Acyclovir: Package Insert and Label Information (Page 2 of 2)

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 indicated.

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).

ADVERSE REACTIONS

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 (see PRECAUTIONS).

Digestive

Diarrhea, gastrointestinal distress, nausea.

Hematologic and Lymphatic

Anemia, leukocytoclastic vasculitis, leukopenia, lymphadenopathy, thrombocytopenia.

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, renal pain (may be associated with renal failure), elevated blood urea nitrogen, elevated creatinine, hematuria (see WARNINGS).

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).

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).

HOW SUPPLIED

Acyclovir Tablets USP are available containing 400 mg acyclovir, USP. Each blue colored, biconvex, capsule shaped, compressed unscored tablet is debossed with N943 on one side and 400 on the other side.

They are supplied as follows:

NDC 12634-520-00 Bottles of 10

NDC 12634-520-01 Bottles of 100

NDC 12634-520-09 Bottles of 35

NDC 12634-520-40 Bottles of 40

NDC 12634-520-52 Blister Pack of 12

NDC 12634-520-54 Blister Pack of 14

NDC 12634-520-57 Blister Pack of 20

NDC 12634-520-59 Blister Pack of 30

NDC 12634-520-60 Bottles of 60

NDC 12634-520-61 Blister Pack of 10

NDC 12634-520-63 Blister Pack of 3

NDC 12634-520-66 Blister Pack of 6

NDC 12634-520-67 Blister Pack of 7

NDC 12634-520-69 Blister Pack of 9

NDC 12634-520-71 Bottles of 30

NDC 12634-520-74 Bottles of 24

NDC 12634-520-78 Bottles of 28

NDC 12634-520-79 Bottles of 25

NDC 12634-520-80 Bottles of 20

NDC 12634-520-81 Bottles of 21

NDC 12634-520-82 Bottles of 12

NDC 12634-520-85 Bottles of 15

NDC 12634-520-91 Blister Pack of 1

NDC 12634-520-94 Bottles of 4

NDC 12634-520-95 Bottles of 5

NDC 12634-520-96 Bottles of 6

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

Manufactured In Czech Republic By:

TEVA Czech Industries, s.r.o.

Opava-Komarov, Czech Republic

Manufactured For:

TEVA PHARMACEUTICALS USA, INC.

North Wales, PA 19454

Repackaged and Distributed by: Apotheca Inc.

Phoenix, AZ 85006

Package/Label Display Panel

label
(click image for full-size original)

ACYCLOVIR
acyclovir tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:12634-520(NDC:0093-8943)
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ACYCLOVIR (ACYCLOVIR) ACYCLOVIR 400 mg
Inactive Ingredients
Ingredient Name Strength
SILICON DIOXIDE
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
CELLULOSE, MICROCRYSTALLINE
POVIDONE K25
STARCH, CORN
SODIUM STARCH GLYCOLATE TYPE A POTATO
FD&C BLUE NO. 2
ALUMINUM OXIDE
Product Characteristics
Color blue Score no score
Shape OVAL (capsule shaped) Size 15mm
Flavor Imprint Code N943;400
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:12634-520-00 10 TABLET in 1 BOTTLE None
2 NDC:12634-520-01 100 TABLET in 1 BOTTLE None
3 NDC:12634-520-09 35 TABLET in 1 BOTTLE None
4 NDC:12634-520-40 40 TABLET in 1 BOTTLE None
5 NDC:12634-520-52 12 TABLET in 1 BLISTER PACK None
6 NDC:12634-520-54 14 TABLET in 1 BLISTER PACK None
7 NDC:12634-520-57 20 TABLET in 1 BLISTER PACK None
8 NDC:12634-520-59 30 TABLET in 1 BLISTER PACK None
9 NDC:12634-520-60 60 TABLET in 1 BOTTLE None
10 NDC:12634-520-61 10 TABLET in 1 BLISTER PACK None
11 NDC:12634-520-63 3 TABLET in 1 BLISTER PACK None
12 NDC:12634-520-66 6 TABLET in 1 BLISTER PACK None
13 NDC:12634-520-67 7 TABLET in 1 BLISTER PACK None
14 NDC:12634-520-69 9 TABLET in 1 BLISTER PACK None
15 NDC:12634-520-71 30 TABLET in 1 BOTTLE None
16 NDC:12634-520-74 24 TABLET in 1 BOTTLE None
17 NDC:12634-520-78 28 TABLET in 1 BOTTLE None
18 NDC:12634-520-79 25 TABLET in 1 BOTTLE None
19 NDC:12634-520-80 20 TABLET in 1 BOTTLE None
20 NDC:12634-520-81 21 TABLET in 1 BOTTLE None
21 NDC:12634-520-82 12 TABLET in 1 BOTTLE None
22 NDC:12634-520-85 15 TABLET in 1 BOTTLE None
23 NDC:12634-520-91 1 TABLET in 1 BLISTER PACK None
24 NDC:12634-520-94 4 TABLET in 1 BOTTLE None
25 NDC:12634-520-95 5 TABLET in 1 BOTTLE None
26 NDC:12634-520-96 6 TABLET in 1 BOTTLE None
Image of Product
(click image for full-size original)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA074556 04/23/1997
Labeler — Apotheca Inc. (051457844)
Establishment
Name Address ID/FEI Operations
Apotheca Inc. 051457844 repack (12634-520), relabel (12634-520)

Revised: 06/2016 Apotheca Inc.

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