2009 Influenza A, H1N1: An Update for Pharmacists (October 7, 2009)

Transcription

1 2009 Influenza A, H1N1: An Update for Pharmacists (October 7, 2009) APHA-ASP COP Fall Seminar Dan Healy, Pharm.D., FCCP, FIDSA Winkle College of Pharmacy University of Cincinnati

2 Objectives Discuss the similarities and differences between H1N1 and seasonal strains of influenza with respect to risk factors, high-risk populations, infectivity and disease transmission, signs/symptoms, and complications. Discuss with the most recent and available data on the safety and efficacy of the H1N1 vaccine under the various conditions and studies (e.g., 1 vs 2 dose, simultaneous vs sequential administration with the seasonal vaccine, young, elderly, pregnancy, obesity)

3 Objectives (continued) Recommend the most recent data on the appropriate use of antivirals for the prophylaxis and treatment of H1N1. Counsel patients with respect to disease prevention, vaccine administration and antiviral management.

4

5 Hey, you re the ones that need to be quarantined, not us!

6 1918 Pandemic H1N1 strain: million deaths worldwide (>2% death rate)

7 Seasonal Influenza 3 5 million cases of severe illness WW 250, ,000 annual deaths WW 200,000 hospitalizations and 36,000 deaths in US (ACM 50,000 deaths/yr) o >90% of deaths occur in > age 65 o Overall death rate < 0.01% cdc.gov

8 Novel H1N1 Influenza The first cases of human infection with novel H1N1 influenza virus were detected in April 2009 in San Diego and Imperial County, California and in Guadalupe County, Texas. Swine, avian human genetic material The virus has spread rapidly. The virus is widespread in US and has been detected internationally

9 April 09 June 09

10 MMWR, Sept 2009

11

12

13

14 Influenza A H1N1 HA (1-16), NA (1-9); capable of shift and drift Adamantanes inhibit M2 protein (uncoating) Neuraminidase inhibitors interfere with release of the virus

15 Viral Replication

16 Immune System Challenge H1N1

17 2009 Influenza A, H1N1 Strain Shorter incubation time Viral shedding (infectivity): 1 day pre-sx, for 5-7 days Strikes younger adults-those generally not thought to be high-risk Some immune recognition in those > 50 yr Replicates significantly better in lungs Obesity a risk factor? 9/10 in ICU U Mich; unusual findings; organ dysfunction; 3/10 died.

18 2009 Influenza A, H1N1 Strain Distant cousin to H1N1, 1918 pandemic strain Est. > 1 million cases in US (10/09) Pandemic spread globally in < 2 months 191 countries to date >4,000 deaths worldwide, >600 in US (10/09) Stopped counting in July 2009 Expected death rate: % Susceptible to oseltamivir, zanamivir Safe, effective vaccine currently being distributed

19 Signs and Symptoms Symptoms of novel H1N1 flu in people are similar to those associated with seasonal flu. Fever Cough Sore throat Runny or stuffy nose Body aches Headache Chills Fatigue Vomiting (25%), diarrhea (25%) (Higher rate than for seasonal flu.)

20 How does novel H1N1 Influenza spread? Same way as seasonal flu Primarily through respiratory droplets Coughing Sneezing Touching respiratory droplets on yourself, another person, or an object, then touching mucus membranes (e.g., mouth, nose, eyes) without washing hands

21 Everyday steps to protect your health Wash your hands often with soap and warm water, especially after you cough or sneeze. Wash for seconds. Alcohol-based hand wipes or gel sanitizers are also effective.

22 Everyday steps to protect your health Cover your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash after you use it. If no tissue, use arm/upper sleeve Avoid touching your eyes, nose or mouth. Avoid contact with sick people.

23 If you get sick Stay home if you re sick for 7 days after your symptoms begin or until you ve been symptom-free, fever-free, for 24 hr whichever is longer. If you are sick, limit your contact with other people as much as possible.

24 Watch for emergency warning signs Most people should be able to recover at home, but watch for emergency warning signs that mean you should seek immediate medical care. In adults: Difficulty breathing or shortness of breath Pain or pressure in the chest or abdomen Sudden dizziness Confusion Severe or persistent vomiting Flu-like symptoms improve but then return with fever and worse cough

25 Emergency warning signs in children In children: Fast breathing or trouble breathing Bluish or gray skin color Not drinking enough fluids Severe or persistent vomiting Not waking up or not interacting Irritable, the child does not want to be held Flu-like symptoms improve but then return with fever and worse cough Seek emergency medical care.

26 Testing Viral culture- not timely real-time RT-PCR conducted at a State Health Department Laboratory. Confirmation of H1N1 is now performed at the CDC but is now available in many state public health laboratories. Rapid Tests % sensitive Utility: only if positive, distinguishes A vs B DFA, IFA- distinguishes A vs B, helpful if (+) Currently, testing only on hospitalized patients

27 Current Guidelines for Antiviral Use Updated 9/8/09 (CDC) Suspected or confirmed influenza requiring hospitalization- may require longer than 5 days of treatment Those at risk for influenza-related complications (< 2 yr, >65 yr, pregnancy, chronic medical conditions, immunosuppressed) Clinical judgement for those not in above groups Post-exposure prophylaxis discouraged in healthy patients- early treatment preferred Must balance those who will most benefit with minimizing antiviral resistance

28 Anti-viral Treatment Suspected cases: Zanamivir or oseltamivir as soon as possible after the onset of symptoms and for a duration of 5 days. Confirmed cases: Zanamivir or oseltamivir for 5 days. Pregnant women: Antiviral medications are in Pregnancy Category C, so they should be used during pregnancy only if the potential benefit outweighs the potential risk to the embryo or fetus. Children younger than 1 year: Because infants typically have high rates of morbidity and mortality from influenza, infants with swine influenza A (H1N1) infections may benefit from treatment with oseltamivir. Detailed guidance on antiviral treatment for swine flu may be found here:

29 Table 1.Antiviral medication dosing recommendations for treatment or chemoprophylaxis of 2009 H1N1 infection. (Table extracted from product information for Tamiflu and Relenza ) Medication Oseltamivir (Tamiflu) Treatment (5 days) Adults 75-mg capsule twice per day Children 12 months Chemoprophylaxis (10 days) 75-mg capsule once per day Body Weight (kg) Body Weight (lbs) Treatment Prophylaxis 15 kg 33lbs 30 mg twice daily 30 mg once per day > 15 kg to 23 kg >33 lbs to 51 lbs 45 mg twice daily 45 mg once per day >23 kg to 40 kg >51 lbs to 88 lbs 60 mg twice daily 60 mg once per day >40 kg >88 lbs 75 mg twice daily 75 mg once per day

30 Table 2. Dosing recommendations for antiviral treatment or chemoprophylaxis of children younger than 1 year using oseltamivir. Age Recommended treatment dose for 5 days Recommended prophylaxis dose for 10 days Younger than 3 months 12 mg twice daily Not recommended unless situation judged critical due to limited data on use in this age group 3-5 months 20 mg twice daily 20 mg once daily 6-11 months 25 mg twice daily 25 mg once daily Children younger than 1 year of age are at higher risk for influenza-related complications and have a higher rate of hospitalization compared to older children. Oseltamivir is not approved for use in children younger than 1 year of age. However, limited safety data on oseltamivir treatment of seasonal influenza in children younger than 1 year of age suggest that severe adverse events are rare. Oseltamivir is authorized for emergency use in children younger than 1 year of age under an EUA issued by FDA, subject to the terms and conditions of the EUA.

31 Tamiflu Oral Suspensions: Special Instructions Health care providers and pharmacists should be aware that an oral dosing dispenser with 30 mg, 45 mg, and 60 mg graduations is provided with TAMIFLU for Oral Suspension, rather than graduations in milliliters (ml) or teaspoons (tsp). There have been cases where the units of measure on the prescription instructions (ml, tsp) do not match the units on the dosing device (mg), which has lead to patient or caregiver confusion and dosing errors. When dispensing commercially manufactured TAMIFLU for Oral Suspension, pharmacists should ensure the units of measure on the prescription instructions match the dosing device. If prescription instructions specify administration using millilters (ml) or teaspoons (tsp), then the device included in the Tamiflu product package should be removed and replaced with an appropriate measuring device, such as an oral syringe if the prescribed dose is in milliliters (ml). Adverse Effects: mostly mild, GI (nausea, vomiting) rare, but severe (delirium, abnormal behavior)

32 Zanamivir (Relenza) Adults 10 mg (two 5-mg inhalations) twice daily 10 mg (two 5-mg inhalations) once daily Children ( 7 years or older for treatment, 5 years for chemoprophylaxis) 10 mg (two 5-mg inhalations) twice daily 10 mg (two 5-mg inhalations) once daily Not for those with underlying respiratory and cardiac disease, including those with asthma. Side effects mild and infrequent (<5%): nasal symptoms, HA, dizziness, nausea, diarrhea

33 Samples tested (n) Resistant Viruses, Number (%) Samples tested (n) Resistant Viruses, Number (%) Samples tested (n) Resistant Viruses, Number (%) Oseltamivir Zanamivir Adamantan es Seasonal Influenza A (H1N1) 1,148 1,143 (99.6%) 1,148 0 (0) 1,153 6 (0.5%) Influenza A (H3N2) (0) (0) (100%) Influenza B (0) (0) N/A* N/A* 2009 Influenza A (H1N1) 1,865 9 (0.6) (0) (100%)

34

35 Response after One dose of a Monovalent Influenza A (H1N1) 2009 Vaccine- A Preliminary Report 240 healthy adults (18-49 yr [120], yr [120]) Randomized, observer-blind, parallel group, single-site trial in Australia Inactivated, split virus (A/California/7/2009) 15 µg, 30 µg HA antigen (1:1) multi-dose vials w/ thimerosol 0.01% w/v Endpoints: antibody titers t= 0, 21 days; adverse events Greenberg et al. NEJM 2009;361, pub;lished online 9/10/09

36 Response after One dose of a Monovalent Influenza A (H1N1) 2009 Vaccine- A Preliminary Report Immunogenicity Endpoint HI titer 1:40 % (95%CI) Seroconversion or significant increase in titer % (95%CI) Factor increase in geometric mean titer 15 µg dose (all ages) 116/ % ( ) 30 µg dose (all ages) 112/ % ( ) 70.8 ( ) 77.5 ( ) 10.7 ± ± 5.64 Robust immune response even in subjects without measurable antibodies at baseline: possible cross protection from other H1N1; shares gene sequences from seasonal H1N1, H3N2 strains Greenberg et al. NEJM 2009;361, published online ahead of print 9/10/09

37 Response after One dose of a Monovalent Influenza A (H1N1) 2009 Vaccine- A Preliminary Report Adverse Event Any Local Event Pain Tenderness Redness Any Systemic Event Fever Headache Malaise Myalgia Chills Nausea Vomiting Proportion (n=240) Within 7 days 46.3 (43.8% mild, 2.5% mod) 21.7 (20.8% mild, 0.8% mod) 36.7 (35.0% mild, 1.7% mod) 9.2 (8.8% mild, 0.4% mod) 45.0 (35.8% mild, 8.3% mod, 0.8 severe) 3.8 (2.1% mild, 1.7% mod) 31.3 (27.1% mild, 4.2% mod) 17.5 (14.2% mild, 2.9% mod, 0.4% severe) 17.1 (13.8%, 2.9%, 0.4%) 6.7 (5.8% mild, 0.8% mod) 7.1 (5.0% mild, 1.3% mod, 0.8% severe) 0.8 (0% mild, 0.8% mod) Greenberg et al. NEJM 2009;361, published online ahead of print 9/10/09

38 Response after One dose of a Monovalent Influenza A (H1N1) 2009 Vaccine- A Preliminary Report Conclusions: Even a single 15 µg dose produced significant Ab response Proportion of subjects with HI titer 1:40 was similar between doses and between age groups Proportion of subject with seroconversion was slightly higher in younger age group and in higher dose Absolute geometric mean titers were substantially higher in the younger age group Frequency and severity of adverse events consistent with seasonal influenza vaccines in adults Full safety profile not yet elucidated (post-licensure surveillance required for rare events) Greenberg et al. NEJM 2009;361, published online ahead of print 9/10/09

39 Preliminary Results from Influenza A H1N1 Vaccine Trial in Pediatrics Blood samples from approx. 600 children 8-10 days following one 15 µg dose of inactivated, unadjuvanted vaccine (Sanofi Pasteur) revealed robust immune responses (i.e., 1:40 hemagluttinin inhibition titers) in: 76% of children aged years 10 yrs: single dose 36% of children aged 3-9 years >35 mo 9 yrs: 2 doses separated by days 25% of children aged 6-35 months 6-35 months: 2 vaccinations at ½ dose separated by days Dr. Fauci, NIAID, press briefing, 9/21/09 infectiousdiseasesnews.com

40 Comparison of Inactivated (shot) vs Live-Attenuated (nasal) Seasonal Flu Vaccine in Adults Randomized, placebo-controlled trial on 4 Univ of Michigan campuses 1,952 volunteers, age years comparing Trivalent Inactivated (Fluzone, Sanofi-Pasteur) vs Live-Attenuated (Flu-Mist), Medimmune) Absolute efficacy: Inactivated: 68% (60-81%); 72% vs Influenza A only LAIV: 36% (0-59%); 29% vs Influenza A only Unclear as to why LAIV is less effective in adults than children Will there be differences in protection with H1N1 vaccines? Monto et al. NEJM, 2009;Sep 24; 36(13):1260-7

41 2009 H1N1 Influenza Vaccine Inactivated (IM); Live-attenuated (intranasal) A/California/07/2009 (H1N1) 4 vaccines FDA-approved 9/15/09 CSL Biotherapeutics Astra Zeneca MedImmune Novartis Sanofi Pasteur GlaxoSmithKline- soon to be approved Non-adjuvanted Some lots to contain thimerosol

42 5 Priority Groups for H1N1 Vaccine (est.159 million) Pregnant women* Health-care & emergency medical services personnel o Direct contact- highest priority* Those who live with or care for infants age < 6 months* Anyone age 6 months through 24 years (6 mos 4 yr)* Age years with chronic medical conditions or weakened immune systems (high-risk for influenza-related complications) (5-18 yr w/chronic condition*) *highest priority if vaccine is insufficient for demand CDC ACIP Guidelines, MMWR, Aug 21, 2009 (Epub online)

43 CDC ACIP Guidelines for Use of Influenza A (H1N1) Monovalent Vaccine The guiding principle of these recommendations is to vaccinate as many persons as possible as quickly as possible. ACIP will review new epidemiologic and clinical data as they become available and might revise these recommendations. MMWR, Aug 21, 2009 (online)

44 CDC ACIP Guidelines for Use of Influenza A (H1N1) Monovalent Vaccine Once demand is met for targeted groups, vaccination expanded to all persons aged years followed by adults > 65 years The number of doses required has not been fully established. Age 10 yrs and older- one dose Age 6 months to 9 years- two doses separated by 4 wks (3 wks min) Simultaneous administration of inactivated seasonal and inactivated H1N1 is okay- different sites Simultaneous administrated of live attenuated seasonal (Flu-Mist) and live-attenuated (intranasal H1N1) is NOT recommended All persons recommended to receive seasonal influenza vaccine should do so as soon as possible. Seasonal and H1N1 can be given simultaneous with pneumococcal polysaccharide vaccine MMWR, Aug 21, 2009 (online)

45 Contraindications to H1N1 Vaccine Severe, life-threatening egg allergy Severe allergic reaction to any seasonal flu vaccine Guillain Barré Syndrome (GBS) Note: pregnancy or breastfeeding are not contraindications; however they should get the inactivated vaccine (shot), not live-attenuated (nasal).

46 Adverse Effects of H1N1 Vaccine Soreness, redness, tenderness, swelling at injection site (most common) Fainting Headaches, muscle aches Fever Nausea Usually occurs soon after the shot and may last 1-2 days; treat symptomatically

47 Live, Attenuated H1N1 Vaccine (nasal spray vaccine) Healthy, non-pregnant, age 2 49 years 1 st priority: age 2-24 years 2 nd : age years who live with or care for infants younger than 6 months of age OR are health care or emergency medical personnel. 3 rd : remainder of age years VIS H1N1 LAIV, 10/2/09

48 Live, Attenuated H1N1 Vaccine NOT recommended for: (nasal spray vaccine) Children < 2 years or adults 50 years Pregnancy Weakened immune system or close contacts of severely weakened immune system Chronic health problems Children < age 5 yr with asthma or 1 or more episodes of wheezing in the past year Muscle or nerve disorders Should not be given together with seasonal Flu-Mist

49 Adverse Effects of H1N1 Nasal Spray Vaccine Runny nose, nasal congestion (most common in all ages), cough Sore throat (adults) Fever (more common in children 2-6 yrs), chills Headaches, muscle aches Tiredness, weakness Wheezing Abdominal pain or occasional d, v Usually occurs within minutes to hours after nasal delivery; treat symptomatically VIS H1N1 LAIV, 10/2/09

50 In the Event of Rare, Severe Reactions High fever Behavior changes neuromuscular (either IM or nasal spray) Difficulty breathing, hoarseness, wheezing, hives, paleness, weakness, tachycardia, dizziness Seek immediate medical treatment Report to Vaccine Adverse Event Reporting System VIS H1N1 Inactivated, LAIV, 10/2/09

51 H1N1 Vaccine Roll-Out: Many May Wait Until November Week 1: million doses Mid-October: million doses November: >100 million doses End of 2009: 200 million doses? Only as shipments start arriving will doctors, clinics, school vaccination programs, and drugstores get word that their doses are coming, and how much. Each state health department will decide that.

52 October 6, 2009 (New York Times) Swine Flu Vaccine Reaches an Anxious Nation By ANEMONA HARTOCOLLIS The fear of swine flu is being compounded by new worries, this time among primary care doctors who say that they are swamped by calls from patients seeking the new vaccine, and that they are ill-prepared to cope with the nationwide drive to immunize everyone, particularly children and chronically ill adults. The federal Centers for Disease Control and Prevention released the first doses of vaccine on Monday. But many doctors, especially pediatricians, say they know little about the program and have been deluged with questions.

53 October 6, 2009 (New York Times) Swine Flu Vaccine Reaches an Anxious Nation By ANEMONA HARTOCOLLIS I ve heard a lot about how much confusion there is about how to get the vaccine, Ms. Sebelius said Friday. We ll never, from the mother ship, give one national picture, she added. It s going to be many, many local decisions. What we do need to know is, if that information isn t getting across, then maybe we can do something about it. Some doctors wondered whether the vaccination drive was necessary for a flu that has caused only mild symptoms in most cases. They said some of their patients had expressed doubts about whether the vaccine had been sufficiently tested for safety, and they admitted that they were sympathetic to those fears.

54 The Current Challenge Logistics How to organize thousands of workers at >90,000 sites to administer 250 million doses in 3-4 months making sure those greatest at risk are first in line Vaccine coming out in 6-20 million dose batches Kids under 9 needs 2 doses of seasonal (1 st time) and 2 doses of H1N1 separated by 4 weeks A skeptical public Consumer Reports poll: 34% of adult Americans plan to get vaccine; 35% plan to vaccinate their children Mild flu, not necessary Safety concerns: Guillain-Barré syndrome, thimersol

55 Moving Forward Continued preparedness planning and execution Exercise appropriate level of concern Global infections require global effort Educate yourself and the community (cdc.gov) Understand and practice prevention Get your seasonal and H1N1 flu vaccinations Live your life

56 Living with Viruses

57 Dancing with the SARS?