CLASSES
Combinations of Corticosteroids with Antivirals
Topical Antivirals
DESCRIPTION
Topical antiviral and steroid combination agent for herpes labialis (cold sores).
COMMON BRAND NAMES
Xerese
HOW SUPPLIED
Xerese Topical Cream: 5-1%
DOSAGE & INDICATIONS
For the early treatment of recurrent herpes labialis (cold sores) to reduce the likelihood of ulcerative cold sores and to shorten the lesion healing time.
Topical dosage
Adults, Adolescents, and Children >= 6 years
Apply topically to orofacial affected area 5 times per day for 5 days as early as possible after the first signs and symptoms of herpes labialis occur (during the prodrome or when lesions appear).
MAXIMUM DOSAGE
Adults
Apply 5x/day.
Geriatric
Apply 5x/day.
Adolescents
Apply 5x/day.
Children
>= 6 years: Apply 5x/day.
< 6 years: Safety and efficacy have not been established.
Infants
Safety and efficacy have not been established.
Neonates
Safety and efficacy have not been established.
DOSING CONSIDERATIONS
Hepatic Impairment
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Renal Impairment
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
ADMINISTRATION
Topical Administration
Cream/Ointment/Lotion Formulations
Apply acyclovir; hydrocortisone cream topically to cold sore lesions.
Apply a quantity sufficient to cover the affected area, including the outer margin.
Avoid unnecessary rubbing of the affected area to avoid aggravating or transferring the infection.
Do not apply the topical cream to the eye, inside the mouth or nose, or on the genitals.
Use a finger cot or rubber glove when applying to avoid transmission of the virus to other sites or persons.
Wash hands thoroughly after administration.
Do not cover cold sore with an occlusive dressing or bandage.
Do not use other skin products (make-up, sun screen, lip balm) or other skin medications on the cold sore or around the cold sore.
Do not bathe, shower, or swim, within 30 minutes of applying acyclovir; hydrocortisone.
STORAGE
Xerese:
- Do not freeze
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
CONTRAINDICATIONS / PRECAUTIONS
General Information
NOTE: This monograph discusses the use of the acyclovir; hydrocortisone topical combination product. Clinicians may wish to consult the individual monographs of acyclovir or hydrocortisone for more information about each specific agent.
Fungal infection
Acyclovir; hydrocortisone is for herpes labialis infections. Other orofacial lesions, including those caused by a bacterial or fungal infection, may be difficult to distinguish from cold sores. Patients should seek medical advice when a potential cold sore fails to heal within 2 weeks to determine if another infectious process is taking place.
Ophthalmic administration
Acyclovir; hydrocortisone is intended for cutaneous herpes labialis use only. Avoid ophthalmic administration, administration inside the mouth or nose, or administration to the genitals.
Immunosuppression
Acyclovir; hydrocortisone has been studied in immunocompromised patients; however, data are insufficient to support its use in patients with immunosuppression. Immunocompromised patients should consult a physician regarding the treatment of herpes labialis. In clinical trials of immunocompromised patients, the mean healing time for cold sores was similar between the acyclovir; hydrocortisone group (6.6 days) and the 5% topical acyclovir group (6.9 days).
Children, infants, neonates
The safety and effectiveness of acyclovir; hydrocortisone in neonates, infants, and children less than 6 years of age have not been established.
Geriatric
In clinical studies of acyclovir; hydrocortisone, there were insufficient patients greater than 65 years of age to make any conclusions regarding safety and efficacy. However, the available data suggest that results were similar between geriatric patients and younger patients.
Pregnancy
There are no data available on acyclovir; hydrocortisone use during pregnancy; however, published studies of topical acyclovir and low and medium potency topical corticosteroids during pregnancy have not established any association between use of these products and major birth defects, miscarriage, or adverse maternal or fetal outcomes. Systemic exposure of acyclovir and hydrocortisone after topical administration for herpes labialis is expected to be minimal.
Breast-feeding
There are no data available on the presence of acyclovir or hydrocortisone in human milk, the effect on the breastfed infant, or the effect on milk production. However, systemic exposure of acyclovir and hydrocortisone after topical administration for herpes labialis is expected to be minimal. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for acyclovir; hydrocortisone and any potential adverse effects on the breast-fed infant from acyclovir; hydrocortisone or the underlying maternal condition.
ADVERSE REACTIONS
Moderate
erythema / Early / 0-1.0
contact dermatitis / Delayed / Incidence not known
Mild
xerosis / Delayed / 0-1.0
skin irritation / Early / Incidence not known
DRUG INTERACTIONS
There are no drug interactions associated with Acyclovir; Hydrocortisone products.
PREGNANCY AND LACTATION
Pregnancy
There are no data available on acyclovir; hydrocortisone use during pregnancy; however, published studies of topical acyclovir and low and medium potency topical corticosteroids during pregnancy have not established any association between use of these products and major birth defects, miscarriage, or adverse maternal or fetal outcomes. Systemic exposure of acyclovir and hydrocortisone after topical administration for herpes labialis is expected to be minimal.
There are no data available on the presence of acyclovir or hydrocortisone in human milk, the effect on the breastfed infant, or the effect on milk production. However, systemic exposure of acyclovir and hydrocortisone after topical administration for herpes labialis is expected to be minimal. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for acyclovir; hydrocortisone and any potential adverse effects on the breast-fed infant from acyclovir; hydrocortisone or the underlying maternal condition.
MECHANISM OF ACTION
Acyclovir is an antiviral agent; hydrocortisone is a corticosteroid.
Acyclovir: Acyclovir has inhibitory activity against herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) in vitro and in vivo. Acyclovir selectively binds the thymidine kinase (TK) enzyme to inhibit viral DNA synthesis. The viral TK enzyme converts acyclovir into acyclovir monophosphate (a nucleotide analogue), which is further converted into acyclovir diphosphate and then acyclovir triphosphate. Acyclovir triphosphate competitively inhibits and inactivates viral DNA polymerase. It is also incorporated into and terminates the viral DNA chain. Viral resistance can result from qualitative and quantitative changes in the viral TK enzyme and/or viral DNA polymerase. HSV isolates with reduced acyclovir susceptibility have been recovered from immunocompromised patients. Viral resistance should be considered in patients who fail to respond or experience recurrent viral shedding during therapy. Cross-resistance has been observed among HSV isolates carrying mutations and resistance-associated substitutions, which confer reduced susceptibility to penciclovir, famciclovir, and foscarnet.
Hydrocortisone: Hydrocortisone is the main glucocorticoid secreted by the adrenal cortex. When used topically, hydrocortisone exhibits anti-inflammatory properties that help suppress the clinical manifestations associated with the herpes infection outbreak.
PHARMACOKINETICS
Acyclovir; hydrocortisone is administered topically.
Acyclovir: Minimal absorption of acyclovir is expected after topical application of acyclovir; hydrocortisone. If acyclovir does reach systemic circulation, it would be expected to undergo metabolism and excretion similar to systemically administered acyclovir. After systemic administration, infected viral cells transform acyclovir to its active triphosphate, and a small proportion may be metabolized extracellularly. Renal elimination via glomerular filtration and tubular secretion of unchanged drug is the major route of elimination accounting for 62—91% of the dose. The elimination half-life of acyclovir is 2.5—3.3 hours.
Hydrocortisone: If hydrocortisone is absorbed through the skin, it binds to plasma proteins. Hydrocortisone is metabolized primarily in the liver and then excreted by the kidneys.
Topical Route
Acyclovir: Acyclovir; hydrocortisone plasma concentrations have not been measured after topical administration on cold sores; however, when applied as a single ingredient topically, systemic absorption is minimal with no drug detected in the blood or urine.
Hydrocortisone: Acyclovir; hydrocortisone plasma concentrations have not been measured after topical administration on cold sores. However, many factors determine the extent of percutaneous absorption of topical corticosteroids, including the vehicle used, the integrity of the epidermal barrier, and the use of occlusive dressings. Topical corticosteroids can be absorbed from normal, intact skin and can have systemic side effects depending on the potency of the steroid and the size of the surface area to which the steroid is applied. Inflammation and other diseases of the skin that disrupt the skin barrier can increase percutaneous absorption.