Usual Adult Dose for Herpes Simplex - Mucocutaneous/Immunocompetent Host

Treatment of First Episode of Genital Herpes:
200 mg orally every 4 hours 5 times a day for 10 days (manufacturer dosing)
400 mg orally 3 times a day for 5 to 10 days (CDC recommendation)

Severe Disease or Complications Requiring Hospitalization:
5 mg/kg IV every 8 hours for 5 days (manufacturer dosing)
5 to 10 mg/kg IV every 8 hours for 2 to 7 days or until clinical improvement is observed, followed by oral antiviral therapy to complete at least 10 days of total therapy (CDC recommendation)

Episodic (Intermittent) Therapy: Effective treatment requires therapy initiation within 1 day of lesion onset or during the prodrome preceding an episode/recurrence
200 mg orally every 4 hours 5 times a day for 5 days (manufacturer dosing)
400 mg orally 3 times a day for 5 days OR 800 mg orally 2 times a day for 5 days OR 800 mg orally 3 times a day for 2 days (CDC recommendations)

Comments:

• All patients with newly acquired genital herpes should receive antiviral therapy as first episodes can cause a prolonged clinical illness, even among persons with mild clinical manifestations initially; therapy should be initiated at the earliest sign or symptom of primary infection.
• IV therapy is indicated for patients with severe infection.
• CDC STD treatment Guidelines may be consulted for additional guidance.

Use: For the initial treatment and recurrent episodes of mucosal and cutaneous herpes simplex (HSV-1 and HSV-2).

Usual Adult Dose for Herpes Simplex - Mucocutaneous/Immunocompromised Host

Concomitant HIV infection:

• Treatment of First Episode of Genital Herpes:

400 mg orally 3 times a day for 5 to 10 days (guideline recommendation)
Duration of therapy: 5 to 10 days

• Severe Disease:

5 mg/kg IV every 8 hours after lesions begin to regress, may change to oral therapy; continue treatment until lesions have completely healed (guideline recommendation)

Episodic (Intermittent) Therapy: Effective treatment requires therapy initiation within 1 day of lesion onset or during the prodrome preceding an episode/recurrence
400 mg orally 3 times a day for 5 to 14 days

Comments:

• Immunocompromised patients can have prolonged or severe episodes of genital, perianal, or oral herpes.
• Clinical manifestations of genital herpes may worsen during immune reconstitution early after initiation of antiretroviral therapy.
• Suppressive or episodic therapy with oral antiviral agents is effective in decreasing the clinical manifestations of HSV in persons with HIV infection.
• Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Infected Adults and Adolescents may be consulted for additional guidance.

Use: For the treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in immunocompromised patients.

Usual Adult Dose for Herpes Simplex Encephalitis

10 mg/kg IV every 8 hours
Duration of therapy: 10 days (manufacturer); 21 days (CDC)

Comments:

• The Center for Disease Control and Prevention (CDC) recommends 21 days of IV therapy to treat HSV encephalitis.

Use: For the treatment of HSV encephalitis.

Usual Adult Dose for Herpes Zoster

800 mg orally every 4 hours 5 times a day for 7 to 10 days

Immunocompromised host:
10 mg/kg IV every 8 hours for 7 days

Concomitant HIV infection:

• Localized Dermatomal: 800 mg orally 5 times a day for 7 to 10 days (alternative therapy; oral valacyclovir or famciclovir are preferred therapy)
• Extensive Cutaneous Lesion or Visceral Involvement: 10 to 15 mg/kg IV every 8 hours until clinical improvement (i.e. no new vesicle formation or improvement of signs and symptoms of visceral disease), then switch to oral therapy

Duration of therapy: 7 to 14-day course (oral plus IV)

Comments:

• Treatment should be initiated as soon as possible after a diagnosis of herpes zoster; parenteral dosing is based on ideal body weight (IBW).
• Oral acyclovir therapy should be considered an alternative therapy to treat acute localized dermatomal herpes zoster in HIV-infected adults according to the Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents; IV acyclovir is preferred therapy with extensive cutaneous lesion or visceral involvement.

Use: For the acute treatment of herpes zoster (shingles).

Usual Adult Dose for Varicella-Zoster

Immunocompetent Host: 800 mg orally 4 times a day for 5 days
Immunocompromised Host: 10 mg/kg IV every 8 hours for 7 days

HIV-Infected Adults:

• Uncomplicated course: 800 mg orally 5 times a day for 5 to 7 days (alternative therapy; oral valacyclovir or famciclovir are preferred therapy)
• Severe or complicated course: 10 to 15 mg/kg IV every 8 hours for 7 to 10 days; may switch to oral therapy after defervescence if no evidence of visceral involvement

Comments:

• Therapy should be initiated at the earliest sign or symptom of chickenpox; there is no information of efficacy when initiated more than 24 hours after onset of symptoms.
• According to the Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, oral acyclovir therapy should be considered alternative therapy for the treatment of uncomplicated cases of chickenpox; IV acyclovir is the preferred therapy for severe or complicated cases.

Use: For the treatment of chickenpox (varicella).

Usual Adult Dose for Herpes Simplex Labialis

Immunocompetent host:
Apply 50 mg (1 buccal tablet) as a single-dose to the upper gum region (canine fossa)

Comments:

• Tablet should be applied within 1 hour after the onset of prodromal symptoms and before the appearance of any signs of herpes labialis lesions.
• Tablet should be applied on the same side of the mouth as the herpes labialis symptoms.
• Use of buccal tablets has not been studied in immunocompromised subjects.

Concomitant HIV infection:
Oral tablets: 400 mg orally 3 times a day for 5 to 10 days

Comment: Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Infected Adults and Adolescents may be consulted for additional guidance.

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

Usual Adult Dose for Herpes Simplex - Suppression

Daily Suppressive Therapy for Recurrent Disease: 400 mg orally 2 times a day

• Alternative regimens from 200 mg orally 3 times a day to 200 mg orally 5 times a day have been used

Concomitant HIV infection: 400 to 800 mg orally 2 to 3 times a day

Comments:

• Suppressive therapy has been shown to reduce the frequency of recurrences by 70% to 80% in patients who have frequent recurrences.
• The frequency of recurrences has been shown to decrease over time and therefore continued therapy should be reevaluated at least annually.
• Experience has shown immunocompromised persons (i.e. hematopoietic stem-cell recipients) who received daily suppressive antiviral therapy were less likely to develop drug-resistant

HSV compared with those receiving episodic therapy; however, resistance is possible and should be suspected and investigated if lesions persist or recur.

• CDC STD Treatment Guidelines and the Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Infected Adults and Adolescents may be consulted for additional guidance.

Use: For secondary prophylaxis and treatment of recurrent HSV disease.

Usual Adult Dose for Herpes Zoster - Prophylaxis

HIV-Infected Adults (guideline dosing):

• Post-Exposure Prophylaxis: 800 mg orally 5 times a day for 5 to 7 days; begin 7 to 10 days after exposure

Comments:

• Varicella-zoster immune globulin is the preferred therapy for postexposure prophylaxis; oral antiviral therapy may be used when passive immunization is not possible; if antiviral therapy is used, varicella vaccines should not be given for at least 72 hours following last dose.
• Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Infected Adults and Adolescents may be consulted for additional guidance.

Use: For HIV-infected person who has had close contact with a person who has active varicella or herpes zoster and is susceptible to the virus (e.g. no history of vaccination or either condition, or is known to be seronegative).

Usual Adult Dose for Varicella-Zoster - Prophylaxis

HIV-Infected Adults (guideline dosing):

• Post-Exposure Prophylaxis: 800 mg orally 5 times a day for 5 to 7 days; begin 7 to 10 days after exposure

Comments:

• Varicella-zoster immune globulin is the preferred therapy for postexposure prophylaxis; oral antiviral therapy may be used when passive immunization is not possible; if antiviral therapy is used, varicella vaccines should not be given for at least 72 hours following last dose.
• Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Infected Adults and Adolescents may be consulted for additional guidance.

Use: For HIV-infected person who has had close contact with a person who has active varicella or herpes zoster and is susceptible to the virus (e.g. no history of vaccination or either condition, or is known to be seronegative).

Usual Pediatric Dose for Herpes Simplex - Congenital

Neonatal Herpes:
Birth to 3 months: 10 mg/kg IV every 8 hours for 10 days (manufacturer dosing)

Birth to 3 months: 20 mg/kg IV every 8 hours (CDC recommendation)

• Duration of therapy: Disease limited to the skin and mucous membranes: 14 days; Disseminated disease or disease involving the CNS: 21 days

Follow with oral suppressive therapy: 300 mg/m2 orally 3 times a day for 6 months

Comments:

• Neonates born to women who acquire HSV near term should be treated due to high risk of infection; infants exposed to HSV during birth should be followed by a pediatric infectious-disease specialist.
• For neonatal HSV with CNS involvement, confirm virus is absent from cerebrospinal fluid prior to stopping therapy; CSF HSV DNA PCR should be performed on days 19 and 21 and repeated as needed.
• Following IV treatment, oral prophylaxis for 6 months should be considered in those with CNS or skin, eyes, and mouth disease as it may be associated with superior neurodevelopmental outcome and prevent cutaneous recurrences.
• CDC STD Treatment Guidelines and the Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Exposed and HIV-Infected Children may be consulted for additional guidance.

Use: For known or suspected neonatal HSV.

Usual Pediatric Dose for Herpes Simplex - Mucocutaneous/Immunocompetent Host

Treatment of First Episode of Genital Herpes:
Less than 12 years: 40 to 80 mg/kg/day orally in divided doses 3 to 4 times a day for 5 to 10 days
Maximum dose: 1000 mg/day

12 years or older: 200 mg orally every 4 hours 5 times a day OR 400 mg orally 3 times a day
Duration of therapy: 7 to 10 days

Severe Disease or Complications Requiring Hospitalization:
Less than 12 years: 10 mg/kg IV every 8 hours for 7 days
12 years or older: 5 mg/kg IV every 8 hours for 7 days

Recurrence of Genital HSV Infection:
Less than 12 years: 20 to 25 mg/kg orally twice a day; Maximum dose: 400 mg
12 years or older: 200 mg orally 5 times a day for 5 days OR 800 mg orally 2 times a day for 5 days OR 800 mg orally 3 times a day for 2 days

Comments:

• All patients with newly acquired genital herpes should receive antiviral therapy as first episodes can cause a prolonged clinical illness, even among persons with mild clinical manifestations initially; therapy should be initiated at the earliest sign or symptom of primary infection; IV therapy is indicated for patients with severe infection.

Use: For the treatment of first episode or recurrence of mucosal and cutaneous herpes simplex (HSV-1 and HSV-2).

Usual Pediatric Dose for Herpes Simplex Encephalitis

3 months to 12 years old: 10 to 20 mg/kg IV every 8 hours

12 years or older: 10 mg/kg IV every 8 hours

Duration of therapy: 10 days (manufacturer); 21 days (CDC)

Comments:

• The Center for Disease Control and Prevention (CDC) recommends 21 days of IV therapy to treat HSV encephalitis.
• Acyclovir is the drug of choice for local and disseminated herpes simplex infection in infants and children.
• CDC STD Treatment Guidelines and the Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Exposed and HIV-Infected Children may be consulted for additional guidance.

Use: For the treatment of Herpes Simplex Encephalitis

Usual Pediatric Dose for Herpes Simplex - Mucocutaneous/Immunocompromised Host

Less than 12 years: 10 mg/kg IV every 8 hours for 7 days (manufacturer dosing)
12 years or older: 5 mg/kg IV every 8 hours for 7 days (manufacturer dosing)

Concomitant HIV infection (guideline dosing):

• Mild Symptomatic Gingivostomatitis:

20 mg/kg orally 4 times a day for 7 to 10 days
Maximum dose: 400 mg

• Moderate to Severe Gingivostomatitis:

5 to 10 mg/kg IV 3 times a day

• May switch to oral therapy after lesions have begun to regress; treat until lesions have completely healed

Comments:

• Acyclovir is the drug of choice for local and disseminated herpes simplex in HIV-infected and exposed infants and children; children with severe immunosuppression and moderate to severe lesions should be treated initially with IV therapy and may require longer therapy.
• Immunocompromised patients may have prolonged or severe episodes; clinical manifestations of genital herpes may worsen during immune reconstitution early after initiation of antiretroviral therapy.
• CDC STD Treatment Guidelines and the Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Exposed and HIV-Infected Children may be consulted for additional guidance.

Use: For the treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in immunocompromised patients

Usual Pediatric Dose for Herpes Zoster

Immunocompetent Host:

• Parenteral:

Less than 1 year: 10 mg/kg IV every 8 hours for 7 to 10 days
1 year or older: 500 mg/m2 IV every 8 hours for 7 to 10 days

• Oral: 12 years or older: 800 mg orally 5 times a day for 5 to 7 days

Immunocompromised Host: 10 mg/kg IV every 8 hours for 7 to 10 days

HIV-exposed and HIV-Infected Children:

• Uncomplicated Zoster:

20 mg/kg orally 4 times a day for 7 to 10 days; Maximum dose: 800 mg

• Severe immunosuppression (CDC immunologic category 3), trigeminal or sacral nerve involvement, extensive multidermatomal, or disseminated zoster:

10 mg/kg IV every 8 hours until cutaneous lesions and visceral disease are clearly resolving; then may switch to oral therapy to complete a 10 to 14-day course

HIV-Infected Adolescents:

• Localized Dermatomal: 800 mg orally 5 times a day for 7 to 10 days (alternative therapy; oral valacyclovir or famciclovir are preferred therapy)
• Extensive Cutaneous Lesion or Visceral Involvement: 10 to 15 mg/kg IV every 8 hours until clinical improvement (i.e. no new vesicle formation or improvement of signs and symptoms of visceral disease), then switch to oral therapy

Duration of therapy: 7 to 14-day course (oral plus IV)

Comments:

• Acyclovir is the oral drug of choice for treating herpes zoster in HIV-infected children; it should be given for 7 to 10 days, although longer durations should be considered if lesions are slow to resolve.
• Initial IV therapy is recommended in children with more severe immunosuppression.
• According to the Guidelines for the Prevention and Treatment of Opportunistic Infections, oral acyclovir therapy in adolescents should be considered alternative therapy for the treatment of uncomplicated cases of herpes zoster; IV acyclovir is preferred therapy for extensive cutaneous lesion or visceral involvement.
• Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Exposed and HIV-Infected Children and HIV- Infected Adults and Adolescents may be consulted for additional guidance.

Use: For the acute treatment of herpes zoster (shingles).

Usual Pediatric Dose for Varicella-Zoster

Immunocompetent host:
2 years or older (40 kg or less): 20 mg/kg orally 4 times a day for 5 days
2 years or older (over 40 kg): 800 mg orally 4 times a day for 5 days
Maximum doses: Single: 800 mg; Daily: 3200 mg/day

Immunocompromised host:
Less than 1 year: 10 mg/kg IV 3 times a day for 7 to 10 days
1 year or older: 500 mg/m2 IV 3 times a day for 7 to 10 days

HIV-exposed and HIV-infected Children

• Mild disease with no or moderate immune suppression (CDC immunologic category 1 and 2): 20 mg/kg orally 4 times a day for 7 to 10 days and until no new lesions for 48 hours

Maximum dose: 800 mg

• Severe immune suppression (CDC immunologic category 3): 10 mg/kg or 500 mg/m2 IV every 8 hours for 7 to 10 days and until no new lesions for 48 hours

HIV-Infected Adolescents:

• Uncomplicated course: 800 mg orally 5 times a day for 5 to 7 days (alternative therapy; oral valacyclovir or famciclovir are preferred therapy)
• Severe or complicated course: 10 to 15 mg/kg IV every 8 hours for 7 to 10 days; may switch to oral therapy after defervescence if no evidence of visceral involvement

Comments:

• Therapy should be initiated at the earliest sign of chickenpox, no later than 24 hours after onset of rash.
• In children 1 year or older, body surface area may be used for dosing instead of body weight.
• Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Exposed and HIV-Infected Children and HIV- Infected Adults and Adolescents may be consulted for additional guidance.

Use: For the treatment of chickenpox (varicella).

Usual Pediatric Dose for Herpes Simplex - Suppression

Neonatal period (less than 1 year): 300 mg/m2 orally 3 times a day for 6 months

Secondary Prophylaxis in HIV-Exposed and HIV-infected Children:
20 mg/kg orally twice a day
Maximum dose: 800 mg

Comments:

• Suppressive therapy following treatment of neonatal HSV disease involving the CNS or skin, eyes, and mouth may prevent cutaneous recurrences and possibly provide superior neurodevelopmental outcomes.
• Beyond the neonatal period, recurrent HSV episodes can be treated successfully and chronic prophylaxis is generally not warranted; however, it may be considered for children with severe and recurrent mucocutaneous (oral or genital) disease.
• Secondary prophylaxis should be re-evaluated periodically (at least annually) as the frequency and severity of infection changes over time.
• Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Exposed and HIV-Infected Children and HIV- Infected Adults and Adolescents may be consulted for additional guidance.

Use: For the secondary prophylaxis of recurrent HSV disease.

Usual Pediatric Dose for Herpes Simplex Labialis

Concomitant HIV infection:

20 mg/kg orally 4 times a day for 5 days
Maximum dose: 400 mg

Adolescents: 400 mg orally 3 times a day for 5 to 10 days

Comments:

• The safety and efficacy of buccal tablets in pediatric patients has not been evaluated.
• Use of buccal tablets in younger children may present a choking risk.
• Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Infected Adults and Adolescents may be consulted for additional guidance.

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

Usual Pediatric Dose for Herpes Zoster - Prophylaxis

HIV-Infected Children or Adolescents (guideline dosing):

Post-exposure Prophylaxis in HIV-Infected Children or Adolescents:
20 mg/kg orally 4 times a day (maximum dose 800 mg) for 7 days beginning 7 to 10 days after exposure

Comments:

• Varicella-zoster immune globulin is the preferred therapy for postexposure prophylaxis; oral antiviral therapy may be used when passive immunization is not possible; if antiviral therapy is used, varicella vaccines should not be given for at least 72 hours following last dose.
• Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Exposed and HIV-Infected Children or HIV- Infected Adults and Adolescents may be consulted for additional guidance.

Use: For HIV-infected person who has had close contact with a person who has active varicella or herpes zoster and is susceptible to the virus (e.g. no history of vaccination or either condition, or is known to be seronegative).

Usual Pediatric Dose for Varicella-Zoster - Prophylaxis

HIV-Infected Children or Adolescents (guideline dosing):

Post-exposure Prophylaxis in HIV-Infected Children or Adolescents:
20 mg/kg orally 4 times a day (maximum dose 800 mg) for 7 days beginning 7 to 10 days after exposure

Comments:

• Varicella-zoster immune globulin is the preferred therapy for postexposure prophylaxis; oral antiviral therapy may be used when passive immunization is not possible; if antiviral therapy is used, varicella vaccines should not be given for at least 72 hours following last dose.
• Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV- Exposed and HIV-Infected Children or HIV- Infected Adults and Adolescents may be consulted for additional guidance.

Use: For HIV-infected person who has had close contact with a person who has active varicella or herpes zoster and is susceptible to the virus (e.g. no history of vaccination or either condition, or is known to be seronegative).

Renal Dose Adjustments

Oral:
For CrCl 0 to 10 mL/min/1.73 m2:

• If normal dose is 200 mg orally every 4 hours 5 times a day: Reduce dose to 200 mg orally every 12 hours
• If normal dose is 400 mg orally every 12 hours: Reduce dose to 200 mg orally every 12 hours
• If normal dose is 800 mg orally every 4 hours 5 times a day: Reduce dose to 800 mg orally every 12 hours

For CrCl 10 to 25 mL/min/1.73 m2:

• If normal dose is 800 mg orally every 4 hours 5 times a day: Reduce dose to 800 mg orally every 8 hours

IV:
For CrCl 0 to 10 mL/min/1.73 m2: Give 50% of dose every 24 hours
For CrCl 10 to 25 mL/min/1.73 m2: Give 100% of dose every 24 hours
For CrCl 25 to 50 mL/min/1.73 m2: Give 100% of dose every 12 hours
For CrCl greater than 50 mL/min/1.73 m2: Give 100% of dose every 8 hours

Liver Dose Adjustments

No adjustment recommended

Dose Adjustments

Obese patients should be dosed at the recommended doses using Ideal Body Weight (IBW)

Elderly patients are more likely to have reduced renal function and require dose reduction.

Precautions

Safety and efficacy of oral formulations have not been established in patients younger than 2 years.
Safety and efficacy of buccal tablets have not been established in pediatric patients.

Consult WARNINGS section for additional precautions.

Dialysis

Hemodialysis: Adjust dosing interval to provide an additional dose after each dialysis
Peritoneal Dialysis: No supplemental dose necessary after adjustment of the dosing interval

Other Comments

Administration advice:

• Maintain adequate hydration

Parenteral:

• Administer via IV infusion over at least 1 hour; infused concentration should not exceed 7 mg per mL
• Do not administer by rapid or bolus IV injections; not for IM or subcutaneous injection

Oral:

• May take with or without food

Buccal tablet:

• Apply to upper gum just above the incisor tooth with a dry finger immediately after taking it out of the blister; hold in place for 30 seconds to ensure adhesion.
• For comfort, the rounded side should be placed to the gum (but either side can be placed)
• Tablet should be applied on the same side of the mouth as the herpes labialis symptoms.
• Tablet should stay in position and gradually dissolve throughout the day
• Buccal tablet should not be crushed, chewed, sucked, or swallowed
• Food and drink can be taken normally; avoid chewing gum, touching, pressing, or moving tablet
• If buccal tablet does not adhere or falls off within the first 6 hours; reposition immediately, if the tablet does not adhere, a new tablet should be placed
• If buccal tablet is swallowed within the first 6 hours, patient should be instructed to drink a glass of water and apply a new tablet
• If buccal tablet falls out or is swallowed after the first 6 hours, no need to reapply

Reconstitution/storage/preparation techniques:

• For IV infusion only; must be diluted prior to use
• Reconstitute with sterile water for injection (do not use bacteriostatic water for injection containing benzyl alcohol or parabens); use within 12 hours (refrigeration of reconstituted solution may result in the formation of a precipitate)
• Infusion concentrations must be 7 mg/mL or lower; once diluted, use within 24 hours

IV compatibility: Standard, commercially available electrolyte and glucose solutions are suitable for IV administration; biologic or colloidal fluids (e.g., blood products, protein solutions) are not recommended

General:

• Maximum dose of 20 mg/kg every 8 hours should not be exceeded
• Therapy should be initiated as early as possible following onset of symptoms.

Monitoring:

• Assess renal function prior to therapy

Patient advice:

• Patients should be advised to maintain adequate hydration during therapy.
• Patients should understand this drug is not a cure for genital herpes; proper precautions should be discussed and practiced to prevent transmission.

Frequently asked questions

• Can you drink alcohol while taking acyclovir?
• What would be the benefits of taking valacyclovir vs acyclovir?