Acyclovir 200 MG Oral Capsule
Generic Name: ACYCLOVIR
Brand Name: Acyclovir
- Substance Name(s):
- ACYCLOVIR
WARNINGS
Acyclovir capsules and tablets 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.
DRUG INTERACTIONS
Drug Interactions See CLINICAL PHARMACOLOGY , Pharmacokinetics .
OVERDOSAGE
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 DOSAGE AND ADMINISTRATION ).
DESCRIPTION
Acyclovir is a synthetic nucleoside analogue active against herpesviruses.
Each capsule, for oral administration, contains 200 mg of acyclovir.
In addition, each capsule contains the following inactive ingredients: corn starch, lactose monohydrate, magnesium stearate and sodium lauryl sulfate.
The capsule shell consists of gelatin, FD&C blue No.
1, D&C red No.
28, D&C red No.
33 and titanium dioxide.
Printed with edible black ink that contains FD&C blue No.
1, FD&C blue No.
2, FD&C red No.
40 and D&C yellow No.
10.
Each tablet, for oral administration, contains 400 mg or 800 mg of acyclovir.
In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch and sodium starch glycolate.
The 400 mg tablets also contain FD&C blue No.
2.
Acyclovir is a white to off-white, crystalline powder.
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]-6 H- purin-6-one; it has the following structural formula: C 8 H 11 N 5 O 3 M.W.
225 Structural formula for acyclovir
CLINICAL STUDIES
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 quarter.
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 hours.
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.
HOW SUPPLIED
Acyclovir capsules USP are available containing 200 mg acyclovir.
Each opaque blue cap and body size #1 hard gelatin capsule is imprinted with black ink N 940 and 200 on opposing cap and body portion of the capsule.
They are supplied as follows: NDC 63187-154-90 Bottles of 90 Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Protect from light and moisture.
Manufactured In Canada By: TEVA CANADA LIMITED Toronto, Canada M1B 2K9 Manufactured For: TEVA PHARMACEUTICALS USA Sellersville, PA 18960 Rev.
H 8/2012 Repackaged by: PROFICIENT RX LP Thousand Oaks, CA 91320
GERIATRIC USE
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 ).
INDICATIONS AND USAGE
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).
PEDIATRIC USE
Pediatric Use Safety and effectiveness of oral formulations of acyclovir in pediatric patients younger than 2 years of age have not been established.
PREGNANCY
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.
NUSRING MOTHERS
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 indicated.
INFORMATION FOR PATIENTS
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 breastfeed 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.
DOSAGE AND ADMINISTRATION
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 re-evaluation.
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 symptoms.
Patients With Acute or Chronic Renal Impairment In patients with renal impairment, the dose of acyclovir capsules and tablets should be modified as shown in Table 3 : Table 3: Dosage Modification for Renal Impairment Normal Dosage Regimen Creatinine Clearance (mL/min/1.73 m 2 ) Adjusted Dosage Regimen Dose (mg) Dosing Interval 200 mg every 4 hours > 10 200 every 4 hours, 5x daily 0 to 10 200 every 12 hours 400 mg every 12 hours > 10 400 every 12 hours 0 to 10 200 every 12 hours 800 mg every 4 hours > 25 800 every 4 hours, 5x daily 10 to 25 800 every 8 hours 0 to 10 800 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 interval.
Bioequivalence of Dosage Forms Acyclovir suspension was shown to be bioequivalent to acyclovir capsules (n = 20) and 1 acyclovir 800 mg tablet was shown to be bioequivalent to 4 acyclovir 200 mg capsules (n = 24).