One of the physicians in town calls you this afternoon about a 36 year old female (64”, 72 kg) who has come into his office complaining of an abrupt onset of fever, headache, muscle aches, and fatigue that started at 8 am yesterday. He suspects she may have uncomplicated seasonal influenza and would like your recommendation regarding appropriate treatment. Which of the following would be an appropriate treatment recommendation(s) to make to the physician? Select all that apply.
A. Oseltamivir 75 mg PO BID x 5 days
B. Peramivir 600 mg IV x 1 dose
C. Baloxavir 40 mg PO x 1 dose
D. Zanamivir 10 mg inhalation BID x 5 days
E. None of the above. Antiretrovirals are not recommended for use in seasonal influenza after 24 hours of symptom onset
Answers with rationale:
The correct answers are A, B, C, and D.
As flu season approaches, it is important that pharmacists be aware of the common signs and symptoms of influenza as well as appropriate treatment. While antivirals are a mainstay in seasonal influenza treatment, there are many things to consider before dispensing influenza medications.
Oseltamivir, or Tamiflu, is a neuraminidase inhibitor. This drug is the most commonly prescribed antiviral for influenza and the preferred drug for severe and uncomplicated influenza in patients > 14 days old. It is important to note that oseltamivir should not be used if oseltamivir-resistant influenza is suspected. Tamiflu is also the preferred agent for pregnant or breastfeeding women in the treatment of flu. Common side effects include nausea and vomiting. In some patients (especially pediatrics) neuropsychiatric side effects such as confusion have been reported. Oseltamivir is dosed 75 mg PO BID and the duration of therapy is 5 days, making Answer A correct.
Peramivir, or Rapivab, is also a neuraminidase inhibitor. Like oseltamivir, peramivir should not be used if oseltamivir-resistant influenza is suspected. The FDA has only approved IV peramivir for patients > 2 years old with uncomplicated influenza and is to be given as an IV administration of 600 mg x 1 dose, making Answer B correct. The most common side effect of this medication include diarrhea. While FDA approved and indicated for the treatment of uncomplicated influenza, it is important to note that peramivir is not commonly seen in the outpatient setting as there are many oral options that are more cost-effective in the treatment of seasonal influenza.
Baloxavir, or Xofluza, is a cap-dependent endonuclease inhibitor that is an oral antiviral pro-drug given as one single dose of 40 mg for patients > 12 years old that are 40 to 80 kg for the treatment of uncomplicated influenza, making Answer C correct. Patients > 80 kg should receive 80 mg PO as a single dose. Baloxavir should not be given with dairy products, calcium fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (eg. Calcium, iron, magnesium, selenium, zinc). In clinical trials, baloxavir did not show any side effects more common than placebo. However there have been some postmarketing reports of anaphylaxis which merit further monitoring.
Zanamivir, or Relenza, is another neuraminidase inhibitor that is used to treat uncomplicated influenza in patients > 7 years old. The treatment dose for zanamivir is 10 mg (two inhalations) twice daily for 5 days, making Answer D correct. It is supplied in a foil blister disk that is inserted into a breath-actuated Diskhaler delivery device. The patient should be instructed to exhale fully prior to placing mouth on mouthpiece, close lips around mouthpiece, inhale steadily and deeply, and hold breath for a few seconds. This should be repeated for a total of 2 inhalations. Common side effects of this drug include sore throat and cough. It is important to note that this medication can cause bronchospasm in patients with underlying respiratory conditions and is contraindicated in patients with known underlying respiratory diseases such as asthma and COPD. The blister package of medication also contains milk derivatives and is contraindicated in patients with a history of allergy to milk protein.
For all patients presenting with uncomplicated influenza, any of the medications listed above should be started within 48 hours of symptom onset, making Answer E incorrect. Providers should not wait for a test result to come back at the risk of delaying therapy as these antivirals showed the most efficacy when started within 48 hours of symptom onset in clinical trials.
Patients taking medications for the treatment of seasonal influenza should also be counseled on important supportive care measures. Hydration is essential to replace insensible losses and prevent dehydration in patients with the flu. Antipyretics such as ibuprofen or acetaminophen can also be given to reduce fever and make the patient more comfortable. Aspirin or aspirin-containing medications should be avoided due to the concern for Reye Syndrome. Patients symptoms should typically resolve in about 1 week however if symptoms persist, the patient should contact their physician as this could be a sign of a secondary complication.
Community pharmacies play an important role in preventing the spread of flu by encouraging and practicing proper hand hygiene as well as encouraging a seasonal flu vaccine for all patients.