acyclovir

REMS

PO: Treatment of:
- Recurrent genital herpes infections,
- Localized cutaneous herpes zoster infections (shingles) and chickenpox (varicella).
Buccal: Recurrent herpes labialis (cold sores) in nonimmunosuppressed patients
IV: Treatment of:
- 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,
- Neonatal herpes simplex infections.
Topical Cream: Recurrent herpes labialis (cold sores). Ointment: Treatment of limited non-life-threatening herpes simplex infections in immunocompromised patients (systemic treatment is preferred).

Contraind./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);
Obese patients (dose should be based on ideal body weight);
Patients with hypoxia;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk; systemic exposure minimal following buccal or topical administration;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant; systemic exposure minimal following buccal or topical administration;
Pedi: Safety and effectiveness of buccal formulation not established in children;
Geri: May need to ↓ dose in older adults due to age-related ↓ in renal function.

Adv. Reactions/Side Effects ⬆ ⬇

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

Endo: changes in menstrual cycle

F and E: polydipsia

GI: diarrhea, nausea, vomiting, ↑liver enzymes, abdominal pain, anorexia, hyperbilirubinemia

GU: crystalluria, hematuria, RENAL FAILURE, renal pain

Hemat: THROMBOTIC THROMBOCYTOPENIC PURPURA/HEMOLYTIC UREMIC SYNDROME (HIGH DOSES IN IMMUNOSUPPRESSED PATIENTS)

Local: pain, phlebitis, local irritation

MS: joint pain

Neuro: dizziness, headache, hallucinations, SEIZURES, trembling

Interactions ⬆ ⬇

Drug-drug:

Probenecid and theophylline may ↑ levels and risk of toxicity.
Valproic acid or phenytoin may ↓ levels and effectiveness.
Concurrent use of other nephrotoxic drugs may ↑ risk nephrotoxicity.
Zidovudine and intrathecal methotrexate may ↑ risk of CNS side effects.

Availability ⬆ ⬇

(Generic available)

Tablets: 200 mg; 400 mg; 800 mg
Capsules: 200 mg
Oral suspension banana flavor: 200 mg/5 mL
Solution for injection: 25 mg/mL; 50 mg/mL
Buccal tablets: 50 mg
Cream: 5%
Ointment: 5%
In combination with: hydrocortisone (Xerese). See Appendix [not included in this PDA edition].

Route/Dosage ⬆ ⬇

Initial Genital Herpes

PO (Adults and Children ): 200 mg every 4 hr while awake (5 times/day) for 7–10 days or 400 mg every 8 hr for 7–10 days; maximum dose in children: 80 mg/kg/day in 3–5 divided doses.
IV (Adults and Children ≥12 yr): 5 mg/kg every 8 hr for 5 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 every 4 hr while awake (5 times/day) or 400 mg every 8 hr or 800 mg every 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 every 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) 4 times daily 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 every 8 hr for 7 days.
IV (Children 3 mo–12 yr): 10 mg/kg every 8 hr for 7 days.
(Adults ): ½-inch ribbon of 5% ointment for every 4-square-inch area every 3 hr (6 times/day) for 7 days.

Herpes Simplex Encephalitis

IV (Adults and Children ≥12 yr): 10 mg/kg every 8 hr for 10 days.
IV (Children 3 mo–12 yr): 20 mg/kg every 8 hr for 10 days.
IV (Children birth–3 mo): 20 mg/kg every 8 hr for 14–21 days.
IV (Neonates , premature): 10 mg/kg every 12 hr for 14–21 days.

Neonatal Herpes Simplex Infections

IV (Children postmenstrual age of ≥34 wk): 20 mg/kg every 8 hr for 21 days.
IV (Children postmenstrual age of <34 wk): 20 mg/kg every 12 hr for 21 days.

Varicella Zoster Infections in Immunosuppressed Patients

IV (Adults and Children ≥12 yr): 10 mg/kg every 8 hr for 7 days.
IV (Children <12 yr): 20 mg/kg every 8 hr for 7 days.

Renal Impairment

PO IV (Adults and Children >3 mo): CCr 25.1–50 mL/min/1.73 m²: Normal dose every 12 hr; CCr 10.1–25 mL/min/1.73 m²: Normal dose every 24 hr; CCr ≤10 mL/min/1.73 m²: 50% of dose every 24 hr.

Herpes Labialis

(Adults and Children >12 yr): Apply 5 times/day for 4 days; start at first symptoms.
(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).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Interferes with viral DNA synthesis.

Therapeutic effects:

Inhibition of viral replication, decreased viral shedding, and reduced time for healing of lesions.

Classifications ⬆ ⬇

Therapeutic Classification: antivirals

Pharmacologic Classification: purine analogues

Pharmacokinetics ⬆ ⬇

Absorption: Despite poor absorption (15–30%), therapeutic plasma concentrations are achieved.

Distribution: Widely distributed. CSF concentrations are 50% of plasma.

Metabolism/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 (↑ in renal failure).

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1.5–2.5 hr	4 hr
IV	prompt	end of infusion	8 hr
Buccal	unknown	12 hr (7 hr‡)	unknown

‡Salivary concentrations

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of acyclovir. Instruct patient to take medication as directed for the full course of therapy. Take missed doses as soon as possible but not just before next dose is due; do not double doses. Acyclovir should not be used more frequently or longer than prescribed. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
- Advise patients that the additional use of OTC creams, lotions, and ointments may delay healing and may cause spreading of lesions.
- Inform patient that acyclovir is not a cure; the virus lies dormant in the ganglia. Acyclovir will not prevent the spread of infection to others.
- Instruct patient to consult health care professional if symptoms are not relieved after 7 days of topical therapy or if oral acyclovir does not decrease the frequency and severity of recurrences. Immunocompromised patients may require a longer time, usually 2 wk, for crusting over of lesions.
- Instruct women with genital herpes to have yearly Papanicolaou smears because they may be more likely to develop cervical cancer.
Topical Instruct patient to apply ointment in sufficient quantity to cover all lesions every 3 hr, 6 times/day, for 7 days. A ½-inch ribbon of ointment covers approximately 4 square inches. Use a finger cot or glove when applying to prevent inoculation of other areas or spread to other people. Keep affected areas clean and dry. Loose-fitting clothing should be worn to prevent irritation.
- Avoid drug contact in or around eyes. Report any unexplained eye symptoms to health care professional immediately; ocular herpetic infection can lead to blindness.
Buccal: Instruct patient on correct application and use of buccal tablet. If buccal tablet does not adhere or falls off within 1st 6 hr, reposition immediately with same tablet. If tablet cannot be repositioned, apply new tablet. If swallowed within 1st 6 hr, advise patient to drink a glass of water and apply a new tablet. Do not reapply if tablet falls out after 6 hr.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise patient that condoms should be used during sexual contact and to avoid sexual contact while lesions are present.

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Indications ⬇