XERESE- acyclovir and hydrocortisone cream
Valeant Pharmaceuticals North America LLC
1 INDICATIONS AND USAGE
XERESE, a combination of acyclovir, a herpes simplex virus nucleoside analog DNA polymerase inhibitor, and hydrocortisone, a corticosteroid, 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 children (6 years of age and older).
2 DOSAGE AND ADMINISTRATION
Topically apply XERESE 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 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 children 6 years of age and older, the dosage is the same as in adults.
3 DOSAGE FORMS AND STRENGTHS
Each gram of XERESE contains 5% (w/w) acyclovir and 1% (w/w) hydrocortisone in an aqueous cream base.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 General
XERESE is intended for cutaneous use only for herpes labialis of the lips and around the mouth. XERESE 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.
XERESE has a potential for irritation and contact sensitization.
OVERDOSAGE
Overdosage by topical application of XERESE is unlikely because of minimal systemic exposure [see Clinical Pharmacology (12.3)].
11 DESCRIPTION
XERESE 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 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 have been 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 C8 H11 N5 O3 .
Hydrocortisone, pregn-4-ene-3, 20-dione, 11, 17, 21-trihydroxy-(11(beta))-, is an anti-inflammatory corticosteroid. Its empirical formula is C21 H30 O5
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Acyclovir is an antiviral drug and hydrocortisone an anti-inflammatory drug
Microbiology
Mechanism of Action
Acyclovir is a synthetic purine nucleoside analogue with inhibitory activity against herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) in cell culture and in vivo.
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 is the main glucocorticoid secreted by the adrenal cortex. It is used topically for its anti-inflammatory effects which suppress the clinical manifestations of the disease in a wide range of disorders where inflammation is a prominent feature.
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 (EC50 ), vary greatly depending upon a number of factors. Using plaque-reduction assays on Vero cells, the median EC50 value of acyclovir against clinical herpes virus isolates (subjects receiving placebo) was 1.3 �M (range: <0.56 to 3.3 �M).
