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Title: Aciclovir  
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Subject: List of drugs: Ac, Thymidine kinase from herpesvirus, Imiquimod, Edoxudine, Resiquimod
Collection: Anti-Herpes Virus Drugs, Purines, Rtt, World Health Organization Essential Medicines
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Systematic (IUPAC) name
Clinical data
Trade names Zovirax, others[1]
Licence data US FDA:
  • AU: B3
  • US: B (No risk in non-human studies)
Legal status
Routes of
Intravenous, oral, topical (including eye ointment)
Pharmacokinetic data
Bioavailability 15–20% (oral)[2]
Protein binding 9–33%[2]
Metabolism Hepatic
Biological half-life 2-4 hours
Excretion Renal (62-90% as unchanged drug)
CAS Registry Number  Y
ATC code J05 D06 S01
PubChem CID:
DrugBank  Y
ChemSpider  Y
Synonyms acycloguanosine
PDB ligand ID AC2 (, )
Chemical data
Formula C8H11N5O3
Molecular mass 225.21 g·mol−1
Physical data
Melting point 256.5 °C (493.7 °F)

Aciclovir (ACV), also known as acyclovir and acycloguanosine, is an health system.[8] It is available as a generic medication and is marketed under many brand names worldwide.[1] The wholesale cost is between 0.03 and 0.12 USD per dose.[9] In the United States it is not very expensive at about 0.50 USD per dose.[4][6]


  • Medical use 1
    • Pregnancy 1.1
  • Adverse effects 2
    • Systemic therapy 2.1
    • Topical therapy 2.2
  • Drug interactions 3
  • Detection in biological fluids 4
  • Mechanism of action 5
    • Microbiology 5.1
    • Resistance 5.2
  • Pharmacokinetics 6
  • History 7
  • Society and culture 8
    • Cost 8.1
    • Names 8.2
  • See also 9
  • Notes 10
  • References 11
  • Further reading 12
  • External links 13

Medical use

400 mg pills of aciclovir

Aciclovir is used for the treatment of herpes simplex virus and varicella zoster virus infections, including:[2][10][11]

Oral aciclovir, however, does not appear to decrease the risk of pain after shingles.[13] In those with herpes of the eye, aciclovir was found to be more effective than idoxuridine or vidarabine in relative number of successfully healed eyes.[14]

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 & encephalitis. It is also effective in systemic or traumatic herpes infections, eczema herpeticum and Herpes simplex meningitis. Reviews of research dating from the 1980s show there is some effect in reducing the number and duration of lesions if aciclovir is applied at an early stage of an outbreak.[15] Recent research shows effectiveness of topical Aciclovir in both the early and late stages of the outbreak as well as improving methodologically and in terms of statistical certainty from previous studies.[16] Aciclovir trials show that this agent has no role in preventing HIV transmission, but it can help slow HIV disease progression in people not taking anti-retroviral therapy (ART). This finding emphasizes the importance of testing simple, inexpensive non-ART strategies, such as aciclovir and cotrimoxazole, in people with HIV.[17]


Classified as a Category B Drug,[18] the CDC and others have declared that during severe recurrent or first episodes of genital herpes, aciclovir may be used.[19] For severe HSV infections (especially disseminated HSV), IV aciclovir may also be used.[20] Studies in mice, rabbits and rats (with doses more than 10 times the equivalent of that used in humans) given during

  • U.S. National Library of Medicine: Drug Information Portal–Aciclovir

External links

  • Hazra, S; Konrad, M; Lavie, A (2010). "The sugar ring of the nucleoside is required for productive substrate positioning in the active site of human deoxycytidine kinase (dCK): Implications for the development of dCK-activated acyclic guanine analogues". Journal of Medicinal Chemistry 53 (15): 5792–800.  
  • Harvey Stewart C. in Remington’s Pharmaceutical Sciences 18th edition: (ed. Gennard, Alfonso R.) Mack Publishing Company, 1990. ISBN 0-912734-04-3.
  • Huovinen P., Valtonen V. in Kliininen Farmakologia (ed. Neuvonen et al.). Kandidaattikustannus Oy, 1994. ISBN 951-8951-09-8.
  • Périgaud C., Gosselin G., Imbach J. -L.: Nucleoside analogues as chemotherapeutic agents: a review. Nucleosides and nucleotides 1992; 11(2–4)
  • Rang H.P., Dale M.M., Ritter J.M.: Pharmacology, 3rd edition. Pearson Professional Ltd, 1995. 2003 (5th) edition ISBN 0-443-07145-4; 2001 (4th) edition ISBN 0-443-06574-8; 1990 edition ISBN 0-443-03407-9.

Further reading

  1. ^ a b c "Aciclovir". Retrieved 6 September 2015. 
  2. ^ a b c d "Zovirax (acyclovir) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 5 February 2014. 
  3. ^ a b de Clercq, Erik; Field, Hugh J (5 October 2005). "Antiviral prodrugs – the development of successful prodrug strategies for antiviral chemotherapy".  
  4. ^ a b c d e f "Acyclovir". The American Society of Health-System Pharmacists. Retrieved Jan 1, 2015. 
  5. ^ "Prescribing medicines in pregnancy database". Australian Government. 3 March 2014. Retrieved 22 April 2014. 
  6. ^ a b c Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 59.  
  7. ^ Clercq, edited by Erik De (2013). Anti-viral agents (1 ed.). San Diego, CA: Academic Press. p. 5.  
  8. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  9. ^ a b "Aciclovir". International Drug Price Indicator Guide. Retrieved 6 September 2015. 
  10. ^ a b c d Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust.  
  11. ^ Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press.  
  12. ^ Elad S, Zadik Y, Hewson I; et al. (August 2010). "A systematic review of viral infections associated with oral involvement in cancer patients: a spotlight on Herpesviridea". Support Care Cancer 18 (8): 993–1006.  
  13. ^ Chen, N; Li, Q; Yang, J; Zhou, M; Zhou, D; He, L (Feb 6, 2014). "Antiviral treatment for preventing postherpetic neuralgia.". The Cochrane database of systematic reviews 2: CD006866.  
  14. ^ Wilhelmus KR (2010). "Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis". Cochrane Database Syst Rev 12: CD002898.  
  15. ^ Graham Worrall (6 Jan 1996). "Acyclovir in recurrent herpes labialis". BMJ 312 (7022): 6.   – Editorial
  16. ^
  17. ^ Mascolinli, M; Kort, R (June 2010). "5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention: summary of key research and implications for policy and practice - biomedical prevention" (PDF). Journal of the International AIDS Society. 13 Suppl 1 (Suppl 1): S4.  
  18. ^ a b GlaxoSmithKline. Zovirax® (acyclovir) capsules, tablets, and suspension prescribing information. Research Triangle Park, NC; 2005 Jun
  19. ^ "Drugs for non-HIV viral infections". Treatment guidelines from the Medical Letter 3 (32): 23–32. 2005.  
  20. ^ Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America. MMWR Recomm Rep. 2004; 53(RR-15):1-112. [Fulltext MMWR]
  21. ^ a b c d "PRODUCT INFORMATION NAME OF THE DRUG OZVIR TABLETS" (PDF). TGA eBusiness Services. Ranbaxy Australia Pty Ltd. 26 August 2011. Retrieved 6 February 2014. 
  22. ^ Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. 9th ed. Public Health Foundation; 2006 Jan:171-92
  23. ^ Gartner LM, Morton J, Lawrence RA, et al, "Breastfeeding and the Use of Human Milk," Pediatrics, 2005, 115(2):496-506
  24. ^ Razonable, RR (October 2011). "Antiviral drugs for viruses other than human immunodeficiency virus" (PDF). Mayo Clinic proceedings. Mayo Clinic 86 (10): 1009–26.  
  25. ^ Brigden D, Rosling AE, Woods NC (July 1982). "Renal function after acyclovir intravenous injection". The American Journal of Medicine 73 (1A): 182–5.  
  26. ^ Sawyer MH, Webb DE, Balow JE, Straus SE (June 1988). "Acyclovir-induced renal failure. Clinical course and histology". The American Journal of Medicine 84 (6): 1067–71.  
  27. ^ Pottage Jr, J. C.; Kessler, H. A.; Goodrich, J. M.; Chase, R; Benson, C. A.; Kapell, K; Levin, S (1986). "In vitro activity of ketoconazole against herpes simplex virus". Antimicrobial agents and chemotherapy 30 (2): 215–9.  
  28. ^ GlaxoSmithKline. Zovirax® (acyclovir sodium) for injection prescribing information. Research Triangle Park, NC; 2003 Nov
  29. ^ Bach, M. C. (1987). "Possible drug interaction during therapy with azidothymidine and acyclovir for AIDS". New England Journal of Medicine 316 (9): 547.  
  30. ^ Baselt, RC (2008). Disposition of toxic drugs and chemicals in man (8th ed.). Foster City, CA: Biomedical Publications. pp. 29–31.  
  31. ^ "Acyclovir (acyclovir) Capsule Acyclovir (acyclovir) Tablet [Genpharm Inc.]". DailyMed. Genpharm Inc. November 2006. Retrieved 5 February 2014. 
  32. ^ "Aciclovir Tablets BP 400mg - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Actavis UK Ltd. 20 August 2012. Retrieved 5 February 2014. 
  33. ^ O'Brien, JJ; Campoli-Richards, DM (1989). "Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy". Drugs 37 (3): 233–309.  
  34. ^ Wagstaff, AJ; Faulds, D; Goa, KL (January 1994). "Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy.". Drugs 47 (1): 153–205.  
  35. ^ Sweetman, S, ed. (7 August 2013). "Aciclovir". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 6 February 2014. 
  36. ^ Piret J, Boivin G (2011). "Resistance of herpes simplex viruses to nucleoside analogues: mechanisms, prevalence, and management". Antimicrob. Agents Chemother. 55 (2): 459–72.  
  37. ^ Aciclovir Tablets BP 400mg - Summary of Product Characteristics (SPC) - (eMC)
  38. ^ Garrison, Tom (1999). Oceanography: An Invitation to Marine Science, 3rd ed. Belmont, CA: Wadsworth Publishing Company. p. 471. 
  39. ^ Sepčić, K. (2000). "Bioactive Alkylpyridinium Compounds from Marine Sponges". Toxin Reviews 19 (2): 139–160.  
  40. ^ Laport, M. S.; Santos, O. C.; Muricy, G (2009). "Marine sponges: Potential sources of new antimicrobial drugs". Current pharmaceutical biotechnology 10 (1): 86–105.  
  41. ^ Schaffer, Howard; Robert Vince; S. Bittner; S. Gurwara (1971). "Novel substrate of adenosine deaminase". Journal of Medicinal Chemistry 14 (4): 367–369.  
  42. ^ Elion, Gertrude; Furman, Fyfe, Miranda, Beauchamp and Schaffer; Fyfe, James A.; De Miranda, Paulo; Beauchamp, Lilia; Schaeffer, Howard J. (1977). "Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine". Proc Natl Acad Sci USA 74 (12): 5716–5720.  
  43. ^ US 4146715 
  44. ^ Vince, R. "A brief history of the development of Ziagen" Chemtracts 2008, 21, 127–134.


  1. ^ Subject to the same conditions as before


See also

It was originally marketed as Zovirax; patents expired in the 1990s and since then it is generic and is marketed under many brand names worldwide.[1]

Aciclovir is the INN and BAN while acyclovir is the USAN and former BAN.


The wholesale cost is between 0.03 and 0.12 USD per dose.[9] In the United States it is not very expensive at about 0.50 USD per dose.[4][6]


Society and culture

Vince later went on to invent abacavir, an nRTI drug for HIV patients.[44] Elion was awarded the 1988 Nobel Prize in Medicine, partly for the development of aciclovir. Richard Whitley, a University of Alabama at Birmingham researcher and pioneer in antiviral therapy, was the first to successfully use the drug in humans.

Aciclovir was seen as the start of a new era in antiviral therapy, as it is extremely selective and low in cytotoxicity.[3] Since discovery in mid 1970s, it is being used as an effective drug for the treatment of infections caused by most known species of the Herpes virus family including Herpes zoster & Varicella zoster viruses. Nucleosides isolated from a Caribbean sponge, Cryptotethya crypta, were the basis for the synthesis of aciclovir.[38][39][40] It was codiscovered by Howard Schaffer following his work with Robert Vince, S. Bittner and S. Gurwara on the adenosine analog acycloadenosine which showed promising antiviral activity.[41] Later, Schaffer joined Burroughs Wellcome and continued the development of aciclovir with pharmacologist Gertrude B. Elion.[42] A U.S. patent on aciclovir listing Schaffer as inventor was issued in 1979.[43]


Acyclovir is poorly water-soluble and has poor oral bioavailability (15–30%), hence intravenous administration is necessary if high concentrations are required. When orally administered, peak plasma concentration occurs after 1–2 hours. Aciclovir has a high distribution rate; protein binding is reported to range from 9 to 33%.[37] The elimination half-life (t1/2) of aciclovir depends according to age group; neonates have a t1/2 of 4 hours, children 1–12 years have a t1/2 of 2–3 hours whereas adults have a t1/2 of 3 hours.[2]


Resistance to aciclovir is rare in people with healthy immune systems, but is more common (up to 10%) in people with immunodeficiencies on chronic antiviral prophylaxis (transplant recipients, people with acquired immunodeficiency syndrome due to HIV infection). Mechanisms of resistance in HSV include deficient viral thymidine kinase; and mutations to viral thymidine kinase or DNA polymerase, altering substrate sensitivity.[35][36]


Aciclovir is active against most species in the herpesvirus family. In descending order of activity:[33][34]


Aciclovir is converted by viral thymidine kinase to aciclovir monophosphate, which is then converted by host cell kinases to aciclovir triphosphate (ACV-TP).[21] ACV-TP, in turn, competitively inhibits and inactivates HSV-specified DNA polymerases preventing further viral DNA synthesis without affecting the normal cellular processes.[21][31][32]

Structures of guanosine and aciclovir compared

Mechanism of action

Aciclovir may be quantitated in plasma or serum to monitor for drug accumulation in patients with renal dysfunction or to confirm a diagnosis of poisoning in acute overdose victims.[30]

Detection in biological fluids

Zidovudine: Although administered often with aciclovir in HIV patients, neurotoxicity has been reported in at least one patient who presented with extreme drowsiness and lethargy 30–60 days after receiving IV aciclovir; symptoms resolved when aciclovir was discontinued.[29]

Interferon: Synergistic effects when administered with aciclovir and caution should be taken when administering aciclovir to patients recieiving IV interferon.[28]

Probenecid: Reports of increased half life of aciclovir, as well as decreased urinary excretion and renal clearance have been shown in studies where probenecid is given simultaneously with aciclovir.[18]

Ketoconazole: In-vitro replication studies have found a synergistic, dose-dependent antiviral activity against HSV-1 and HSV-2 when given with aciclovir. However, this effect has not been clinically established and more studies need to be done to evaluate the true potential of this synergy.[27]

Drug interactions

Aciclovir topical cream is commonly associated (≥1% of patients) with: dry or flaking skin or transient stinging/burning sensations. Infrequent adverse effects include erythema or itch.[10] When applied to the eye, aciclovir is commonly associated (≥1% of patients) with transient mild stinging. Infrequently (0.1–1% of patients), ophthalmic aciclovir is associated with superficial punctate keratitis or allergic reactions.[10]

Topical therapy

Intravenous aciclovir may cause reversible nephrotoxicity in up to 5% to 10% of patients because of precipitation of aciclovir crystals in the kidney. Aciclovir crystalline nephropathy is more common when aciclovir is given as a rapid infusion and in patients with dehydration and preexisting renal impairment. Adequate hydration, a slower rate of infusion, and dosing based on renal function may reduce this risk.[24][25][26]

Common adverse drug reactions (≥1% of patients) associated with systemic aciclovir therapy (oral or IV) include: nausea, vomiting, diarrhea, encephalopathy (with IV use only), injection site reactions (with IV use only) and headache. In high doses, hallucinations have been reported. Infrequent adverse effects (0.1–1% of patients) include: agitation, vertigo, confusion, dizziness, oedema, arthralgia, sore throat, constipation, abdominal pain, hair loss, rash and weakness. Rare adverse effects (<0.1% of patients) include: coma, seizures, neutropenia, leukopenia, crystalluria, anorexia, fatigue, hepatitis, Stevens–Johnson syndrome, toxic epidermal necrolysis, thrombotic thrombocytopenic purpura and anaphylaxis.[10]

Systemic therapy

Adverse effects

Aciclovir is excreted in the breast milk, therefore it is recommended that caution should be used in breast-feeding women. It has been shown in limited studies that the nursing infant is exposed to approximately 0.3 mg/kg/day following oral administration of aciclovir to the mother. If nursing mothers have herpetic lesions near or on the breast, breast-feeding should be avoided.[23]

Aciclovir is recommended by the CDC for treatment of Varicella during pregnancy, especially during the second and third trimesters[22]

[21] on day 10 of gestation showed head and tail anomalies.[Note 1] Studies in rats in which they were given the equivalent to 63 times the standard steady-state humans concentrations of the drug[21]

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