• Maintain Airway, Breathing and Circulation (ABC)
• Maintain hydration, electrolyte balance and nutrition
• Oxygen therapy is suggested if the patient presents with tachypnea, dyspnea, respiratory distress and less than 90% oxygen saturation. Oxygen cannula, simple mask, partial re-breathing mask (mask with reservoir bag) or non re-breathing mask can be used depending upon the severity of hypoxia. Oxygen hood or head boxes must be used in case of children.
• (mechanical ventilation) with oxygen therapy atSpO2 < 90% and PaO2 < 60 mmHg) is to be given in patients with severe pneumonia and acute respiratory failure. Usually invasive mechanical ventilation is the preferred but in case of unavailability non invasive ventilation remains the option. HEPA filters use is recommended on expiratory ports of the ventilator circuit / high flow oxygen masks for reducing spread of infectious aerosols.
• Vasopressors- for shock.
• It is recommended to drink plenty of fluids. Smokers are suggested to avoid smoking. Lower respiratory tract infection and hypoxia must be constantly monitored clinically / radiologically in every suspected case.
• Medication
  1. Antibiotics- for secondary infection. Patient on mechanical ventilation should be administered antibiotics for prophylaxis of hospital associated infections.
  2. Paracetamol or Ibuprofen is prescribed for fever, myalgia and headache.
  3. For sore throat, short course of topical decongestants, saline nasal drops, throat lozenges and steam inhalation may be beneficial.
  4. Salicylate / Aspirin is strictly contra-indicated in any influenza patient due to its potential to cause Reye’s syndrome.
  5. If the laboratory reports are negative, the patient would be discharged after giving full course of Oseltamivir. Even if the test results are negative, all cases with strong epidemiological criteria need to be followed up.
  6. Immunomodulating drugs have not been found to be beneficial in treatment of ARDS or sepsis associated multi organ failure. High dose corticosteroids in particular have no evidence of benefit and there is potential for harm. Low dose corticosteroids (Hydrocortisone 200-400 mg/ day) may be useful in persisting septic shock (SBP < 90).
  7. Suspected cases without pneumonia do not require antibiotic therapy. Antibacterial agents should be administered, if required, as per locally accepted clinical practice guidelines. ¹⁶

Research revealed that clinical isolates are resistant to Adamantanes (M2 inhibitors), a class of flu drugs but are still sensitive to neuraminidase inhibitors. ⁸

There are four antiviral agents that act against H1N1 influenza A virus.

1. Amantadine,
2. Rimantadine,
3. Oseltamivir and
4. Zanamivir.

• These drugs are prescriptions drugs! Only drugs that work against it now, are neuraminidase inhibitors- Oseltamivir and Zanamivir. This is because Novel Flu A infection is already resistant to the Adamantane antivirals like Amantadine and Rimantadine. Oseltamivir and Zanamivir can also be used for prevention in people not infected by H1N1, but has been in close contact with an already infected patient. These drugs decrease the viral effect and also prevent complications.
• Persons with suspected novel H1N1 influenza presenting with uncomplicated illness do not require treatment except for higher risk for influenza complications,

Indications for treatment:

• All hospitalized patients with confirmed, probable or suspected novel influenza (H1N1).
• Patients who are at higher risk for seasonal influenza complications.

Chemoprophylaxis:
Oseltamivir or Zanamivir are recommended for antiviral chemoprophylaxis of novel (H1N1) influenza virus infection.

Post-exposure:
Duration of post-exposure chemoprophylaxis is 10 days after the last known exposure to novel (H1N1) influenza. The indication for post-exposure chemoprophylaxis is contact with a confirmed, probable or suspected case of novel influenza A (H1N1) virus infection during the infectious period of the case.

Pre-exposure:
For pre-exposure chemoprophylaxis, antiviral medications should be started during potential exposure period which should be continued for 10 days after the last known exposure to a novel (H1N1) influenza virus infected person during the infectious period. ¹²

Drugs, Dosage and their Adverse Reactions:

1. Oseltamivir

The dosage details of this neuraminidase inhibitor are given below in the table.

Agent, group		Treatment	Chemoprophylaxis
Oseltamivir
Adults		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
	16-23 kg	90 mg per day divided into 2 doses	45 mg once per day
	24-40 kg	120 mg per day divided into 2 doses	60 mg once per day
	>40 kg	150 mg per day divided into 2 doses	75 mg once per day
Children < 12 months	<3 months	12 mg twice daily for 5 days	Not recommended unless situation judged  critical due to limited data on use in this age group
	3-5 months	20 mg twice daily for 5 days	20 mg once daily for 10 days
	6-11 months	25 mg twice daily for 5 days	25 mg once daily for 10 days

Adverse Drug Reactions of Oseltamivir

• Nausea and vomiting are frequently and common among adults. Severity of nausea and vomiting decreases if taken with food.
• Transient neuropsychiatric events (self-injury or delirium) were found in post marketing studies; majority reported were among adolescents and adults in Japan. The persons should be monitored closely for abnormal behavior.
• No published studies have assessed whether Oseltamivir impairs the immunologic response to TIV. ¹⁷

2. Zanamivir

Zanamivir, neuraminidase inhibitor drug is also effective for treatment and chemoprophylaxis. Dosages are given in the table below.

Zanamivir
Adults	Two 5-mg inhalations (10 mg total) twice per day	Two 5-mg inhalations (10 mg total) once per day
Children	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)

Adverse Drug Reactions of Zanamivir

1. Most common: Diarrhea, nausea, sinusitis, bronchitis, cough, headache, dizziness, and ear, nose, and throat infections.
2. Limited data is available regarding safety or efficacy of Zanamivir in patients with underlying respiratory disease or for persons with complications of acute influenza. In the postmarketing surveillance, cases of respiratory function deterioration after inhalation of Zanamivir have been reported. Hence, Zanamivir is licensed only for use in persons without underlying respiratory or cardiac disease.
3. Allergic reactions: oropharyngeal and facial edema have also been reported during post marketing surveillance. ¹⁷

Drug Interactions

• Clinical data is limited regarding drug interactions with Zanamivir. However, no known drug interactions with Zanamivir have been reported, and no clinically critical drug interactions have been found in preclinical studies. No clinically identified interactions withRimantadine.
• Limited clinical data is available regarding drug interactions with Oseltamivir. Coadministration of Oseltamivir and probenecidresulted in approximately 50% reduction of clearance of Oseltamivir carboxylate and a corresponding approximate two-fold increase in the plasma levels of Oseltamivir carboxylate. This is because Oseltamivir and Oseltamivir carboxylate urinary excretion by glomerular filtration and tubular secretion via the anionic pathway, potentially interacts with other agents excreted by this pathway.
• Concomitant administration of antihistamines or anticholinergic drugs with Amantadine can increase the incidence of adverse CNS reactions. Monitoring is advised when Amantadine is administered concurrently with CNS drugs including CNS stimulants.
• No published data is available regarding safety or efficacy of using combinations of these antiviral drugs. Package inserts should be read for further information about potential drug interactions. ¹⁷