Xerese Information
Xerese (Acyclovir) Indications And Usage
Xerese (Acyclovir) 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).
Xerese (Acyclovir) Dosage And Administration
Topically apply Xerese (Acyclovir) 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 Xerese (Acyclovir) 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.
Xerese (Acyclovir) Dosage Forms And Strengths
Each gram of Xerese (Acyclovir) contains 5% (w/w) acyclovir and 1% (w/w) hydrocortisone in an aqueous cream base.
Xerese (Acyclovir) Contraindications
Xerese (Acyclovir) Adverse Reactions
Because clinical studies are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical studies and may not reflect the rates observed in clinical practice.
The majority of the adverse reactions were local and occurred in the area of the application site.
Skin and Subcutaneous Tissue Disorders
The following most common adverse reactions (
Contact dermatitis following application has been observed when applied under occlusion in dermal safety studies. Where contact sensitivity tests have been conducted, the reactive substances were hydrocortisone or a component of the cream base.
A study enrolling 225 healthy adults was conducted to evaluate the contact sensitization potential of Xerese (Acyclovir) 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 Xerese (Acyclovir) 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 study in 36 healthy subjects. Xerese (Acyclovir) , its cream base and Zovirax® (acyclovir) Cream 5% all showed a high and cumulative irritation potential under occlusive and semi occlusive conditions.
Photoallergic potential and phototoxicity were assessed in two studies in 50 and 30 healthy volunteers, respectively. No photoallergic or phototoxicity potential was identified for Xerese (Acyclovir) .
Xerese (Acyclovir) Drug Interactions
No drug interaction studies have been performed with Xerese (Acyclovir) .
Xerese (Acyclovir) Use In Specific Populations
Category B
Teratogenic Effects
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 studies 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 Xerese (Acyclovir) . No studies have been performed in pregnant women. Systemic exposure of acyclovir and hydrocortisone following topical administration of Xerese (Acyclovir) is minimal.
Even though the safety of Xerese (Acyclovir) 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 study 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/mm (range 100 500/mm). Subjects were treated with Xerese (Acyclovir) or 5% acyclovir in Xerese (Acyclovir) 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 Xerese (Acyclovir) and 6.9 days for 5% acyclovir in Xerese (Acyclovir) vehicle.
Xerese (Acyclovir) Overdosage
Overdosage by topical application of Xerese (Acyclovir) is unlikely because of minimal systemic exposure [].
Xerese (Acyclovir) Description
Xerese (Acyclovir) contains acyclovir, a synthetic nucleoside analogue active against herpes viruses, and hydrocortisone, an anti inflammatory corticosteroid, combined in a cream for topical administration. Each gram of Xerese (Acyclovir) contains 5% (w/w) of acyclovir, 1% (w/w) of hydrocortisone and the following inactive ingredients: cetostearyl alcohol, mineral oil, Poloxamer 188, propylene glycol, isopropyl myristate, sodium lauryl sulfate, white petrolatum, citric acid, sodium hydroxide and water. Sodium hydroxide or hydrochloric acid may be added to adjust the pH to approximately pH 5.
Acyclovir, 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one, is a synthetic nucleoside analogue active against herpes viruses. The maximum solubility of acyclovir in water at 37°C is 2.5 mg/mL. The pKa’s of acyclovir are 2.27 and 9.25. Its empirical formula is CHNO. The structural formula is provided in Figure 1:
Hydrocortisone, pregn-4-ene-3, 20-dione, 11, 17, 21-trihydroxy-(11(beta))-, is an anti inflammatory corticosteroid. Its empirical formula is CHO. The structural formula is provided in Figure 2:
Xerese (Acyclovir) Clinical Pharmacology
The plasma concentrations of acyclovir and hydrocortisone were not measured following topical administration of Xerese (Acyclovir) 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.
Mechanism of Action
The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In cell culture, acyclovir triphosphate stops replication of herpes viral DNA. This inhibition is accomplished in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation into and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase.
Hydrocortisone
Antiviral Activity
The quantitative relationship between the cell culture susceptibility of herpes viruses to antivirals and the clinical response to therapy has not been established in humans, and virus sensitivity testing has not been standardized. Sensitivity testing results, expressed as the concentration of drug required to inhibit by 50% the growth of virus in cell culture (EC ), vary greatly depending upon a number of factors. Using plaque reduction assays on Vero cells, the median EC value of acyclovir against clinical herpes virus isolates (subjects receiving placebo) was 1.3 µM (range:
Resistance
Resistance of HSV to acyclovir can result from qualitative and quantitative changes in the viral TK and/or DNA polymerase. Clinical isolates of HSV with reduced susceptibility to acyclovir have been recovered from immunocompromised subjects, especially with advanced HIV infection. While most of the acyclovir resistant mutants isolated from immunocompromised subjects thus far have been found to be TK-deficient mutants, other mutants involving the viral TK gene (TK partial and TK altered) and DNA polymerase have been isolated. TK-negative mutants may cause severe disease in infants and immunocompromised adults.
The possibility of viral resistance to acyclovir should be considered in patients who show poor clinical response during therapy.
Xerese (Acyclovir) How Supplied/storage And Handling
Xerese (Acyclovir) is supplied in plastic-laminated aluminum tubes containing 2 gm or 5 gm of Xerese (Acyclovir) . Each gram of Xerese (Acyclovir) contains 5% (w/w) acyclovir and 1% (w/w) hydrocortisone in an aqueous cream base.
NDC 0037-0501-02: 2 gm tubes
NDC 0037-0501-05: 5 gm tubes
Store at controlled room temperature [20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F). Do not freeze.]
Xerese (Acyclovir) Patient Counseling Information
Xerese (Acyclovir)
Xerese (Acyclovir)
