Acyclovir IV

Indications

Acyclovir IV is used for: Herpes simplex infections, Herpes Simplex Virus Encephalitis, Mucocutaneous Herpes Simplex Virus Infection, Varicella Zoster (Chickenpox), Herpes zoster (shingles), Severe Genital Herpes

Adult Dose

Adult IV Herpes simplex (except herpes encephalitis) infections in Immunocompromised patients I.V. 5 mg/kg body weight every 8 hours for 7 days provided renal function is not impaired. Herpes simplex encephalitis in Normal OR in Immunocompromised patients I.V. 10 mg/kg body weight every 8 hours for 10 days provided renal function is not impaired. Varicella Zoster (Chickenpox), Herpes Zoster (Shingles) infections in Immunocompromised patients I.V. 10 mg/kg body weight every 8 hours for 7 days provided renal function is not impaired. In obese patients dosed with intravenous aciclovir based on their actual body weight, higher plasma concentrations may be obtained. Consideration should therefore be given to dosage reduction in obese patients and especially in those with renal impairment or the elderly.

Child Dose

IV Neonatal Herpes Simplex Virus Infection Neonates and Infants up to 3 months of age is calculated on the basis of body weight. PMA ?34 weeks: 20 mg/kg IV q8hr for 21 days for disseminated and CNS disease. or for 14 days for disease limited to the skin and mucous membranes. PMA <34 weeks: 20 mg/kg IV q12hr for 21 days for disseminated and CNS disease. or for 14 days for disease limited to the skin and mucous membranes. Children aged between 3 months -12 years (calculated on the basis of body surface area) Herpes simplex (except herpes encephalitis) infections in Immunocompromised patients 250 mg/m2 every 8 hours calculated on the basis of body surface area. Herpes Simplex Encephalitis in Normal patients 500 mg/m2 every 8 hours calculated on the basis of body surface area. Varicella Zoster (Chickenpox), Herpes Zoster (Shingles) infections in Immunocompromised patients 500 mg/m2 every 8 hours calculated on the basis of body surface area. OR Herpes Simplex Virus Encephalitis 3 months-12 years: 20 mg/kg IV 8hourly for 10 days; up to 14-21 days reported ?12 years: 10-15 mg/kg IV q8hr for 14-21 days Mucocutaneous Herpes Simplex Virus Infection Treatment in immunocompromised patients <12 years: 10 mg/kg IV q8hr for 7 days ?12 years: 5-10 mg/kg/day IV divided q8hr for 5-7 days; up to 14 days reported Herpes Zoster (Shingles) <12 years (immunocompromised): 20 mg/kg IV q8hr for 7 days >12 years (immunocompromised): 30 mg/kg/day IV divided q8hr for 7-10 days Varicella Zoster (Chickenpox) Immunocompromised patients <12 years: 20 mg/kg/dose IV q8hr for 7 days >12 years: 10 mg/kg/dose IV q8hr for 7 days

Renal Dose

Renal impairment (IV) CrCl 25-50 mL/min/1.73 m²: Give recommended dose q12hr CrCl 10-25 mL/min/1.73 m²: Give recommended dose q24hr CrCl <10 mL/min/1.73 m²: Give 50% of recommended dose q24hr

Administration

IV Preparation Reconstitute with 10 mL (500-mg vial) or 20 mL (1000-mg vial) with Sterile Water Add 10 mL or 20 mL of sterile water for inj to a vial labeled as containing 500 mg or 1,000 mg of aciclovir, respectively, to provide a soln containing 50 mg/mL. The appropriate dose of reconstituted soln should then be withdrawn from the vial and diluted w/ 50-125 mL of a compatible IV infusion soln. Injection For IV infusion, dilute solution in D5W or 0.9% NaCl to a final concentration ?7 mg/mL. Concentrations >10 mg/mL increase the risk of phlebitis IV Administration For IV infusion only Avoid rapid infusion; infuse over 1 hr at constant rate to prevent renal damage Maintain adequate hydration Check for phlebitis, and rotate infusion sites

Contra Indications

Hypersensitivity to the active substance or to any of the excipients.

Precautions

Avoid rapid infusion because of risk of renal damage Renal failure, resulting in death, has occurred Use with caution in immunocompromised patients (potential risk of thrombotic thrombocytopenic purpura [TTP]/hemolytic uremic syndrome [HUS]) Use with caution in patients with renal impairment Treatment should begin within 24 hours of appearance of rash Use with caution in patients receiving nephrotoxic drugs Maintain adequate hydration during PO or IV therapy Thrombocytopenic purpura/hemolytic uremic syndrome reported

Pregnancy-Lactation

Pregnancy The use of aciclovir should be considered only when the potential benefits outweigh the possibility of unknown risks. A post-marketing aciclovir pregnancy registry has documented pregnancy outcomes in women exposed to any formulation of aciclovir. The registry findings have not shown an increase in the number of birth defects amongst aciclovir exposed subjects compared with the general population, and any birth defects showed no uniqueness or consistent pattern to suggest a common cause. Systemic administration of aciclovir in internationally accepted standard tests did not produce embryotoxic or teratogenic effects in rabbits, rats or mice. In a non-standard test in rats, foetal abnormalities were observed but only following such high subcutaneous doses that maternal toxicity was produced. The clinical relevance of these findings is uncertain. Caution should however be exercised by balancing the potential benefits of treatment against any possible hazard. Breast-feeding Following oral administration of 200mg aciclovir five times a day, aciclovir has been detected in breast milk at concentrations ranging from 0.6 to 4.1 times the corresponding plasma levels. These levels would potentially expose nursing infants to aciclovir dosages of up to 0.3mg/kg/day. Caution is therefore advised if aciclovir is to be administered to a nursing woman. Fertility There is no information on the effect of aciclovir on human female fertility. In a study of 20 male patients with normal sperm count, oral aciclovir administered at doses of up to 1g per day for up to six months has been shown to have no clinically significant effect on sperm count, motility or morphology.

Interactions

Probenecid, cimetidine and mycophenolate mofetil may increase the plasma concentration of aciclovir. Increased nephrotoxic effects w/ drugs that affect renal physiology (e.g. ciclosporin, tacrolimus).

Side Effects

Side effects of Acyclovir IV : 1-10% Parenteral Inflammation or phlebitis at injection site (9%) Nausea (7%) Vomiting (7%) Rash or hives (2%) Elevated transaminase levels (1-2%) <1% Abdominal pain Aggression/confusion Agitation Alopecia Anaphylaxis Anemia Angioedema Anorexia Ataxia Coma Disseminated intravascular coagulation (DIC) Dizziness Fatigue

Mode of Action

Activity against HSV types I and II and varicella-zoster virus is due to intracellular conversion of aciclovir to the monophosphate by viral thymidine kinase with subsequent conversion to the diphosphate and active triphosphate by cellular enzymes. This active form inhibits viral DNA synthesis and replication by interfering with viral DNA polymerase enzyme and being incorporated into viral DNA.