What it is:An acute respiratory viral illness spread by droplets, hitting hardest at the extremes of age (under 2, over 65) and anyone with cardiopulmonary disease, immunosuppression, or pregnancy. It looks like a dozen other respiratory bugs on day one, which is exactly why testing and timing matter.
The core problem:The virus replicates fast in respiratory epithelium, and the two enzymes it depends on to do that (cap-dependent endonuclease for transcription, neuraminidase for release) are the only two drug targets that actually work anymore. Everything pharmacologic in this chapter is built around blocking one of those two enzymes, or preventing infection before it starts.
What you do about it:Prevent first (annual vaccination for everyone 6 months and up), treat early if infected (antivirals only help if started within 48 hours, ideally within 12), and know that the adamantanes are dead weight now because of resistance.
Think of this chapter as two enzymes and a clock.Cap-dependent endonuclease and neuraminidase are the only druggable targets left. The clock is the 48-hour window (12 hours is better) after symptom onset, after which antivirals stop meaningfully helping. Almost every fact in this chapter hangs off one of those two ideas.
Influenza spreads person-to-person through inhaled respiratory droplets from an infected person's cough or sneeze. Incubation is 1–7 days, averaging 2.Adults are contagious starting the day beforesymptoms appear through about 7 days after onset. Kids shed virus longer, past 10 days, and severely immunocompromised patients can shed for weeks to months. That shedding-before-symptoms detail is exactly why droplet precautions and hand hygiene matter more than "isolating the sick person" alone.
| Viral enzyme | Job | Drug class that blocks it |
|---|---|---|
| Cap-dependent endonuclease | Snips the cap off host mRNA so the virus can use it to prime its own viral mRNA transcription | Baloxavir (single agent in this class) |
| Neuraminidase | Cleaves sialic acid so newly made virions can bud off and release from the infected cell instead of clumping on the surface | Oseltamivir, zanamivir, peramivir |
Baloxavir stops the virus from getting started(blocks transcription before new virus is even made). Neuraminidase inhibitors stop the virus from getting out(blocks release of virus that's already been made). Different points in the replication cycle, which is why baloxavir works as a single dose while the NA inhibitors need days of dosing to keep suppressing ongoing release.
Amantadine and rimantadine block the M2 ion channel, a third mechanism that used to work against influenza A. Widespread resistance means the CDC no longer recommends them for treatment orprophylaxis in the United States. If you see them on an exam as an answer choice for current influenza management, they're almost always the trap.
Influenza looks like a lot of other respiratory illnesses on presentation, which is why testing exists. Course and severity are shaped by age, immune status, viral strain, smoking, comorbidities, pregnancy, and how much preexisting immunity a person has (from prior infection or vaccination).
| Category | Findings |
|---|---|
| Classic | Rapid-onset fever, myalgia, headache, malaise, nonproductive cough, sore throat, rhinitis |
| Pediatric-specific | Nausea, vomiting, and otitis media are more commonly reported in children than adults |
| Timeline | Symptoms typically resolve in 3–7 days, though cough and malaise can drag on past 2 weeks |
Exacerbation of underlying comorbidities, primary viral pneumonia, secondary bacterial pneumonia, other secondary respiratory infections (sinusitis, bronchitis, otitis), encephalopathy, transverse myelitis, myositis, myocarditis, pericarditis, and Reye syndrome.
Hits pregnant patients and those with underlying cardiovascular disease hardest. Starts as fever and dry cough, then the cough turns productive with blood-tinged sputum, then rapidly progresses to dyspnea, hypoxemia, and cyanosis with bilateral interstitial infiltrates on imaging. Get a chest radiograph any time pneumonia is suspected. This is not "just the flu" anymore, it's an admission.
Primary viral pneumonia(direct viral invasion, rapid progression, days 1–3) is a different beast from secondary bacterial pneumonia(a second illness that shows up after the patient seemed to be improving, classically around day 5–7). The improve-then-worsen pattern is the tell for secondary bacterial infection, and it's exactly the pattern the handbook's evaluation criteria are built around (more in Monitoring).
CBC and chemistry panels assess overall status but don't diagnose influenza. The actual diagnosis rests on virus-specific testing, and the gold standard is RT-PCR or viral culture.
| Test | Sensitivity / Specificity | Turnaround | Notes |
|---|---|---|---|
| RIMA(rapid influenza molecular assay) | 90–95% sens · 55–99% spec | ~15–30 min | Detects viral RNA, point-of-care friendly |
| RT-PCR | High sens and spec (gold standard) | ~45 min – 6 hours | Nucleic acid amplification, most reliable |
| RIDT(rapid antigen / point-of-care) | Lower than RIMA/PCR | Fast | Also includes DFA/IFA fluorescence antibody methods |
RIMA and RT-PCR both detect viral RNA and both run circles around older antigen-based RIDTs on sensitivity. The tradeoff is speed vs accuracy: RIDT/RIMA are fast enough to inform same-visit antiviral decisions, RT-PCR is the confirmatory gold standard when the stakes are higher (hospitalized patient, outbreak investigation, high-risk patient where a false negative changes management).
Vaccination is the single best way to cut morbidity and mortality from influenza. Hand hygiene, covering coughs, and avoiding sick contacts help too, and chemoprophylaxis has a role in specific situations (see next section), but none of those replace the vaccine.
| Characteristic | IIV (inactivated) | LAIV (live-attenuated) |
|---|---|---|
| Age approved | ≥6 months | 2–49 years |
| Immune status requirement | Immunocompetent orimmunocompromised | Immunocompetent only |
| Viral properties | Inactivated (killed) A(H3N2), A(H1N1), B | Live-attenuated A(H3N2), A(H1N1), B |
| Route | Intramuscular | Intranasal |
| Immune response | High serum IgG | Lower IgG, higher mucosal IgA |
Older adults still benefit from vaccination (fewer complications, less hospitalization, lower death), but they mount a weaker antibody response and stay more susceptible. That's the rationale behind high-dose (Fluzone HD Quadrivalent) and adjuvanted (Fluad Quadrivalent) IIV products specifically approved for age ≥65.
This is a favorite exam trap because "egg allergy = no flu vaccine" used to be the rule and is now outdated. ACIP's current approach is tiered by whichvaccine caused the prior severe reaction:
The pattern: match the patient to whichever egg-free product they haven't already reacted to. A simple egg allergy without anaphylaxis to the vaccine itself is not a contraindication to standard vaccination at all.
Some patients (especially parents of young children) worry about thimerosal, a mercury-based preservative in some multidose vials, because of an unfounded and thoroughly debunked link to autism. There is no scientifically persuasive evidence of harm from thimerosal exposure via vaccination, and accumulating evidence actually supports the lack of harm. This is worth knowing cold for patient counseling, since "does the flu shot cause autism" is a real question you will get asked.
Antiviral drugs used for prevention are adjuncts to vaccination, never a substitute for it. Oseltamivir and zanamivir are roughly 70–90% effectiveat preventing susceptible-strain influenza when used prophylactically, useful both for seasonal prophylaxis and for post-exposure prophylaxis after a household contact is diagnosed. Peramivir is not approved for chemoprophylaxisat all, treatment only. Baloxavir given within 24 hours of symptom onset in an index case cut household transmission by 86%.
Postexposure prophylaxis should notbe started if more than 48 hours has passed since exposure. Same clock as treatment, different indication.
If the patient gets vaccinated, prophylaxis can generally stop 14 days after vaccination (once titers are up) in non-institutionalized people. Post-exposure prophylaxis runs for 10 days after the last exposure. For high-risk patients where vaccination is contraindicated or expected to be ineffective, chemoprophylaxis continues for as long as flu is circulating in the community that season.
Influenza antivirals inhibit viral replication, which also cripples the live-attenuated vaccine. Don't give LAIV until 48 hoursafter the last antiviral dose, and don't give antivirals for 2 weeksafter LAIV. Antivirals given anywhere from 48 hours before to 14 days after LAIV can blunt the vaccine response; if that happens, the patient can just be revaccinated with IIV or RIV4 instead.
Goals:control symptoms, prevent complications, cut down work/school absenteeism, and limit spread to others.
Antivirals work best started within 48 hoursof symptom onset. Benefit is highly time-dependent: the earlier, the better, with the real sweet spot being within 12 hoursof onset. Past 48 hours, the evidence for benefit falls apart for most patients. This single fact drives triage: don't wait on confirmatory testing if the clinical picture is clear and the clock is running.
Supportive care runs alongside antivirals, not instead of them: adequate sleep, low activity level, staying home from work or school (rest andinfection control), adequate fluids, and symptomatic measures like acetaminophen for fever, antihistamines for rhinitis, and lozenges/warm tea/soup for cough and sore throat.
Delirium, seizures, hallucinations, and self-injury have been reported in pediatric patients on oseltamivir and peramivir.Worth flagging to parents before starting therapy, not after.
Age cutoffs and duration are the two things that get tested here. Oseltamivir is approved for treatment past 14 days of age, zanamivir past 7 years, peramivir at 2 years and up (IV only, and it's the only IV option).
| Drug | Adult treatment | Adult prophylaxis | Duration |
|---|---|---|---|
| Cap-dependent endonuclease inhibitor | |||
| Baloxavir | 40–<80 kg: 40 mg ×1 >80 kg: 80 mg ×1 | Not approved | Single dose |
| Neuraminidase inhibitors | |||
| Oseltamivir | 75 mg BID | 75 mg daily | Tx 5 days · Ppx 10 days |
| Zanamivir | 10 mg (2×5 mg inhalations) BID | 10 mg daily | Tx 5 days · Ppx 10 days |
| Peramivir(IV only) | 600 mg IV over 15–30 min ×1 | Not approved | Single dose (13 yrs+) |
| Age / weight | Treatment dose (BID) | Prophylaxis dose (daily) |
|---|---|---|
| Term infant 0–8 months | 3 mg/kg/dose BID | Not recommended if <3 months |
| 9–11 months | 3.5 mg/kg/dose BID (AAP) or 3 mg/kg/dose BID (CDC/FDA) | 3.5 mg/kg/dose daily |
| ≥1 year, ≤15 kg | 30 mg BID | 30 mg daily |
| ≥1 year, >15–23 kg | 45 mg BID | 45 mg daily |
| ≥1 year, >23–40 kg | 60 mg BID | 60 mg daily |
| ≥1 year, >40 kg | 75 mg BID | 75 mg daily |
Pediatric treatment runs 5 days across all weight bands, prophylaxis runs 10 days. Preterm infants are dosed by postmenstrual age(gestational + chronological): <38 weeks 1 mg/kg BID, 38–40 weeks 1.5 mg/kg BID, >40 weeks 3 mg/kg BID.
Single oral dose based on weight (40 mg for 40 to <80 kg, 80 mg for >80 kg), no titration, no multi-day course. That convenience is a real adherence win over a 5-day BID regimen.
Time to peak concentration is about 4 hours, and food plus polyvalent cations(calcium, aluminum, magnesium, iron) can drop peak concentration by up to 48%. Same logic as counseling on tetracyclines or fluoroquinolones: separate from dairy products, antacids, and mineral/multivitamin supplements. Long half-life (~79 hours) is why one dose covers the whole course. Metabolized via UGT1A3 and CYP3A4.
Longer dosing (i.e., considering NA inhibitor or repeat dosing strategies) is only entertained for patients who remain severely ill after 5 days, which is an exception, not the norm.
All three are active against influenza A andB, which sets them apart from the extinct adamantanes (influenza A only, and irrelevant now anyway due to resistance).
Renal impairment requires dose adjustment for all three based on creatinine clearance; check current CDC clinician guidance for the specific adjustment table rather than guessing.
Amantadine and rimantadine used to be first-line for influenza A. Widespread resistance among circulating strains means the CDC no longer recommends them for treatment orprophylaxis in the US. If an exam question describes a patient with influenza and lists amantadine as an answer choice, it's testing whether you know it's obsolete, not whether you'd actually prescribe it.
| Population | Vaccination | Antivirals |
|---|---|---|
| Pregnancy | IIV yes, every trimester. LAIV no. | Not a contraindication to oseltamivir/zanamivir; oseltamivir preferred for treatmentgiven its systemic activity. Drug of choice for prophylaxis in pregnancy is undefined. |
| Breastfeeding | Standard recommendations apply | Both adamantanes and NA inhibitors are excreted in breast milk; avoid in nursing mothers |
| Immunocompromised | Annual IIV yes. LAIV no(live virus) | Consider post-exposure prophylaxis given blunted vaccine response; oseltamivir/zanamivir class is not preferred during pregnancy for the fetal-effect concerns noted above, and adamantanes/NAIs generally carry fetal-effect caution language in labeling |
| Age <9 years, first-time vaccinees | Two IIV doses ≥4 weeks apart | Weight/age-banded oseltamivir dosing; zanamivir needs age ≥7 and inhaler coordination |
Vaccinate with IIV (never LAIV), and if she gets influenza, oseltamivir is the preferred treatment because it has systemic (not just local) antiviral activity. Some experts push oseltamivir to 150 mg BID for severe illness in pregnancy, though optimal prophylactic dosing in pregnancy simply isn't established yet.
| Parameter | When | Watching for |
|---|---|---|
| Fever, myalgia, headache, malaise, cough, sore throat, rhinitis | Daily during illness | Expected resolution within ~1 week |
| Symptom trajectory past day 7 | Day 7–10 | Worsening after day 7, or persistence past day 10, suggests secondary bacterial infectionand warrants a physician visit |
| Respiratory status | Throughout, especially pregnant/cardiopulmonary patients | Dyspnea, hypoxemia, blood-tinged sputum → think primary viral pneumonia, get imaging |
| Neuropsychiatric status (pediatric) | Throughout oseltamivir/peramivir therapy | Delirium, hallucinations, self-injurious behavior |
| Renal function | Baseline in patients with renal impairment | NA inhibitor dose adjustment needs |