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| Product NDC Code | 71205-391 | ||||||||||
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| Drug Name | Acyclovir |
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| Type | Generic | ||||||||||
| Pharm Class | DNA Polymerase Inhibitors [MoA], Herpes Simplex Virus Nucleoside Analog DNA Polymerase Inhibitor [EPC], Herpes Zoster Virus Nucleoside Analog DNA Polymerase Inhibitor [EPC], Herpesvirus Nucleoside Analog DNA Polymerase Inhibitor [EPC], Nucleoside Analog [EXT] |
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| Route | ORAL | ||||||||||
| Dosage Form | TABLET | ||||||||||
| RxCUI drug identifier | 197311 | ||||||||||
| Application Number | ANDA077309 | ||||||||||
| Labeler Name | Proficient Rx LP | ||||||||||
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Overdosage of acyclovir
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.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 ).
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.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, elevated blood urea nitrogen, elevated creatinine, hematuria (see WARNINGS).
acyclovir Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.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.
Drug Interactions See CLINICAL PHARMACOLOGY: Pharmacokinetics .
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.CLINICAL PHARMACOLOGY 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) Parameter Range Plasma protein binding 9% to 33% Plasma elimination half-life 2.5 to 3.3 h Average oral bioavailability 10% to 20% Bioavailability decreases with increasing dose. 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 Parameter 200 mg 400 mg 800 mg Table 2: Acyclovir Peak and Trough Concentrations at Steady State 0.83 mcg/mL 1.21 mcg/mL 1.61 mcg/mL Table 2: Acyclovir Peak and Trough Concentrations at Steady State 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 tablets may be administered with or without food. The only known urinary metabolite is 9-[(carboxymethoxy)methyl]guanine. acyclovir-02 acyclovir-03 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 ADMINISTRATION ). 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 2 and 600 mg/m 2 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 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.
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Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.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.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.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) Parameter Range Plasma protein binding 9% to 33% Plasma elimination half-life 2.5 to 3.3 h Average oral bioavailability 10% to 20% Bioavailability decreases with increasing dose. 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 Parameter 200 mg 400 mg 800 mg Table 2: Acyclovir Peak and Trough Concentrations at Steady State 0.83 mcg/mL 1.21 mcg/mL 1.61 mcg/mL Table 2: Acyclovir Peak and Trough Concentrations at Steady State 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 tablets may be administered with or without food. The only known urinary metabolite is 9-[(carboxymethoxy)methyl]guanine. acyclovir-02 acyclovir-03
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Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.CONTRAINDICATIONS Acyclovir is contraindicated for patients who develop hypersensitivity to acyclovir or valacyclovir.
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.DESCRIPTION Acyclovir is a synthetic nucleoside analogue active against herpes viruses. Acyclovir tablets are a formulation for oral administration. Each 800 mg tablet of acyclovir contains 800 mg of acyclovir and the inactive ingredients colloidal silicon dioxide, croscarmellose sodium, magnesium stearate and microcrystalline cellulose. Each 400 mg tablet of acyclovir contains 400 mg of acyclovir and the inactive ingredients colloidal silicon dioxide, croscarmellose sodium, magnesium stearate and microcrystalline cellulose. Acyclovir is a white, crystalline powder with the molecular formula C 8 H 11 N 5 O 3 and a molecular weight of 225.2. 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: acyclovir structure
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.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 should be modified as shown in Table 3: Table 3. Dosage Modification for Renal Impairment Creatinine Adjusted Dosage Regimen Normal Dosage Regimen Clearance (mL/min/1.73 m 2 ) Dose (mg) Dosing Interval 200 mg every 4 hours >10 200 every 4 hours, 5x daily 0-10 200 every 12 hours 400 mg every 12 hours >10 0-10 400 200 every 12 hours every 12 hours 800 mg every 4 hours >25 800 every 4 hours, 5x daily 10-25 800 every 8 hours 0-10 800 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.
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Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.INDICATIONS AND USAGE Herpes Zoster Infections Acyclovir tablets are indicated for the acute treatment of herpes zoster (shingles). Genital Herpes Acyclovir tablets are indicated for the treatment of initial episodes and the management of recurrent episodes of genital herpes. Chickenpox Acyclovir tablets are indicated for the treatment of chickenpox (varicella).
Spl product data elements
Usually a list of ingredients in a drug product.acyclovir acyclovir ACYCLOVIR ACYCLOVIR SILICON DIOXIDE CROSCARMELLOSE SODIUM MAGNESIUM STEARATE MICROCRYSTALLINE CELLULOSE Apotex;5306
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.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 assays. 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.
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.PRINCIPAL DISPLAY PANEL - 400 mg Representative sample of the labeling (see the HOW SUPPLIED section for complete listing): PRINCIPAL DISPLAY PANEL - 400 mg BOTTLE LABEL NDC 71205-391-25 ACYCLOVIR TABLETS, USP 400 mg Rx 25 Tablets 71205-391-25
Spl unclassified section
Information not classified as belonging to one of the other fields. Approximately 40% of labeling with effective_time between June 2009 and August 2014 have information in this field.VIROLOGY 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 50 ), vary greatly depending upon a number of factors. Using plaque-reduction assays, the IC 50 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 50 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 50 of 1.35 mcg/mL. 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 therapy.
acyclovir: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.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.
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.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 ).
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 ).
Nursing mothers
Information about excretion of the drug in human milk and effects on the nursing infant, including pertinent adverse effects observed in animal offspring.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
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.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 2 and 600 mg/m 2 in pediatric patients aged 7 months to 7 years was 2.6 hours (range 1.59 to 3.74 hours).
Pediatric Use Safety and effectiveness of oral formulations of acyclovir in pediatric patients younger than 2 years of age have not been established.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)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.
Teratogenic effects
Pregnancy category A: Adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in the first trimester of pregnancy, and there is no evidence of a risk in later trimesters. Pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women. Pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus, there are no adequate and well-controlled studies in humans, and the benefits from the use of the drug in pregnant women may be acceptable despite its potential risks. Pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks (for example, if the drug is needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective). Pregnancy category X: Studies in animals or humans have demonstrated fetal abnormalities or there is positive evidence of fetal risk based on adverse reaction reports from investigational or marketing experience, or both, and the risk of the use of the drug in a pregnant woman clearly outweighs any possible benefit (for example, safer drugs or other forms of therapy are available).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.
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.HOW SUPPLIED Acyclovir Tablets, USP 400 mg are available for oral administration as white to off-white, oval, unscored tablets imprinted "Apotex Logo 5306" on one side and plain on the other side. They are supplied as follows: Bottles of 25 (71205-391-25) Bottles of 30 (71205-391-30) Bottles of 60 (71205-391-60) Bottles of 90 (71205-391-90) Store at 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature] and protect from moisture. ACYCLOVIR TABLETS, USP 400 MG Manufactured by: Manufactured for: Apotex Inc. Apotex Corp. Toronto, Ontario Weston, Florida Canada M9L 1T9 33326 Revised: February 2016 Repackaged by: Proficient Rx LP Thousand Oaks, CA 91320 Rev. 3
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Precautions
Information about any special care to be exercised for safe and effective use of the drug.PRECAUTIONS 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 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. 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 assays. 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 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 ).
Warnings
Information about serious adverse reactions and potential safety hazards, including limitations in use imposed by those hazards and steps that should be taken if they occur.WARNINGS Acyclovir 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.
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API