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

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)

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, 6368, 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.