Acyclovir Injection

Name: Acyclovir Injection

Why is this medication prescribed?

Acyclovir injection is used to treat first-time or repeat outbreaks of herpes simplex (a herpes virus infection of the skin and mucus membranes) and to treat herpes zoster (shingles; a rash that can occur in people who have had chickenpox in the past) in people with weak immune systems. It is also used to treat first-time genital herpes outbreaks (a herpes virus infection that causes sores to form around the genitals and rectum from time to time) in people with normal immune systems. Acyclovir injection is used to treat herpes simplex encephalitis (brain infection with swelling caused by the herpes virus) and herpes infections in newborn infants. Acyclovir injection is in a class of antiviral medications called synthetic nucleoside analogues. It works by stopping the spread of the herpes virus in the body. Acyclovir injection will not cure genital herpes and may not stop the spread of genital herpes to other people.

Other uses for this medicine

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include the following:

  • agitation
  • coma
  • seizures
  • tiredness

Missed dose

For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor or pharmacist immediately to establish a new dosing schedule. Do not double the dose to catch up.

Warnings

Acyclovir for Injection, USP is intended for intravenous infusion only, and should not be administered topically, intramuscularly, orally, subcutaneously, or in the eye. Intravenous infusions must be given over a period of at least 1 hour to reduce the risk of renal tubular damage (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

Renal failure, in some cases resulting in death, has been observed with acyclovir therapy (see ADVERSE REACTIONS: Observed During Clinical Practice and OVERDOSAGE). Thrombotic thrombocytopenic purpura/ hemolytic uremic syndrome (TTP/HUS), which has resulted in death, has occurred in immunocompromised patients receiving acyclovir therapy.

Precautions

General

Precipitation of acyclovir crystals in renal tubules can occur if the maximum solubility of free acyclovir (2.5 mg/mL at 37°C in water) is exceeded or if the drug is administered by bolus injection. Ensuing renal tubular damage can produce acute renal failure.

Abnormal renal function (decreased creatinine clearance) can occur as a result of acyclovir administration and depends on the state of the patient's hydration, other treatments, and the rate of drug administration. Concomitant use of other nephrotoxic drugs, preexisting renal disease, and dehydration make further renal impairment with acyclovir more likely. Administration of acyclovir by intravenous infusion must be accompanied by adequate hydration.

When dosage adjustments are required, they should be based on estimated creatinine clearance (see DOSAGE AND ADMINISTRATION).

Approximately 1% of patients receiving intravenous acyclovir have manifested encephalopathic changes characterized by either lethargy, obtundation, tremors, confusion, hallucinations, agitation, seizures, or coma. Acyclovir should be used with caution in those patients who have underlying neurologic abnormalities and those with serious renal, hepatic, or electrolyte abnormalities, or significant hypoxia.

Drug Interactions

See CLINICAL PHARMACOLOGY: Pharmacokinetics.

 

Carcinogenesis, Mutagenesis, Impairment of Fertility

The data presented below include references to peak steady-state plasma acyclovir concentrations observed in humans treated with 30 mg/kg/day (10 mg/kg every 8 hours, dosing appropriate for treatment of herpes zoster or herpes encephalitis), or 15 mg/kg/day (5 mg/kg every 8 hours, dosing appropriate for treatment of primary genital herpes or herpes simplex infections in immunocompromised patients). Plasma drug concentrations in animal studies are expressed as multiples of human exposure to acyclovir at the higher and lower dosing schedules (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

Acyclovir was tested in lifetime bioassays in rats and mice at single daily doses of up to 450 mg/kg administered by gavage. There was no statistically significant difference in the incidence of tumors between treated and control animals, nor did acyclovir shorten the latency of tumors. At 450 mg/kg/day, plasma concentrations in both the mouse and rat bioassay were lower than concentrations in humans.

Acyclovir was tested in 16 in vitro and in vivo genetic toxicity assays. Acyclovir was positive in 5 of the assays.

Acyclovir did not impair fertility or reproduction in mice (450 mg/kg/day, PO) or in rats (25 mg/kg/day, SC). In the mouse study, plasma levels were the same as human levels, while in the rat study, they were 1 to 2 times human levels. At higher doses (50 mg/kg/day, SC) in rats and rabbits (1 to 2 and 1 to 3 times human levels, respectively) implantation efficacy, but not litter size, was decreased. In a rat peri- and post-natal study at 50 mg/kg/day, SC, there was a statistically significant decrease in group mean numbers of corpora lutea, total implantation sites, and live fetuses.

No testicular abnormalities were seen in dogs given 50 mg/kg/day, IV for 1 month (1 to 3 times human levels) or in dogs given 60 mg/kg/day orally for 1 year (the same as human levels). Testicular atrophy and aspermatogenesis were observed in rats and dogs at higher dose levels.

Pregnancy

Teratogenic Effects

Pregnancy Category B.

Acyclovir administered during organogenesis was not teratogenic in the mouse (450 mg/kg/day, PO), rabbit (50 mg/kg/day, SC and IV) or rat (50 mg/kg/day, SC). These exposures resulted in plasma levels the same as, 4 and 9, and 1 and 2 times, respectively, human levels.

There are no adequate and well-controlled studies in pregnant women. A prospective epidemiologic registry of acyclovir use during pregnancy was established in 1984 and completed in April 1999. There were 749 pregnancies followed in women exposed to systemic acyclovir during the first trimester of pregnancy resulting in 756 outcomes. The occurrence rate of birth defects approximates that found in the general population. However, the small size of the registry is 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. Acyclovir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Acyclovir concentrations have been documented in breastmilk in two women following oral administration of acyclovir and ranged from 0.6 to 4.1 times corresponding plasma levels. These concentrations would potentially expose the nursing infant to a dose of acyclovir up to 0.3 mg/kg/day. Acyclovir should be administered to a nursing mother with caution and only when indicated.

Pediatric Use

See DOSAGE AND ADMINISTRATION.

Geriatric Use

Clinical studies of acyclovir did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has identified differences in the severity of CNS adverse events between elderly and younger patients (see ADVERSE REACTIONS: Observed During Clinical Practice). In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased renal function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Overdosage

Overdoses involving ingestions of up to 20 g have been reported. Adverse events that have been reported in association with overdosage include agitation, coma, seizures, and lethargy. Precipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid. Overdosage has been reported following bolus injections or inappropriately high doses, and in patients whose fluid and electrolyte balance were not properly monitored. This has resulted in elevated BUN and serum creatinine, and subsequent renal failure. In the event of acute renal failure and anuria, the patient may benefit from hemodialysis until

renal function is restored (see DOSAGE AND ADMINISTRATION).

Acyclovir Injection Dosage and Administration

CAUTION - RAPID OR BOLUS INTRAVENOUS INJECTION MUST BE AVOIDED (see WARNINGS and PRECAUTIONS).

INTRAMUSCULAR OR SUBCUTANEOUS INJECTION MUST BE AVOIDED (see WARNINGS).

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.

PATIENTS WITH ACUTE OR CHRONIC RENAL IMPAIRMENT: Refer to DOSAGE AND ADMINISTRATION section for recommended doses, and adjust the dosing interval as indicated in Table 5.

Table 5 Dosage Adjustments for Patients with Renal Impairment
Creatinine Clearance
(mL/min/1.73 m2)
Percent of Recommended Dose
Dosing Interval (hours)
> 50
100%             
8
25 to 50
100%
12
10 to 25
100%
24
0 to 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 six-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.

Method of Preparation:

Each 10 mL vial contains acyclovir sodium equivalent to 500 mg of acyclovir. Each 20 mL vial contains acyclovir sodium equivalent to 1000 mg of acyclovir .The contents of the vial should be dissolved in Sterile Water for Injection as follows:

Contents of Vial
Amount of Diluent
500 mg
10 mL
1000 mg
20 mL

The resulting solution contains 50 mg acyclovir per mL. The pH of the solution is approximately 11. Shake the vial well to assure complete dissolution before measuring and transferring each individual dose. The reconstituted solution should be used within 12 hours. Refrigeration of reconstituted solution may result in the formation of a precipitate which will redissolve at room temperature.

DO NOT USE BACTERIOSTATIC WATER FOR INJECTION CONTAINING BENZYL ALCOHOL OR PARABENS.

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.

Package label - principal display panel

Acyclovir for Injection, USP 500 mg/vial - Vial Label

NDC 68382-125-01

Acyclovir for Injection, USP

Equivalent to

500 mg/vial

acyclovir

For Intravenous Infusion Only

Rx only

zydus pharmaceuticals

Acyclovir for Injection, USP 500 mg/vial - Carton Label

NDC 68382-125-10

Acyclovir for Injection, USP

Equivalent to

500 mg/vial

acyclovir

For Intravenous Infusion Only

10 x 500 mg vials

Rx only

zydus pharmaceuticals

Acyclovir for Injection, USP 1000 mg/vial - Vial Label

NDC 68382-126-01

Acyclovir for Injection, USP

Equivalent to

1000 mg/vial

acyclovir

For Intravenous Infusion Only

Rx only

zydus pharmaceuticals

Acyclovir for Injection, USP 1000 mg/vial - Carton Label

NDC 68382-126-10

Acyclovir for Injection, USP

Equivalent to

1000 mg/vial

acyclovir

For Intravenous Infusion Only

10 x 1000 mg vials

Rx only

zydus pharmaceuticals

ACYCLOVIR 
Acyclovir Injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68382-125
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ACYCLOVIR SODIUM (ACYCLOVIR) ACYCLOVIR 500 mg
Inactive Ingredients
Ingredient Name Strength
SODIUM HYDROXIDE  
WATER  
Packaging
# Item Code Package Description
1 NDC:68382-125-10 10 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 CARTON
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA206606 08/17/2017
ACYCLOVIR 
Acyclovir Injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68382-126
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ACYCLOVIR SODIUM (ACYCLOVIR) ACYCLOVIR 1000 mg
Inactive Ingredients
Ingredient Name Strength
SODIUM HYDROXIDE  
WATER  
Packaging
# Item Code Package Description
1 NDC:68382-126-10 10 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 CARTON
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA206606 08/17/2017
Labeler - Zydus Pharmaceuticals (USA) Inc. (156861945)
Registrant - Zydus Pharmaceuticals (USA) Inc. (156861945)
Establishment
Name Address ID/FEI Operations
Cadila Healthcare Limited 918596198 ANALYSIS(68382-125, 68382-126), MANUFACTURE(68382-125, 68382-126)
Revised: 06/2017   Zydus Pharmaceuticals (USA) Inc.
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