Usual Adult Dose for Herpes Simplex Labialis

2 g orally twice a day for 1 day

Comments:

• The 2 doses should be administered 12 hours apart.
• Therapy should be started at the earliest symptom of a cold sore (e.g., tingling, burning, itching).
• Efficacy of treatment started after the development of clinical signs of a cold sore (e.g., papule, vesicle, ulcer) has not been established.

Use: For the treatment of cold sores (herpes labialis)

US CDC, National Institutes of Health (NIH), and HIV Medicine Association of the Infectious Diseases Society of America (HIVMA/IDSA) Recommendations for HIV-Infected Patients: 1 g orally twice a day for 5 to 10 days

Comments:

• Recommended to treat orolabial herpes simplex virus (HSV) lesions
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Herpes Simplex - Mucocutaneous/Immunocompetent Host

Initial episode: 1 g orally twice a day for 10 days
Recurrent episodes: 500 mg orally twice a day for 3 days

Comments:

• Initial episode: Therapy was most effective when administered within 48 hours of onset of signs/symptoms; the efficacy of treatment started more than 72 hours after onset of signs/symptoms has not been established.
• Recurrent episodes: Therapy should be started at the first sign/symptom of an episode; the efficacy of treatment started more than 24 hours after onset of signs/symptoms has not been established.

Use: For the treatment of the initial and recurrent episodes of genital herpes in immunocompetent patients

US CDC Recommendations:

• First clinical episode: 1 g orally twice a day for 7 to 10 days
• Episodic therapy: 500 mg orally twice a day for 3 days OR 1 g orally once a day for 5 days

Comments:

• Recommended regimen for first clinical episode of genital herpes; recommended regimens for episodic therapy for recurrent herpes simplex virus type 2 (HSV-2) genital herpes
• First clinical episode: If healing is not complete after 10 days, therapy can be extended.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Herpes Simplex - Suppression

Chronic Suppressive Therapy of Recurrent Genital Herpes:

• Immunocompetent patients: 1 g orally once a day
• Alternative dose for patients with history of 9 or fewer recurrences per year: 500 mg orally once a day
• HIV-1-infected patients with a CD4+ cell count at least 100 cells/mm3: 500 mg orally twice a day

Reduction of Transmission of Genital Herpes:

• Patients (source partners) with history of 9 or fewer recurrences per year: 500 mg orally once a day

Comments:

• Suppressive therapy: Safety and efficacy of treatment for the suppression of genital herpes beyond 1 year in immunocompetent patients and beyond 6 months in HIV-1-infected patients have not been established.
• Reduction of transmission: The efficacy of treatment for the reduction of transmission of genital herpes beyond 8 months in discordant couples has not been established; the efficacy of treatment for the reduction of transmission of genital herpes in patients with multiple partners and non-heterosexual couples has not been established.
• Safer sex practices should be used with suppressive therapy; the current US CDC Sexually Transmitted Infections Treatment Guidelines should be consulted.

Uses: For chronic suppressive therapy of recurrent episodes of genital herpes in immunocompetent and in HIV-1-infected patients; for the reduction of transmission of genital herpes in immunocompetent patients

US CDC Recommendations: 500 mg orally once a day OR 1 g orally once a day

• Patients with HIV infection: 500 mg orally twice a day
• Pregnant patients: 500 mg orally twice a day

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-Infected Patients: 500 mg orally twice a day

Comments:

• US CDC guidelines:
• Recommended regimen for suppression of recurrent HSV-2 genital herpes; the 500 mg/day regimen may be less effective than other dosing regimens in patients with frequent recurrences (i.e., at least 10 episodes per year).
• Recommended regimen for daily suppression of genital herpes among patients with HIV infection
• Recommended regimen for suppression of recurrent genital herpes among pregnant patient; suppression therapy is recommended in pregnant patients starting at 36 weeks gestation.
• US CDC, NIH, and HIVMA/IDSA guidelines:
• Recommended as chronic suppressive therapy for patients with severe recurrences OR patients who want to minimize frequency of recurrences (including pregnant women) OR to reduce risk of genital ulcer disease in patients with CD4 counts less than 250 cells/mm3 starting antiretroviral therapy
• The ongoing need for suppressive therapy should be evaluated annually.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Herpes Zoster

1 g orally 3 times a day for 7 days

Comments:

• Therapy should be started at the earliest sign/symptom of herpes zoster and is most effective when started within 48 hours of rash onset.
• Efficacy of treatment started more than 72 hours after onset of rash has not been established.
• Safety and efficacy for treatment of disseminated herpes zoster have not been established.

Use: For the treatment of herpes zoster (shingles) in immunocompetent patients

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-Infected Patients: 1 g orally 3 times a day for 7 to 10 days

Comments:

• Recommended as a preferred regimen for acute, localized, dermatomal herpes zoster (shingles)
• Longer duration of therapy should be considered if lesions are slow to resolve.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Herpes Simplex - Mucocutaneous/Immunocompromised Host

US CDC Recommendations and US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-Infected Patients:

• First clinical episode/initial genital lesions: 1 g orally twice a day for 7 to 10 days
• Episodic therapy/recurrent genital lesions: 1 g orally twice a day for 5 to 10 days

Comments:

• US CDC guidelines:
• Recommended regimen for first clinical episode of genital herpes in HIV-infected patients; duration of therapy may need to be extended for lesion resolution.
• Recommended regimen for episodic genital herpes infection in HIV-infected patients
• US CDC, NIH, and HIVMA/IDSA guidelines:
• Recommended for treating initial or recurrent genital HSV lesions
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Varicella-Zoster

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-Infected Patients: 1 g orally 3 times a day for 5 to 7 days

Comments:

• Recommended as a preferred regimen for uncomplicated cases of primary varicella infection (chickenpox)
• Treatment should be started as early as possible after onset of lesions.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Herpes Zoster - Prophylaxis

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-Infected Patients: 1 g orally 3 times a day for 5 to 7 days

Comments:

• Recommended as an alternative regimen for postexposure prophylaxis of varicella-zoster virus (VZV) primary infection; for close contact with a person who has active varicella or herpes zoster, and susceptible to VZV (i.e., no history of varicella vaccination, no history of varicella or herpes zoster, or known to be VZV seronegative)
• Prophylaxis should begin 7 to 10 days after exposure.
• Varicella zoster immune globulin is the preferred prophylaxis; if this drug is used, varicella vaccines should not be given less than 72 hours after the last dose of this drug.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Varicella-Zoster - Prophylaxis

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-Infected Patients: 1 g orally 3 times a day for 5 to 7 days

Comments:

• Recommended as an alternative regimen for postexposure prophylaxis of varicella-zoster virus (VZV) primary infection; for close contact with a person who has active varicella or herpes zoster, and susceptible to VZV (i.e., no history of varicella vaccination, no history of varicella or herpes zoster, or known to be VZV seronegative)
• Prophylaxis should begin 7 to 10 days after exposure.
• Varicella zoster immune globulin is the preferred prophylaxis; if this drug is used, varicella vaccines should not be given less than 72 hours after the last dose of this drug.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Herpes Simplex Labialis

12 years or older: 2 g orally twice a day for 1 day

Comments:

• The 2 doses should be administered 12 hours apart.
• Therapy should be started at the earliest symptom of a cold sore (e.g., tingling, burning, itching).
• Efficacy of treatment started after the development of clinical signs of a cold sore (e.g., papule, vesicle, ulcer) has not been established.

Use: For the treatment of cold sores (herpes labialis)

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-Infected Adolescents: 1 g orally twice a day for 5 to 10 days

Comments:

• Recommended to treat orolabial HSV lesions
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Varicella-Zoster

2 to less than 18 years: 20 mg/kg orally 3 times a day for 5 days
Maximum dosage: 1 g orally 3 times a day

Comments:

• Therapy should be started at the earliest sign/symptom of chickenpox, within 24 hours after onset of rash.
• An oral suspension may be prepared extemporaneously for use in patients for whom the tablet formulation is not appropriate.

Use: For the treatment of chicken pox in immunocompetent patients

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-Infected Adolescents: 1 g orally 3 times a day for 5 to 7 days

Comments:

• Recommended as a preferred regimen for uncomplicated cases of primary varicella infection (chickenpox)
• Treatment should be started as early as possible after onset of lesions.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Herpes Simplex - Suppression

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-Infected Adolescents: 500 mg orally twice a day

Comments:

• Recommended as chronic suppressive therapy for patients with severe recurrences OR patients who want to minimize frequency of recurrences (including pregnant women) OR to reduce risk of genital ulcer disease in patients with CD4 counts less than 250 cells/mm3 starting antiretroviral therapy
• The ongoing need for suppressive therapy should be evaluated annually.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Herpes Simplex - Mucocutaneous/Immunocompromised Host

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-Infected Adolescents:

• Initial genital lesions: 1 g orally twice a day for 7 to 10 days
• Recurrent genital lesions: 1 g orally twice a day for 5 to 10 days

Comments:

• Recommended for treating initial or recurrent genital HSV lesions
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Herpes Zoster - Prophylaxis

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-Infected Adolescents: 1 g orally 3 times a day for 5 to 7 days

Comments:

• Recommended as an alternative regimen for postexposure prophylaxis of VZV primary infection; for close contact with a person who has active varicella or herpes zoster, and susceptible to VZV (i.e., no history of varicella vaccination, no history of varicella or herpes zoster, or known to be VZV seronegative)
• Prophylaxis should begin 7 to 10 days after exposure.
• Varicella zoster immune globulin is the preferred prophylaxis; if this drug is used, varicella vaccines should not be given less than 72 hours after the last dose of this drug.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Varicella-Zoster - Prophylaxis

US CDC, NIH, and HIVMA/IDSA Recommendations for HIV-Infected Adolescents: 1 g orally 3 times a day for 5 to 7 days

Comments:

• Recommended as an alternative regimen for postexposure prophylaxis of VZV primary infection; for close contact with a person who has active varicella or herpes zoster, and susceptible to VZV (i.e., no history of varicella vaccination, no history of varicella or herpes zoster, or known to be VZV seronegative)
• Prophylaxis should begin 7 to 10 days after exposure.
• Varicella zoster immune globulin is the preferred prophylaxis; if this drug is used, varicella vaccines should not be given less than 72 hours after the last dose of this drug.
• Current guidelines should be consulted for additional information.

Renal Dose Adjustments

Adult Patients:
Cold sores (herpes labialis):

• CrCl at least 50 mL/min: No adjustment recommended.
• CrCl 30 to 49 mL/min: 1 g orally twice a day for 1 day; the 2 doses should be administered 12 hours apart.
• CrCl 10 to 29 mL/min: 500 mg orally twice a day for 1 day; the 2 doses should be administered 12 hours apart.
• CrCl less than 10 mL/min: 500 mg orally as a single dose

Genital herpes, initial episode:

• CrCl at least 30 mL/min: No adjustment recommended.
• CrCl 10 to 29 mL/min: 1 g orally every 24 hours
• CrCl less than 10 mL/min: 500 mg orally every 24 hours

Genital herpes, recurrent episode:

• CrCl at least 30 mL/min: No adjustment recommended.
• CrCl less than 30 mL/min: 500 mg orally every 24 hours

Genital herpes, suppressive therapy in immunocompetent patients:

• CrCl at least 30 mL/min: No adjustment recommended.
• CrCl less than 30 mL/min: 500 mg orally every 24 hours
• Alternate dose in those with 9 or fewer recurrences per year: 500 mg orally every 48 hours

Genital herpes, suppressive therapy in HIV-1-infected patients:

• CrCl at least 30 mL/min: No adjustment recommended.
• CrCl less than 30 mL/min: 500 mg orally every 24 hours

Herpes zoster:

• CrCl at least 50 mL/min: No adjustment recommended.
• CrCl 30 to 49 mL/min: 1 g orally every 12 hours
• CrCl 10 to 29 mL/min: 1 g orally every 24 hours
• CrCl less than 10 mL/min: 500 mg orally every 24 hours

Pediatric Patients:

• CrCl less than 50 mL/min/1.73 m2: Data not available

Liver Dose Adjustments

Cirrhosis: No adjustment recommended.

Comments:

• Administration of this drug to subjects with moderate (biopsy-proven cirrhosis) or severe (biopsy-proven cirrhosis, with and without ascites) liver dysfunction showed the rate, but not the extent, of conversion to acyclovir was reduced and the acyclovir half-life was not affected.

Precautions

CONTRAINDICATIONS:
Demonstrated clinically significant hypersensitivity reaction (e.g., anaphylaxis) to this drug, acyclovir, or any of the ingredients

Safety and efficacy have not been established in patients younger than 18 years with genital herpes or herpes zoster, younger than 12 years with cold sores, younger than 2 years with chickenpox, or for suppressive treatment after neonatal HSV infection.

Consult WARNINGS section for additional precautions.

Dialysis

Hemodialysis: The recommended dose should be administered after hemodialysis.
Peritoneal dialysis: Data not available

• Chronic ambulatory peritoneal dialysis (CAPD) and continuous arteriovenous hemofiltration/dialysis (CAVHD): Supplemental doses should not be needed after CAPD or CAVHD.

Comments:

• During hemodialysis, the acyclovir half-life after administration of this drug is about 4 hours; about one-third of acyclovir in the body is removed during a 4-hour hemodialysis session.
• No information specific to administration of this drug available in patients receiving peritoneal dialysis; the effect of CAPD and CAVHD on acyclovir pharmacokinetics (PKs) has been studied.
• Removal of acyclovir after CAPD and CAVHD is less pronounced than with hemodialysis; the PK parameters closely resemble those seen in patients with ESRD not receiving hemodialysis.

Other Comments

Administration advice:

• May administer without regard to meals
• Maintain adequate hydration during therapy.
• An oral suspension may be prepared extemporaneously for use in pediatric patients for whom the solid dosage form is not appropriate; shake the oral suspension well prior to use.
• Consult the manufacturer product information regarding missed doses.

Storage requirements:

• Oral suspension: Store between 2C to 8C (36F to 46F) in a refrigerator; discard after 28 days.

Reconstitution/preparation techniques:

• Extemporaneous preparation of oral suspension:
• Prepare Suspension Structured Vehicle USP-NF (SSV) according to the USP-NF.
• Using a pestle and mortar, grind 5 valacyclovir tablets for 25 mg/mL suspension or 10 valacyclovir tablets for 50 mg/mL suspension until a fine powder is produced.
• Gradually add about 5 mL aliquots of SSV to mortar and triturate powder until paste has been produced, ensuring the powder has been adequately wetted.
• Continue to add about 5 mL aliquots of SSV to mortar, mixing thoroughly between additions, until a concentrated suspension is produced, to a minimum total quantity of 20 mL SSV and a maximum total quantity of 40 mL SSV for both the 25 mg/mL and 50 mg/mL suspensions.
• Transfer mixture to suitable 100 mL measuring flask.
• Transfer cherry flavor (add amount as instructed by suppliers of cherry flavor) to mortar and dissolve in about 5 mL of SSV; once dissolved, add to measuring flask.
• Rinse mortar at least 3 times with about 5 mL aliquots of SSV, transferring the rinsing to measuring flask between additions.
• Add SSV until suspension volume is 100 mL and shake thoroughly to mix.
• Transfer suspension to an amber glass bottle with a child-resistant closure.

General:

• Limitations of Use: Safety and efficacy have not been established in:
• Immunocompromised patients except for the suppression of genital herpes in HIV-1-infected adult patients with CD4+ cell count at least 100 cells/mm3.
• Patients younger than 12 years with cold sores (herpes labialis).
• Patients younger than 2 years or at least 18 years of age with chickenpox.
• Patients younger than 18 years with genital herpes.
• Patients younger than 18 years with herpes zoster.
• Neonates and infants as suppressive therapy after neonatal HSV infection.

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information).
• Maintain adequate hydration during therapy.
• Cold sores:
• Start treatment at the earliest symptom of a cold sore (e.g., tingling, itching, burning); treatment should not exceed 1 day, and the 2 doses should be taken about 12 hours apart.
• This drug is not a cure for cold sores.
• Genital herpes:
• This drug is not a cure for genital herpes; avoid contact with lesions or intercourse when lesions and/or symptoms develop to avoid infecting partner(s).
• Use safer sex practices in conjunction with suppressive therapy.
• If using this drug to medically manage recurrence, start therapy at first sign/symptom of an episode.
• Herpes zoster: Start treatment as soon as possible after diagnosis of herpes zoster.
• Chickenpox: Start treatment at the earliest sign/symptom of chickenpox.

Frequently asked questions

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