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Acyclovir☆
Acyclovir☆ D Mondal, Tulane University Health Sciences Center, New Orleans, LA, United States ã 2016 Elsevier Inc. All rights reserved.
Introduction Basic Chemistry Human Pharmacokinetics Pharmacokinetic Properties Mechanism of Action Target Name(s) Indications Contraindications Side Effects Pharmacokinetics Major Drug Interactions Pre-Clinical and Clinical Research Resistance References
Name of the Clinical Form Related Names Source: EMTREE
Chemical Names CAS Number
1 1 2 2 3 3 3 3 3 4 4 4 4 5
Acyclovir or acycloguanosine • Acyclovir; Zovirax (GlaxoWellcome) www.rxlist.com (Zovirax®) 2-Amino-9-(2-hydroxy-ethoxymethyl)-1,9-dihydro-purin-6-one; 2-Amino-9-(2-hydroxy-ethoxymethyl)-1,9-dihydropurin-6-one; Zovirax (trade); aciclovir; 2 amino 6 hydroxy 9 (2 hydroxyethoxymethyl)purine; 9 (2 hydroxyethoxymethyl) guanine; 9 [(2 hydroxyethoxy)methyl]guanine; acg; acic; acicloftal; aciclostad; aciclovir sodium; activir; acv; acycloguanosine; acyclovidar; bw 248u; bw248u; cicloviran; cycloviran; genvir; guanine, 9 (2 hydroxyethoxymethyl); herpetad; herpofug; virolex; viropump; virupos; viruseen; wellcome 248 u; zaclovir; zovirax; zyclir 2-amino-1,9-dihydro9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one 59277-89-3
Introduction Intravenous (i.v.) acyclovir is the drug of choice for treatment of serious infections caused by herpes simplex virus (HSV) or varicella-zoster virus (VZV) (Safrin, 2012; Razonable, 2011). Intravenous aciclovir is effective to treat severe medical conditions caused by different species of herpes virus family includes severe localized infections of herpes virus, severe genital herpes, chickenpox and encephalitis. It is also effective in systemic or traumatic herpes infections, eczema herpeticum and Herpes simplex meningitis. A guanosine analog, it was the first anti-viral drug to specifically target a viral enzyme, DNA polymerase, inhibiting DNA chain elongation. Acyclovir is activated intracellularly by the viral thymidine kinase to the monophosphate derivative, which is then converted by the cellular enzymes to the diphosphate and then to the triphosphate analog, which inhibits viral DNA polymerase. Common side effects include nausea and diarrhea. Potentially serious side effects include kidney problems and low platelets. Greater care is recommended in those with poor liver or kidney function. It is generally considered safe for use in pregnancy with no harms having been observed. It is safe during breastfeeding (Hamilton, 2015). Viral resistance can occur due to mutations in viral thymidine kinase gene.
Basic Chemistry Acyclovir is a guanosine analog containing an acyclic side chain in place of ribose.
☆ Change History: April 2016. D Mondal updated Abstract, extensively changed the content format, included new research findings, and included new references.
Reference Module in Biomedical Sciences
http://dx.doi.org/10.1016/B978-0-12-801238-3.99396-6
1
2
Acyclovir
Chemical structure Structure
Comments
Acyclovir is a synthetic nucleoside analog. It is available in capsules, tablets and suspension. Acyclovir sodium is used for injection. C8 H11 N5 O3
Chemical formula Properties Physical Properties Molecular Weight Solubility
Acyclovir is a white crystalline powder. 225.207 2.5 mg mL1 in water at 37 C for acyclovir and >100 mg mL1 for acyclovir sodium.
Ionization constant Value pKa pKa
Salt
Conditions
Reference
2.2 9.25
Comments
Physician’s Desk Reference (2000) Physician’s Desk Reference (2000)
Human Pharmacokinetics Can be given orally, intravenously or topically. Low bioavailability (15–20%), but sufficient to achieve therapeutic plasma levels. Renal excretion with half-life of 2.5 h (15% metabolized, 85% excreted unchanged). The half-life and total body clearance of acyclovir are dependent on renal function. Acyclovir plasma concentrations are higher in geriatric patients as compared to young subjects due to changes in renal function. Thus, a dose reduction may be necessary in the elderly. Only 50% of the plasma levels of acyclovir penetrate the cerebrospinal fluid (CSF), hence dose escalation is required for the treatment of HSV encephalitis.
Pharmacokinetic Properties
Absorption Bioavailability
Distribution Volume of distribution Plasma protein binding Metabolism Plasma half-life Bio half-life Clearance
Routes of elimination
Value
Units
Prep. and route of admin.
10–20
%
p.o.
Physician’s Desk Reference (2000)
9–33
%
p.o. or i.v.
Physician’s Desk Reference (2000)
2.5–3.3
h
p.o. or i.v.
Drug Facts and Comparisons (2001)
62–91
%
p.o. or i.v.
Reference
Comments
Drug Facts and The only known urinary metabolite of acyclovir is 9-[(carboxymethoxy) Comparisons methyl]guanine which accounts for 14.1% of the dose in patients with (2001) normal renal function (Baselt, 2008)]. Renal excretion of the unchanged drug is the major route of elimination.
Acyclovir
3
Mechanism of Action Acyclovir is selectively activated by the HSV and VZV thymidine kinase to the monophosphate form. The monophosphate is converted into diphosphate by cellular guanylate kinase and into triphosphate by cellular kinases. Viral DNA replication is blocked by the triphosphate form by competitive inhibition of viral DNA polymerase. The incorporation of acyclovir triphosphate into the growing viral DNA chain results in termination of viral DNA synthesis. Not effective against CMV infections because CMV TK does not activate acyclovir.
Target Name(s)
• •
Viral thymidine kinases Viral DNA polymerase
Indications Effective against HSV-2 (genital), HSV encephalitis and Varicella-Zoster. Acyclovir can be used orally, intravenously, or topically (in creams). A Drug of choice for parenteral treatment of herpes zoster (shingles), oral therapy for recurrent genital herpes (HSV-2). Also indicated for HSV encephalitis and Varicella zoster (chickenpox). Acyclovir is used for the treatment of initial episodes, and the management of recurrent episodes, of genital herpes (HSV-2), and HSV encephalitis. The greater antiviral activity of acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the viral thymidine kinase. It is not effective against CMV infections because CMV-thymidine kinase does not activate the drug. A valine ester of acyclovir, Valacyclovir, acts as a prodrug and substantially increases the oral bioavailability over Acyclovir.
Value
Units
Prep. and route of admin.
Reference
Comments
Treatment of initial HSV and VZV infections. p.o. Dosage 200–800 mg 4 h1
Physician’s Dosing interval is dependent on the patient’s creatinine clearance rate Desk and renal function. Reference (2000) Treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) and VZV infections in immunocompromised patients, neonatal herpes infections, and for the treatment of herpes encephalitis. Dosage 5 mg kg1 8 h1 i.v. For cutaneous HSV infections in immunocompromised adults and for 7 days adolescents. Dosing interval is dependent on the patient’s creatinine clearance rate. Treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) and VZV infections in immunocompromised patients, neonatal herpes infections and for the treatment of herpes encephalitis. Dosage 10 mg kg1 8 h1 i.v. Pediatrics (<12 years). Dosing interval is dependant on the patient’s for 7 days creatinine clearance rate. Treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) and VZV infections in immunocompromised patients, neonatal herpes infections, and for the treatment of herpes encephalitis. Dosage 10 or 20 mg kg1 8 h1 i.v. For HSV encephalitis. Dosing interval is dependent on the patient’s for 10 days creatinine clearance rate.
Contraindications Hypersensitivity or chemical intolerance. Acyclovir is contraindicated in those who are hypersensitivity to acyclovir or valacyclovir.
Side Effects Inflammation or phlebitis, malaise, nausea and headache. Encephalopathic changes and renal function impairment may occur. Acyclovir is generally well tolerated. Adverse reactions (when given parenterally) occur in 3–5% of patients and include inflammation or phlebitis at the injection site, transient elevations of serum creatinine, nausea, and vomiting. Oral acyclovir may be associated with malaise, nausea, gastrointestinal problems, rash, and headache. The intravenous use of acyclovir has been associated (rarely) with encephalopathy, tremors, hallucinations, seizures, and coma. Renal dysfunctions can occur with long term use. Another serious complication with long-term acyclovir is the development of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP/HUS). Encephalopathic changes and renal function impairment may also occur.
4
Acyclovir
Acyclovir pharmacokinetic characteristics (range)
Table 1 Parameter
Range
Plasma protein binding Plasma elimination half-life Average oral bioavailability
9–33% 2.5–3.3 h 10–20%a
a
Bioavailability decreases with increasing dose.
Table 2
Acyclovir peak and trough concentrations at steady state
Parameter
200 mg
400 mg 1
CSS max CSS trough
0.83 mcg mL 0.46 mcg mL1
800 mg 1
1.21 mcg mL 0.63 mcg mL1
1.61 mcg mL1 0.83 mcg mL1
Pharmacokinetics Acyclovir can be given orally, i.v. or topically. It has low bioavailability (15–20%), but sufficient to achieve therapeutic plasma levels. Renal excretion with half-life of 2.5 h (15% metabolized, 85% excreted unchanged) Only 50% of plasma levels penetrate into the CSF, hence dose escalation is required for HSV encephalitis. 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.
•
In one multiple-dose, crossover study in healthy subjects (n ¼ 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. There was no effect of food on the absorption of acyclovir (n ¼ 6); therefore, acyclovir capsules and tablets may be administered with or without food. The only known urinary metabolite is 9-[(carboxymethoxy) methyl]guanine.
Major Drug Interactions
Agent name
Mode of interaction
Probenecid Zidovudine Cimetidine
Probenecid may inhibit the renal excretion of acyclovir (Bach, 1987). As a nucleoside analog, acyclovir may increase the toxic effects of zidovudine. Antihistamine (H2-receptor antagonist). Decrease Cyp450 mediated degradation of acyclovir and valacyclovir
Pre-Clinical and Clinical Research
• • • •
In dogs, 50 mg kg1 day1 of acyclovir given orally for one month, which is 1–3 times human dose, did not show testicular abnormalities, although at higher doses both testicular atrophy and aspermatogenesis were observed. Because acyclovir is detected in breast milk, administration to a nursing mother should be done with caution. Double-blind, placebo-controlled studies have demonstrated that orally administered acyclovir significantly reduced the duration of acute infection and duration of lesion healing. 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. 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.
Resistance
•
Viral Resistance can occur due to mutations in viral TK enzyme (Piret and Boivin, 2011).
Acyclovir
5
References Bach MC (1987) Possible drug interaction during therapy with azidothymidine and acyclovir for AIDS. New England Journal of Medicine 316(9): 547. http://dx.doi.org/10.1056/ NEJM198702263160912. PMID 3468354. Baselt RC (2008) Disposition of toxic drugs and chemicals in man, 8th edn. Foster City, CA: Biomedical Publications. ISBN 9780962652370. Cada DJ (2001) Drug facts and comparisons antiviral agents. Drug facts and comparisons, 5th edn. St. Louis, MI: A Wolters Kluwer Company. 846–848. Hamilton R (2015) Tarascon pocket pharmacopoeia 2015 deluxe lab-coat edition. Burlington, MA: Jones & Bartlett Learning. ISBN 9781284057560. p. 59. Piret J and Boivin G (2011) Resistance of herpes simplex viruses to nucleoside analogues: Mechanisms, prevalence, and management. Antimicrobial Agents and Chemotherapy 55(2): 459–472. http://dx.doi.org/10.1128/AAC.00615-10 PMC 3028810, PMID 21078929. Razonable RR (2011) Antiviral drugs for viruses other than human immunodeficiency virus. Mayo Clinic Proceedings 86(10): 1009–1026. http://dx.doi.org/10.4065/mcp.2011.0309 PMC 3184032, PMID 21964179. Sifton DW (2000) Physician’s desk reference, Physicians’ desk reference, 54th edn. Montvale, NJ: Medical Economics Company. Safrin S (2012) Antiviral agents. In: Katzung BG, Masters SB, and Trevor AJ (eds.) Basic and clinical pharmacology, 12th edn, New York, NY: McGraw-Hill/Lange (Access-Medicine) (Chapter 49).
Relevant website ACYCLOVIR – acyclovir capsule, ACYCLOVIR – acyclovir tablet.
Introduction Basic Chemistry Human Pharmacokinetics Pharmacokinetic Properties Mechanism of Action Target Name(s) Indications Contraindications Side Effects Pharmacokinetics Major Drug Interactions Pre-Clinical and Clinical Research Resistance References
Name of the Clinical Form Related Names Source: EMTREE
Chemical Names CAS Number
1 1 2 2 3 3 3 3 3 4 4 4 4 5
Acyclovir or acycloguanosine • Acyclovir; Zovirax (GlaxoWellcome) www.rxlist.com (Zovirax®) 2-Amino-9-(2-hydroxy-ethoxymethyl)-1,9-dihydro-purin-6-one; 2-Amino-9-(2-hydroxy-ethoxymethyl)-1,9-dihydropurin-6-one; Zovirax (trade); aciclovir; 2 amino 6 hydroxy 9 (2 hydroxyethoxymethyl)purine; 9 (2 hydroxyethoxymethyl) guanine; 9 [(2 hydroxyethoxy)methyl]guanine; acg; acic; acicloftal; aciclostad; aciclovir sodium; activir; acv; acycloguanosine; acyclovidar; bw 248u; bw248u; cicloviran; cycloviran; genvir; guanine, 9 (2 hydroxyethoxymethyl); herpetad; herpofug; virolex; viropump; virupos; viruseen; wellcome 248 u; zaclovir; zovirax; zyclir 2-amino-1,9-dihydro9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one 59277-89-3
Introduction Intravenous (i.v.) acyclovir is the drug of choice for treatment of serious infections caused by herpes simplex virus (HSV) or varicella-zoster virus (VZV) (Safrin, 2012; Razonable, 2011). Intravenous aciclovir is effective to treat severe medical conditions caused by different species of herpes virus family includes severe localized infections of herpes virus, severe genital herpes, chickenpox and encephalitis. It is also effective in systemic or traumatic herpes infections, eczema herpeticum and Herpes simplex meningitis. A guanosine analog, it was the first anti-viral drug to specifically target a viral enzyme, DNA polymerase, inhibiting DNA chain elongation. Acyclovir is activated intracellularly by the viral thymidine kinase to the monophosphate derivative, which is then converted by the cellular enzymes to the diphosphate and then to the triphosphate analog, which inhibits viral DNA polymerase. Common side effects include nausea and diarrhea. Potentially serious side effects include kidney problems and low platelets. Greater care is recommended in those with poor liver or kidney function. It is generally considered safe for use in pregnancy with no harms having been observed. It is safe during breastfeeding (Hamilton, 2015). Viral resistance can occur due to mutations in viral thymidine kinase gene.
Basic Chemistry Acyclovir is a guanosine analog containing an acyclic side chain in place of ribose.
☆ Change History: April 2016. D Mondal updated Abstract, extensively changed the content format, included new research findings, and included new references.
Reference Module in Biomedical Sciences
http://dx.doi.org/10.1016/B978-0-12-801238-3.99396-6
1
2
Acyclovir
Chemical structure Structure
Comments
Acyclovir is a synthetic nucleoside analog. It is available in capsules, tablets and suspension. Acyclovir sodium is used for injection. C8 H11 N5 O3
Chemical formula Properties Physical Properties Molecular Weight Solubility
Acyclovir is a white crystalline powder. 225.207 2.5 mg mL1 in water at 37 C for acyclovir and >100 mg mL1 for acyclovir sodium.
Ionization constant Value pKa pKa
Salt
Conditions
Reference
2.2 9.25
Comments
Physician’s Desk Reference (2000) Physician’s Desk Reference (2000)
Human Pharmacokinetics Can be given orally, intravenously or topically. Low bioavailability (15–20%), but sufficient to achieve therapeutic plasma levels. Renal excretion with half-life of 2.5 h (15% metabolized, 85% excreted unchanged). The half-life and total body clearance of acyclovir are dependent on renal function. Acyclovir plasma concentrations are higher in geriatric patients as compared to young subjects due to changes in renal function. Thus, a dose reduction may be necessary in the elderly. Only 50% of the plasma levels of acyclovir penetrate the cerebrospinal fluid (CSF), hence dose escalation is required for the treatment of HSV encephalitis.
Pharmacokinetic Properties
Absorption Bioavailability
Distribution Volume of distribution Plasma protein binding Metabolism Plasma half-life Bio half-life Clearance
Routes of elimination
Value
Units
Prep. and route of admin.
10–20
%
p.o.
Physician’s Desk Reference (2000)
9–33
%
p.o. or i.v.
Physician’s Desk Reference (2000)
2.5–3.3
h
p.o. or i.v.
Drug Facts and Comparisons (2001)
62–91
%
p.o. or i.v.
Reference
Comments
Drug Facts and The only known urinary metabolite of acyclovir is 9-[(carboxymethoxy) Comparisons methyl]guanine which accounts for 14.1% of the dose in patients with (2001) normal renal function (Baselt, 2008)]. Renal excretion of the unchanged drug is the major route of elimination.
Acyclovir
3
Mechanism of Action Acyclovir is selectively activated by the HSV and VZV thymidine kinase to the monophosphate form. The monophosphate is converted into diphosphate by cellular guanylate kinase and into triphosphate by cellular kinases. Viral DNA replication is blocked by the triphosphate form by competitive inhibition of viral DNA polymerase. The incorporation of acyclovir triphosphate into the growing viral DNA chain results in termination of viral DNA synthesis. Not effective against CMV infections because CMV TK does not activate acyclovir.
Target Name(s)
• •
Viral thymidine kinases Viral DNA polymerase
Indications Effective against HSV-2 (genital), HSV encephalitis and Varicella-Zoster. Acyclovir can be used orally, intravenously, or topically (in creams). A Drug of choice for parenteral treatment of herpes zoster (shingles), oral therapy for recurrent genital herpes (HSV-2). Also indicated for HSV encephalitis and Varicella zoster (chickenpox). Acyclovir is used for the treatment of initial episodes, and the management of recurrent episodes, of genital herpes (HSV-2), and HSV encephalitis. The greater antiviral activity of acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the viral thymidine kinase. It is not effective against CMV infections because CMV-thymidine kinase does not activate the drug. A valine ester of acyclovir, Valacyclovir, acts as a prodrug and substantially increases the oral bioavailability over Acyclovir.
Value
Units
Prep. and route of admin.
Reference
Comments
Treatment of initial HSV and VZV infections. p.o. Dosage 200–800 mg 4 h1
Physician’s Dosing interval is dependent on the patient’s creatinine clearance rate Desk and renal function. Reference (2000) Treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) and VZV infections in immunocompromised patients, neonatal herpes infections, and for the treatment of herpes encephalitis. Dosage 5 mg kg1 8 h1 i.v. For cutaneous HSV infections in immunocompromised adults and for 7 days adolescents. Dosing interval is dependent on the patient’s creatinine clearance rate. Treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) and VZV infections in immunocompromised patients, neonatal herpes infections and for the treatment of herpes encephalitis. Dosage 10 mg kg1 8 h1 i.v. Pediatrics (<12 years). Dosing interval is dependant on the patient’s for 7 days creatinine clearance rate. Treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) and VZV infections in immunocompromised patients, neonatal herpes infections, and for the treatment of herpes encephalitis. Dosage 10 or 20 mg kg1 8 h1 i.v. For HSV encephalitis. Dosing interval is dependent on the patient’s for 10 days creatinine clearance rate.
Contraindications Hypersensitivity or chemical intolerance. Acyclovir is contraindicated in those who are hypersensitivity to acyclovir or valacyclovir.
Side Effects Inflammation or phlebitis, malaise, nausea and headache. Encephalopathic changes and renal function impairment may occur. Acyclovir is generally well tolerated. Adverse reactions (when given parenterally) occur in 3–5% of patients and include inflammation or phlebitis at the injection site, transient elevations of serum creatinine, nausea, and vomiting. Oral acyclovir may be associated with malaise, nausea, gastrointestinal problems, rash, and headache. The intravenous use of acyclovir has been associated (rarely) with encephalopathy, tremors, hallucinations, seizures, and coma. Renal dysfunctions can occur with long term use. Another serious complication with long-term acyclovir is the development of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP/HUS). Encephalopathic changes and renal function impairment may also occur.
4
Acyclovir
Acyclovir pharmacokinetic characteristics (range)
Table 1 Parameter
Range
Plasma protein binding Plasma elimination half-life Average oral bioavailability
9–33% 2.5–3.3 h 10–20%a
a
Bioavailability decreases with increasing dose.
Table 2
Acyclovir peak and trough concentrations at steady state
Parameter
200 mg
400 mg 1
CSS max CSS trough
0.83 mcg mL 0.46 mcg mL1
800 mg 1
1.21 mcg mL 0.63 mcg mL1
1.61 mcg mL1 0.83 mcg mL1
Pharmacokinetics Acyclovir can be given orally, i.v. or topically. It has low bioavailability (15–20%), but sufficient to achieve therapeutic plasma levels. Renal excretion with half-life of 2.5 h (15% metabolized, 85% excreted unchanged) Only 50% of plasma levels penetrate into the CSF, hence dose escalation is required for HSV encephalitis. 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.
•
In one multiple-dose, crossover study in healthy subjects (n ¼ 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. There was no effect of food on the absorption of acyclovir (n ¼ 6); therefore, acyclovir capsules and tablets may be administered with or without food. The only known urinary metabolite is 9-[(carboxymethoxy) methyl]guanine.
Major Drug Interactions
Agent name
Mode of interaction
Probenecid Zidovudine Cimetidine
Probenecid may inhibit the renal excretion of acyclovir (Bach, 1987). As a nucleoside analog, acyclovir may increase the toxic effects of zidovudine. Antihistamine (H2-receptor antagonist). Decrease Cyp450 mediated degradation of acyclovir and valacyclovir
Pre-Clinical and Clinical Research
• • • •
In dogs, 50 mg kg1 day1 of acyclovir given orally for one month, which is 1–3 times human dose, did not show testicular abnormalities, although at higher doses both testicular atrophy and aspermatogenesis were observed. Because acyclovir is detected in breast milk, administration to a nursing mother should be done with caution. Double-blind, placebo-controlled studies have demonstrated that orally administered acyclovir significantly reduced the duration of acute infection and duration of lesion healing. 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. 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.
Resistance
•
Viral Resistance can occur due to mutations in viral TK enzyme (Piret and Boivin, 2011).
Acyclovir
5
References Bach MC (1987) Possible drug interaction during therapy with azidothymidine and acyclovir for AIDS. New England Journal of Medicine 316(9): 547. http://dx.doi.org/10.1056/ NEJM198702263160912. PMID 3468354. Baselt RC (2008) Disposition of toxic drugs and chemicals in man, 8th edn. Foster City, CA: Biomedical Publications. ISBN 9780962652370. Cada DJ (2001) Drug facts and comparisons antiviral agents. Drug facts and comparisons, 5th edn. St. Louis, MI: A Wolters Kluwer Company. 846–848. Hamilton R (2015) Tarascon pocket pharmacopoeia 2015 deluxe lab-coat edition. Burlington, MA: Jones & Bartlett Learning. ISBN 9781284057560. p. 59. Piret J and Boivin G (2011) Resistance of herpes simplex viruses to nucleoside analogues: Mechanisms, prevalence, and management. Antimicrobial Agents and Chemotherapy 55(2): 459–472. http://dx.doi.org/10.1128/AAC.00615-10 PMC 3028810, PMID 21078929. Razonable RR (2011) Antiviral drugs for viruses other than human immunodeficiency virus. Mayo Clinic Proceedings 86(10): 1009–1026. http://dx.doi.org/10.4065/mcp.2011.0309 PMC 3184032, PMID 21964179. Sifton DW (2000) Physician’s desk reference, Physicians’ desk reference, 54th edn. Montvale, NJ: Medical Economics Company. Safrin S (2012) Antiviral agents. In: Katzung BG, Masters SB, and Trevor AJ (eds.) Basic and clinical pharmacology, 12th edn, New York, NY: McGraw-Hill/Lange (Access-Medicine) (Chapter 49).
Relevant website ACYCLOVIR – acyclovir capsule, ACYCLOVIR – acyclovir tablet.