Oralsone (Aciclovir,Hydrocortisone)

Oralsone (Aciclovir,Hydrocortisone) (acyclovir and hydrocortisone cream) is indicated 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 in adults and adolescents (12 years of age and older).

Topically apply Oralsone (Aciclovir,Hydrocortisone) (acyclovir and hydrocortisone cream) 5 times per day for 5 days. Therapy should be initiated as early as possible after the first signs and symptoms (i.e., during the prodrome or when lesions appear).

For each dose, topically apply a quantity of Oralsone (Aciclovir,Hydrocortisone) (acyclovir and hydrocortisone cream) sufficient to cover the affected area, including the outer margin. Avoid unnecessary rubbing of the affected area to avoid aggravating or transferring the infection. For adolescents 12 years of age and older, the dosage is the same as in adults.

None.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

General

Oralsone (Aciclovir,Hydrocortisone) is intended for cutaneous use only for herpes labialis of the lips and around the mouth. Oralsone (Aciclovir,Hydrocortisone) should not be used in the eye, inside the mouth or nose, or on the genitals. There are other orofacial lesions, including bacterial and fungal infections, which may be difficult to distinguish from a cold sore. Patients should be encouraged to seek medical advice when a cold sore fails to heal within 2 weeks.

Oralsone (Aciclovir,Hydrocortisone) has a potential for irritation and contact sensitization.

Patient Counseling Information

See FDA-approved patient labeling (PATIENT INFORMATION)

General

Patients should be informed that Oralsone (Aciclovir,Hydrocortisone) is not a cure for cold sores. Patients should be instructed that Oralsone (Aciclovir,Hydrocortisone) is intended for cutaneous use only for herpes labialis of the lips and around the mouth. Patients should be advised that Oralsone (Aciclovir,Hydrocortisone) should not be used in the eye, inside the mouth or nose, or on the genitals.

Instructions for Use

Patients should be advised to apply Oralsone (Aciclovir,Hydrocortisone) topically 5 times per day for 5 days. Patients should be instructed to topically apply a quantity of Oralsone (Aciclovir,Hydrocortisone) sufficient to cover the affected area, including the outer margin. Patients should be advised to avoid unnecessary rubbing of the affected area to avoid aggravating or transferring the infection.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Systemic exposure following topical administration of acyclovir is minimal. Results from previous studies of carcinogenesis, mutagenesis and fertility for acyclovir and hydrocortisone are not included in the full prescribing information for Oralsone (Aciclovir,Hydrocortisone) due to the minimal exposures that result from dermal application. Information on these studies following systemic exposure is available in the full prescribing information for acyclovir and hydrocortisone products approved for oral or parenteral administration. Dermal carcinogenicity studies have not been conducted.

Use In Specific Populations

Pregnancy

Teratogenic Effects

Pregnancy Category B. Acyclovir was not teratogenic in the mouse, rabbit or rat at exposures greatly in excess of human exposure. There are no adequate and well-controlled trials of systemic acyclovir in pregnant women. A prospective epidemiologic registry of acyclovir use during pregnancy between 1984 and 1999 followed 749 pregnancies in women exposed to systemic acyclovir during the first trimester of pregnancy resulting in 756 outcomes. The occurrence rate of birth defects approximated that found in the general population. However, the size of the registry was insufficient to evaluate the risk for less common defects or to permit reliable or definitive conclusions regarding the safety of acyclovir in pregnant women and their developing fetuses.

Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.

Animal reproduction studies have not been conducted with Oralsone (Aciclovir,Hydrocortisone). No trials have been performed in pregnant women. Systemic exposure of acyclovir and hydrocortisone following topical administration of Oralsone (Aciclovir,Hydrocortisone) is minimal.

Nursing Mothers

It is not known whether topically applied acyclovir or hydrocortisone is excreted in breast milk. Systemic exposure following topical administration of either drug is expected to be below detection limits. Because many drugs are excreted in human milk, caution should be exercised when Oralsone (Aciclovir,Hydrocortisone) is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric subjects less than 6 years of age have not been established.

Geriatric Use

In clinical studies, there were insufficient subjects above 65 years of age to reach a firm conclusion regarding safety and efficacy of Oralsone (Aciclovir,Hydrocortisone) in this group, although the available results were similar to lower age subjects.

Immunocompromised Subjects

Even though the safety of Oralsone (Aciclovir,Hydrocortisone) has been studied in immunocompromised subjects, data are insufficient to support use in this population. Immunocompromised subjects should be encouraged to consult a physician concerning the treatment of any infection.

Benefit has not been adequately assessed in immunocompromised patients. A randomized, double-blind trial was conducted in 107 immunocompromised subjects with stable HIV infection and recurrent herpes labialis. Subjects had on average 3.7 episodes of herpes labialis in the previous 12 months. The median age was 30 years (range 19 to 64 years), 46% were female, and all Caucasian. Median CD4+ T-cell count at screening was 344/mm³ (range 100-500/mm³ ). Subjects were treated with Oralsone (Aciclovir,Hydrocortisone) or 5% acyclovir in Oralsone (Aciclovir,Hydrocortisone) vehicle. The primary objective was to exclude a doubling of the healing time in either treatment arm. The mean healing time for cold sores was similar between the two treatment groups: 6.6 days for Oralsone (Aciclovir,Hydrocortisone) and 6.9 days for 5% acyclovir in Oralsone (Aciclovir,Hydrocortisone) vehicle.

Adverse Reactions In Clinical Trials

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice.

The safety data derived from Oralsone (Aciclovir,Hydrocortisone) clinical trials reflect exposure to Oralsone (Aciclovir,Hydrocortisone) in 1056 subjects with recurrent herpes labialis treated 5 times daily for 5 days. The most common adverse reactions ( < 1%) were local skin reactions, and occurred in the area of the application site, including:

• Drying or flaking of the skin; burning or tingling following application; erythema; pigmentation changes; application site reaction including signs and symptoms of inflammation.

Contact dermatitis following application has been observed when applied under occlusion in dermal safety trials. Where contact sensitivity tests have been conducted, the reactive substances were hydrocortisone or a component of the cream base.

A trial enrolling 225 healthy adults was conducted to evaluate the contact sensitization potential of Oralsone (Aciclovir,Hydrocortisone) using repeat insult patch testing methodology. Of 205 evaluable subjects, one confirmed case (0.5%) of sensitization to hydrocortisone and 2 additional cases (1.0%) of possible sensitization to the Oralsone (Aciclovir,Hydrocortisone) base were identified. Additionally, one subject developed a contact allergy in the photosafety study to propylene glycol, one of the inactive ingredients of the cream base.

Dermal tolerance was assessed in a 21-day cumulative irritation trial in 36 healthy subjects. Oralsone (Aciclovir,Hydrocortisone), its cream base and Zovirax® (acyclovir) Cream 5% all showed a high and cumulative irritation potential under occlusive and semiocclusive conditions.

Photoallergic potential and phototoxicity were assessed in two trials in 50 and 30 healthy volunteers, respectively. No photoallergic or phototoxicity potential was identified for Oralsone (Aciclovir,Hydrocortisone).

Overdosage by topical application of Oralsone (Aciclovir,Hydrocortisone) is unlikely because of minimal systemic exposure.

The plasma concentrations of acyclovir and hydrocortisone were not measured following topical administration of Oralsone (Aciclovir,Hydrocortisone) on cold sores.

The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, 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 both the potency of the corticosteroid and the surface area of application. Inflammation and/or other disease processes in the skin that disrupt the skin barrier can increase percutaneous absorption.

Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. They are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.