Brand name: Zovirax
Drug class: Antivirals

Medically reviewed by Drugs.com on Oct 10, 2024. Written by ASHP.

Introduction

Antiviral; purine nucleoside analog derived from guanine.^{101 112}

Uses for Acyclovir (Topical)

Herpes Labialis

Treatment of recurrent herpes labialis (perioral herpes, cold sores, fever blisters) in immunocompetent adults and children ≥12 years of age.^{111 112 114}

Genital Herpes

Has been used for topical treatment of initial episodes of genital herpes in immunocompromised or immunocompetent adults.^{101 a}

Topical antivirals generally not recommended for treatment of genital herpes.^{106 110 114} CDC and others recommend oral acyclovir, oral famciclovir, or oral valacyclovir as drugs of choice for treatment of initial episodes of genital herpes and for episodic treatment or chronic suppressive therapy of recurrent genital herpes.^{106 110 114}

Has not been effective for prevention of recurrent genital herpes when initiated immediately following development of prodromal symptoms (e.g., itching, burning, tingling, numbness).^{107 109}

No evidence that topical acyclovir prevents transmission of infection to other individuals.¹⁰¹

Mucocutaneous Herpes Simplex Virus (HSV) Infections

Has been used for topical treatment of non-life-threatening, nongenital, mucocutaneous HSV infections in immunocompromised adults;^{101 113} efficacy of such treatment not established in immunocompetent individuals.^{101 113}

Systemic therapy (e.g., oral or IV acyclovir) usually recommended for treatment of mucocutaneous HSV infections.^{113 114}

Should not be used for prevention of recurrent HSV infections.¹⁰¹ No evidence that topical acyclovir prevents transmission of HSV or prevents recurrent HSV infections when applied in the absence of signs and symptoms of infection.¹⁰¹

Acyclovir (Topical) Dosage and Administration

Administration

Topical Administration

Apply topically to lesions of the lips and surrounding skin as a 5% cream or ointment,^{101 112} and apply to lesions of the skin as a 5% ointment.¹⁰¹

Do not apply 5% cream or ointment in or near the eyes.^{101 112} For external use only; do not apply inside mouth or nose.^{101 112}

The 5% cream should be used only for treatment of herpes labialis (perioral herpes, cold sores, fever blisters) and should not be used to treat genital herpes.¹¹²

After applying 5% cream, rub until the cream disappears.¹¹² Do not use with occlusive dressings unless otherwise directed by clinician.¹¹² Do not bathe, shower, or swim immediately after application.¹¹²

When applying 5% ointment, use finger cot or rubber glove to prevent autoinoculation of other sites and transmission of herpes virus to other individuals.¹⁰¹

Dosage

Pediatric Patients

Herpes Labialis

Topical

Children ≥12 years of age: Apply 5% cream to affected area 5 times daily for 4 days.¹¹² Use sufficient quantity to adequately cover lesions or symptomatic area (e.g., area with tingling).¹¹²

Initiate at the earliest sign or symptom of herpes labialis (i.e., during the prodrome or when lesions appear).¹¹²

Do not exceed recommended dosage, frequency, and duration of therapy.¹¹²

Adults

Herpes Labialis

Topical

Apply 5% cream to affected area times 5 times daily for 4 days.¹¹² Use sufficient quantity to adequately cover lesions or symptomatic area (e.g., area with tingling).¹¹²

Initiate at the earliest sign or symptom of herpes labialis (i.e., during the prodrome or when lesions appear).^{101 112}

Do not exceed recommended dosage, frequency, and duration of therapy.^{101 112}

Genital Herpes

Treatment of First Episodes

Topical

Rub 5% ointment gently into the affected area every 3 hours 6 times daily for 7 days.¹⁰¹ Use sufficient quantity to adequately cover all lesions;¹⁰¹ usual dose varies according to total lesion area but should approximate a 1.25-cm (0.5-inch) ribbon of ointment for a skin surface area of 2.5 cm² (4 inch²).¹⁰¹

Initiate at the earliest sign or symptom of genital herpes (i.e., during the prodrome or when lesions appear).¹⁰¹

Do not exceed recommended dosage, frequency, and duration of therapy.¹⁰¹

Mucocutaneous Herpes Simplex Virus (HSV) Infections

Non-life-threatening, Nongenital, Mucocutaneous HSV Infections

Topical

Immunocompromised adults: Rub 5% ointment gently into the affected area every 3 hours 6 times daily for 7 days.¹⁰¹ Use sufficient quantity to adequately cover all lesions;¹⁰¹ usual dose varies according to total lesion area but should approximate a 1.25-cm (0.5-inch) ribbon of ointment for a skin surface area of 2.5 cm² (4 inch²).¹⁰¹

Do not exceed recommended dosage, frequency, and duration of therapy.¹⁰¹

Cautions for Acyclovir (Topical)

Contraindications

• Hypersensitivity to acyclovir, valacyclovir, or any ingredient in the formulations.^{101 112}

Warnings/Precautions

Sensitivity Reactions

Potential for irritation and contact sensitization with 5% cream; contact dermatitis reported.¹¹²

General Precautions

Immunocompromised Patients

Efficacy of 5% cream not established in immunocompromised patients.¹¹²

Viral Resistance

Clinically important viral resistance associated with use of topical acyclovir not reported to date.¹⁰¹ The possibility of such resistance should be considered, especially in those with poor clinical response.¹⁰¹

Specific Populations

Pregnancy

Category B.^{101 112}

Lactation

Not known whether distributed into human milk after topical application, but systemic exposure after topical administration is minimal.^{101 112} Distributed into human milk following oral or IV administration.^{101 112 117}

Women with active herpetic lesions near or on the breast should refrain from breast-feeding.^{101 112 113}

Pediatric Use

Safety and efficacy of 5% cream not established in children <12 years of age.¹¹²

Safety and efficacy of 5% ointment not established in children.¹⁰¹

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^{101 112} Clinical experience has not revealed age-related differences.^{101 112}

Common Adverse Effects

Local effects such as mild pain,¹⁰¹ transient burning or stinging,^{101 112} pruritus,^{101 112} cracked or dry lips,¹¹² desquamation,¹¹² dry or flaking skin.¹¹²

Drug Interactions

No interactions identified to date when topical acyclovir used concomitantly with other topical or systemic drugs.^{101 112} Because systemic absorption appears to be minimal following topical application to intact skin,^{101 112} drug interactions between topical acyclovir and systemically administered drugs are unlikely.^a

Acyclovir (Topical) Pharmacokinetics

Absorption

Bioavailability

Not appreciably absorbed into systemic circulation following topical application to intact skin.^{101 112}

Not detected in blood or urine of immunocompromised adults following application of 5% ointment to intact skin (4.5 inch²) at a dosage of 25 mg (1-cm ribbon) 4 times daily for 7 days.^{101 112}

Following topical application of 5% ointment in patients with localized varicella-zoster virus (VZV) infections, plasma acyclovir concentrations were ≤0.28 mcg/mL or ≤0.78 mcg/mL in those with normal or impaired renal function, respectively.¹⁰¹

Following repeated (5 times daily for 4 days) topical application of 5% cream to intact skin (710 cm²) in adult males, plasma acyclovir concentrations measured 1 hour after the final application were undetectable or just above the limits of detection.¹¹²

Systemic absorption of 5% cream not evaluated in children <18 years of age.¹¹²

Distribution

Not fully characterized following topical application.^a

Crosses placenta following oral or IV administration.^{105 117}

Not known if drug or its metabolites distributed into human milk following topical application.¹⁰¹ Following oral or IV administration, distributed into human milk in concentrations greater than concurrent maternal plasma concentrations.^{100 101 117}

Elimination

Metabolism

Not fully characterized following topical application.^a

Converted in vivo to the pharmacologically active triphosphate metabolite.¹⁰¹

Elimination Route

Following systemic absorption, excreted principally in urine.¹⁰¹

Following topical application of 5% ointment in immunocompromised patients with localized VZV infections, ≤9.4% of total daily dose excreted in urine.¹⁰¹

Following repeated (5 times daily for 4 days) topical application of 5% cream to intact skin (710 cm²) in adult males, 0.04% of the daily dose was detected in urine within 24 hours.¹¹²

Stability

Storage

Topical

Cream

≤25°C (may be exposed to 15°–30°C).¹¹²

Ointment

15°–25°C in dry place.¹⁰¹

Actions and Spectrum

• Converted in vivo to the pharmacologically active triphosphate metabolite.¹⁰¹

• Exerts antiviral effect by interfering with DNA synthesis and inhibiting viral replication.¹⁰¹

• Active against various Herpesviridae,^a including herpes simplex virus types 1 and 2 (HSV-1 and HSV-2)¹⁰¹ and varicella-zoster virus (VZV).¹⁰¹ Also active against cytomegalovirus (CMV), Epstein-Barr virus (EBV), and herpes simiae,^a but these viruses not generally associated with dermatologic infections.^a

• Resistance to acyclovir reported in HSV and VZV.¹⁰¹

• Some acyclovir-resistant HSV and VZV are cross-resistant to penciclovir.^{115 116}

Advice to Patients

• Importance of using only for condition prescribed.¹¹² Advise patient that 5% cream is only for treatment of herpes labialis (perioral herpes, cold sores, fever blisters) and should not be used to treat genital herpes.¹¹²

• Ensure that the affected areas are clean and dry before application.¹¹²

• Do not apply to unaffected skin or inside the mouth or nose.^{101 112} For external use only.^{101 112}

• Importance of avoiding contact with eyes.^{101 112}

• Importance of avoiding use of occlusive dressings unless otherwise directed by clinician.¹¹²

• Importance of washing hands before and after application.¹¹² Advise patients not to bathe, shower, or swim immediately after application.¹¹²

• Advise patients not to apply other topical products (e.g., cosmetics, lip balms, sunscreens, other topical medications) to treated areas unless otherwise directed by clinician.¹¹²

• For treatment of herpes labialis, importance of applying to affected areas as directed and at the first sign or symptom (e.g., tingling, redness, bump, itching).¹¹²

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹⁰¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹⁰¹

• Importance of advising patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

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