Acyclovir

225.2

225.20

261-685-1

X4HES1O11F

758477|645011

DTXSID1022556

C205

Crystals from methanol|Crystals from ethanol|White, crystalline powder

J05AB01|D - Dermatologicals|J - Antiinfectives for systemic use|S - Sensory organs

2933990090

115

-1.6

white powder

1.8±0.1 g/cm3

256.5-257 °C

595°C at 760 mmHg

302.4±32.3 °C

1.762

soluble in 1M HCl at 50mg/ml. soluble in water at 0.7mg/ml. Also soluble in DMSO

−20°C

5.4X10-15 mm Hg at 25 deg C (est)

Subcutaneous-rat LD50: 620 mg/kg; peritoneal-rat LD50: 860 mg/kg

Flammable; burning releases toxic nitrogen oxide fumes; drug side effects; allergic dermatitis, dreams, fantasy

2.52and 9.35

Henry's Law constant = 3.2X10-22 atm-cu m/mol at 25 °C (est)

2.52 and 9.35|pKa1= 2.27; pKa2 = 9.25

146.5 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydroxyl radical reaction rate constant = 7.94X10-11 cu cm/molecule-sec at 25 °C (est)

IRRITANT

NONH for all modes of transport

2

36/37/38-40-20/21/22

22-24/25-36-26-23

UP0791400

Xi,Xn

Treasury is ventilated, low temperature and dry; stored separately from food materials

Stable. Incompatible with strong oxidizing agents.

P201, P202, P264, P270, P280, P281, P301+P312, P302+P352, P308+P313, P312, P322, P330, P363, P405, P501

H302

Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.|SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including acyclovir, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.|The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including acyclovir sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Acyclovir sodium/

|Warning|H315 (91.14%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 93 companies from 18 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Not flammable or combustible.

Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

May cause eye irritation. May be harmful if inhaled. May cause respiratory tract irritation. May be harmful if absorbed through skin. May cause skin irritation.

Acyclovir was detected in influent and effluent of two waste water treatment plants in Germany at 1780 and 27.3-53.3 ng/L, respectively; all samples were collected in September 2009(1).

moderately

Symptoms of overdose include agitation, coma, seizures, lethargy, and precipitation in renal tubules. These symptoms are more common in patients given high doses without monitoring of fluid and electrolyte balance or reduced kidney function. In the case of an overdose, treat with symptomatic and supportive care.

Despite widespread use, there is little evidence that acyclovir when given orally causes significant liver injury. Serum enzyme levels generally do not change during oral acyclovir therapy. High dose intravenous administration of acyclovir is associated with renal dysfunction and thrombocytopenia, and occasionally with transient mild-to-moderate elevations in serum ALT levels, which have been asymptomatic and self-limited. There have rare instances of acute, clinically apparent liver injury reported that were attributed to acyclovir or valacyclovir (a prodrug of acyclovir with better oral absorption), but these have not been particularly convincing. Some degree of liver injury and even jaundice can occur during the course of herpes simplex or varicella zoster infection, and these complications could be mistaken for drug induced liver injury. Furthermore, in the reported cases, patients were receiving other medications and had other unlying comorbidities that may have been responsible for the liver injury.

Acyclovir has been used concomitantly with zidovudine ... without evidence of increased toxicity; however, neurotoxicity (profound drowsiness and lethargy), which recurred on rechallenge, has been reported in at least one patient with acquired immunodeficiency syndrome (AIDS) during concomitant therapy with the drugs. Neurotoxicity was evident within 30-60 days after initiation of IV acyclovir therapy, persisted with some improvement when acyclovir was administered orally, and resolved following discontinuance of acyclovir in this patient.|This study reports the effects of a combination of azidothymidine plus acyclovir on both pluripotent (spleen colony forming units) and committed (granulocyte-macrophage colony forming units; erythroid burst forming units) murine hemopoietic progenitors. Administration of azidothymidine alone was associated with severe hematotoxicity, as shown by the marked decrease of all the hemopoietic progenitor populations tested, that is, spleen colony forming units, granulocyte-macrophage colony forming units, and erythroid burst forming units. This, however, was followed by a prompt recovery of hemopoiesis. Administration of acyclovir alone did not modify the hematological parameters studied, whereas the combined administration of azidothymidine and acyclovir led to changes in peripheral blood cells and bone marrow hemopoietic progenitors that were, on the whole, not significantly different from those observed with azidothymidine alone. Only the decrease in spleen colony forming units was significantly more severe, but their recovery was as rapid as that of the committed progenitors. Thus, in this experimental setting, the addition of acyclovir to azidothymidine does not appear to increase the hematotoxicity of the latter.|The combined effect of acyclovir and chlorhexidine on the replication and DNA synthesis of herpes simplex virus was studied. Acyclovir and chlorhexidine showed synergism in the inhibition of the viral replication by enhancing in part the reduction of viral DNA synthesis. These data indicate that combined therapy with acyclovir and chlorhexidine might be beneficial for the control of intraoral herpetic infections.|Acyclovir may decrease the renal clearance of other drugs eliminated by active renal secretion, such as methotrexate.|For more Interactions (Complete) data for ACYCLOVIR (6 total), please visit the HSDB record page.

LD50 Mouse oral > 10,000 mg/kg|LD50 Mouse ip 1000 mg/kg

SRP: Acyclovir in elderly patients may cause CNS reactions (eg, decrease level of consciousness, speech disorders, psychotic episodes with visual and auditory hallucinations).|The drug is excreted primarily by the kidney, which may require smaller doses in patients with decreased kidney function.

Acyclovir is 9-33% protein bound in plasma.

Acyclovir's production and use as an antiviral(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that acyclovir is expected to have very high mobility in soil(SRC). Volatilization of acyclovir from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.2X10-22 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Acyclovir is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.4X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). A biodegradation half-life of 5.3 hours using activated sludge(5) suggests that biodegradation may be an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that acyclovir is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.2X10-22 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of -1.56(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Hydrolysis is not expected to be an important environmental fate process since this compound lacks groups that hydrolyze under environmental conditions(3). A biodegradationhalf-life of 5.3 hours using activated sludge(7) suggests that biodegradation may be an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), acyclovir, which has an estimated vapor pressure of 5.4X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase acyclovir may be removed from the air by wet or dry deposition(SRC). Acyclovir contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Acycloviris not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Acyclovir contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for acyclovir(SRC), using a log Kow of -1.56(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of acyclovir can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that acyclovir is expected to have very high mobility in soil.

The Henry's Law constant for acyclovir is estimated as 3.2X10-22 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that acyclovir is expected to be essentially nonvolatile from moist soil and water surfaces(2). Acyclovir is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.4X10-15 mm Hg(SRC), determined from a fragment constant method(3).

SURFACE WATER: Acyclovir was detected in rivers and streams in the Hessian Ried Region of Germany at 2.2-190 ng/L, in the Ruhr River at 2.6-8.9 ng/L and in the Ruhr River tributaries at 3.5-31 ng/L; all samples were collected in September 2009(1).

Limited data indicate that the drug is distributed into milk, generally in concentrations greater than concurrent maternal plasma concentrations, possibly via an active transport mechanism.

Occupational exposure to acyclovir may occur through dermal contact with this compound at workplaces where acyclovir is produced or used. The general population may be exposed to acyclovir via medical administration of this compound for the treatment of viral infection. (SRC)

Limited data indicate that the drug is distributed into milk, generally in concentrations greater than concurrent maternal plasma concentrations, possibly via an active transport mechanism.

An acyclovir topical cream is indicated to treat recurrent herpes labialis in immunocompetent patients 12 years and older. Acyclovir oral tablets, capsules, and suspensions are indicated to treat herpes zoster, genital herpes, and chickenpox. An acyclovir topical ointment is indicated to treat initial genital herpes and limited non-life-threatening mucocutaneous herpes simplex in immunocompromised patients. An acyclovir cream with hydrocortisone is indicated to treat recurrent herpes labialis, and shortening lesion healing time in patients 6 years and older. An acyclovir buccal tablet is indicated for the treatment of recurrent herpes labialis. An acyclovir ophthalmic ointment is indicated to treat acute herpetic keratitis.|Treatment of herpes simplex labialis|Prevention of recurrences of herpes simplex labialis, Treatment of recurrent herpes simplex labialis|Herpes simplex labialis

Acyclovir is a nucleoside analogue and antiviral agent used in therapy of herpes and varicella-zoster virus infections. Acyclovir has not been associated with clinically apparent liver injury.

Antiviral Agents

Antiviral Agents|IV acyclovir sodium is used for the treatment of initial and recurrent mucocutaneous herpes simplex virus (HSV-1 and HSV-2) infections and the treatment of varicella-zoster infections in immunocompromised adults and children; for the treatment of severe first episodes of genital herpes infections in immunocompetent individuals; and for the treatment of HSV encephalitis and neonatal HSV infections.|Acyclovir is used orally for the treatment of initial and recurrent episodes of genital herpes; for the acute treatment of herpes zoster (shingles, zoster) in immunocompetent individuals; and for the treatment of varicella (chickenpox) in immunocompetent individuals.|Oral acyclovir is indicated in the treatment of initial episodes of genital herpes infection in immunocompetent and immunocompromised patients. Parenteral acyclovir is indicated in the treatment of severe initial episodes of genital herpes infection in immunocompetent patients and in patients who are unable to take (or absorb) oral acyclovir. /Included in US product labeling/|For more Therapeutic Uses (Complete) data for ACYCLOVIR (15 total), please visit the HSDB record page.

Parenteral acyclovir therapy can cause signs and symptoms of encephalopathy. ... Acyclovir should be used with caution in patients with underlying neurologic abnormalities and in patients with serious renal, hepatic, or electrolyte abnormalities or substantial hypoxia. The drug also should be used with caution in patients who have manifested prior neurologic reactions to cytotoxic drugs or those receiving intrathecal methotrexate or interferon.|Acyclovir should be used with caution in patients receiving other nephrotoxic drugs concurrently since the risk of acyclovir-induced renal impairment and/or reversible CNS symptoms is increased in these patients. Adequate hydration should be maintained in patients receiving IV acyclovir; however, in patients with encephalitis, the recommended hydration should be balanced by the risk of cerebral edema. Because the risk of acyclovir-induced renal impairment is increased during rapid IV administration of the drug, acyclovir should be given only by slow IV infusion (over 1 hour).|There are no adequate and controlled studies to date using acyclovir in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.|Maternal Medication usually Compatible with Breast-Feeding: Acyclovir: Reported Sign or Symptom in Infant or Effect on Lactation: None. /from Table 6/|For more Drug Warnings (Complete) data for ACYCLOVIR (20 total), please visit the HSDB record page.

Eleven strains of acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) were generated from HSV-1 clinical isolates by exposure to ACV. Genotype of the thymidine kinase (TK) and DNA polymerase (pol) genes from these mutants were further analyzed. Genotypic analysis revealed four non-synonymous mutations in TK gene associated with gene polymorphism and two to three non-synonymous mutations in DNA pol gene. Seven and six strains contained at least one resistance-associated mutation at TK and DNA pol gene, respectively. Resistance-associated mutations within the TK gene consisted of 64% of non-synonymous frameshift mutations within the homopolymer region of G's and C's, and 36% of non-synonymous nucleotide substitutions of the conserved gene region (C336Y, R51W and R222H), nucleotide that produced stop codon (L288Stop) and two amino acid substitutions outside the conserved region (E39G & L208F). There were 10 non-synonymous amino acid substitutions located outside the conserved region with the unclear significance to confer resistance observed. Resistance-associated mutations in DNA pol gene include insertion of G at the homopolymer region of G's (794-797) and amino acid substitutions inside (V621S) or outside (H1228D) the conserved region. In silico analysis of the mutated TK (C336Y, R51W and L208F), and DNA pol (V621S and H1228D) suggested structural changes that might alter the stability of these proteins. However, there were several mutations with unclear significance to confer ACV-resistance identified, especially mutations outside the conserved region.|Acyclovir (ACV)-resistant (ACV(r)) mutants were generated from plaque-purified ACV-sensitive herpes simplex virus type 1 (HSV-1) by culturing the virus in Vero cells in the presence of 2-amino-7-(1,3-dihydroxy-2-propoxymethyl) purine (S2242). Three DNA polymerase (DNApol)-associated ACV(r) HSV-1 generated under ACV selection in a previous study were also included. The sensitivity of the mutants to other antivirals and their neurovirulence were determined. The treatment efficacy of ACV and ganciclovir (GCV) against ACV(r) HSV-1 infections was evaluated in mice. Amino acid substitutions were demonstrated in conserved regions II and III in DNApol in 5 of the 6 mutants, while the other substitution was located in non-conserved regions. DNApol-associated ACV(r) clones showed cross-resistance to foscarnet, penciclovir, and vidarabine but were sensitive or hypersensitive to GCV, brivudin, sorivudine, and spongothymidine. The ACV(r) clone with an N815S mutation in DNApol showed similar neurovirulence to that of the parent virus; however, those with other mutations showed attenuation. GCV was effective in the treatment of the ACV(r) clone with similar virulence to that of parent HSV-1, while ACV was less effective in mice. These results indicate the importance of the characterization of HSV-1 isolates for the proper treatment of HSV-1 infections exhibiting ACV-resistance.

Acyclovir is a nucleoside analog that inhibits the action of viral DNA polymerase and DNA replication of different herpesvirus. Acyclovir has a wide therapeutic window as overdose is rare in otherwise healthy patients.

Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)

The oral bioavailability of acyclovir is 10-20% but decreases with increasing doses. Acyclovir ointment is <0.02-9.4% absorbed. Acyclovir buccal tablets and ophthalmic ointment are minimally absorbed. The bioavailability of acyclovir is not affected by food. Acyclovir has a mean T_max of 1.1±0.4 hours, mean C_max of 593.7-656.5ng/mL, and mean AUC of 2956.6-3102.5h\*ng/mL.|The majority of acyclovir is excreted in the urine as unchanged drug. 90-92% of the drug can be excreted unchanged through glomerular filtration and tubular secretion. <2% of the drug is recovered in feces and <0.1% is expired as CO₂.|The volume of distribution of acyclovir is 0.6L/kg.|The renal clearance of acyclovir is 248mL/min/1.73m². The total clearance in neonates if 105-122mL/min/1.73m².|Absorption of acyclovir from the GI tract is variable and incomplete. 15-30% of an oral dose of the drug is absorbed. Some data suggest that GI absorption of acyclovir may be saturable; in a crossover study in which acyclovir was administered orally to healthy adults as 200 mg capsules, 400 mg tablets, or 800 mg tablets 6 times daily, the extent of absorption decreased with increasing dose, resulting in bioavailabilities of 20, 15, or 10%, respectively. ... This decrease in bioavailability appears to be a function of increasing dose, not differences in dosage forms. In addition, steady-state peak and trough plasma acyclovir concentrations were not dose proportional over the oral dosing range of 200-800 mg 6 times daily, averaging 0.83 and 0.46, 1.21 and 0.63, or 1.61 and 0.83 ug/ml for the 200, 400, or 800 mg dosing regimens, respectively. Peak plasma concentrations usually occur within 1.5-2.5 hours after oral administration.|In a multiple dose study in neonates up to 3 months of age, IV infusion over 1 hour of 5, 10, or 15 mg/kg of acyclovir every 8 hours resulted in mean steady state peak serum concentrations of 6.8, 13.9, and 19.6 ug/ml, respectively, and mean steady state trough serum concentration of 1.2, 2.3, and 3.1 ug/ml, respectively. In another multiple dose study in pediatric patients, IV infusion over 1 hour of 250 or 500 mg/sq m of acyclovir every 8 hours resulted in mean steady state peak serum concentrations of 10.3 and 20.7 ug/ml, respectively.|Acyclovir is widely distributed into body tissues and fluids including the brain, kidney, saliva, lung, liver, muscle, spleen, uterus, vaginal mucosa and secretions, cerebrospinal fluid, and herpetic vesicular fluid. The drug also is distributed into semen, achieving concentrations about 1.4 and 4 times those in plasma during chronic oral therapy at dosages of 400 mg and 1 g daily, respectively. The apparent volume of distribution of acyclovir is reported to be 32.4-61.8 liter/1.73 sq m in adults and 28.8, 31.6, 42, or 51.2-53.6 liter/1.73 sq m in neonates up to 3 months of age, children 1-2 years; 2-7 years; or 7-12 years of age, respectively.|Acyclovir crosses the placenta. Limited data indicate that the drug is distributed into milk, generally in concentrations greater than concurrent maternal plasma concentrations, possibly via an active transport mechanism.|For more Absorption, Distribution and Excretion (Complete) data for ACYCLOVIR (13 total), please visit the HSDB record page.

Acyclovir is <15% oxidized to 9-carboxymethoxymethylguanine by alcohol dehydrogenase and aldehyde dehydrogenase and 1% 8-hydroxylated to 8-hydroxy-acyclovir by aldehyde oxidase. Acyclovir is becomes acyclovir monophosphate due to the action of viral thymidine kinase. Acyclovir monophosphate is converted to the diphosphate form by guanylate kinase. Acyclovir diphosphate is converted to acyclovir triphosphate by nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase.|Acyclovir is metabolized partially to 9-carboxymethoxymethylguanine and minimally to 8-hydroxy-9-(2-hydroxyethoxymethyl)guanine. In vitro, acyclovir also is metabolized to acyclovir monophosphate, diphosphate, and triphosphate in cells infected with herpes viruses, principally by intracellular phosphorylation of the drug by virus coded thymidine kinase and several cellular enzymes.

The clearance of acyclovir varies from 2.5-3 hours depending on the creatinine clearance of the patient. The plasma half life of acyclovir during hemodialysis is approximately 5 hours. The mean half life in patients from 7 months to 7 years old is 2.6 hours.|Plasma concentrations of acyclovir appear to decline in a biphasic manner. In adults with normal renal function, the half-life of acyclovir in the initial phase averages 0.34 hours and the half-life in the terminal phase averages 2.1-3.5 hours. In adults with renal impairment, both half-life in the initial phase and half-life in the terminal phase may be prolonged, depending on the degree of renal impairment. In a study in adults with anuria, the half-life in the initial phase of acyclovir averaged 0.71 hours. In several studies, the half-life in the terminal phase of acyclovir averaged 3,3.5, or 19.5 hours in adults with creatinine clearances of 50-80 or 15-50 ml/minute per 1.73 sq m or with anuria, respectively. In patients undergoing hemodialysis, the half-life in the terminal phase of acyclovir during hemodialysis averaged 5.4-5.7 hours.|In neonates, the half-life of acyclovir depends principally on the maturity of renal mechanisms for excretion as determined by gestational age, chronologic age, and weight. In children older than 1 year of age, the half-life of the drug appears to be similar to that of adults. The half-life in the terminal phase averages 3.8-4.1, 1.9, 2.2-2.9, or 3.6 hours in neonates up to 3 months of age, children 1-2 years, 2-12 years, or 12-17 years of age, respectively.

Acyclovir is becomes acyclovir monophosphate due to the action of viral thymidine kinase. Acyclovir monophosphate is converted to the diphosphate form by guanylate kinase. Acyclovir diphosphate is converted to acyclovir triphosphate by nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase. Acyclovir triphosphate has higher affinity for viral DNA polymerase than cellular DNA polymerase and incorporates into the DNA where the missing 2' and 3' carbons causes DNA chain termination. In other cases acyclovir triphosphate competes so strongly for viral DNA polymerase that other bases cannot associate with the enzyme, inactivating it.|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 is 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 adn into triphosphate by a number of cellualr enzymes. In vitro, acyclovir triphosphate stops replication of herpes viral DNA.|Acyclovir inhibits viral DNA synthesis ... . Its selectivity of action depends on interaction with two distinct viral proteins. Cellular uptake and initial phosphorylation are facilitated by HSV thymidine kinase. The affinity of acyclovir for HSV thymidine kinase is about 200-fold greater than for the mammalian enzyme. Cellular enzymes convert the monophosphate to acyclovir triphosphate, which is present in 40- to 100-fold higher concentrations in HSV-infected than in uninfected cells, and competes for endogenous deoxyguanosine triphosphate (dGTP). The immunosuppressive agent mycophenolate mofetil potentiates the antiherpes activity of acyclovir and related agents by depleting intracellular dGTP pools. Acyclovir triphosphate competitively inhibits viral DNA polymerases and, to a much smaller extent, cellular DNA polymerases. Acyclovir triphosphate also is incorporated into viral DNA, where it acts as a chain terminator because of the lack of 3'-hydroxyl group. By a mechanism termed suicide inactivation, the terminated DNA template containing acyclovir binds the enzyme and leads to irreversible inactivation of the DNA polymerase.|The concentration of the endogenous neurotoxin quinolinic acid (QA) is increased in the central nervous system of mice with herpes simplex encephalitis. /The authors/ have previously shown that the antiherpetic agent acyclovir (AC) has the ability to reduce QA-induced neuronal damage in rat brain, by attenuating lipid peroxidation. The mechanism by which QA induces lipid peroxidation includes the enhancement of the iron (Fe)-mediated Fenton reaction and the generation of free radicals, such as the superoxide anion (O(2)(-)). Thus, the present study determined whether AC has the ability to reduce Fe(2+)-induced lipid peroxidation, O(2)(-) generation and QA-induced superoxide anion generation, and to bind free Fe. O(2)(-) and Fe(2+) are also cofactors of the enzymes, indoleamine-2,3-dioxygenase (IDO) and 3-hydroxyanthranilate-3,4-dioxygenase (3-HAO) respectively. These enzymes catalyse steps in the biosynthesis of QA; thus, the effect of AC on their activity was also investigated. AC significantly attenuates Fe(2+)-induced lipid peroxidation and O(2)(-) generation. AC reduces O(2)(-) generation in the presence of QA and strongly binds Fe(2+) and Fe(3+). It also reduces the activity of both IDO and 3-HAO, which could be attributed to the superoxide anion scavenging and iron binding properties, respectively, of this drug.

There are no clinical data to guide management of acyclovir overdose. Treatment is supportive. Adequate urine flow should be maintained to prevent precipitation of acyclovir in the renal tubules. Hemodialysis is generally not recommended because even very large overdoses do not usually result in major toxicity.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|For more Antidote and Emergency Treatment (Complete) data for ACYCLOVIR (7 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ In a controlled study in men receiving chronic oral acyclovir (400 mg or 1 g daily) therapy, there was no evidence of clinically important effects on sperm count, motility, or morphology during 6 months of therapy and 3 months of post-treatment follow-up.|/HUMAN EXPOSURE STUDIES/ Acyclovir is used to treat herpes infections in preterm and term infants; however, the influence of maturation on drug disposition and dosing requirements is poorly characterized in this population. /The authors/ administered intravenous acyclovir to preterm and term infants <31 days postnatal age and collected plasma samples. /Researchers/ performed a population pharmacokinetic analysis. The primary pharmacodynamic target was acyclovir concentration >/= 3 mg/L for >/=50% of the dosing interval. The final model was simulated using infant data from a clinical database. The analysis included 28 infants (median 30 weeks gestation). Acyclovir pharmacokinetics was described by a 1-compartment model: clearance (L/hr/kg) = 0.305 x (postmenstrual age (PMA)/31.3 weeks). This equation predicts a 4.5-fold increase in clearance from 25 to 41 weeks PMA. With proposed dosing, the pharmacodynamic target was achieved in 91% of infants: 20 mg/kg every 12 hr in infants <30 weeks PMA; 20 mg/kg every 8 hours in infants 30 to <36 weeks PMA; 20 mg/kg every 6 hr in infants 36-41 weeks PMA. Acyclovir clearance increased with infant maturation. A dosing strategy based on PMA accounted for developmental changes in acyclovir disposition to achieve the surrogate pharmacodynamic target in the majority of infants.|/SIGNS AND SYMPTOMS/ Overdoses involving ingestions 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.|/SIGNS AND SYMPTOMS/ Aciclovir, like other anti-HIV nucleoside analogues, has been associated with a rare (1 in 10(+5) to 1 in 10(+6) patients) idiosyncratic syndrome of a progressive increase in the activity of liver enzymes in serum, fulminating hepatic steatosis and lactic acidosis. Failure to discontinue the drug can lead to death.|For more Human Toxicity Excerpts (Complete) data for ACYCLOVIR (16 total), please visit the HSDB record page.

9-((2-Hydroxyethoxy)methyl)guanine

Topical: Ointment: 5%, Zovirax (Biovail)|Oral: Capsules: 200 mg Zovirax (with parabens), (GlaxoSmithKline); Suspension: 200 mg/5mL Acyclovir Suspension (with parabens), (Alpharma), Zovirax (with glycerin parabens and sorbitol), (GlaxoSmithKline); Tablets: 400 mg Zovirax (with povidone), GlaxoSmithKline, 800 mg Zovirax (with povidone), GlaxoSmithKline.|Acyclovir sodium: Parenteral: For injection, concentrate, for IV infusion only: 25 mg (of acyclovir) per mL (500 mg, 1 g) Acyclovir Sodium Injection (Mayne), 50 mg (of acyclovir) per mL (500 mg, 1 g) Acyclovir Sodium Injection (American Pharmaceutical Partners), For Injection, for IV infusion only: 500 mg (of acyclovir) Acyclovir Sodium for Injection (Abbott, American Pharmaceutical Partners, Bedford), Zovirax (GlaxoSmithKline), 1 g (of acyclovir) Acyclovir Sodium for Injection (Abbott, Bedford), Zovirax (GlaxoSmithKline).

Determination of acyclovir in human serum by high-performance liquid chromatography. Detection limit of 0.3 ug/ml.|Determination of acyclovir in human plasma and urine with ion-pair high performance liquid chromatography with ultraviolet detection at a wavelength of 254 nm. The min detectable quantity and concn were 5 ug and 0.5 ug/ml, resp, and the recovery was > 94%.

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