Zovirax topical

Pronunciation

Generic Name: Acyclovir topical
Class: Antivirals
VA Class: DE103
Chemical Name: 9-[(2-Hydroxyethoxy)methyl]guanine
CAS Number: 59277-89-3

Introduction

Antiviral; purine nucleoside analog derived from guanine.101 112

Uses for Zovirax

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

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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

Zovirax 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 Zovirax

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

Interactions for Zovirax

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

Zovirax 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. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Acyclovir

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Cream

5%

Zovirax (with propylene glycol)

Biovail

Ointment

5%

Zovirax

Biovail

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Zovirax 5% Cream (VALEANT): 2/$211.99 or 4/$241.76

Zovirax 5% Cream (VALEANT): 5/$223.20 or 15/$619.16

Zovirax 5% Ointment (VALEANT): 30/$441.99 or 90/$1,230.93

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Lau RJ, Emery MG, Galinsky RE. Unexpected accumulation of acyclovir in breast milk with estimation of infant exposure. Obstet Gynecol. 1987; 60:468-71.

101. Bioavail Pharmaceuticals, Inc. Zovirax (acyclovir) ointment 5% prescribing information. Bridgewater, NJ; 2004 Jan.

102. Stahlmann R, Klug S, Lewandowski C et al. Teratogenicity of acyclovir in rats. Infection. 1987; 15:261-2. [PubMed 3666969]

103. Chahoud I, Stahlmann R, Bochert G et al. Gross-structural defects in rats after acyclovir application on day 10 of gestation. Arch Toxicol. 1988; 62:8-14. [PubMed 3190462]

104. Stahlmann R, Klug S, Lewandowski C et al. Prenatal toxicity of acyclovir. Arch Toxicol. 1988; 61:468-79. [PubMed 3190444]

105. Greffe BS, Dooley SL, Deddish RB et al. Transplacental passage of acyclovir. J Pediatr. 1986; 108:1020-1. [IDIS 217560] [PubMed 3012053]

106. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006; 55(RR-11):1-95.

107. O’Brien JJ, Campoli-Richards DM. Acyclovir: an update review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1989; 37:233-309. [PubMed 2653790]

108. Fawcett HA, Wansbrough-Jones MH. Prophylactic topical acyclovir for frequent recurrent herpes simplex infection with and without erythema multiforme. BMJ. 1983; 287:798-9. [IDIS 176287] [PubMed 6412833]

109. Luby JP, Gnann JW, Alexander WJ et al. A collaborative study of patient-initiated treatment of recurrent genital herpes with topical acyclovir or placebo. J Infect Dis. 1984; 150:1-6. [IDIS 187753] [PubMed 6086765]

110. Anon. Drugs for sexually transmitted infections. Treat Guidel Med Lett. 2004; 2:67-74. [PubMed 15529116]

111. Spruance SL, Nett R, Marbury T et al. Acyclovir cream for treatment of herpes simplex labialis: results of two randomized, double-blind, vehicle-controlled, multicenter clinical trials. Antimicrob Agents Chemother. 2002; 46:2238-43. [IDIS 483104] [PubMed 12069980]

112. Bioavail Pharmaceuticals, Inc. Zovirax (acyclovir) cream 5% prescribing information. Bridgewater, NJ; 2004 Jan.

113. Committee on Infectious Diseases, American Academy of Pediatrics. Red book: 2006 report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

114. Anon. Drugs for non-HIV viral infections. Treat Guidel Med Lett. 2005; 3:23-32. [PubMed 15767977]

115. Safrin S, Phan L. In vitro activity of penciclovir against clinical isolates of acyclovir-resistant and foscarnet-resistant herpes simplex virus. Antimicrob Agents Chemother. 1993; 37:2241-3. [IDIS 320621] [PubMed 8257152]

116. Hasegawa T, Kurokawa M, Yukawa TA et al. Inhibitory action of acyclovir (ACV) and penciclovir (PCV) on plaque formation and partial cross-resistance of ACV-resistant varicella-zoster virus to PCV. Antiviral Res. 1995; 27:271-9. [PubMed 8540749]

117. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2005: 23-9.

a. AHFS drug information 2007. McEvoy GK, ed. Acyclovir. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 3456-8.

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