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Zovirax Ointment (Acyclovir)
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Pharmacology
Acyclovir, an acyclic nucleoside analog, is a substrate specific for herpesvirus-specified thymidine kinase. It inhibits replication of these viruses. Normal cellular thymidine kinase does not effectively utilize acyclovir as a substrate. Herpes-virus-specified thymidine kinase transforms acyclovir to its monophosphate, which is then transformed by cellular enzymes to acyclovir diphosphate and acyclovir triphosphate. Acyclovir triphosphate is both an inhibitor of, and a substrate for, herpesvirus-specified DNA polymerase. Although the cellular a-DNA polymerase in infected cells may also be inhibited by acyclovir triphosphate, this occurs only at concentrations of acyclovir triphosphate which are higher than those which inhibit the herpesvirus-specified DNA polymerase. Acyclovir is preferentially taken up and selectively converted to its active form by herpesvirus-infected cells. Thus, acyclovir has a very much lower toxic potential for normal uninfected cells because: 1)less is taken up; 2)less is converted to the active form; 3)cellular a-DNA polymerase has a lower affinity for the active form of the drug. A combination of the thymidine kinase specificity, inhibition of DNA polymerase and premature termination of DNA synthesis results in inhibition of herpesvirus replication. No effect on latent non-replicating virus has been demonstrated. Inhibition of the virus reduces the period of viral shedding, limits the degree of spread and level of pathology, and thereby facilitates healing.
Acyclovir, an acyclic nucleoside analog, is a substrate specific for herpesvirus-specified thymidine kinase. It inhibits replication of these viruses. Normal cellular thymidine kinase does not effectively utilize acyclovir as a substrate. Herpes-virus-specified thymidine kinase transforms acyclovir to its monophosphate, which is then transformed by cellular enzymes to acyclovir diphosphate and acyclovir triphosphate. Acyclovir triphosphate is both an inhibitor of, and a substrate for, herpesvirus-specified DNA polymerase. Although the cellular a-DNA polymerase in infected cells may also be inhibited by acyclovir triphosphate, this occurs only at concentrations of acyclovir triphosphate which are higher than those which inhibit the herpesvirus-specified DNA polymerase. Acyclovir is preferentially taken up and selectively converted to its active form by herpesvirus-infected cells. Thus, acyclovir has a very much lower toxic potential for normal uninfected cells because: 1)less is taken up; 2)less is converted to the active form; 3)cellular a-DNA polymerase has a lower affinity for the active form of the drug. A combination of the thymidine kinase specificity, inhibition of DNA polymerase and premature termination of DNA synthesis results in inhibition of herpesvirus replication. No effect on latent non-replicating virus has been demonstrated. Inhibition of the virus reduces the period of viral shedding, limits the degree of spread and level of pathology, and thereby facilitates healing.
Indications
Acyclovir, An Acyclic Nucleoside Analog, Is A Substrate Specific For Herpesvirus-specified Thymidine Kinase. It Inhibits Replication Of These Viruses. Normal Cellular Thymidine Kinase Does Not Effectively Utilize Acyclovir As A Substrate. Herpes-virus-specified Thymidine Kinase Transforms Acyclovir To Its Monophosphate, Which Is Then Transformed By Cellular Enzymes To Acyclovir Diphosphate And Acyclovir Triphosphate. Acyclovir Triphosphate Is Both An Inhibitor Of, And A Substrate For, Herpesvirus-specified DNA Polymerase. Although The Cellular A-DNA Polymerase In Infected Cells May Also Be Inhibited By Acyclovir Triphosphate, This Occurs Only At Concentrations Of Acyclovir Triphosphate Which Are Higher Than Those Which Inhibit The Herpesvirus-specified DNA Polymerase. Acyclovir Is Preferentially Taken Up And Selectively Converted To Its Active Form By Herpesvirus-infected Cells. Thus, Acyclovir Has A Very Much Lower Toxic Potential For Normal Uninfected Cells Because: 1)less Is Taken Up; 2)less Is Converted To The Active Form; 3)cellular A-DNA Polymerase Has A Lower Affinity For The Active Form Of The Drug. A Combination Of The Thymidine Kinase Specificity, Inhibition Of DNA Polymerase And Premature Termination Of DNA Synthesis Results In Inhibition Of Herpesvirus Replication. No Effect On Latent Non-replicating Virus Has Been Demonstrated. Inhibition Of The Virus Reduces The Period Of Viral Shedding, Limits The Degree Of Spread And Level Of Pathology, And Thereby Facilitates Healing.
Acyclovir, An Acyclic Nucleoside Analog, Is A Substrate Specific For Herpesvirus-specified Thymidine Kinase. It Inhibits Replication Of These Viruses. Normal Cellular Thymidine Kinase Does Not Effectively Utilize Acyclovir As A Substrate. Herpes-virus-specified Thymidine Kinase Transforms Acyclovir To Its Monophosphate, Which Is Then Transformed By Cellular Enzymes To Acyclovir Diphosphate And Acyclovir Triphosphate. Acyclovir Triphosphate Is Both An Inhibitor Of, And A Substrate For, Herpesvirus-specified DNA Polymerase. Although The Cellular A-DNA Polymerase In Infected Cells May Also Be Inhibited By Acyclovir Triphosphate, This Occurs Only At Concentrations Of Acyclovir Triphosphate Which Are Higher Than Those Which Inhibit The Herpesvirus-specified DNA Polymerase. Acyclovir Is Preferentially Taken Up And Selectively Converted To Its Active Form By Herpesvirus-infected Cells. Thus, Acyclovir Has A Very Much Lower Toxic Potential For Normal Uninfected Cells Because: 1)less Is Taken Up; 2)less Is Converted To The Active Form; 3)cellular A-DNA Polymerase Has A Lower Affinity For The Active Form Of The Drug. A Combination Of The Thymidine Kinase Specificity, Inhibition Of DNA Polymerase And Premature Termination Of DNA Synthesis Results In Inhibition Of Herpesvirus Replication. No Effect On Latent Non-replicating Virus Has Been Demonstrated. Inhibition Of The Virus Reduces The Period Of Viral Shedding, Limits The Degree Of Spread And Level Of Pathology, And Thereby Facilitates Healing.
Contraindications
Hypersensitivity or chemical intolerance to any of the components of the formulation, such as polyethylene glycol.
Hypersensitivity or chemical intolerance to any of the components of the formulation, such as polyethylene glycol.
Safety Information / Warning
5% is intended for topical use only and should not be used in the eye or on mucous membranes.
5% is intended for topical use only and should not be used in the eye or on mucous membranes.
Precautions
General: The recommended dosage, frequency of application and duration of treatment should not be exceeded.
There exist no data, at this time, which demonstrate that the use of acyclovir ointment 5% will prevent transmission of infection to other persons.
Since most cutaneous herpes simplex virus infections result from reactivation of latent virus, is is unlikely that acyclovir ointment 5% will prevent recurrence of infections when applied in the absence of signs and symptoms. Acyclovir ointment 5% should not be applied in an attempt to prevent recurrences; application should commence only at the earliest prodromal sign of disease onset.
Although clinically significant viral resistance associated with the use of acyclovir ointment 5% has not been observed, this possibility exists.
Lactation: Acyclovir, when given systemically, is known to be excreted into human milk. Although evidence suggests that absorption of acyclovir through the skin is minimal, caution should be exercised when acyclovir is administered to a nursing mother.
Pregnancy: All animal studies carried out to date on reproduction and teratology studies have been negative in general. However, in a non-standard test in rats, there were fetal abnormalities such as head and tail anomalies, and maternal toxicity; since such studies are not always predictive of human response, acyclovir should not be used during pregnancy unless the physician feels the potential benefit justifies the risk of possible harm to the fetus. The potential for high concentrations of acyclovir to cause chromosome breaks in vitro should be taken into consideration in making this decision.
A postmarketing acyclovir pregnancy registry has documented pregnancy outcomes in women exposed to any formulations of acyclovir. The registry findings have not shown an increase in the number of birth defects amongst acyclovir-exposed subjects compared with the general population, and any birth defects showed no uniqueness or consistent pattern to suggest a common cause.
Children: Safety of use of acyclovir ointment 5% in children has not been established.
Drug Interactions : Clinical experience has identified no known interactions resulting from topical or systemic administration of other drugs concomitantly with acyclovir ointment 5%.
General: The recommended dosage, frequency of application and duration of treatment should not be exceeded.
There exist no data, at this time, which demonstrate that the use of acyclovir ointment 5% will prevent transmission of infection to other persons.
Since most cutaneous herpes simplex virus infections result from reactivation of latent virus, is is unlikely that acyclovir ointment 5% will prevent recurrence of infections when applied in the absence of signs and symptoms. Acyclovir ointment 5% should not be applied in an attempt to prevent recurrences; application should commence only at the earliest prodromal sign of disease onset.
Although clinically significant viral resistance associated with the use of acyclovir ointment 5% has not been observed, this possibility exists.
Lactation: Acyclovir, when given systemically, is known to be excreted into human milk. Although evidence suggests that absorption of acyclovir through the skin is minimal, caution should be exercised when acyclovir is administered to a nursing mother.
Pregnancy: All animal studies carried out to date on reproduction and teratology studies have been negative in general. However, in a non-standard test in rats, there were fetal abnormalities such as head and tail anomalies, and maternal toxicity; since such studies are not always predictive of human response, acyclovir should not be used during pregnancy unless the physician feels the potential benefit justifies the risk of possible harm to the fetus. The potential for high concentrations of acyclovir to cause chromosome breaks in vitro should be taken into consideration in making this decision.
A postmarketing acyclovir pregnancy registry has documented pregnancy outcomes in women exposed to any formulations of acyclovir. The registry findings have not shown an increase in the number of birth defects amongst acyclovir-exposed subjects compared with the general population, and any birth defects showed no uniqueness or consistent pattern to suggest a common cause.
Children: Safety of use of acyclovir ointment 5% in children has not been established.
Drug Interactions : Clinical experience has identified no known interactions resulting from topical or systemic administration of other drugs concomitantly with acyclovir ointment 5%.
Side Effects / Adverse Effects
Because ulcerated genital lesions are characteristically tender and sensitive to any contact or manipulation, patients may experience discomfort upon application of ointment. In the controlled clinical trials, mild pain (including transient burning and stinging) was reported by 103 (28.3%) of 364patients treated with acyclovir ointment 5% and by 115(31.1%) of 370patients treated with placebo; treatment was discontinued in 2of these patients. Other local reactions among acyclovir-treated patients included pruritus in 15(4.1%), rash in 1(0.3%) and vulvitis in 1(0.3%). Among the placebo-treated patients, pruritus was reported by 17(4.6%) and rash by 1(0.3%).
In all studies, there was no significant difference between the drug and placebo group in the rate or type of reported adverse reactions.
There have been very rare reports of immediate hypersensitivity reactions including angioedema with topical acyclovir.
Because ulcerated genital lesions are characteristically tender and sensitive to any contact or manipulation, patients may experience discomfort upon application of ointment. In the controlled clinical trials, mild pain (including transient burning and stinging) was reported by 103 (28.3%) of 364patients treated with acyclovir ointment 5% and by 115(31.1%) of 370patients treated with placebo; treatment was discontinued in 2of these patients. Other local reactions among acyclovir-treated patients included pruritus in 15(4.1%), rash in 1(0.3%) and vulvitis in 1(0.3%). Among the placebo-treated patients, pruritus was reported by 17(4.6%) and rash by 1(0.3%).
In all studies, there was no significant difference between the drug and placebo group in the rate or type of reported adverse reactions.
There have been very rare reports of immediate hypersensitivity reactions including angioedema with topical acyclovir.
Overdose
ymptoms and Treatment: Overdosage by topical application of acyclovir ointment 5% is unlikely because of limited transcutaneous absorption.
ymptoms and Treatment: Overdosage by topical application of acyclovir ointment 5% is unlikely because of limited transcutaneous absorption.
Recommended Dosage
Apply acyclovir ointment 5% liberally to the affected area 4to 6times daily for up to 10days. A sufficient quantity of ointment should be applied to adequately cover all lesions. A finger cot or rubber glove should be used while applying acyclovir in order to prevent: (1)autoinoculation of other body sites or (2)transmission of infection to other persons. Therapy should be initiated as early as possible following onset of signs and symptoms.
Apply acyclovir ointment 5% liberally to the affected area 4to 6times daily for up to 10days. A sufficient quantity of ointment should be applied to adequately cover all lesions. A finger cot or rubber glove should be used while applying acyclovir in order to prevent: (1)autoinoculation of other body sites or (2)transmission of infection to other persons. Therapy should be initiated as early as possible following onset of signs and symptoms.
Supplied / Packaging
Each g contains: acyclovir 50mg in a polyethylene glycol base. Tubes of4, 15and 30g. Store between 15to25°C and keep dry.
Each g contains: acyclovir 50mg in a polyethylene glycol base. Tubes of4, 15and 30g. Store between 15to25°C and keep dry.
