LRTI Therapeutics: Bronchiolitis, Influenza, and COVID-19 - 3-Lectures Notes - 11/7/2023

Therapeutics: Lower respiratory tract infections (LRTI) Bronchiolitis, influenza, and COVID-19 Dhara Surati, Pharm.D., BCPS Clinical Associate Professor PHAR 5338 – ID 2 University of Houston-College of Pharmacy November 7, 2023 [email protected] 1 Format: • Slide deck • Interactive/active le...

Therapeutics: Lower respiratory tract infections (LRTI) Bronchiolitis, influenza, and COVID-19 Dhara Surati, Pharm.D., BCPS Clinical Associate Professor PHAR 5338 – ID 2 University of Houston-College of Pharmacy November 7, 2023 [email protected] 1 Format: • Slide deck • Interactive/active learning component 2 Learning objectives for bronchiolitis ▪ Identify the organism(s) associated and pathogenesis ▪ Recognize clinical presentation ▪ Select an appropriate treatment and/or prophylactic option 3 Reference (for all the slides on bronchiolitis): • Zasowski EJ, Blackford M. Chapter 129: Lower Respiratory Tract Infections. In: DiPiro JT, Yee GC, Michael Posey LL, Haines ST, Nolin TD, Ellingrod VL. eds. DiPiro: Pharmacotherapy A Pathophysiologic Approach, 12e. McGraw Hill; 2021. • www.cdc.gov – RSV (for healthcare professionals) 4 Bronchiolitis • Acute viral infection of the lower respiratory tract • Peak time: • Disease of infancy – 50% of children: 1st year of life – ~100%: by age 2 years 5 Bronchiolitis: Organisms involved Respiratory syncytial virus (RSV) Parainfluenza Adenovirus Influenza 75% of all cases (Up to 90%) Bacteria (secondary pathogen) 6 Bronchiolitis: S/S and PE S/S: • Prodrome: irritability, restlessness, mild fever, rhinorrhea, decrease appetite • Cough • Noisy / labored breathing • Vomiting, diarrhea PE: • Wheezing and inspiratory rales • Tachycardia with respiratory rate of 40 – 80/min → in hospitalized infants • Mild conjunctivitis • Otitis media (5-10%) 7 Bronchiolitis: Diagnostics/Labs • Real-time reverse transcriptase-polymerase chair reaction (rRTPCR) - RSV • White blood cells (WBC): ↔, ↑ • Abnormal arterial blood gases (ABG) – Hypoxemia is common 8 Bronchiolitis: treatment • Otherwise healthy infants • Self-limiting illness – What may help? • Reassurance • Antipyretics – AVOID: Aspirin and aspirin-containing products: » Should NOT be given to children (Reye’s syndrome characterized by change in mental status, coma, death • Adequate fluid intake • In-hospital support – Oxygen therapy – IV fluids 9 Pharmacologic therapy • NOT recommended by the American Academy of Pediatrics (AAP): – Aerosolized bronchodilators (some patients) – Systemic corticosteroids • Route use is NOT recommended: – Ribavirin – aerosol inhalation 10 Role of ribavirin in bronchiolitis • Reserved for severely ill patients: – Chronic lung disease (especially bronchopulmonary dysplasia) – Congenital heart disease – Premature infants – Immunodeficiency (example: HIV) 11 Prophylaxis against RSV • Infants with underlying pulmonary or cardiovascular disease: – Administered monthly during the RSV season • Prophylactic option: – Monoclonal antibody for RSV • Palivizumab • Nirsevimab (July 2023) 12 Is there a vaccine for RSV? • Now, yes (May 2023), indicated for: – Pregnant individuals at 32 – 36 weeks gestational age – Individuals 60 years of age and older 13 Check any/all correct statement(s): ❑Bronchiolitis is the same as bronchitis ❑RSV IG is indicated for all infants over the age of 1 month ❑Ribavirin PO is the first line agent for RSV infection 14 Learning objectives for influenza • Recognize the mode of transmission • Recognize the clinical presentation, influenza-related complications, diagnostic tests, and therapeutic goals • Recommend an appropriate intervention for treatment or prevention • Choose appropriate efficacy and safety monitoring parameters • Navigate through and apply based on latest resources 15 Reference: www.cdc.gov 16 Quick Review How influenza spreads? Incubation period: 1-4 days Person to person www.cdc.gov Virus shed (in adults): Begin ~1 day prior to symptoms through ~5-10 days after illness onset 17 Quick Review Uncomplicated influenza illness Fever Myalgia Headache Sore throat Rhinitis Malaise Non-productive cough 18 Influenza: Diagnostics/labs • • • • Method Types detected Test time RT-PCR* and other molecular assays A and B Varies (~1 – 6 hours) Rapid Influenza diagnostic test (RIDT) (various) A and B < 30 minutes Complete blood count (CBC) Chemistry panel Cultures Chest x-ray *Reverse-transcription polymerase chain reaction http://www.cdc.gov/flu/professionals/diagnosis/clinician_guidance_ridt.htm#Table2 19 Complications of influenza • Pneumonia / other respiratory illnesses • Encephalopathy • Exacerbation of underlying medical conditions http://www.cdc.gov/flu/professionals/acip/clinical.htm 20 High risk for complications, hospitalizations, and death www.cdc.gov 21 Out of the options given below, who is least likely to develop influenza-related complications? A. 2-year-old girl B. 30-year-old pregnant person C. 45-year-old male with a history of congestive heart failure and diabetes D. 35-year-old female with a history of urinary tract infection 22 Treatment 23 Goals of therapy • • • • Control symptoms of influenza Prevent complications Decrease work/school missed days Prevent the spread of infection Njoku J. Influenza. In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V. eds. Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw-Hill; Accessed November 02, 2020. https://accesspharmacy.mhmedical.com/content.aspx?bookid=2577&sectionid=224360594 24 Non-pharmacologic therapy • Adequate sleep • Stay home • Adequate fluid intake Njoku JC, Hermsen ED. Njoku J.C., Hermsen E.D. Chapter 87. Influenza. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. DiPiro J.T., Talbert R.L., Yee G.C., Matzke G.R., Wells B.G., Posey L eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014. 25 Supportive pharmacologic therapy • For symptomatic relief: – OTC products • AVOID: Aspirin and aspirin-containing products: – Should NOT be given to children (Reye’s syndrome characterized by change in mental status, coma, death) 26 General key points – Pharmacologic therapy • Challenges: – Pandemic – Increasing resistant viruses • Timing is essential – Available antiviral: most effective if started w/in 48 hours of onset of illness Njoku JC, Hermsen ED. Njoku J.C., Hermsen E.D. Chapter 87. Influenza. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. DiPiro J.T., Talbert R.L., Yee G.C., Matzke G.R., Wells B.G., Posey L eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014. 27 Initiate antiviral treatment as early as possible • In the following patients: – Hospitalized – Severe, complicated, or progressive illness – Higher risk of influenza complications 28 Overall treatment options Drug Route Recommended for: Not recommended for: Oseltamivir (Tamiflu®) PO Any age* --- Zanamivir (Relenza®) PO inhalation 7 years and older Underlying respiratory diseases (e.g., asthma, COPD) Contraindicated: History of allergy to milk protein Peramivir (Rapivab®) IV 2 years and older --- Baloxavir marboxil (Xofluza ®) PO 12 years and older Uncomplicated influenza; not for hospitalized patients *will discuss further in class http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm 29 Dosing information for adults – Treatment of uncomplicated influenza in an outpatient setting Drug Adult Dose Treatment Duration (days)^ Oseltamivir (Tamiflu®) * 75 mg twice daily 5** Zanamivir (Relenza®) Two oral inhalations (10 mg total) twice daily Total daily dose: 20 mg 5** Peramivir (Rapivab®)* 600 mg once Single dose Baloxavir marboxil (Xofluza®) 40 to <80 kg: 40 mg as a single dose ≥80 kg: 80 mg as a single dose Single dose www.online.lexi.com *Adjust for renal insufficiency ** Longer treatment can be considered in severely ill patients 30 Recommendations for severe influenza (requiring hospitalization) • May be effective even if started >48 hours after onset of illness • Recommended: Oseltamivir (oral or enterically) • Not recommended: _________________ – If oseltamivir is not an option: • Peramivir IV – duration of therapy: up to 5 to 10 days 31 Efficacy monitoring • Resolution of signs/symptoms (fever, myalgia, headache, malaise, non-productive cough, sore throat and rhinitis) – Monitor daily – Should resolve in ~1 week • Longer lasting symptoms: seek physician’s help 32 Safety monitoring Safety monitoring: Dependent on antimicrobial(s) selected; please refer to appropriate reference(s) for adverse effects profile / safety monitoring parameters of individual antimicrobials http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm 33 Which of the following is the most appropriate regimen for an adult patient (weight 77 kg) with normal renal function that is being treated at home for seasonal flu – with no complications? • a. peramivir 600 mg IV X 5 days • b. baloxavir marboxil 80 mg PO X 5 days • c. oseltamivir 75 mg PO once daily X 2 weeks • d. oseltamivir 75 mg PO twice daily X 5 days 34 Who should people be vaccinated? When should people be vaccinated? • All persons aged ≥ 6 months of age who do not have contraindications • As soon as vaccine becomes available • ~ 2 weeks after vaccination for antibodies to develop in the body and protect 35 Highlights of 2023-24 flu vaccine – U.S. egg-based: contain hemagglutinin (HA) derived from egg-based : • an A/Victoria/4897/2022 (H1N1)pdm09-like virus; (Updated) • an A/Darwin/9/2021 (H3N2)-like virus (updated); • a B/Austria/1359417/2021-like virus (B/Victoria lineage) (updated); • a B/Phuket/3073/2013-like virus (B/Yamagata lineage) https://www.cdc.gov/flu/season/faq-flu-season-2023-2024.htm; Accessed: 11-3-2023 36 Highlights of 2023-24 flu vaccine – U.S. cell- or recombinant-based: contain hemagglutinin (HA) derived from: • an A/Wisconsin/67/2022 (H1N1)pdm09-like virus; (Updated) • an A/Darwin/6/2021 (H3N2)-like virus (updated); • a B/Austria/1359417/2021-like virus (B/Victoria lineage) (updated); • a B/Phuket/3073/2013-like virus (B/Yamagata lineage). https://www.cdc.gov/flu/season/faq-flu-season-2023-2024.htm; Accessed: 11-3-2023 37 Highlights of 2023-24 flu vaccine • PDF 1_acip-2023-24-Summary-Flu-Vaccine-Recommendations – downloaded: 11/3/2023 https://www.cdc.gov/flu/pdf/professionals/acip/acip-2023-24Summary-Flu-Vaccine-Recommendations.pdf 38 Administration of vaccines Yes? or No? Can IIV4s and RIV4 be administered concurrently or sequentially with other inactivated or live-vaccines? Can LAIV4 be administered simultaneously with other inactivated or live vaccines? 39 Consider antivirals agents for prophylaxis (Examples in whom to consider) • Persons with: – Contraindication to an influenza vaccine – High risk of influenza complications during the first two weeks following vaccination after exposure to an infectious person – May have an inadequate response to vaccination (e.g., advanced HIV disease; on immunosuppressive medications) after exposure to an infectious person • Long-term care facility residents, regardless of vaccination status, when an outbreak has occurred in the institution http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm 40 Antiviral dosing for prophylaxis Drug Option for pre-exposure prophylaxis Option for post-exposure prophylaxis Oseltamivir Yes Yes Zanamivir Yes Yes Baloxavir marboxil --- Yes http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm 41 42 Therapeutics: COVID-19 43 Learning objectives • Identify the mode of transmission and incubation period • Recognize the clinical presentation/severity of illness • Navigate through and apply based on latest resources – Vaccines – Clinical management • Recognize the general approach to management • Recognize various treatment options and selected key points 44 Highly recommended website for updates: www.cdc.gov https://www.covid19treatmentguidelines.nih.gov 45 Quick Review COVID-19 • Transmission SARS-CoV-2 – Person to person – Respiratory droplets – Can transmit before the onset of symptoms • Incubation period – May differ by variant of the virus 46 Quick Review Clinical presentation of COVID-19 • • • • https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/clinicalconsiderations-presentation.html; accessed 11-3-2023 Fatigue Headache Sore throat Congestion or runny nose 47 Severity of illness Severity of illness Presentation Asymptomatic or presymptomatic Positive for SARS-CoV-2 but no symptoms Mild Any of the various symptoms But no SOB, dyspnea, or abnormal chest imaging Evidence of lower respiratory disease and O2 sat ≥ 94% O2 sat <94%, RR>30, lung infiltrates >50% Moderate Severe Critical Respiratory failure, septic shock, and/or multiple organ dysfunction https://www.covid19treatmentguidelines.nih.gov/overview/clinicalspectrum/?utm_source=site&utm_medium=home&utm_campaign=highlights; Accessed 11-3-2023 48 Risk factors for progressing to severe COVID-19 Sickle cell disease Diabetes Cancer Obesity CKD Cigarette smoking https://www.covid19treatmentguidelines.nih.gov/overview/ clinicalspectrum/?utm_source=site&utm_medium=home&utm_ca mpaign=highlights; Accessed 11-3-2023 Transplant Immunosuppressive therapy 49 Information on COVID-19 vaccines: • https://www.cdc.gov/vaccines/covid-19 – Accessed 11-3-2023 50 General approach to clinical management Clinical course Early Pathogenesis of COVID-19 General approach Replication of SARS-CoV-2 Later Dysregulated immune/inflammatory response Therapies that directly target SARSCoV-2 Immunosuppressive /anti-inflammatory therapies https://www.covid19treatmentguidelines.nih.gov/management/clinical-management-ofadults/clinical-management-of-adultssummary/?utm_source=site&utm_medium=home&utm_campaign=highlights; last updated: 10/10/2023; accessed: 11/3/2023 51 Therapeutic management - Adults Therapeutic management Nonhospitalized Hospitalized https://www.covid19treatmentguidelines.nih.gov/management/clinical-management-of-adults/clinicalmanagement-of-adults-summary/?utm_source=site&utm_medium=home&utm_campaign=highlights; last updated: 10/10/2023; accessed: 11/3/2023 52 Management of non-hospitalized adults • Supportive care • Reduce the risk of transmission • Seeking appropriate healthcare https://www.covid19treatmentguidelines.nih.gov/management/clinical-management-ofadults/nonhospitalized-adults--therapeutic-management/ last updated: 11/2/2023; accessed: 11/3/2023 53 Management of non-hospitalized patients https://files.covid19treatmentguidelines.nih.gov/guide lines/section/section_140.pdf Refer to PDF Document 2 Options Nirmatrelvir and ritonavir - Paxlovid® Remdesivir Molnupiravir -Lagevrio® Last updated: 10/10/2023; accessed: 11/3/2023 Management of hospitalized adults https://files.covid19treatmentguidelines.nih.gov/guidelines/section/se ction_140.pdf Refer to PDF Document 2 Last updated: 10/10/2023; accessed: 11/3/2023 Options: Remdesivir dexamethasone Janus Kinase (JAK) inhibitor baricitinib IL-6 Receptor antagonist tocilizumab 55 Snapshot of JAK inhibitors and IL-6 receptor antagonists Medication baricitinib Administration PO Blackbox warning • Serious infections • Mortality • Malignancies • Major adverse CV events • Thrombosis tocilizumab Single dose IV infusion • Serious infections 56 Continue to check for updates: www.cdc.gov https://www.covid19treatmentguidelines.nih.gov 57 Therapeutics: Lower respiratory tract infections (LRTI) Bronchiolitis, influenza, and COVID-19 Dhara Surati, Pharm.D., BCPS Clinical Associate Professor PHAR 5338 – ID 2 University of Houston-College of Pharmacy November 7, 2023 [email protected] 58