Tamiflu (Generic Name: Oseltamivir) is an antiviral medicine that inhibits viral replication.

Tamiflu Indications:

• Prophylaxis of Seasonal Influenza:

  • It is used for the prophylaxis of seasonal influenza A or B infection in patients 1 year of age or older.

• Treatment of Seasonal Influenza:

  • It is used in the treatment of seasonal influenza in patients with uncomplicated acute illness due to influenza A or B infection in patients 2 weeks of age or older who have been symptomatic for no more than 48 hours.

• Prophylaxis and treatment of Avian influenza:

  • It is also used as an off-label medicine for the treatment and prophylaxis of Avian Influenza A (H7N9 or H5N1).

• Tamiflu (Oseltamivir) as off-label use in the treatment of Coronavirus infection (COVID-19):

  • Oseltamivir is being used in the treatment algorithm of COVID-19 patients along with chloroquine and remdesivir.

Note: It is not a substitute of the annual influenza vaccination and is not indicated in patients with ESRD who are not on dialysis.

Tamiflu Dose in Adults

Tamiflu Dose in the prophylaxis of Seasonal Influenza:

• 75 mg orally once a day.

Tamiflu dose in individuals with Postexposure prophylaxis:

Note: For the treatment of post-exposure prophylaxis, it should be used in patients at risk of developing complications such as the immunocompromised, diabetics and the elderly. Treatment should be initiated within 48 hours of the exposure. Treatment must be continued for one week following the last exposure in individuals who were previously vaccinated and two weeks in unvaccinated individuals.

• Tamiflu in institutional outbreaks:

  • It is recommended for all residents regardless of the previous vaccination status. Treatment should be continued for at least 2 weeks and 1 week after the last known case.
  • All the employees may also receive prophylactic treatment depending on their vaccination status.

• Preexposure prophylaxis:

  • At least two weeks following the vaccination and until the outbreak is over, individuals who are at risk of developing complications such as the elderly, diabetic, and immunocompromised individuals should receive preexposure prophylactic treatment.

Dose in the treatment of Seasonal Influenza:

• 75 mg two times a day.

• When to initiate Tamiflu treatment:

  • The treatment should be initiated as soon as possible (even after 48 hours of the onset of the symptoms) in the following group of patients:
    • In patients with severe or complicated illnesses.
    • Patients with a progressive illness
    • All hospitalized patients
    • All patients at risk of developing complications
  • Laboratory confirmation should not delay the initiation of the treatment.
  • For symptomatic patients who have mild symptoms but are not at the increased complication of the disease, treatment may be considered within 48 hours of the onset of symptoms.

• For how long should oseltamivir treatment be given:

  • The usual duration of the treatment is 5 days.
  • Severely ill or immunocompromised patients may be given the treatment for a prolonged duration.

Tamiflu Dose in the prophylaxis of Influenza A and avian (H7N9 or H5N1):

• Postexposure prophylaxis:

  • 75 mg orally two times a day.
  • Post-exposure prophylaxis depends on the time of the complication and the baseline health status of the patient (individuals who are at risk of developing complications should receive the prophylactic treatment).

• Duration of therapy:

  • 5 days from the last known exposure if the exposure was time-limited and not ongoing or
  • 10 days if the exposure is likely to be ongoing as in household settings due to the potential for prolonged infectiousness in the case-patient.

Tamiflu Dose in the prophylaxis of Influenza A and avian (H7N9 or H5N1):

• 75 mg orally two times a day.

Note: Treatment should not be delayed while awaiting laboratory confirmation. The treatment must be initiated within 48 hours of the onset of symptoms. The usual duration of the treatment is 5 days but the longer duration may be considered in individuals at risk of developing complications.

Who are at an increased risk of developing complications?

• Adults 65 years of age or older
• Women who are pregnant or postpartum (within 2 weeks after delivery)
• Residents of long-term care facilities,
• Native Americans and Alaska natives,
• Persons with a BMI of 40 or more and
• Individuals with chronic medical conditions. These include:
  • Chronic pulmonary disease,
  • Cardiovascular disease,
  • Chronic kidney disease
  • Cirrhosis or other chronic liver diseases.
  • Blood disorders such as plastic anemia or leukemia
  • Metabolic disorders such as diabetes
  • Neurologic disorders such as stroke
  • HIV
  • malignancy or
  • Patients on immunosuppressive medications.

Tamiflu Dose in the treatment of COVID-19 infection (Coronavirus infection) associated upper respiratory tract symptoms:

• Oseltamivir 150 mg twice daily plus chloroquine 500 mg twice daily for five days.

Tamiflu Dose in Children

Oseltamivir (Tamiflu) Dose in the treatment of Seasonal Influenza:

Note: Treatment should ideally begin within 48 hours of symptoms onset. Patients at risk of developing complications, those with severe or progressive disease, and hospitalized patients may be given treatment even after 48 hours of symptoms onset. However, treatment should be initiated as soon as possible. Furthermore, the treatment duration may be prolonged in patients who are immunocompromised or have a severe disease [Ref].

• Infants 8 months of age or younger:

  • 3 mg/kg/dose orally two times a day for five days.

• Infants 9 months of age or older:

  • 3 mg/kg/dose orally two times a day for five days.

• Children and Adolescents:

  • ≤15 kg:

    • 30 mg orally two times a day

  • >15 to 23 kg:

  • 45 mg orally two times a day

  • >23 to 40 kg:

  • 60 mg orally two times a day

  • >40 kg:

  • 75 mg orally two times a day.

Tamiflu Dose in the prophylaxis of Influenza:

• Infants 3 months of age and older:

  • 3 mg/kg/dose orally once a day.

• Children and Adolescents:

  • ≤15 kg:

    • 30 mg orally once a day

  • >15 kg to 23 kg:

    • 45 mg orally once a day

  • >23 kg to 40 kg:

    • 60 mg orally once a day

  • >40 kg: Oral:

    • 75 mg orally once a day

Tamiflu in pregnancy: C

• However, it crosses the placental boundary.
• It is recommended for pregnant women and two weeks after delivery to prevent and treat seasonal influenza.

Use of oseltamivir during breastfeeding  

• Breastmilk contains small amounts of the drug.
• Manufacturer suggests weighing the benefits and risks of drug therapy for lactating mothers.

Renal dosing of Oseltamivir:

• For the treatment of seasonal Influenza:

  • CrCl >60 mL/minute:

    • No adjustment in the dose is necessary

  • CrCl >30 to 60 mL/minute:

    • 30 mg two times a day.

  • CrCl >10 to 30 mL/minute:

    • 30 mg once a day.

  • ESRD not undergoing dialysis:

    • Avoid using it in ESRD patients, not on dialysis.

• For the prophylactic treatment of seasonal:

  • CrCl >60 mL/minute:

    • No dosage adjustment is required.

  • CrCl >30 to 60 mL/minute:

    • 30 mg once a day

  • CrCl >10 to 30 mL/minute:

    • 30 mg on alternate days

  • ESRD not undergoing dialysis:

    • Avoid using it in ESRD patients who are not on dialysis.

• Patients who are on intermittent hemodialysis:

  • Treatment of seasonal influenza:

    • Assuming three hemodialysis sessions in 5 days, administer 30 mg immediately and then 30 mg after every hemodialysis session for 5 days.

  • Alternative recommendations: 

    • Low-flux hemodialysis:

      • 30 mg after each dialysis session for 5 days

    • High-flux hemodialysis:

      • 75 mg after each dialysis session for 5 days

  • Prophylaxis of seasonal influenza:

    • 30 mg immediately and then 30 mg after every alternate hemodialysis session for the recommended duration.

  • Patients on continuous ambulatory peritoneal dialysis (CAPD):

    • Treatment of seasonal influenza:

      • 30 mg immediately as a single dose (single dose of oseltamivir provides a 5-day duration)

    • Prophylaxis of influenza:

      • 30 mg immediately and then 30 mg once a week for the recommended prophylaxis duration

  • Patients on High-flux continuous renal replacement therapy (CRRT):

    • Treatment of seasonal influenza:

      • 30 mg once a day for 5 days or 75 mg every 48 hours to provide a 5-day duration.

    • Prophylaxis of seasonal influenza:

      • No data is available.

Tamiflu dose in liver disease:

• Mild-to-moderate impairment:

  • Adjustment in the dose is not necessary.

• Severe impairment:

  • It has not been studied in patients with severe liver disease. The manufacturer has not provided any adjustments in the dose in these patients.

Side Effects of Tamiflu (Oseltamivir):

• Central nervous system:

  • Headache

• Gastrointestinal:

  • Vomiting

Less Common Side Effects of Oseltamivir (Tamiflu) Include:

• Central nervous system:

  • Pain

• Gastrointestinal:

  • Nausea

Contraindication to Oseltamivir (Tamiflu) Include:

You may have severe allergic reactions to any ingredient of the drug.

Warnings and precautions

• Anaphylaxis or hypersensitivity reactions

  • After its use, severe allergic reactions such as anaphylaxis and erythema multiflora, steven Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme have been reported.
  • If hypersensitivity reaction is suspected it should be immediately stopped and the appropriate treatment given to the patient.

• Events in neuropsychiatrics:

  • Neuropsychiatric symptoms in children have been identified following post-marketing surveillance.
  • These include confusion, delirium and hallucinations as well as self-injury.
  • These neuropsychiatric symptoms may be caused by the influenza virus infection. Encephalitis and encephalopathy may be signs of the influenza virus infection.
  • Although the direct cause of the symptoms has not been proven, it is important to monitor patients for any new neuropsychiatric signs.

• Cardiovascular disease

  • Patients suffering from chronic heart disease should be cautious.

• Hepatic impairment

  • Patients with liver disease have not been able to establish the safety and efficacy oseltamivir.
  • These patients should be cautious when using it.

• Renal impairment

  • Patients with ESRD should not be on dialysis.
  • It should not be used in patients with mild or moderate renal impairment. The CrCl should be followed to adjust the dosage.

• Respiratory disease

  • Pre-existing conditions such as asthma should be avoided.

Oseltamivir: Drug Interaction

Monitor:

• Monitor the patient for new-onset or worseining of psychiatric features.
• Signs and symptoms of delirium, confusion, unusual behavior, and attempts at self-injury should be observed.
• In critically ill patients, a repeat rRT-PCR or viral culture may be done to determine an on-going viral replication.

How to administer Oseltamivir (Tamiflu)?

• It may be administered without regard to meals, however, to improve gastrointestinal tolerance, it may be taken with meals.
• Individuals who can not take the capsules can open the capsules and mix them with sweetened liquid like chocolate syrup, corn syrup, caramel topping, light brown sugar dissolved in water and take it.
• In patients who prepare the oral suspension from the capsules because of the unavailability of age-appropriate strength of the capsules or because the capsule can not be swallowed, an extemporaneous preparation may be prepared.
• The suspension should be shaken well prior to its use and immediately administered.
• It may also be administered in mechanically ventilated patients who are critically ill via a nasogastric or orogastric tube.
• In these patients, the powder from the capsules should be dissolved in 20 ml of sterile water and injected down the tube followed by a 10 ml sterile water flush.

Mechanism of action of Oseltamivir (Tamiflu):

• Tamiflu (Oseltamivir), inhibits viral replication by blocking the enzyme neuraminidase, which cleaves budding viral progeny at its attachment point to cellular envelope before it is released.
• Oseltamivir can be absorbed easily. Oseltamivir carboxylate, the prodrug, is only 3% bound to plasma proteins; whereas oseltamivir active drug is 42% bound.
• 90% of the prodrug can be metabolized in liver. However, it cannot be metabolized by the hepatic enzyme, cytochrome-p450.
• Oseltamivir carboxylate is bioavailable at 75% and has a half life of 6 to 10 hours. Oseltamivir's half-life is between 1 and 3 hours. It is excreted mostly in the urine and feces.

Brands of Oseltamivir (International):

• Tamiflu
• NAT-Oseltamivir

Oseltamivir Brand Names in Pakistan: