate, and LOW calcium.
2. These laboratory abnormalities cause acute kidney injury (via crystal formation in the kidney), arrhythmias (from hyperkalemia), and seizures (from high phosphate and low calcium).
3. Patients at highest risk for TLS are those with hematologic malignancies (lymphomas and leukemias), especially if WBC or LDH labs are very high.
4. Prevention is the Key! The primary prevention approach for TLS is hydration, allopurinol, and sometimes a low dose of rasburicase. The treatment of TLS involves more aggressive hydration and rasburicase.

References

• Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review [published correction appears in J Clin Oncol. 2010 Feb 1;28(4):708]. J Clin Oncol. 2008;26(16):2767-2778. doi:10.1200/JCO.2007.15.0177
• Cairo MS, Coiffier B, Reiter A, Younes A; TLS Expert Panel. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010;149(4):578-586. doi:10.1111/j.1365-2141.2010.08143.x
• Jones GL, Will A, Jackson GH, Webb NJ, Rule S; British Committee for Standards in Haematology. Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in Haematology. Br J Haematol. 2015;169(5):661-671. doi:10.1111/bjh.13403

In this episode, we review Paxlovid (nirmatrelvir/ritonavir) from the perspective of its pharmacology, efficacy, safety, pharmacists' authority to prescribe, drug interactions, and rebound symptoms after Paxlovid therapy.

Key Concepts

1. Paxlovid is the preferred outpatient therapy for COVID-19 in patients at high risk for progressing to severe COVID-19. It likely has similar efficacy to IV monoclonal antibodies and IV outpatient remdesivir but differences in vaccination rates and patient populations makes a direct comparison difficult.
2. The 5-day course of Paxlovid is generally well tolerated. "Paxlovid mouth" (dysgeusia) is relatively common and is characterized by a terrible metallic or garbage-like taste in the mouth during therapy.
3. As of July 2022, licensed pharmacists have the authority to assess patients for Paxlovid and prescribe the therapy; however, Medicare/Medicaid reimbursement has not clearly established how reimbursement of clinical services can occur.
4. "Rebound" COVID-19 symptoms may or may not be due to Paxlovid (versus the natural course of the disease). If rebound symptoms occur, they are almost always mild or asymptomatic in nature and do not require additional treatment.

References

• DailyMed - PAXLOVID- nirmatrelvir and ritonavir kit (nih.gov). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7bdddfba-bd31-44cb-ba9e-23a4e17a4691
• Underlying Medical Conditions Associated with Higher Risk for Severe COVID-19: Information for Healthcare Professionals. CDC. June 15, 2022. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html
• EPIC-HR Study: Hammond J, Leister-Tebbe H, Gardner A, et al. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. 2022;386(15):1397-1408. doi:10.1056/NEJMoa2118542. https://www.nejm.org/doi/full/10.1056/NEJMoa2118542
• COVID-19 Rebound After Paxlovid Treatment. CDC Health Alert Network. May 24, 2022. https://emergency.cdc.gov/han/2022/han00467.asp
• FDA Authorizes Pharmacists to Prescribe Paxlovid with Certain Limitations. Administration for Strategic Preparedness & Response (ASPR). July 6, 2022. https://aspr.hhs.gov/COVID-19/Therapeutics/updates/Pages/important-update-06July2022.aspx
• PAXLOVID Patient Eligibility Screening Checklist Tool for Prescribers. https://www.fda.gov/media/158165/download

In this episode, we will discuss mechanism, pharmacokinetics, efficacy, safety, and possible place in therapy for tirzepatide (Mounjaro), a new treatment for type 2 diabetes.

Key Concepts

1. Tirzepatide is a novel GIP and GLP-1 receptor agonist resulting in glucose-dependent secretion of insulin and a decrease in glucagon secretion.
2. This medication was FDA approved in May 2022 for the treatment of type 2 diabetes as an adjunct to diet and exercise. It is available as a long-acting once weekly pen injection to be administered subcutaneously.
3. Current efficacy data exist from a 40-week trial which showed that tirzepatide was superior to semaglutide in A1c reduction and weight loss.
4. The most common adverse effects of tirzepatide include GI concerns such as nausea, vomiting, and diarrhea as well as hypoglycemia.

References

1. Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021;385:503-515. https://www.nejm.org/doi/full/10.1056/NEJMoa2107519
2. Mounjaro. Package insert. Elli Lilly and Company. 2022.

In this episode, we will discuss the rationale behind the FDA approval of two new pneumococcal conjugate vaccines (PCV20 and PCV15), the characteristics of these vaccines, their place in therapy as recommended by the ACIP, and subsequent CDC immunization schedule changes.

Key Concepts

1. Pneumococcal disease is mainly caused by various serotypes of Streptococcus pneumoniae and presentation can vary from mild forms (sinusitis, otitis media) to more severe (pneumonia, bacteremia, or meningitis).
2. Previously we used PCV13 and PPSV23 vaccines for adults ages 18 years and older for prevention of pneumococcal disease, but the recommendations were rather complicated based on age, underlying condition/immune status, and vaccination status.
3. Two new conjugate-type pneumococcal vaccines, PCV20 (Prevnar 20) and PCV15 (Vaxneuvance) are now approved by the FDA and were recently added to the CDC's adult immunization schedules. These updated recommendations are more simplified where adults with high-risk conditions and those ages 65 years and older should receive either 1 dose of PCV20 vaccine or 1 dose of PCV15 and then 1 dose of PPSV23 a year later to complete their pneumococcal vaccine series.
4. PCV15 is now FDA approved for children and updated recommendations for children have been voted upon by the Advisory Committee on Immunization Practices (ACIP) and will be final once it is made official policy by the CDC.

References and Resources

• Kobayashi M, Farrar JL, Gierke R, Britton A, Childs L, Leidner AJ, et al. Use of 15-Valent Pneumococcal Conjugate Vaccine and 20-Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Updated Recommendations of the Advisory Committee on Immunization Practices — United States, 2022. MMWR. 2022;71(4);109–117. https://www.cdc.gov/mmwr/volumes/71/wr/mm7104a1.htm?s_cid=mm7104a1_w
• Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. 14th ed. Hall E., Wodi A.P., Hamborsky J., et al., eds. Washington DC: Public Health Foundation; 2021.
• Goldblatt D, O'Brien KL. Pneumococcal Infections. In: Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson J. eds. Harrison's Principles of Internal Medicine 21e. McGraw Hill; 2022. Accessed August 04, 2022.
• Wagner AL, Boulton ML. Pneumococcal Infections. In: Boulton ML, Wallace RB. eds. Maxcy-Rosenau-Last Public Health & Preventive Medicine, 16e. McGraw Hill; 2022. Accessed August 04, 2022.
• CDC's PneumoRecs VaxAdvisor mobile app: https://www.cdc.gov/vaccines/vpd/pneumo/hcp/pneumoapp.html
• CDC's Pneumococcal vaccine timing for adults: https://www.cdc.gov/vaccines/vpd/pneumo/downloads/pneumo-vaccine-timing.pdf

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.