Viral Infections

Nirmatrelvir/Ritonavir (Paxlovid) MOA

Inhibits main protease blocking viral replication

Nirmatrelvir/Ritonavir (Paxlovid) Adverse effects and pearls

Screen for drug interactions!

If eGFR >60 —> Nirmatrelvir 300/ Ritonavir 100 every 12 hours
If eGFR 30-60 —> Nirmatrelvir 150/ Ritonavir 100 every 12 hours
If eGFR <30, not recommended

Recommended for ambulatory pts at high risk for progression to severe disease:

• 50 and older

• Any high risk condition

Treatment duration 5 days

Remdesvir MOA

Inhibits viral RNA polymerase

Remdesivir pearls

Not for eGFR <30

Reduces risk of hospitalization and death by 87% in unvaccinated high risk amb pts

Molnupiravir pearls

MOA: Prodrug, Introduces errors into the viral RNA

Use when there's no other treat options

Not for preg or 18 or under

VV116

Inhibits SARS-CoV-2 RNA-dependent RNA polymerase (RdRp)

• VV116 is a deuterated prodrug of GS-441524, the active metabolite of Remdesivir.

No drug interactions

Long covid

affects 5-15% of patients, with no clear definition or treatment. The CDC defines it as a chronic condition lasting at least 3 months, involving relapsing or progressive symptoms affecting multiple organs. Treatment focuses on symptom management.

Are covid rebound sx better with antiviral tx

Rebound symptoms occur at the same rate with or without antiviral treatment and are generally mild.

Loss of taste and smell affects ___% of vaccinated COVID-19 patients.

50-60%

Acyclovir MOA

Intracellularly phosphorylated by viral thymidine kinase

Host cell kinases phosphorylate it to tri-phosphate

Triphosphorylated acyclovir is incorporated into viral DNA

• Acts as a strand terminator

Acyclovir Indications

HSV-1 and HSV-2 in immunocompromised hosts, primary HSV infection, HSV suppression, HSV encephalitis, neonatal HSV infection, VZV infection.

Acyclovir Considerations and Adverse Effects

Considerations: Slow, incomplete oral absorption; renal clearance; hydration!!!! minimizes renal toxicity; removed by hemodialysis; infuse over one hour.

Adverse Effects: Reversible elevation in Scr and renal dysfunction (prevented by slow infusion and hydration); neurotoxicity (confusion, seizures, agitation); phlebitis (IV); local irritation (topical).

Valacyclovir Indications

Herpes zoster, recurrent genital herpes

Valacyclovir Considerations

Well absorbed orally (3-5x greater bioavailability than acyclovir); adequate hydration needed; therapy should be initiated early (within 48 hours of zoster, within 24 hours of recurrent genital herpes).

For recurrent infection; short Duration

Suppressive Therapy for HSV

Recommended for individuals with 6+ annual recurrences, significant anxiety/distress, or a discordant partner. (continuous duration)

Neuraminidase Inhibitors

Inhibits Infleunza viral release

Zanamivir: adults and kids >7 (inhalation) , no drug inxns, caution in chronic resp disease 

Oseltamivir: adults and children, take with food!!!

Peramivir: IV daily in hospital

Baloxavir

Single oral dose superior to placebo and oseltamivir for reduction of viral load No difference in length of hospital stay Interferes with virus RNA transcription

Develop an effective regimen to treat a viral infection based on patient characteristics and preferences

• Antiviral treatment has more benefit if initiated early in the course of the infection.

• Duration of treatment shorter for recurrent herpes infection compared to duration for primary infection.

• Treat influenza in those at high risk for complications.  Unless supply issues exist, it is acceptable to treat anyone with influenza.

• Treat COVID-19 in those at high risk for complications.  Manage drug interactions.