ID Exam 3: Guarascio Antiviral Agents for Treatment of Herpesvirus

HSV-1 commonly manifests as ___ ___

oral herpes

HSV-2 commonly manifests as ___ ___

genital herpes

VZV commonly manifests as __/___

chickenpox/shingles

CMV commonly manifests as __, ___

retinitis, colitis

Herpes Simplex Virus (HSV)

-nuclear replicating DNA virus

-presents in cycles of ___ and ___

latency, activation

Herpes Simplex Virus (HSV)

-HSV-1 becomes latent in → ____ ___, leading to lesions on ___ and ___

trigeminal ganglion, hips, face

Herpes Simplex Virus (HSV)

-HSV-2 becomes latent in → ____ ___, leading to lesions on ____

sacral ganglion, genitals

Herpes Simplex Virus (HSV)

-treatment most effective when started within __ ___ of active symptoms/lesion

24 hours

VZV

-DNA virus

-causes acute infection of ____ commonly in childhood

-lies dormant in dorsal root ganglion, can return as herpes zoster infection (___)

chickenpox, shingles

VZV can return as shingles primarily in the following populations:

-____

-_____ ____

-_____ ___

-___ ____

immunocompromised, high stress, acutely ill, aging population

VZV

-risk of _________ (skin rash resolves but nerve pain remains)

post-herpetic neuralgia

VZV vaccination recommended:

-for patients ≥ ___ years of age

-for immunocompromised patients ≥___ years of age

50, 18

Acyclovir (IV, PO)

-activity is ____ > HSV-2 > VZV

-oral bioavailability is __-__% (poor)

HSV-1, 15-30

Acyclovir (IV, PO)

-____ ______, _____ ______ needed for ___ _____

renal elimination, dose reduction, renal insufficieny

Acyclovir (IV, PO) AEs

-_____ ______ ____ (so patient needs to ____)

-_____

-___ ____

-_____ (eg neutropenia)

-_____

-___ ____ (rare, only in young and old patients)

acyclovir crystalline nephropathy, hydrate, headache, GI upset, myelosuppression, rash, CNS abnormalities

Valacyclovir (PO)

-L-valyl ester ___ of acyclovir (converted via ____ pass metabolism) with similar MOA, antiviral spectrum, and AEs

-oral bioavailability is __% (____ than acyclovir - preferred)

prodrug, first, 60, better

Valacyclovir (PO)

-useful for VZV because we can achieve ___ drug concentrations for efficacy (bc good oral bioavailability)

higher

Valacyclovir (PO)

-also undergoes ____ _____, so _____ _____ needed for ____ ______

renal elimination, dose reduction, renal insufficiency

Famciclovir (PO)

-analog of _______ and metabolized to active penciclovir

-same ___ and antiviral spectrum as _____

-used mainly for tx failure with ______, which is not often because HSV resistance is rare

-oral bioavailability ____% (good)

penciclovir, MOA, acyclovir, valacyclovir, 75

Famciclovir (PO)

-also undergoes ____ _____, so ____ ______needed for ____ ______

renal elimination, dose reduction, renal insufficieny

Famciclovir (PO) ADEs

-_____

-__/__/__

-some ____ manifestations noted in the ___

-______ ___ at ___ ____

headache, N/V/D, CNS manifestations, elderly, renal toxicity, high doses

Treatment of Mucocutaneous Infection (cold sores) (HSV-1 and HSV-2)

1. ____

2. _____

3. ____

docosanol, acyclovir, penciclovi

Docosanol Dosage for Mucocutaneous Infection (cold sores) (HSV-1 and HSV-2)

Docosanol 10% cream 5x daily until resolution

Acyclovir Dosage for Mucocutaneous Infection (cold sores) (HSV-1 and HSV-2)

Acyclovir 5% cream 5x daily for 4 days

Penciclovir Dosage for Mucocutaneous Infection (cold sores) (HSV-1 and HSV-2)

Penciclovir 1% cream every 2 hours for 4 days

If patient has multiple cold sores/genital infection from HSV, use ___ therapy (not topical)

systemic

HSV Systemic Treatment

First Episode → ____

Valacyclovir

what medication and dosage should be used for first episode systemic HSV? (high dose, long duration)

Valacyclovir 1g PO BID x 7-10 days

HSV Systemic Treatment

Recurrent Episode → ____

Valacyclovir

what medication and dosage should be used for recurrent episode systemic HSV? (lower dose, shorter duration)

Valacyclovir 500mg PO BID x 3-5 days

HSV Systemic Treatment

Severe Disease/Hospitalized → ____

Acyclovir

what medication and dosage should be used for severe disease/ hospitalized systemic HSV?

Acyclovir 5-10mg/kg IV q8h

HSV Systemic Treatment

If patient has ___, must use higher dose of Acyclovir

encephalitis

what medication and dosage must be used for encephalitis?

Acyclovir 10mg/kg IV

HSV Systemic Treatment

Suppressive therapy→ ____ (used in cases of extensive oral herpes infections, a lower dose as a preventative measure)

Valacyclovir

what medication and dosage should be suppressive therapy HSV?

Valacyclovir 500mg - 1g PO daily

Clinical Pearl: Whenever possible, start treatment within __ hours of symptoms

24

Shingles Patient Presentation

1. Systemic Symptoms (___): ______, ______, _____, ______

prodrome, fatigue, fever, headache, photophobia

Shingles Patient Presentation

2. Painful _____, ______, ______ ______ prior to ____ ______

itching, tingling, burning sensation, rash development

Shingles Patient Presentation

3. Progressive ___, _____ ______ that _____ and _____

red, vesicular rash, scabs, crusts

Shingles Patient Presentation

4. ________ + _____-______ ______

treatment, post-herpetic neuralgia

VZV Treatment

Inpatient → ____

Acyclovir

what is the medication and dosage used for Herpes Zoster Infection (___) ?

Acyclovir 10mg/kg IV q8 hours for 7-10 days, VZV

VZV Treatment

Outpatient, Oral Therapy option → ____ or ______

Valacyclovir, Famciclovir

what medication and dosage should be used for as an oral therapy?

Valacyclovir 1g PO TID (preferred), Famiciclovir 500mg TID

Cytomegalovirus (CMV)

-large, double-stranded DNA virus (HHV5)

-latent, infects >50% of population, but most people with CMV are ___

asymptomatic

Cytomegalovirus (CMV)

-causes disease in ____ (HIV transplant, etc)

-various disease state manifestations-pneumonia, hepatitis, encephalitis, myelitis, colotis, uveitis, retinitis

immunocompromised

Ganciclovir (IV, PO)

-antiviral activity: ____, ____, ___, ___, ____

-PO bioavailability <__% (poor)

-___ ____ and ____ _____

CMV, HSV-1, HSV-2, VZV, EBV, 10%, renal elimination, dose adjustment

Induction Dosage for Ganciclovir

Ganciclovir 5mg/kg IV q12 hours for 14-21 days

Maintenance Dosage for Ganciclovir

Ganciclovir 5mg/kg IV q24 hours, 1g PO TID

Ganciclovir (IV, PO) ADEs

-___ ___ ______ (_______, ________, _____)

-___

-____

bone marrow suppression, neutropenia, thrombocytopenia, anemia, nephrotoxicity, teratogenic

Think ____ = ____

When granulocyte levels drop on ganciclovir, this indicates ___

gan, gran, neutropenia

Valganciclovir (PO)

-activated to _____ in the GI tract/liver, has similar MOA, antiviral spectrum, and AEs

-PO bioavailability ___%, increases with ____

ganciclovir, 60, food

Valganciclovir (PO)

5mg/kg QD ganciclovir = ___mg valganciclovir QD

900

Induction Dosage of Valganciclovir

Valganciclovir 900mg PO BID x 21 days

Maintenance Dosage of Valganciclovir

Valganciclovir 900mg PO QD

Valganciclovir (PO)

-____ ____ for ___ _____

-similar AEs to gangiclovir including __ __ ___

dose reduction, renal impairment, bone marrow suppression

Foscarnet (IV)

-antiviral activity: ____, ____, ____, ____, ____

-almost complete excretion by _____ (so _____ is important)

CMV, HSV-1, HSV-2, VZV, EBV, kidneys, hydration

Foscarnet (IV) ADEs

-dose-dependent _____ ____ and ____ _____ (Mg, PO4, Ca, K)

-___

renal toxicity, electrolyte abnormalities, anemia

Maribavir (PO)

-treatment of CMV following ___/treatment ___ with ganciclovir or foscarnet

resistance, failure

Maribavir (PO)

-do NOT use in combination with ___/___ due to antagonism of antiviral activity

ganciclovir/valganciclovir

CMV Treatment Progression

First-line: ___

Second-line: ____

Third-line: ____

Ganciclovir, Foscarnet, Maribavir

HSV Prophylaxis

1. ___

2. ____

Acyclovir, Valacyclovir

what is the first prophylaxis medication and dosage for HSV Prophylaxis?

Acyclovir 800-1200mg PO BID daily

what is the second prophylaxis medication and dosage for HSV Prophylaxis?

Valacyclovir 500mg PO BID daily or TID daily

CMV Prophylaxis

1. ____

2. ___

Valganciclovir, Letermovir

what is the first prophylaxis medication and dosage for CMV Prophylaxis?

Valganciclovir 450-800mg PO daily

what is the second prophylaxis medication and dosage for CMV Prophylaxis?

Letermovir 480mg PO/IV daily