Nucleoside Analogues Tables

Table 1. Summary of In vitro Antiviral Activity (ID₅₀*) of Acyclovir and Penciclovir

Virus	ID₅₀ (mg/L) Acyclovir	ID₅₀ (mg/L) Penciclovir
HSV-1	0.02 – 0.9	0.2 – 0.6
HSV-2	0.03 – 2.2	0.3 – 2.4
VZV	0.8 – 4	0.9 – 4
EBV	Ca. 1.5	---
CMV	2 – >50	52

* ID₅₀ = the concentration of drug required to inhibit 50% of viral growth in cell culture

(references 17, 18, 40)

Table 2. Pharmacokinetic Parameters

Parameter	Acyclovir/Valacyclovir	Penciclovir/Famciclovir
Total Clearance	19 L/h/1.73m²	32 L/h/1.73m²
Renal Clearance	15 – 17 L/h/1.73m²	25 – 32 L/h/1.73m²
Vd steady-state	46.6 ± 13.5 L/1.73m² (range,22.5 – 101 L/ m²)	111.9 L (range, 102 – 125 L)
Half-life (mean; range)	2.93 h; 1.5 – 6.3 h	2.16 – 2.31 h
Plasma protein binding	15.4% (range, 9 – 24%)	20%
Urinary excretion	80% unchanged	50 – 60% unchanged
Bioavailability	Acyclovir: 13 –21 % Valacyclovir: 54%	Penciclovir: 5% Famciclovir: 77%

Vd = volume of distribution

(references 46, 79)

Table 3. Available Dosage Forms

Generic Name	Trade Name	Dosage Forms
Acyclovir	Zovirax®	200, 400, 800 mg tablets 200 mg/5 mL suspension 400 mg/5 mL suspension 250, 500 mg IV injection 3% ophthalmic ointment 5% topical cream
Valacyclovir	Valtrex®	500 mg tablets
Penciclovir	Denavir®	1% topical cream
Famciclovir	Famvir®	125, 250, 500 mg tablets

(references 32, 41, 103, 114)

Table 4. Indications and Dosing Regimens [Download PDF]

Indication	Drug	Adult Dosing Regimen	Pediatric Dosing Regimen
HSV infections of skin and mucous membranes including initial and recurrent genital herpes	Acyclovir	200 mg po 5 x daily for 5 days 400 mg po 5 x daily or 5 mg/kg IV q8h for 5 days in severely infected or immunocompromised patients Initial genital: 400 mg po tid x 7 – 10 days or 200 mg po 5 x daily x 7 – 10 days Recurrent genital: 400 mg po tid x 5 days or 200 mg po 5 x daily x 5 days or 800 mg po bid x 5 days	Age ≥ 2 years = adult dose Age < 2 years = half adult dose Neonates and infants = 20 mg/kg IV q8h for 14 days (21 days for disseminated or CNS infection)
	Valacyclovir	Initial genital: 1 g po bid for 7 – 10 days Recurrent genital: 500 mg bid for 3 – 5 days or 1 g po qd x 5 days	Safety and efficacy in pre-pubertal pediatric patients not established.
	Famciclovir	Initial genital: 250 mg po tid x 7 – 10 days Recurrent genital: 125 mg bid for 5 days	No data
Episodic HSV treatment in HIV-infected patients	Acyclovir	400 mg po tid x 5 – 10 days or 200 mg 5 times daily for 5 – 10 days	No data
	Valacyclovir	1 g po bid x 5 – 10 days	No data
	Famciclovir	500 mg po bid x 5 – 10 days
Suppression of recurrent HSV in immunocompetent patients	Acyclovir	400 mg bid	No data
	Valacyclovir	1 g qd or 500 mg qd if ≤ 9 recurrences per year	No data
	Famciclovir	250 mg bid	No data
Prophylaxis of HSV in immunocompromised patients	Acyclovir	400 – 800 mg po 2 or 3 times daily 5 mg/kg IV q8h in severely immunocompromised (i.e. bone marrow transplant) patients or those with impaired absorption from gut	Age ≥ 2 years = adult dose Age < 2 years = half adult dose
	Valacyclovir	500 mg bid	No data
	Famciclovir	500 mg bid	No data
Herpes encephalitis	Acyclovir	10 mg/kg IV q8h	500 mg/m² IV q8h
Herpes labialis (cold sores)	Valacyclovir	2 g bid for 1 day taken 12 hours apart (initiate at earliest symptom of cold sore i.e. tingling, itching, burning) Recurrent orolabial infection in HIV-infected patients: 500 mg bid	No data
Herpes labialis (cold sores)	Penciclovir	Apply cream to cold sore every 2 hours during waking periods for 4 days (initiate at earliest symptom)	No data
VZV infections including varicella (chicken pox) and herpes zoster (shingles)	Acyclovir	800 mg po 5 x daily for 7 days 10 mg/kg IV q8h in severely immunocompromised patients or those with impaired absorption from gut (treat for 2 – 7 days or until clinical improvement, followed by po therapy to complete 10 days of total treatment)	Varicella infections: Age > 6 years = 800 mg po 4 x daily Age 2 – 5 years = 400 mg po 4 x daily Age < 2 years = 200 mg po 4 x daily Continue treatment for 5 days Alternatively: calculate dosing at 20 mg/kg po (max 800 mg) 4 x daily IV dose = 250 mg/m² q8h Immunocompromised children = 500 mg/m² IV q8h No data on treatment of herpes zoster in immunocompetent children
	Valacyclovir	1 g po q8h x 7 days	No data
	Famciclovir	500 mg po q8h x 7 days	No data

(References 23, 32, 41, 103, 114)

Table 5. Intravenous (IV) Dosing of Acyclovir in Renal Impairment

Indication	Creatinine Clearance (mL/min/1.73 m²)
Indication	25 – 50	10 – 25	0 - 10
HSV dose	5 mg/kg q12h	5 mg/kg q24h	2.5 mg/kg q24h
VZV dose	10 mg/kg q12h	10 mg/kg q24h	5 mg/kg q24h

(Reference 114)

Table 6. Current and Potential Clinical Indications

Drug

Food and Drug Administration (FDA) Indications

Other Therapeutic Uses

Acyclovir

Treatment of initial and prophylaxis of recurrent HSV-1 and HSV-2 infections:

Genital herpes

Herpes labialis

Herpes simplex encephalitis

HSV in immunocompromised patients

Leukoderma; punch grafting

Mucotaneous HSV

Neonatal HSV infections

Herpes zoster - shingles

Varicella zoster - chicken pox

Bell’s Palsy

Chicken Pox prophylaxis

Eczema herpeticum

Epilepsia partialis continua

Epstein-Barr virus

Hepatitis B

Herpes Simplex meningitis

Herpetic proctitis

Herpes zoster ophthalmic infections

Ocular HSV

Papillomatosis

Varicella pneumonia

Varicella zoster encephalitis

Varicella zoster myelitis

Viral encephalitis

Famciclovir

Genital and non-genital recurrent HSV –treatment and suppression

Herpes zoster

Hepatitis B

HSV initial episode

Penciclovir

Herpes labialis – recurrent HSV-1 and HSV-2 cold sores

Mucotaneous HSV

Genital herpes

Valacyclovir

Genital HSV – initial and recurrent treatment and suppression

Herpes labialis

Herpes zoster

CMV prophylaxis

Non-genital HSV

(References: 1, 2, 10, 16, 20, 22, 24, 27, 31, 33, 35, 36, 37, 38, 42, 45, 48, 49, 51, 63 – 68, 75, 82, 86, 99, 100, 107, 108, 112)

Table 7: Dosing During Continuous Renal Replacement Therapy

CVVH (Continuous venovenous hemofiltration): 5-7.5mg/kg q24h

CVVHD (Continuous venovenous hemodialysis): 5-7.5mg/kg q24h

CVVHDF (Continuous venovenous hemodiafiltration) 5-7.5mg/kg q24h

Note: CVVH is mainly for fluid removal alone. Many institutions will employ

more CVVHD or CVVHDF which combine dialysis with fluid removal.

Virus

Indication

Drug

Adult Dosing Regimen

Pediatric Dosing Regimen