196.1 🎓 醫孞生版

196.1.0.1 📌 䞀頁重點

196.1.0.1.1 Herpesvirus (HSV, VZV, EBV, CMV, HHV-6, KSHV)
Drug Target Indications
Acyclovir / Valacyclovir HSV / VZV thymidine kinase + DNA polymerase HSV genital/orolabial/encephalitis, VZV chickenpox/zoster
Famciclovir / Penciclovir HSV / VZV Same as above (oral, BID dosing)
Ganciclovir / Valganciclovir CMV phosphotransferase (UL97) + DNA polymerase CMV retinitis, pneumonia, prophylaxis
Foscarnet Direct DNA polymerase inhibitor (no TK requirement) Acyclovir-resistant HSV/VZV, ganciclovir-resistant CMV
Cidofovir DNA polymerase Adenovirus, BK, JC, CMV-resistant
Letermovir (Prevymis, 2017) CMV terminase CMV prophylaxis post-HSCT (no marrow toxicity!)
Maribavir (Livtencity, FDA 2021) CMV UL97 kinase Refractory/resistant CMV (transplant)
Trifluridine (eye drops) HSV ocular Topical only
196.1.0.1.2 Influenza
  • Oseltamivir (Tamiflu) — neuraminidase inhibitor; 75 mg PO bid × 5d, started < 48 hr
  • Zanamivir — inhaled, neuraminidase
  • Peramivir — IV, neuraminidase
  • Baloxavir (Xofluza, 2018) — endonuclease inhibitor, single dose oral
196.1.0.1.3 RSV
  • Nirsevimab (Beyfortus, FDA 2023) — long-acting mAb against F protein; single dose for infants entering RSV season — universal infant immunization 2024 ACIP
  • Palivizumab (Synagis) — older mAb, monthly during RSV season, high-risk infants only
  • Ribavirin — historic, inhaled, limited efficacy
196.1.0.1.4 SARS-CoV-2
  • Nirmatrelvir-ritonavir (Paxlovid) — main protease inhibitor; 5-day oral, high-risk patients
  • Remdesivir (Veklury) — RNA polymerase inhibitor; IV, hospitalized + outpatient (3-day course)
  • Molnupiravir (Lagevrio) — RNA polymerase mutagen; less effective; EUA
  • Monoclonal antibodies: variant-resistance has eliminated most (bamlanivimab, sotrovimab, tixagevimab-cilgavimab all replaced/withdrawn)
196.1.0.1.5 Mpox / Smallpox
  • Tecovirimat (TPOXX) — orthopoxvirus VP37 inhibitor; FDA-approved smallpox; expanded access for Mpox 2022 (efficacy data mixed — STOMP trial 2024 negative)
  • Brincidofovir — long-acting cidofovir, FDA smallpox
  • VIG (Vaccinia Immune Globulin) — for vaccine complications
196.1.0.1.6 Adenovirus
  • Cidofovir + brincidofovir in immunocompromised
196.1.0.1.7 CMV New Drugs (22E)
  • Letermovir (Prevymis): prophylaxis ≀ 100d post-HSCT; no myelo toxicity
  • Maribavir (Livtencity): refractory/resistant CMV in transplant
  • Cytotect (CMV IVIG) — adjunct
196.1.0.1.8 Common Pitfalls
  • Acyclovir nephrotoxicity (crystals) — hydration + IV slow infusion
  • Ganciclovir / cidofovir bone marrow + nephrotoxic
  • Foscarnet electrolyte derangement (hypocalcemia, hypomagnesemia, hypokalemia, AKI) + 倧量 IV fluid
  • Oseltamivir GI + rare neuropsych (Japanese pediatric)

196.1.0.2 1⃣ Nucleoside Analogs (Herpesvirus)

196.1.0.2.1 Acyclovir / Valacyclovir / Famciclovir
  • Mechanism: Pro-drug — phosphorylated by viral thymidine kinase (TK) → triphosphate → incorporated into viral DNA → chain termination + viral DNA polymerase inhibition
  • Selectivity: requires viral TK → active only in infected cells; HSV + VZV have TK
  • Acyclovir: oral (5×/d for HSV; 5×/d zoster) or IV (encephalitis, severe immunocompromise)
  • Valacyclovir: prodrug → acyclovir, 3-5× higher bioavailability, BID dosing
  • Famciclovir: prodrug → penciclovir, BID
  • Indications: HSV oral/genital/encephalitis/disseminated; VZV chickenpox (esp adult) + zoster (especially within 72 hr) + ophthalmicus + disseminated
  • Toxicity: nephrotoxicity (crystal nephropathy) — IV slow infusion + hydration; neurotoxicity in renal failure (confusion, myoclonus) — adjust dose
  • Resistance: TK mutation → 甹 foscarnet (no TK requirement)
196.1.0.2.2 Ganciclovir / Valganciclovir
  • Mechanism: phosphorylated by CMV UL97 phosphotransferase → triphosphate → DNA polymerase inhibition
  • CMV-specific (UL97); also has some HHV-6, HHV-7 activity
  • Valganciclovir = prodrug; 900 mg PO bid (induction), 900 mg qd (maintenance)
  • Ganciclovir IV for severe CMV pneumonia, retinitis, encephalitis
  • Indications: CMV retinitis (AIDS), pneumonia (transplant), prophylaxis (transplant — letermovir alternative)
  • Toxicity: Bone marrow suppression (neutropenia 25-40% — major), thrombocytopenia, anemia, nephrotoxic, teratogenic, infertility
  • G-CSF for neutropenia
196.1.0.2.3 Foscarnet
  • Mechanism: Direct DNA polymerase inhibitor (no TK requirement) — so works against acyclovir-R HSV/VZV + ganciclovir-R CMV
  • Indications: refractory/resistant HSV/VZV/CMV
  • Toxicity: severe — nephrotoxicity (electrolyte derangement, AKI), hypocalcemia, hypomagnesemia, hypokalemia, seizures, genital ulcers
  • IV; pre-hydration + electrolyte monitoring
196.1.0.2.4 Cidofovir
  • Mechanism: Nucleotide analog (already phosphorylated) → DNA polymerase inhibition; no kinase requirement
  • Activity: CMV, BK, JC, adenovirus, HSV/VZV, HPV (off-label, topical)
  • Toxicity: Severe nephrotoxicity — probenecid + IV hydration pretreatment essential
  • Brincidofovir = oral lipid-conjugate version; less nephrotoxic; for smallpox

196.1.0.3 2⃣ Newer Herpesvirus Drugs (22E)

196.1.0.3.1 Letermovir (Prevymis)
  • Mechanism: CMV terminase complex inhibitor (different from polymerase) — pUL56 subunit
  • CMV-specific — no activity against other viruses
  • NO bone marrow toxicity (key advantage)
  • Indication: CMV prophylaxis post-HSCT (day 0-100); investigated in solid organ transplant
  • Dose: 480 mg PO qd (240 if cyclosporine)
  • Drug interaction: CYP3A4 substrate
196.1.0.3.2 Maribavir (Livtencity, FDA 2021)
  • Mechanism: CMV UL97 kinase inhibitor (different from ganciclovir — direct inhibits, not requiring phosphorylation)
  • Indication: refractory + resistant CMV post-transplant (≥ 12 yr)
  • Activity against ganciclovir-R CMV
  • Dose: 400 mg PO bid × 8 weeks
  • Toxicity: dysgeusia (taste change, very common), nausea, diarrhea, fatigue
  • Drug interaction: CYP3A4 substrate + inducer

196.1.0.4 3⃣ Influenza Antivirals

196.1.0.4.1 Oseltamivir (Tamiflu)
  • Mechanism: Neuraminidase inhibitor → prevents budding of progeny virions
  • Indication: Influenza A + B; treat (75 mg bid × 5d) or PEP (75 mg qd × 7-10d post-exposure)
  • Effective if < 48 hr of onset (most benefit)
  • Toxicity: GI; rare neuropsych (Japanese pediatric warnings)
  • Pregnancy: safe + recommended
  • Resistance: H275Y mutation in N1 — historic concern
196.1.0.4.2 Zanamivir
  • Inhaled, 同 mechanism
  • Bronchospasm in asthma/COPD
  • Alt for oseltamivir-resistant
196.1.0.4.3 Peramivir
  • IV single dose 600 mg
  • Alt when PO not tolerated
196.1.0.4.4 Baloxavir Marboxil (Xofluza)
  • Mechanism: Cap-dependent endonuclease inhibitor (PA subunit) — different mechanism
  • Single oral dose 40-80 mg
  • Reduces viral shedding
  • Resistance: PA I38 mutation emerges (post-treatment, ~ 5-10%)
  • Approved adult + pediatric

196.1.0.5 4⃣ RSV (Respiratory Syncytial Virus)

196.1.0.5.1 Nirsevimab (Beyfortus, FDA 2023)
  • Mechanism: Long-acting mAb against F protein (prevents fusion)
  • Half-life ~ 70 days → single dose covers RSV season
  • Indication: Universal infants entering 1st RSV season (2024 ACIP); high-risk children entering 2nd season
  • Dose: 50 mg IM (< 5 kg) or 100 mg (≥ 5 kg)
  • Replaces palivizumab in most situations
  • Maternal RSVpreF vaccine (Abrysvo) — alternative at 32-36 wk gestation
196.1.0.5.2 Palivizumab (Synagis)
  • Older mAb, monthly during RSV season (5 doses)
  • Historically high-risk infants only (prematurity, CHD, chronic lung)
  • Less used now (nirsevimab替代)
196.1.0.5.3 Ribavirin
  • Inhaled, limited efficacy
  • Historic, rarely used now
  • Teratogenic (pregnancy contraindicated near patient)
196.1.0.5.4 Adults — High Risk
  • Older adult RSV: supportive
  • No FDA-approved adult treatment yet (RSV vaccines for prevention: Arexvy, Abrysvo)

196.1.0.6 5⃣ SARS-CoV-2 Antivirals

196.1.0.6.1 Nirmatrelvir-Ritonavir (Paxlovid)
  • Mechanism: Nirmatrelvir = SARS-CoV-2 main protease inhibitor (Mpro); ritonavir = CYP3A4 inhibitor (boosts levels)
  • Indication: outpatient with COVID-19 + high-risk + ≀ 5 days symptom onset
  • Dose: 300/100 mg PO bid × 5d
  • Drug interactions: numerous (ritonavir inhibits CYP3A4) — review carefully (statins, immunosuppressants, anticoagulants)
  • Renal adjust: CrCl 30-60 dose-adjusted; < 30 contraindicated
  • Rebound ~ 5-10% (return of viral shedding + sx after Tx) — managed conservatively, retreatment generally not indicated
196.1.0.6.2 Remdesivir (Veklury)
  • Mechanism: RNA polymerase inhibitor (nucleotide analog)
  • IV, daily × 3 days (outpatient mild-moderate) or 5-10 days (severe hospitalized)
  • ACTT-1 trial 2020 — first IV antiviral for COVID
  • Renal toxicity, transaminitis
  • Now used selectively
196.1.0.6.3 Molnupiravir (Lagevrio)
  • Mechanism: RNA polymerase mutagen (induces viral mutations to catastrophic level)
  • 800 mg PO bid × 5d
  • Less effective than Paxlovid (mixed trial data)
  • Pregnancy contraindicated (theoretical embryotoxic)
  • Reserved when others unavailable
196.1.0.6.4 Monoclonal Antibodies (Variant-Replaced)
  • Bamlanivimab, sotrovimab, tixagevimab-cilgavimab — all replaced/withdrawn due variant escape
  • 2024: pemivibart (Pemgarda) for immunocompromised pre-exposure
  • Newer mAb pipeline continues

196.1.0.7 6⃣ Mpox / Smallpox

196.1.0.7.1 Tecovirimat (TPOXX)
  • Mechanism: Orthopoxvirus VP37 envelope wrap protein inhibitor (prevents extracellular virus formation)
  • FDA-approved smallpox (2018)
  • Mpox expanded access during 2022 outbreak
  • 2024 STOMP trial: NEGATIVE for Mpox treatment efficacy (no clinical benefit)
  • May still use compassionate / severe immunocompromised
  • 14-day course
196.1.0.7.2 Brincidofovir
  • Long-acting cidofovir prodrug, less nephrotoxic
  • FDA smallpox
  • Limited Mpox data
196.1.0.7.3 VIG (Vaccinia Immune Globulin)
  • For vaccinia vaccine adverse events (severe complications)
  • IV preparation

196.1.0.8 7⃣ Adenovirus

  • Severe disease in HSCT, immunocompromise (pneumonia, hepatitis, hemorrhagic cystitis, dissemination)
  • Cidofovir with probenecid + hydration
  • Brincidofovir — better tolerated alternative
  • 0.25-1 mg/kg IV weekly

196.1.0.9 8⃣ JC Virus / PML

  • Progressive multifocal leukoencephalopathy
  • HIV +, natalizumab, immunosuppression
  • No specific antiviral effective
  • Treatment: immune reconstitution (ART for HIV, stop immunosuppressant, plasmapheresis for natalizumab)
  • Mirtazapine, mefloquine — limited evidence
  • Pembrolizumab some case reports

196.1.0.10 9⃣ BK Virus (Polyomavirus)

  • Renal transplant nephropathy
  • Hemorrhagic cystitis in HSCT
  • No specific antiviral fully effective
  • Reduce immunosuppression (renal transplant)
  • IVIG, cidofovir / brincidofovir adjuncts
  • Leflunomide off-label