ents (aged 12 years and older): 10 mg/kg infused at a constant rate over 1 hour, every 8 hours for 10 days. pediatrics (aged 3 months to 12 years): 20 mg/kg infused at a constant rate over 1 hour, every 8 hours for 10 days . 4. neonatal herpes simplex virus infections: pma of at least 34 weeks : 20 mg/kg infused at a constant rate over 1 hour, every 8 hours for 21 days. pma of less than 34 weeks : 20 mg/kg infused at a constant rate over 1 hour, every 12 hours for 21 days. in neonates with ongoing medical conditions affecting their renal function beyond the effect of prematurity, the doses recommended should be used with caution. 5. varicella zoster infections: zoster in immunocompromised patients: adults and adolescents (aged 12 years and older): 10 mg/kg infused at a constant rate over 1 hour, every 8 hours for 7 days. pediatrics (younger than 12 years): 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. 6. patients with acute or chronic renal impairment (older than 3 months): refer to dosage and administration section for recommended doses and adjust the dosing interval as indicated in table 6. table 6 dosage adjustments for patients with renal impairment creatinine clearance (ml/min/1.73 m 2 ) percent of recommended dose dosing interval (hours) > 50 100% 8 >25 to 50 100% 12 >10 to 25 100% 24 ≤ 10 50% 24 hemodialysis for patients who require dialysis, the mean plasma half-life of acyclovir during hemodialysis is approximately 5 hours. this results in a 60% decrease in plasma concentrations following a 6-hour dialysis period. therefore, the patient's dosing schedule should be adjusted so that an additional dose is administered after each dialysis. peritoneal dialysis no supplemental dose appears to be necessary after adjustment of the dosing interval. administration the calculated dose should then be removed and added to any appropriate intravenous solution at a volume selected for administration during each 1 hour infusion. infusion concentrations of approximately 7 mg/ml or lower are recommended. in clinical studies, the average 70 kg adult received between 60 and 150 ml of fluid per dose. higher concentrations (e.g., 10 mg/ml) may produce phlebitis or inflammation at the injection site upon inadvertent extravasation. standard, commercially available electrolyte and glucose solutions are suitable for intravenous administration; biologic or colloidal fluids (e.g., blood products, protein solutions, etc.) are not recommended. once diluted for administration, each dose should be used within 24 hours. parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

ncy of less than 1%: anemia, neutropenia, thrombocytopenia, thrombocytosis, leukocytosis, and neutrophilia. in addition, anorexia and hematuria were observed. neonatal clinical trial in study 2, 72 of the 88 enrolled neonates received 60 mg/kg/day. among subjects with recorded normal baseline values, the following laboratory abnormalities were reported: 6% (4/64) with grade 3 or 4 increase in creatinine; 4% (2/52) with total bilirubin grade 3 or 4 toxicity; 13% (8/64) with hemoglobin < 8 gram%; 16% (10/64) and 3% (2/64) with absolute neutrophil count 500 to 1,000 cells/mm 3 and < 500 cells/mm 3 , respectively; 10% (6/63) and 5% (3/63) with platelet count 50,000 to 100,000 and < 50,000, respectively. observed during clinical practice in addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of acyclovir sodium injection in clinical practice. because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. these events have been chosen for inclusion due to either their seriousness, frequency of reporting, potential causal connection to acyclovir, or a combination of these factors. general: anaphylaxis, angioedema, fatigue, fever, headache, pain, peripheral edema. digestive: abdominal pain, diarrhea, gastrointestinal distress, nausea. cardiovascular: hypotension. hematologic and lymphatic: disseminated intravascular coagulation, hemolysis, leukocytoclastic vasculitis, leukopenia, lymphadenopathy. hepatobiliary tract and pancreas: elevated liver function tests, hepatitis, hyperbilirubinemia, jaundice. musculoskeletal: myalgia. nervous: aggressive behavior, agitation, ataxia, coma, confusion, delirium, dizziness, dysarthria, encephalopathy, hallucinations, obtundation, paresthesia, psychosis, seizure, somnolence, tremor. these symptoms may be marked, particularly in older adults (see precautions ). skin: alopecia, erythema multiforme, photosensitive rash, pruritus, rash, stevens-johnson syndrome, toxic epidermal necrolysis, urticaria. severe local inflammatory reactions, including tissue necrosis, have occurred following infusion of acyclovir into extravascular tissues. special senses: visual abnormalities. urogenital: renal failure, elevated blood urea nitrogen, elevated creatinine (see warnings ).

y only if the potential benefit justifies the potential risk to the fetus.

g site displacement are not anticipated. renal excretion of unchanged drug is the major route of acyclovir elimination accounting for 62% to 91% of the dose. the only major urinary metabolite detected is 9-carboxymethoxymethylguanine accounting for up to 14.1% of the dose in patients with normal renal function. the half-life and total body clearance of acyclovir are dependent on renal function as shown in table 2. table 2 acyclovir half-life and total body clearance total body clearance creatinine clearance (ml/min/1.73 m 2 ) half-life (h) (ml/min/1.73 m 2 ) (ml/min/kg) > 80 2.5 327 5.1 50 to 80 3 248 3.9 15 to 50 3.5 190 3.4 0 (anuric) 19.5 29 0.5 special populations adults with impaired renal function acyclovir was administered at a dose of 2.5 mg/kg to 6 adult patients with severe renal failure. the peak and trough plasma levels during the 47 hours preceding hemodialysis were 8.5 mcg/ml and 0.7 mcg/ml, respectively. consult dosage and administration section for recommended adjustments in dosing based upon creatinine clearance. pediatrics acyclovir pharmacokinetics were determined in 16 pediatric patients with normal renal function ranging in age from 3 months to 16 years at doses of approximately 10 mg/kg and 20 mg/kg every 8 hours (table 3). concentrations achieved at these regimens are similar to those in adults receiving 5 mg/kg and 10 mg/kg every 8 hours, respectively (table 1). acyclovir pharmacokinetics were determined in 12 patients ranging in age from birth to 3 months at doses of 5 mg/kg, 10 mg/kg, and 15 mg/kg every 8 hours (table 3). table 3 acyclovir pharmacokinetics in pediatric patients (mean ± sd) parameter aged from birth to 3 months (n=12) aged 3 months to 12 years (n=16) cl (ml/min/kg) 4.46 ± 1.61 8.44 ± 2.92 vdss (l/kg) 1.08 ± 0.35 1.01 ± 0.28 elimination half-life (hours) 3.80 ± 1.19 2.36 ± 0.97 acyclovir pharmacokinetic samples were collected in full-term and pre-term neonates with normal renal function who received varying dosing regimens of acyclovir for the treatment of suspected neonatal hsv infection. model-predicted pharmacokinetic parameters stratified by post-menstrual age (pma) are summarized in table 4. table 4 acyclovir pharmacokinetics in neonates aged from birth to 3 months post-menstrual age (pma) n iv dose administered over 1 hour. parameter (median [range]) cmin ss (mg/l) cmax ss (mg/l) cl (l/h/kg) v (l/kg) < 30 weeks 13 500 mg/m 2 every 8 h or 3.92 (2.38 to 39.3) 10.3 (4.59 to 110) 0.21 (0.10 to 0.31) 2.88 (0.65 to 5.30) 10 mg/kg or 20 mg/kg every 12 h 30 to < 36 weeks 9 500 mg/m 2 every 8 h or 5.10 (2.54 to 9.62) 8.83 (5.44 to 29.8) 0.45 (0.30 to 0.81) 4.49 (1.87 to 10.85) 10 mg/kg or 20 mg/kg every 12 h or 20 mg/kg every 8 h 36 to 41 weeks 6 500 mg/m 2 every 8 h 2.90 (2.19 to 7.46) 12.4 (10.8 to 86.1) 0.59 (0.13 to 0.77) 2.55 (0.29 to 4.09) overall 28 – 4.15 11.1 0.28 3.34 (2.19 to 39.3) (4.59 to 110) (0.10 to 0.81) (0.29 to 10.9) geriatrics acyclovir plasma concentrations are higher in geriatric patients compared with younger adults, in part due to age-related changes in renal function. dosage reduction may be required in geriatric patients with underlying renal impairment (see precautions:geriatric use ). drug interactions coadministration of probenecid with acyclovir has been shown to increase the mean acyclovir half-life and the area under the concentration-time curve. urinary excretion and renal clearance were correspondingly reduced.

e not anticipated. renal excretion of unchanged drug is the major route of acyclovir elimination accounting for 62% to 91% of the dose. the only major urinary metabolite detected is 9-carboxymethoxymethylguanine accounting for up to 14.1% of the dose in patients with normal renal function. the half-life and total body clearance of acyclovir are dependent on renal function as shown in table 2. table 2 acyclovir half-life and total body clearance total body clearance creatinine clearance (ml/min/1.73 m 2 ) half-life (h) (ml/min/1.73 m 2 ) (ml/min/kg) > 80 2.5 327 5.1 50 to 80 3 248 3.9 15 to 50 3.5 190 3.4 0 (anuric) 19.5 29 0.5