Acyclovir sodium is a white, crystalline powder with the molecular formula C 8 H 10 N 5 NaO 3 and a molecular weight of 247.19. The maximum solubility in water at 25ˇăC exceeds 100 mg/mL. At physiologic pH, acyclovir sodium exists as the un-ionized form with a molecular weight of 225 and a maximum solubility in water at 37ˇăC of 2.5 mg/mL. The pka's of acyclovir are 2.27 and 9.25.
The chemical name of acyclovir sodium is 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6 H -purin-6-one monosodium salt.
The empirical formula of budesonide is C 25 H 34 O 6 and its molecular weight is 430.5.
Mechanism of Antiviral Action: Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV).
The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. 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 vitro, acyclovir triphosphate stops replication of herpes viral DNA. This 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. The greater antiviral activity of acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the viral TK.
Antiviral Activities: The quantitative relationship between the in vitro 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 (IC 50 ), vary greatly depending upon a number of factors. Using plaque-reduction assays, the IC 50 against herpes simplex virus isolates ranges from 0.02 to 13.5 mcg/mL for HSV-1 and from 0.01 to 9.9 mcg/mL for HSV-2. The IC 50 for acyclovir against most laboratory strains and clinical isolates of VZV ranges from 0.12 to 10.8 mcg/mL. Acyclovir also demonstrates activity against the Oka vaccine strain of VZV with a mean IC 50 of 1.35 mcg/mL.
Drug Resistance: Resistance of HSV and VZV to acyclovir can result from qualitative and quantitative changes in the viral TK and/or DNA polymerase. Clinical isolates of HSV and VZV with reduced susceptibility to acyclovir have been recovered from immunocompromised patients, especially with advanced HIV infection. While most of the acyclovir-resistant mutants isolated thus far from such patients 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.
INDICATIONS AND USAGE
Herpes Simplex Infections in Immunocompromised Patients: acyclovirfor sodiumInjection is indicated for the treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in immunocompromised patients.
Initial Episodes of Herpes Genitalis: acyclovir sodiumfor Injection is indicated for the treatment of severe initial clinical episodes of herpes genitalis in immunocompetent patients.
Herpes Simplex Encephalitis: acyclovir sodium for Injection is indicated for the treatment of herpes simplex encephalitis.
Neonatal Herpes Simplex Virus Infection: acyclovir sodium for Injection is indicated for the treatment of neonatal herpes infections.
Varicella-Zoster Infections in Immunocompromised Patients: acyclovir sodium for Injection is indicated for the treatment of varicella-zoster (shingles) infections in immunocompromised patients.
DOSAGE AND ADMINISTRATION
Therapy should be initiated as early as possible following onset of signs and symptoms of herpes infections.
A maximum dose equivalent to 20 mg/kg every 8 hours should not be exceeded for any patient.
Dosage: Herpes Simplex Infections: Mucosal and Cutaneous Herpes Simplex (HSV-1 and HSV-2) Infections in Immunocompromised Patients:
Adults and Adolescents (12 years of age and older): 5 mg/kg infused at a constant rate over 1 hour, every 8 hours for 7 days.
Pediatrics (Under 12 years of age): 10 mg/kg infused at a constant rate over 1 hour, every 8 hours for 7 days.
Severe Initial Clinical Episodes of Herpes Genitalis:
Adults and Adolescents (12 years of age and older): 5 mg/kg infused at a constant rate over 1 hour, every 8 hours for 5 days.
Herpes Simplex Encephalitis:
Adults and Adolescents (12 years of age and older): 10 mg/kg infused at a constant rate over 1 hour, every 8 hours for 10 days.
Pediatrics (3 months to 12 years of age): 20 mg/kg infused at a constant rate over 1 hour, every 8 hours for 10 days.
Neonatal Herpes Simplex Virus Infections (Birth to 3 months): 10 mg/kg infused at a constant rate over 1 hour, every 8 hours for 10 days. In neonatal herpes simplex infections, doses of 15 mg/kg or 20 mg/kg (infused at a constant rate over 1 hour every 8 hours) have been used; the safety and efficacy of these doses are not known.
Varicella Zoster Infections: Zoster in Immunocompromised Patients:
Adults and Adolescents (12 years of age and older): 10 mg/kg infused at a constant rate over 1 hour, every 8 hours for 7 days.
Pediatrics (Under 12 years of age): 20 mg/kg infused at a constant rate over 1 hour, every 8 hours for 7 days.
Obese Patients: Obese patients should be dosed at the recommended adult dose using Ideal Body Weight.