A QUICK GUIDE TO ANTIVIRAL DRUGS FOR THE NOVEL H1N1 INFLUENZA VIRUS
Jaideep A Gogtay, MDMedical Director, Cipla Limited, Mumbai 400008Email: firstname.lastname@example.org
Q1. Which drugs are available for treatment of the new HINI flu virus (also called swine flu)?Currently 2 drugs are recommended, viz. oseltamivir (Tami flu, Ant flu) and Zanamivir (Elena, Vicenza) for the treatment and prophylaxis against flu. Oseltamavir is given orally while Zanamivir is given by the inhaled route. Recommendations for use of antivirals may change as data on antiviral effectiveness, clinical spectrum of illness, adverse events from antiviral use, and antiviral susceptibility data become available. Q2. How do these drugs act?The virus attacks the lungs and replicates in the cells. These drugs act by blocking the release of new virus particles from the cells that the virus has infected. This prevents the spread of the virus to other cells in the lungs. Treatment should be started within 48 hours of onset of symptoms.Q3. Who should be treated?Clinical judgment is an important factor in treatment decisions. Persons with suspected novel H1N1 influenza who present with an uncomplicated febrile illness typically do not require treatment unless they are at higher risk (see Q5) for influenza complications. Treatment is recommended for:
All hospitalized patients with confirmed, probable or suspected novel influenza (H1N1).
Patients who are at higher risk for seasonal influenza complications (see above). If a patient is not in a high-risk group or is not hospitalized, healthcare providers should use clinical judgment to guide treatment decisions, and when evaluating children should be aware that the risk for severe complications from seasonal influenza among children younger than 5 years old is highest among children younger than 2 years old. Many patients who have had novel influenza (H1N1) virus infection, but who are not in a high-risk group have had a self-limited respiratory illness similar to typical seasonal influenza. For most of these patients, the benefits of using antivirals may be modest. Therefore, testing, treatment and chemoprophylaxis efforts should be directed primarily at persons who are hospitalized or at higher risk for influenza complications. Once the decision to administer antiviral treatment is made, treatment with zanamivir or oseltamivir should be initiated as soon as possible after the onset of symptoms. Evidence for benefits from antiviral treatment in studies of seasonal influenza is strongest when treatment is started within 48 hours of illness onset. However, some studies of oseltamivir treatment of hospitalized patients with seasonal influenza have indicated benefit, including reductions in mortality or duration of hospitalization even for patients whose treatment was started more than 48 hours after illness onset. Recommended duration of treatment is five days. Antiviral doses recommended for treatment of novel H1N1 influenza virus infection in adults or children 1 year of age or older are the same as those recommended for seasonal influenza. In India where there is limited antiviral mediation availability, local public health authorities should be contacted for guidance about prioritizing treatment within groups at higher risk for infection. Note: Some areas of the world have seasonal influenza activity with oseltamivir-resistant seasonal human influenza A (H1N1) viruses. In such places, either zanamivir or a combination of oseltamivir and rimantadine or amantadine should be used to provide adequate empiric treatment or chemoprophylaxis for patients who might have seasonal human influenza A (H1N1) virus infection. The status of resistance in India is unknown at the moment. Q4. Who should receive prophylaxis?This again requires clinical judgment. The infectious period for persons infected with the novel influenza A (H1N1) virus is assumed to be similar to that observed in studies of seasonal influenza i.e. beginning one day before they develop symptoms to up to 7 days after the onset of illness. Children, especially younger children, might potentially be infectious for longer periods. If the contact occurred with a case whose illness started more than 7 days before contact with the person under consideration for antivirals, then chemoprophylaxis is not necessary. In general, post exposure antiviral chemoprophylaxis with either oseltamivir or Zanamivir can be considered for the following:
Close contacts of cases (confirmed, probable, or suspected) who are at high-risk for complications of influenza
Health care personnel, public health workers, or first responders who have had a recognized, unprotected close contact exposure to a person with novel (H1N1) influenza virus infection (confirmed, probable, or suspected) during that person’s infectious period. For pre-exposure chemoprophylaxis, antiviral medications should be given during the potential exposure period and continued for 10 days after the last known exposure to a person with novel (H1N1) influenza virus infection during the cases infectious period. Q5. Which is the high risk group?A person who is at high-risk for complications of novel influenza (H1N1) virus infection is the same for seasonal influenza at this time. As more epidemiologic and clinical data become available, these risk groups might be revised.
Children younger than 5 years old. The risk for severe complications from seasonal influenza is highest among children younger than 2 years old.
Adults 65 years of age and older.
Persons with the following conditions:
Chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological (including sickle cell disease), neurologic, neuromuscular, or metabolic disorders (including diabetes mellitus);
Immunosuppression, including that caused by medications or by HIV;
Persons younger than 19 years of age who are receiving long-term aspirin therapy;
Residents of nursing homes and other chronic-care facilities.
Q6. What is the dose of the drugs?Both Oselatamivir and Zanamavir are indicated for treatment and prophylaxis. The tables given below show the dosing of both oseltamivir and Zanamivir as treatment and prophylaxis. Table 1. Antiviral medication dosing recommendations for treatment or chemoprophylaxis of novel influenza A (H1N1) infection. (Table extracted from IDSA guidelines for seasonal influenza.)
75-mg capsule twice per day for 5 days
75-mg capsule once per day
Children >_ 12 months
15 kg or less
60 mg per day divided into 2 doses
30 mg once per day
90 mg per day divided into 2 doses
45 mg once per day
120 mg per day divided into 2 doses
60 mg once per day
150 mg per day divided into 2 doses
75 mg once per day
Two 5-mg inhalations (10 mg total) twice per day
Two 5-mg inhalations (10 mg total) once per day
Two 5-mg inhalations (10 mg total) twice per day (age, 7 years or older)
Two 5-mg inhalations (10 mg total) once per day (age, 5 years or older)Children Under 1 Year of AgeOseltamivir is not licensed for use in children less than 1 year of age. An emergency authorization has been issued for this recently. However, limited safety data on oseltamivir treatment for seasonal influenza in children less than one year of age suggest that severe adverse events are rare. Because infants experience high rates of morbidity and mortality from influenza, infants with novel (H1N1) influenza virus infections may benefit from treatment using oseltamivir. Table 2. Dosing recommendations for antiviral treatment of children younger than 1 year using oseltamivir.
Recommended treatment dose for 5 days
12 mg twice daily
20 mg twice daily
25 mg twice daily Table 3. Dosing recommendations for antiviral chemoprophylaxis of children younger than 1 year using oseltamivir.
Recommended prophylaxis dose for 10 days
Not recommended unless situation judged critical due to limited data on use in this age group
20 mg once daily
25 mg once daily Q7. What are the side effects of these drugs?In general both these drugs are well tolerated. Nausea and vomiting can occur with the use of oseltamivir while transient neuropsychiatric effects have been reported among patients taking Oseltamavir. Zanamivir is not indicated in patients with underlying airway disease. Please consult full prescribing information for further details. Q8. Where are these drugs available?Oseltamavir is available through government hospitals and they should be contacted for more information. (www.mohfw.nic.in). IMPORTANT: The information provided above is as of August 8, 2009. With time this may change. Readers are requested to keep themselves updated. (www.who.int; www.cdc.gov; www.mohfw.nic.in)