Main information

  • Trade name:
  • ACYCLOVIR- acyclovir capsule
  • Composition:
  • ACYCLOVIR 200 mg
  • Administration route:
  • ORAL
  • Prescription type:
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug



  • Available in:
  • ACYCLOVIR- acyclovir capsule
    United States
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  • Herpes Zoster Infections: acyclovir is indicated for the acute treatment of herpes zoster (shingles). Genital Herpes: acyclovir is indicated for the treatment of initial episodes and the management of recurrent episodes of genital herpes. Chickenpox: acyclovir is indicated for the treatment of chickenpox (varicella). Acyclovir is contraindicated for patients who develop hypersensitivity to acyclovir or valacyclovir.
  • Product summary:
  • Product: 50090-0596 NDC: 50090-0596-0 25 CAPSULE in a BOTTLE NDC: 50090-0596-1 50 CAPSULE in a BOTTLE NDC: 50090-0596-7 30 CAPSULE in a BOTTLE


  • Source:
  • DailyMed - NLM - National Library of Medicine
  • Authorization status:
  • Abbreviated New Drug Application
  • Authorization number:
  • 50090-0596-0, 50090-0596-1, 50090-0596-7
  • Last update:
  • 29-05-2019

Summary of Product characteristics: dosage, interactions, side effects

ACYCLOVIR- acyclovir capsule

A-S Medication Solutions


Acyclovir Capsules USP

Rx only


Acyclovir is a synthetic nucleoside analogue active against herpesviruses. Acyclovir capsules are

formulations for oral administration.

Each capsule contains 200 mg of acyclovir and the inactive ingredients: lactose monohydrate, sodium

lauryl sulfate, sodium starch glycolate, and magnesium stearate. The capsule shell consists of FD&C

Blue #1, gelatin, and titanium dioxide. The imprinting ink contains, alcohol, FD&C Blue #2, FD&C Red

#40, FD&C Yellow #10, iron oxide black, shellac Glaze.

Acyclovir is a white, crystalline powder with the molecular formula C H N O and a molecular

weight of 225. The maximum solubility in water at 37°C is 2.5 mg/mL. The pka's of acyclovir are 2.27

and 9.25.

The chemical name of acyclovir is 2-amino-1,9-dihydro-9- [(2-hydroxyethoxy) methyl]-6H-purin-6-

one; it has the following structural formula:


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

), vary greatly depending upon a

number of factors. Using plaque-reduction assays, the IC

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

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

of 1.35


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

immunocompromised 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



Pharmacokinetics: The pharmacokinetics of acyclovir after oral administration have been evaluated in

healthy volunteers and in immunocompromised patients with herpes simplex or varicella-zoster virus

infection. Acyclovir pharmacokinetic parameters are summarized in Table 1.

Table 1. Acyclovir Pharmacokinetic Characteristics (Range)

* Bioavailability decreases with increasing dose.



Plasma protein binding

9% to 33%

Plasma elimination half-life

2.5 to 3.3 h

Average oral bioavailability

10% to 20%*

In one multiple-dose, crossover study in healthy subjects (n = 23), it was shown that increases in plasma

acyclovir concentrations were less than dose proportional with increasing dose, as shown in Table 2.

The decrease in bioavailability is a function of the dose and not the dosage form.

Table 2: Acyclovir Peak and Trough Concentrations at Steady State


200 mg

400 mg

800 mg

0.83 mcg/mL

1.21 mcg/mL

1.61 mcg/mL

0.46 mcg/mL

0.63 mcg/mL

0.83 mcg/mL

There was no effect of food on the absorption of acyclovir (n = 6); therefore, acyclovir capsules may

be administered with or without food.

The only known urinary metabolite is 9-[(carboxymethoxy) methyl ] guanine.

Special Populations: Adults with Impaired Renal Function:

The half-life and total body clearance of acyclovir are dependent on renal function. A dosage

adjustment is recommended for patients with reduced renal function (see DOSAGE AND


Geriatrics: Acyclovir plasma concentrations are higher in geriatric patients compared to 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).

Pediatrics: In general, the pharmacokinetics of acyclovir in pediatric patients is similar to that of adults.

Mean half-life after oral doses of 300 mg/m and 600 mg/m in pediatric patients aged 7 months to 7

years was 2.6 hours (range 1.59 to 3.74 hours).

Drug Interactions: Coadministration of probenecid with intravenous 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.

Clinical Trials:


Initial Genital Herpes: Double-blind, placebo-controlled studies have demonstrated that orally

administered acyclovir significantly reduced the duration of acute infection and duration of lesion

healing. The duration of pain and new lesion formation was decreased in some patient groups.

Recurrent Genital Herpes: Double-blind, placebo-controlled studies in patients with frequent

recurrences (6 or more episodes per year) have shown that orally administered acyclovir given daily

for 4 months to 10 years prevented or reduced the frequency and/or severity of recurrences in greater

than 95% of patients.

In a study of patients who received acyclovir 400 mg twice daily for 3 years, 45%, 52%, and 63% of

patients remained free of recurrences in the first, second, and third years, respectively. Serial analyses

of the 3-month recurrence rates for the patients showed that 71% to 87% were recurrence free in each


Herpes Zoster Infections: In a double-blind, placebo-controlled study of immunocompetent patients with

localized cutaneous zoster infection, acyclovir (800 mg 5 times daily for 10 days) shortened the times

to lesion scabbing, healing, and complete cessation of pain, and reduced the duration of viral shedding

and the duration of new lesion formation.

In a similar double-blind, placebo-controlled study, acyclovir (800 mg 5 times daily for 7 days)

shortened the times to complete lesion scabbing, healing, and cessation of pain; reduced the duration of

new lesion formation; and reduced the prevalence of localized zoster-associated neurologic symptoms

(paresthesia, dysesthesia, or hyperesthesia).

Treatment was begun within 72 hours of rash onset and was most effective if started within the first 48


Adults greater than 50 years of age showed greater benefit.

Chickenpox: Three randomized, double-blind, placebo-controlled trials were conducted in 993

pediatric patients aged 2 to 18 years with chickenpox. All patients were treated within 24 hours after the

onset of rash. In 2 trials, acyclovir was administered at 20 mg/kg 4 times daily (up to 3,200 mg per day)

for 5 days. In the third trial, doses of 10, 15, or 20 mg/kg were administered 4 times daily for 5 to 7

days. Treatment with acyclovir shortened the time to 50% healing; reduced the maximum number of

lesions; reduced the median number of vesicles; decreased the median number of residual lesions on

day 28; and decreased the proportion of patients with fever, anorexia, and lethargy by day 2. Treatment

with acyclovir did not affect varicella-zoster virus-specific humoral or cellular immune responses at 1

month or 1 year following treatment.


Herpes Zoster Infections: acyclovir is indicated for the acute treatment of herpes zoster (shingles).

Genital Herpes: acyclovir is indicated for the treatment of initial episodes and the management of

recurrent episodes of genital herpes.

Chickenpox: acyclovir is indicated for the treatment of chickenpox (varicella).


Acyclovir is contraindicated for patients who develop hypersensitivity to acyclovir or valacyclovir.


Acyclovir capsules are intended for oral ingestion only. 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.


Dosage adjustment is recommended when administering acyclovir to patients with renal impairment (see

DOSAGE AND ADMINISTRATION). Caution should also be exercised when administering acyclovir

to patients receiving potentially nephrotoxic agents since this may increase the risk of renal dysfunction

and/or the risk of reversible central nervous system symptoms such as those that have been reported in

patients treated with intravenous acyclovir. Adequate hydration should be maintained.

Information for Patients: Patients are instructed to consult with their physician if they experience

severe or troublesome adverse reactions, they become pregnant or intend to become pregnant, they

intend to breast feed while taking orally administered acyclovir, or they have any other questions.

Patients should be advised to maintain adequate hydration.

Herpes Zoster: There are no data on treatment initiated more than 72 hours after onset of the zoster rash.

Patients should be advised to initiate treatment as soon as possible after a diagnosis of herpes zoster.

Genital Herpes Infections: Patients should be informed that acyclovir is not a cure for genital herpes.

There are no data evaluating whether acyclovir will prevent transmission of infection to others.

Because genital herpes is a sexually transmitted disease, patients should avoid contact with lesions or

intercourse when lesions and/or symptoms are present to avoid infecting partners. Genital herpes can

also be transmitted in the absence of symptoms through asymptomatic viral shedding. If medical

management of a genital herpes recurrence is indicated, patients should be advised to initiate therapy at

the first sign or symptom of an episode.

Chickenpox: Chickenpox in otherwise healthy children is usually a self-limited disease of mild to

moderate severity. Adolescents and adults tend to have more severe disease. Treatment was initiated

within 24 hours of the typical chickenpox rash in the controlled studies, and there is no information

regarding the effects of treatment begun later in the disease course.

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 800 mg given

orally 5 times a day (dosing appropriate for treatment of herpes zoster) or 200 mg given orally 5 times a

day (dosing appropriate for treatment of genital herpes). 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. Maximum plasma

concentrations were 3 to 6 times human levels in the mouse bioassay and 1 to 2 times human levels in the

rat bioassay.

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


Acyclovir did not impair fertility or reproduction in mice (450 mg/kg/day, p.o.) or in rats (25 mg/kg/day,

s.c.). In the mouse study, plasma levels were 9 to 18 times human levels, while in the rat study, they

were 8 to 15 times human levels. At higher doses (50 mg/kg/day, s.c.) in rats and rabbits (11 to 22 and 16

to 31 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, s.c., 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 (21 to 41 times human

levels) or in dogs given 60 mg/kg/day orally for 1 year (6 to 12 times 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, p.o.), rabbit (50 mg/kg/day, s.c. and IV), or rat (50

mg/kg/day, s.c.). These exposures resulted in plasma levels 9 and 18, 16 and 106, and 11 and 22 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 breast milk in 2 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


Pediatric Use: Safety and effectiveness of oral formulations of acyclovir in pediatric patients younger

than 2 years of age have not been established.

Geriatric Use: Of 376 subjects who received acyclovir in a clinical study of herpes zoster treatment in

immunocompetent subjects ≥50 years of age, 244 were 65 and over while 111 were 75 and over. No

overall differences in effectiveness for time to cessation of new lesion formation or time to healing

were reported between geriatric subjects and younger adult subjects. The duration of pain after healing

was longer in patients 65 and over. Nausea, vomiting, and dizziness were reported more frequently in

elderly subjects. Elderly patients are more likely to have reduced renal function and require dose

reduction. Elderly patients are also more likely to have renal or CNS adverse events. With respect to

CNS adverse events observed during clinical practice, somnolence, hallucinations, confusion, and coma

were reported more frequently in elderly patients (see CLINICAL PHARMACOLOGY, ADVERSE

REACTIONS: Observed During Clinical Practice, and DOSAGE AND ADMINISTRATION).


Herpes Simplex: Short-Term Administration: The most frequent adverse events reported during

clinical trials of treatment of genital herpes with acyclovir 200 mg administered orally 5 times daily

every 4 hours for 10 days were nausea and/or vomiting in 8 of 298 patient treatments (2.7%). Nausea

and/or vomiting occurred in 2 of 287 (0.7%) patients who received placebo.

Long-Term Administration: The most frequent adverse events reported in a clinical trial for the

prevention of recurrences with continuous administration of 400 mg (two 200-mg capsules) 2 times

daily for 1 year in 586 patients treated with acyclovir were nausea (4.8%) and diarrhea (2.4%). The 589

control patients receiving intermittent treatment of recurrences with acyclovir for 1 year reported

diarrhea (2.7%), nausea (2.4%), and headache (2.2%).

Herpes Zoster: The most frequent adverse event reported during 3 clinical trials of treatment of herpes

zoster (shingles) with 800 mg of oral acyclovir 5 times daily for 7 to 10 days in 323 patients was

malaise (11.5%). The 323 placebo recipients reported malaise (11.1%).

Chickenpox: The most frequent adverse event reported during 3 clinical trials of treatment of

chickenpox with oral acyclovir at doses of 10 to 20 mg/kg 4 times daily for 5 to 7 days or 800 mg 4

times daily for 5 days in 495 patients was diarrhea (3.2%). The 498 patients receiving placebo reported

diarrhea (2.2%).

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. 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, fever, headache, pain, peripheral edema.

Nervous: Aggressive behavior, agitation, ataxia, coma, confusion, decreased consciousness, delirium,

dizziness, dysarthria, encephalopathy, hallucinations, paresthesia, psychosis, seizure, somnolence,

tremors. These symptoms may be marked, particularly in older adults or in patients with renal impairment


Digestive: Diarrhea, gastrointestinal distress, nausea.

Hematologic and Lymphatic: Anemia, leukocytoclastic vasculitis, leukopenia, lymphadenopathy,


Hepatobiliary Tract and Pancreas: Elevated liver function tests, hepatitis, hyperbilirubinemia, jaundice.

Musculoskeletal: Myalgia.

Skin: Alopecia, erythema multiforme, photosensitive rash, pruritus, rash, Stevens-Johnson syndrome,

toxic epidermal necrolysis, urticaria.

Special Senses: Visual abnormalities.

Urogenital: Renal failure, elevated blood urea nitrogen, elevated creatinine, hematuria (see



Overdoses involving ingestion of up to 100 capsules (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



Acute Treatment of Herpes Zoster: 800 mg every 4 hours orally, 5 times daily for 7 to 10 days.

Genital Herpes: Treatment of Initial Genital Herpes: 200 mg every 4 hours, 5 times daily for 10 days.

Chronic Suppressive Therapy for Recurrent Disease:

400 mg 2 times daily for up to 12 months, followed by reevaluation. Alternative regimens have included

doses ranging from 200 mg 3 times daily to 200 mg 5 times daily.

The frequency and severity of episodes of untreated genital herpes may change over time. After 1 year

of therapy, the frequency and severity of the patient's genital herpes infection should be re-evaluated to

assess the need for continuation of therapy with acyclovir.

Intermittent Therapy: 200 mg every 4 hours, 5 times daily for 5 days. Therapy should be initiated at the

earliest sign or symptom (prodrome) of recurrence.

Treatment of Chickenpox: Children (2 years of age and older): 20 mg/kg per dose orally 4 times daily

(80 mg/kg/day) for 5 days. Children over 40 kg should receive the adult dose for chickenpox.

Adults and Children over 40 kg: 800 mg 4 times daily for 5 days.

Intravenous acyclovir is indicated for the treatment of varicella-zoster infections in

immunocompromised patients.

When therapy is indicated, it should be initiated at the earliest sign or symptom of chickenpox. There is

no information about the efficacy of therapy initiated more than 24 hours after onset of signs and


Patients With Acute or Chronic Renal Impairment: In patients with renal impairment, the dose of

acyclovir capsules should be modified as shown in Table 3:

Table 3. Dosage Modification for Renal Impairment

Normal Dosage

Creatinine Clearance

Adjusted Dosage Regimen


mL/min/1.73 m )

Dose (mg)

Dosing Interval

200 mg every


every 4 hours,

4 hours

5x daily


every 12 hours

400 mg every


every 12 hours

12 hours


every 12 hours

800 mg every


every 4 hours,

4 hours

5x daily


every 8 hours


every 12 hours

Hemodialysis: For patients who require hemodialysis, 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


Bioequivalence of Dosage Forms: acyclovir Suspension was shown to be bioequivalent to acyclovir

Capsules (n = 20) and 1 acyclovir 800-mg capsule was shown to be bioequivalent to 4 acyclovir 200-

mg capsules (n = 24).


Product: 50090-0596

NDC: 50090-0596-0 25 CAPSULE in a BOTTLE

NDC: 50090-0596-1 50 CAPSULE in a BOTTLE

NDC: 50090-0596-7 30 CAPSULE in a BOTTLE



acyclovir capsule

Product Information

Product T ype


Ite m Code (Source )

NDC:50 0 9 0 -0 59 6 (NDC:6 1442-111)

Route of Administration


Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th



20 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th


19 5.5 mg


21.15 mg


2.12 mg


4.23 mg

Product Characteristics


blue (light blue o paque cap, white o paque bo dy)

S core

no sco re

S hap e


S iz e

10 mm


Imprint Code

20 0 ;CTI;111


Packag ing


Item Code

Package Description

Marketing Start Date

Marketing End Date


NDC:50 0 9 0 -0 59 6 -0

25 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

11/28 /20 14


NDC:50 0 9 0 -0 59 6 -1

50 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

11/28 /20 14


NDC:50 0 9 0 -0 59 6 -7

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

11/28 /20 14

A-S Medication Solutions

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date


ANDA0 750 9 0

10 /22/20 0 9

Labeler -

A-S Medication Solutions (830016429)



Ad d re s s


Busine ss Ope rations

A-S Medicatio n So lutio ns

8 30 0 16 429

RELABEL(50 0 9 0 -0 59 6 ) , REPACK(50 0 9 0 -0 59 6 )

Revised: 4/2019