acyclovir, Sitavig, Xerese, Zovirax

 Classification

Therapeutic: antivirals

Pharmacologic: purine analogues

Indications

PO: Recurrent genital herpes infections. Localized cutaneous

herpes zoster infections (shingles) and chickenpox

(varicella). Buccal: Recurrent herpes labialis

(cold sores) in nonimmunosuppressed patients. IV:

Severe initial episodes of genital herpes in nonimmunosuppressed

patients. Mucosal or cutaneous herpes simplex

infections or herpes zoster infections (shingles) in

immunosuppressed patients. Herpes simplex encephalitis.

Topical: Cream—Recurrent herpes labialis

(cold sores). Ointment—Treatment of limited non–

life-threatening herpes simplex infections in immunocompromised

patients (systemic treatment is preferred).

Action

Interferes with viral DNA synthesis. Therapeutic Effects:

Inhibition of viral replication, decreased viral

shedding, and reduced time for healing of lesions.

Pharmacokinetics

Absorption: Despite poor absorption (15–30%),

therapeutic blood levels are achieved.

Distribution: Widely distributed. CSF concentrations

are 50% of plasma. Crosses placenta; enters breast

milk.

Protein Binding: 30%.

Metabolism and Excretion: 90% eliminated

unchanged by kidneys; remainder metabolized by liver.

Half-life: Neonates: 4 hr; Children 1–12 yr: 2–3 hr;

Adults: 2–3.5 hr (qin renal failure).

TIME/ACTION PROFILE (antiviral blood

levels)

ROUTE ONSET PEAK DURATION

PO unknown 1.5–2.5 hr 4 hr

IV prompt end of infusion

8 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity to acyclovir or

valacyclovir; Hypersensitivity to milk protein concentrate

(buccal only).

Use Cautiously in: Pre-existing serious neurologic,

hepatic, pulmonary, or fluid and electrolyte abnormalities;

Renal impairment (dose alteration recommended

if CCr 50 mL/min); Geri: Due to age relatedpin renal

function; Obese patients (dose should be based on ideal body weight); Patients with hypoxia; OB, Lactation:

Safety not established.

Adverse Reactions/Side Effects

CNS: SEIZURES, dizziness, headache, hallucinations,

trembling. GI: diarrhea, nausea, vomiting,qliver enzymes,

hyperbilirubinemia, abdominal pain, anorexia.

GU: RENAL FAILURE, crystalluria, hematuria, renal pain.

Derm: STEVENS-JOHNSON SYNDROME, acne, hives, rash,

unusual sweating. Endo: changes in menstrual cycle.

Hemat: THROMBOTIC THROMBOCYTOPENIC PURPURA/HEMOLYTIC

UREMIC SYNDROME (high doses in immunosuppressed

patients). Local: pain, phlebitis, local irritation.

MS: joint pain. Misc: polydipsia.

Interactions

Drug-Drug: Probenecidqblood levels of acyclovir.

qblood levels and risk of toxicity from theophylline;

dose adjustment may be necessary.pblood levels and

maypeffectiveness of valproic acid or phenytoin.

Concurrent use of other nephrotoxic drugsqrisk of

adverse renal effects. Zidovudine and IT methotrexate

mayqrisk of CNS side effects.

Route/Dosage

Initial Genital Herpes

PO (Adults and Children): 200 mg q 4 hr while

awake (5 times/day) for 7–10 days or 400 mg q 8 hr

for 7–10 days; maximum dose in children: 80 mg/kg/

day in 3–5 divided doses.

IV (Adults and Children): 5 mg/kg q 8 hr or 750

mg/m2/day divided q 8 hr for 5–7 days.

Chronic Suppressive Therapy for Recurrent

Genital Herpes

PO (Adults and Children): 400 mg twice daily or

200 mg 3–5 times/day for up to 12 mo. Maximum dose

in children: 80 mg/kg/day in 2–5 divided doses.

Intermittent Therapy for Recurrent Genital

Herpes

PO (Adults and Children): 200 mg q 4 hr while

awake (5 times/day) or 400 mg q 8hr or 800 mg q 12

hr for 5 days, start at first sign of symptoms. Maximum

dose in children: 80 mg/kg/day in 2–5 divided doses.

Acute Treatment of Herpes Zoster in Immunosuppressed

Patients

PO (Adults): 800 mg q 4 hr while awake (5 times/

day) for 7–10 days. Prophylaxis—400 mg 5 times/

day.

PO (Children): 250–600 mg/m2/dose 4–5 times/

day.

Herpes Zoster in Immunocompetent Patients

PO (Adults and Children): 4000 mg/day in 5 divided

doses for 5–7 days, maximum dose in children: 80

mg/kg/day in 5 divided doses.

Chickenpox

PO (Adults and Children): 20 mg/kg (not to exceed

800 mg/dose) qid for 5 days. Start within 24 hr of rash

onset.

Mucosal and Cutaneous Herpes Simplex

Infections in Immunosuppressed Patients

IV (Adults and Children 12 yr): 5 mg/kg q 8 hr for

7 days.

IV (Children 12 yr): 10 mg/kg q 8 hr for 7 days.

Topical (Adults): 0.5 in. ribbon of 5% ointment for

every 4-square-in. area q 3 hr (6 times/day) for 7 days.

Herpes Simplex Encephalitis

IV (Adults): 10mg/kg q 8 hr for 14–21 days.

IV (Children 3 mo–12 yr): 10 mg/kg q 8 hr for 14–

21 days.

IV (Children birth–3 mo): 20 mg/kg q 8 hr for 14–

21 days.

IV (Neonates , premature): 10 mg/kg q 12 hr for

14–21 days.

Varicella Zoster Infections in Immunosuppressed

Patients

IV (Adults): 10mg/kg q 8 hr for 7–10 days.

IV (Children 12 yr): 10 mg/kg q 8 hr for 7–10

days.

Renal Impairment

PO, IV (Adults and Children): CCr 50 mL/min/

1.73 m2—no dosage adjustment needed; CCr 25–50

mL/min/1.73 m2—administer normal dose q 12 hr;

CCr 10–25 mL/min/1.73 m2—administer normal

dose q 24 hr; CCr 0–10 mL/min/1.73 m2—50% of

dose q 24 hr.

IV (Neonates): SCr 0.8–1.1 mg/dL: Administer 20

mg/kg/dose q 12 hr; SCr 1.2–1.5 mg/dL: Administer

20 mg/kg/dose q 24 hr; SCr 1.5 m g/dL: Administer

10 mg/kg/dose q 24 hr.

Herpes labialis

Topical (Adults and Children 12 yr): Apply 5

times/day for 4 days; start at first symptoms.

Buccal (Adults): Apply one 50–mg buccal tablet to

the upper gum region within 1 hr of onset of prodromal

symptoms (but before appearance of any lesions).

Availability (generic available)

Capsules: 200 mg. Cost: Generic—$97.70/100.

Tablets: 400 mg, 800 mg. Cost: Generic—400 mg

$6.99/30, 800 mg $17.91/30. Buccal tablets: 50 mg.

Suspension (banana flavor): 200 mg/5 mL. Cost:

Generic—$137.70/473 mL. Powder for injection:

500 mg/vial, 1000 mg/vial. Solution for injection: 25

mg/mL, 50 mg/mL. Cream: 5%. Cost: $565.24/5 g.

Ointment: 5%. Cost: Generic—$797.59/30 g. In

combination with: hydrocortisone (Xerese). See

Appendix B.