Acyclovir and Valacyclovir

Section 1.1

Midwives may independently prescribe, order and administer this drug.

Acyclovir and Valacyclovir are anti-viral agents which inhibit DNA synthesis and viral replication.

Indications and Clinical Use:

Valacyclovir or Acyclovir is recommended for the treatment of symptomatic recurrent herpes simplex virus (HSV) types 1 and 2 outbreaks. Valacyclovir has three to fivefold greater oral bioavailability than acyclovir, but is not recommended for treatment of severe or disseminated disease.

Dosing regimens differ based on the site and type of outbreak (genital vs. oral). For suspected primary infections, clients should be referred to a physician for physical examination and serological confirmation. For known recurrent oral or genital HSV infections, midwives may offer their clients treatment when prodromal symptoms present (tingling, pain and/or aura). Once lesions appear, treatment is no longer considered effective or recommended.

Clients with a history of recurrent genital HSV infections should be offered Acyclovir or Valacyclovir suppression therapy at 36 weeks gestation to decrease the risk of clinical lesions or viral shedding at the time of birth, therefore decreasing the need for a cesarean section (Money, D. et al, 2008). If an HSV lesion or prodrome is present at the time of delivery, an obstetrical consult is indicated, to assess for the need for cesarean section.  When at risk of preterm birth, use of suppressive antivirals may be considered at an earlier gestational age.

Contraindications:

Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation.

Warnings and Precautions:

Maintain adequate hydration and use with caution in patients with renal impairment, hepatic or electrolyte abnormalities.

Pregnancy:

Compatible

Data exists for acyclovir use in all trimesters of human pregnancy; less information for valacyclovir. Combined data regarding use of acyclovir or valacyclovir (pro-drug of acyclovir) has not shown an association of any consistent pregnancy complications or fetal/neonatal adverse effects, however long term follow-up data is needed. Potential benefits of short term use for indications reducing risk of transmission to newborn as well as treatment of genital herpes to prevent prematurity likely outweigh potential risks of therapy.

Lactation:

Acyclovir – Category L2 – Limited Data – Probably Compatible

  • Relative Infant Dose is 1.09-1.53%; acyclovir therapy in neonates is common and produces few toxicities which are usually minor.
  • Infant monitoring: vomiting, diarrhea

Valacyclovir – Category L1 – Limited Data – Compatible

  • Valacyclovir is rapidly metabolized to acyclovir in maternal plasma, resulting in an acyclovir Relative Infant Dose of 4.7%, which is considerably less than that used in therapeutic dosing of neonates.
  • Infant monitoring: vomiting, diarrhea.

Adverse Reactions:

The most common side effects include nausea, vomiting, diarrhea, dehydration and headache. Less commonly, agitation, confusion, rash, anaemia and muscle pain have been reported. Rare hypersensitivity reactions include seizures and hepatitis. Thrombocytopenic purpura has been reported in immunocompromised patients.

Dosage and Administration (Genital HSV):

Symptomatic recurrent episode

Acyclovir: 400mg orally three times daily for 5 days OR 800mg orally three times daily for 2 days, initiate when first prodromal symptoms appear,

OR

Valacyclovir: 1000mg orally once daily OR 500 mg orally two times daily (bid) for three days, initiate when first prodromal symptoms appear.

May be taken with or without food.

Suppressive dosing at 36 weeks until delivery:

Acyclovir: 400 mg orally every 8 hours (tid), or

200 mg orally every 6 hours (qid), from 36 weeks gestation until birth,

OR

Valacyclovir: 500 mg orally every 12 hours (bid) from 36 weeks gestation until birth.

May be taken with or without food.

Dosage and Administration (Oral HSV):

Symptomatic recurrent episode:

Acyclovir: 400 mg orally five times a day for five days, initiate when first prodromal symptoms appear

OR:

Valacyclovir: 2 g orally every 12 hours (bid) for two doses, initiate when first prodromal symptoms appear.

May be taken with or without food.

OR

Acyclovir 5% cream: Apply topically to affected lesion(s) six times per day for 7 days, initiate when first prodromal symptoms appear

Benefit of treatment in Orolabial HSV:

  • Valacyclovir: reduced duration of symptoms by 1 day
  • Acyclovir: reduced duration of symptoms by ½ day
  • Acylcovir topical: reduced duration of symptoms by ½ day

Pharmacokinetics: Time to peak, serum:

  • Acyclovir: 1.5-2 hours
  • Valacyclovir: 1-3 hours

Half-life:

  • Acyclovir: 3 hours
  • Valacyclovir: (rapidly converted to acyclovir by first pass effect in liver) Acyclovir (active metabolite): 3 hours

Elimination:

Acyclovir: Urine (62% to 90% as unchanged drug and metabolite)

Valacyclovir: Urine (as acyclovir 89%)