White Paper: In uenza Treatment Guidelines Update: When are Antiviral Agents Medically Necessary? For Health Plans, Medical Management Organizations and TPAs In uenza Overview In uenza ( u) is a contagious respiratory illness caused by in uenza viruses. Illness can range from mild to severe, but it is important to note that the u is di!erent from a cold or stomach virus, which have similar symptoms. The u usually comes on suddenly, and symptoms are generally worse than a cold and last longer. Most people who get the u recover in a few days to less than two weeks. However, some individuals may develop potentially life threatening complications. The u is caused by two main types of in uenza virus type A, which can be broken down into subtypes depending on the genes that make up the surface proteins, and type B. Di!erent types (A and B) and subtypes (A) of in uenza circulate and cause illness over the course of a u season. In uenza symptoms vary from person to person, but usually include fever, cough, sore throat, runny or stu!y nose, muscle or body aches, headache, and fatigue. Some patients with u may have a fever. In addition, nausea, vomiting, and diarrhea are more common in children than in adults. Flu severity depends on a number of factors, including: what u viruses are spreading, how much u vaccine is available, when the vaccine is available, how many people get vaccinated, and how well the u vaccine is matched to spreading u viruses. Diagnostic Tests The availability and use of commercial in uenza rapid diagnostic tests, which provide results within 15 minutes, has increased signi"cantly in recent years. Some tests can identify in uenza A and B viruses and distinguish between them, and some can identify in uenza A and B viruses but cannot distinguish between them. Most tests can be used with a variety of specimen types (nasopharyngeal or nasal aspirates, swabs; washes or throat swabs), but the accuracy of tests varies based on the type of specimen collected. It is important for specimens to be collected as close as possible to the start of symptoms. Table 1 shows rapid in uenza diagnostic tests that are approved by the U.S. Food and Drug Administration (FDA). Table 1. FDA-Approved Rapid In uenza Diagnostic Tests Antiviral medications with activity against in uenza viruses are an important adjunct to in uenza vaccine in the control of in uenza. They can be used to treat in uenza or to prevent in uenza. Test 3M Rapid Detection Flu A+B test Alere In uenza A & B BinaxNOW In uenza A&B BD Veritor System for Rapid Detection of Flu A+B CLIA-waived Manufacturer 3M Alere Becton Dickinson BD Veritor System for Rapid Detection of Flu A+B Moderately Complex Directigen EZ Flu A+B AllMed Healthcare Management Inc. 1
BioSign Flu A+B OSOM In uenza A&B QuickVue In uenza Test Princeton BioMedtech Sekisui Diagnostics Quidel QuickVue In uenza A+B Test So"a In uenza A+B SAS FluAlert A&B SA Scienti"c SAS FluAlert A SAS FluAlert B TRU FLU XPECT Flu A&B Meridian Bioscience Remel/Thermo"sher Other in uenza virus testing methods include viral cell culture, rapid cell culture (shell vials; cell mixtures), immuno uorescence, direct (DFA) or indirect (IFA) antibody staining, and reverse transcription-polymerase chain reaction (RT-PCR) (singleplex and multiplex; real-time and other RNA-based) and other molecular assays. In uenza Complications Some individuals are at greater risk for developing in uenza complications such as pneumonia, bronchitis, sinus and ear infections, and worsening of chronic health problems. High-risk populations include children under the age of 2, adults who are 65 and older, women who are pregnant or postpartum (within two weeks after delivery), American Indians and Alaska Natives, and residents of nursing homes and other chronic-care facilities. In addition, individuals with certain medical conditions are more likely to develop u complications (Table 2). Table 2. Medical Conditions Associated with with Higher Risk for Complications Asthma; Neurological and neurodevelopmental conditions (for example, cerebral palsy, epilepsy, muscular dystrophy, or spinal cord injury); Chronic lung disease; Heart disease; Blood, endocrine, kidney, liver, or metabolic disorders; Weakened immune system due to disease or medication; People less than 19 years of age who are receiving long-term aspirin therapy; or People who are morbidly obese (BMI #40 kg/m2). 2
Management Strategies for In uenza Prevention Prevention is the most e!ective management strategy for in uenza, and annual u vaccination is the most e!ective strategy for preventing in uenza. The 2014-15 northern hemisphere vaccine contains the following in uenza strains: A/California/7/2009 (H1N1)-like, A/Texas/50/2012 (H3N2), and B/Massachusetts/2/2012-like (B/Yamagata lineage). The quadrivalent vaccines contain an additional B strain: B/Brisbane/60/2008-like (B/Victoria lineage). An in uenza pandemic can occur when a new in uenza virus emerges for which there is little or no immunity in the human population, and it spreads easily from person to person worldwide. All past in uenza pandemics in humans have been caused by in uenza A viruses. Strategies to contain pandemic in uenza are critical and should include: surveillance and diagnostic services, information sharing and dissemination, community support, hospital and physician capacity, and supply and delivery of vaccines and drugs. Antiviral Medications for In uenza Antiviral medications with activity against in uenza viruses are an important adjunct to in uenza vaccine in the control of in uenza. They can be used to treat in uenza or to prevent in uenza (chemoprophylaxis). Prescription antiviral drugs that are FDA-approved for chemoprophylaxis and treatment of in uenza include neuraminidase inhibitors and adamantanes. Neuraminidase inhibitors (oseltamivir and zanamivir) have activity against in uenza A and B viruses (including H1N1). Adamantanes (amantadine, rimantadine) have activity against in uenza A viruses only. Since 2006, only the neuraminidase inhibitors have been recommended because of widespread resistance to the adamantanes among in uenza A virus strains. Oseltamivir (Tami u) has activity against in uenza A and B, and is indicated for the treatment of acute uncomplicated in uenza in persons 14 days and older and for in uenza chemoprophylaxis in persons 1 year and older. Adverse events include nausea and vomiting, as well as sporadic transient neuropsychiatric events (self-injury or delirium) mainly reported among Japanese adolescents and adults. Zanamivir (Relenza) has activity against in uenza A and B, and is indicated for the treatment of in uenza in persons seven years and older and for in uenza chemoprophylaxis in persons "ve years and older. It is not recommended for use in people with underlying respiratory disease (for example, asthma or COPD), and it is contraindicated in patients with a history of allergy to milk protein. Potential allergic reactions include oropharyngeal or facial edema, and adverse events can include diarrhea, nausea, sinusitis, nasal signs and symptoms, bronchitis, cough, headache, dizziness, and ear, nose, and throat infections. Practice Parameters and Guidelines for Antiviral Medications The Centers for Disease Control and Prevention (CDC) does not recommend the widespread or routine use of antiviral medications for in uenza chemoprophylaxis since indiscriminate use of chemoprophylaxis might promote resistance to antiviral medications, and reduce antiviral medication availability for treatment of persons at higher risk for in uenza complications or those who are severely ill. The CDC outlines situations in which antivirals can be considered for in u- enza chemoprophylaxis: Prevention of in uenza in persons at high risk of in uenza complications during the "rst two weeks following vaccination after exposure to an infectious person; Prevention for people with severe immune de"ciencies or others who might not respond to in uenza vaccination, such as persons receiving immunosuppressive medications, after exposure to an infectious person; Prevention for people at high risk for complications from in uenza who cannot receive the in uenza vaccine due to a contraindication after exposure to an infectious person; or Prevention of in uenza among residents of institutions, such as long-term care facilities, during in uenza outbreaks in the institution; 3
According to the CDC Advisory Committee on Immunization Practices (ACIP), antiviral treatment is recommended as early as possible for any patient with con"rmed or suspected in uenza who: is hospitalized; has severe, complicated, or progressive illness; or is at higher risk for in uenza complications. Antiviral treatment also may be considered on the basis of clinical judgment for any outpatient with con"rmed or suspected in uenza who does not have known risk factors for severe illness if treatment can be initiated within 48 hours of illness onset. In addition, decisions about starting antiviral treatment should not wait for laboratory con"rmation of in uenza. Antiviral medications recommended by ACIP include oseltamivir and zanamivir. Amantadine and rimantadine should not be used because of the high levels of resistance to these drugs among circulating in uenza A viruses; however, this may change over time. Oseltamivir may be used for treatment or chemoprophylaxis of in uenza among infants less than one year of age when indicated. Clinicians should monitor local antiviral resistance surveillance data, as antiviral resistance patterns can change over time. With regard to treatment considerations for patients hospitalized with suspected or con"rmed in uenza, ACIP recommends initiation of antiviral treatment as early as possible. Antiviral treatment might be e!ective in reducing morbidity and mortality in hospitalized patients even if treatment is not started until more than 48 hours after onset of illness. For hospitalized patients and patients with severe or complicated illness, treatment with oral or enterically administered oseltamivir is recommended; inhaled zanamivir is not recommended because of the lack of data for use in patients with severe in uenza. Determing Medical Necessity for In uenza Antiviral Medications Most health plans that include a pharmacy bene"t will cover Tami u and/or Relenza for treatment of a diagnosis, or as a preventive measure as prescribed by a healthcare provider. However, antiviral medications for in uenza treatment or chemoprophylaxis are generally not covered for people who are not at higher risk for complications or do not have severe in uenza requiring hospitalization. An independent medical review, which is normally used by healthcare payers, looks at whether a speci"c treatment was medically necessary. The specialty match that an independent review organization (IRO) provides is especially important in considering treatment options for in uenza, as new strains of the virus and antiviral resistance patterns emerge. The board-certi"ed physician specialists who work with IROs keep up-to-date with the latest medical research literature and with the latest standard of care. Physicians who review cases for IROs stay on top of continually evolving treatments as they are studied more extensively and potentially accepted into clinical guidelines. Independent medical reviews also avoid con icts of interest, which can relate to economics, lack of specialists to review cases, or having the same doctor who denied a case review an appeal. Conclusion The CDC continues to recommend annual vaccination as the best tool for preventing in uenza, as well as timely use of antiviral medications to treat in uenza in select patients. While antiviral drugs can help reduce the duration and severity of u symptoms, the decision to use them must be based on individual evaluations of risk and bene"t. 4
Bibliography Epstein LJ, et al. Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009; 5: 263-276. Aurora RN, et al. Practice parameters for the surgical modi"cations of the upper airway for obstructive sleep apnea in adults. Sleep. 2010; 33: 1408-1413. About AllMed AllMed Healthcare Management provides physician review outsourcing solutions to leading health plans, medical management organizations, TPAs and integrated health systems, nationwide. AllMed o!ers MedReview (SM), MedCert (SM), and Medical Director sta$ng services that cover initial pre-authorizations and both internal and external appeals, drawing on a panel of over 400 board-certi"ed specialists in all areas of medicine. Services are deployed through PeerPoint, AllMed s state-of-the-art medical review portal. For more information on how AllMed can help your organization improve the quality and integrity of healthcare, contact us today at info@allmedmd.com or visit us at 621 SW Alder St., Suite 740 Portland, OR 97205 800-400-9916 5