Acyclovir

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Acyclovir quick reference

Acyclovir
Acyclovir general drug information
 Pronunciation ay SYE kloe veer (.wav file)
 Trade Name(s) Zovirax
 How Supplied Capsules: 200 mg
Tablets: 400 mg, 800 mg
Suspension: 200 mg/5 mL
Powder for injection: 500 mg, 1000 mg
Solution for injection: 50 mg/5 mL
Cream: 5%
Ointment: 5%
 Generic Availability Yes, except cream and ointment
 Patent Expiry Date N/A
 Classification antiviral
 Schedule Rx
 Pregnancy Category B
 Breast-feeding Use with caution and only when indicated.
Acyclovir chemical information
 IUPAC Name 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one
 Empirical Formula C8H11N5O3
 Molecular Weight 225 g/mol
pharmacokinetic information  |  pharmacogenomic information

Description

Acyclovir is the prototype antiviral agent used to treat various types of herpes infections. Since acyclovir was the first antiviral to be considered the gold standard for the treatment of herpes infections, all other anti-herpes virus medications are compared to it. The drug is approved for the treatment of herpes simplex encephalitis, herpes genitalis, herpes labialis, herpes zoster, varicella (chickenpox), varicella-zoster virus, and viral conjunctivitis. It is approved for the prophylaxis of herpes genitalis.[1]

Mechanism of Action

After being activated by intracellular phosphorylation, acyclovir inhibits viral DNA synthesis. Acyclovir is converted to acyclovir monophosphate by virus specific thymidine kinase diphosphate by cellular guanylate kinase, and then ultimately converted to acyclovir triphosphate via cellular enzymes. Acyclovir triphosphate inhibits viral DNA synthesis by competing with deoxyguanosine triphosphate for viral DNA polymerase, gaining incorporation into and causing termination of the growing viral DNA chain, or inactivating the viral DNA polymerase. Acyclovir is only effective against actively replicating viruses.[1]

Time Required for Therapeutic Response

  • Initial: 3-5 days
  • Maximum: N/A

Pharmacokinetics

Absorption
Acyclovir is poorly absorbed from the GI tract following oral administration. The oral bioavailability ranges from 10 to 20% and decreases with increased doses. The Cmax and AUC are dose dependent and show no proportionality. The Cmax for a 200 mg dose is 0.83 mcg/ml, 1.21 mcg/ml with a dose of 400 mg, and 1.61 mcg/ml with a 800 mg dose. Oral absorption is not affected by food consumption.[1]

There is minimal systemic absorption following topical administration of acyclovir. No drug is detectable in the blood or urine.

Following intravenous administration of acyclovir, the mean Cmax is 9.8 mcg/ml with a dose of 5 mg/kg every 8 hours and 20.7 mcg/ml with a dose of 10 mg/kg every 8 hours.[2][3]

Distribution
The volume of distribution is 0.8 L/kg. Protein binding of acyclovir ranges from 9% to 33%, and distributes extensively throughout the body. The highest concentrations are in the kidneys, liver, and intestines. CSF concentrations are about 50% that of the plasma. Acyclovir does cross the placenta.[1][2][3][4]

Metabolism
Acyclovir is converted to acyclovir monophosphate by virus-specific thymidine kinase, diphosphate by cellular guanylate kinase, and then ultimately converted to acyclovir triphosphate via cellular enzymes. Acyclovir undergoes minimal hepatic metabolism by aldehyde oxidase, alcohol dehydrogenase, and aldehyde dehydrogenase to form inactive metabolites.[1]

Excretion
Acyclovir is primarily eliminated by the kidneys via glomerular filtration and tubular secretion. It is found in the urine from 62% to 90% as unchanged drug and metabolites. The plasma elimination half-life of acyclovir ranges from 2.5 to 3.3 hours in patients with normal renal function.[1][2][3][5][4]

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Special Population Pharmacokinetics

  • Renal insufficiency: The elimination half life and total body clearance of acyclovir are dependent on renal function. Patients with renal dysfunction should follow a modified dosing regimen.[1][2][3]
  • Hepatic insufficiency: No dosing changes required.[1]
  • Hemodialysis: During hemodialysis approximately 60% of the dose of acyclovir is removed. Replacement doses should be considered for patients undergoing hemodialysis.[2][4]
  • Geriatric: The elimination half life of acyclovir is slightly longer in healthy geriatric patients when compared to healthy volunteers. This is expected due to the drug's clearance being dependent on renal function, which decreases with age. Therefore, dose adjustments may be necessary and should be based on the patient's current renal status.[1][3]
  • Pediatric: The pharmacokinetics of acyclovir in pediatric patients are very similar to those in the adult population. The mean Cmax for pediatric patients was 18 mcg/ml with a dose of 250 mg/m2 and 14-30 mcg/ml with a dose of 500 mg/m2. These max concentrations were similar to the adult Cmax with doses of 5 and 10 mg/kg every 8 hours.[2]
  • Gender: No dosage adjustment is needed.[2]

Indications and Dosages

FDA Approved Indications

Herpes genitalis (adult and adolescent immunocompetent patients)[6][7]

  • Starting dose (first episode):
    • ORAL: 200 mg every 4 hours, 5 times per day for 7 to 10 days or 400 mg three times per day for 7 to 10 days.
    • IV: 5 mg/kg every 8 hours for 5 days. Use ideal body weight when dosing obese adult patients.
  • Maintenance dose (recurrent episodes):
    • ORAL: 400 mg three times per day for 5 days or 800 mg three times per day for 2 days or 800 mg twice daily for 5 days, initiated at the first sign of prodrome or genital lesions.
    • TOPICAL: Apply sufficient quantity of cream/ointment to adequately cover all lesions every 3 hours, six times a day for 7 days.

Herpes zoster (shingles - adult and adolescent immunocompetent patients)[1]

  • Starting dose (first episode):
    • 800 mg PO every 4 hours, five times a day for 7—10 days. Initiate therapy within 48—72 hours of rash onset.
  • Maintenance dose (recurrent episodes):
    • N/A

Herpes labialis (adult and adolescent immunocompetent patients)[8]

  • Starting dose (initial infection):
    • 400 mg PO three times per day or 200 mg PO five times per day for 7—10 days or until clinical resolution occurs, or 800 mg PO every 8 hours for 7—10 days or 200—400 mg PO 5 times per day for 10 days has also been recommended.
  • Maintenance dose (recurrent infections):
    • ORAL: 400 mg three times per day for 5 days; 200 mg five times per day for 5 days; or 800 mg twice daily for 5 days, initiated at the first sign of prodrome or lesions.
    • TOPICAL: Apply sufficient quantity of cream/ointment to adequately cover all lesions every 3 hours, six times a day for 7 days; initiate at the first sign of symptoms or lesions.

Herpes genitalis prophylaxis[9]
Herpes simplex virus type 1[10]
Herpes simplex virus type 2[10]
Varicella-zoster virus[1]
Varicella virus[1]
Viral conjunctivitis
Herpes Simplex Encephalitis[11]

Non-FDA Approved Indications

  • Bell's palsy[12]
  • Cytomegalovirus (CMV)[13][14]
  • Cytomegalovirus (CMV) infection prophylaxis[13][14]
  • Epstein-Barr virus[15][16][17]
  • Esophagitis[18]
  • Hairy leukoplakia[19][20]
  • Herpes labialis prophylaxis[21]
  • Herpes simplex infection prophylaxis[10]
  • Herpes simplex ocular infection prophylaxis[22]
  • Keratoconjunctivitis[23]
  • Pharyngitis
  • Pneumonitis[24]
  • Postherpetic neuralgia prophylaxis[25]
  • Proctitis[26]
  • Stomatitis[27]
  • Tracheobronchitis[28]
  • Varicella prophylaxis[29]

Dosage Adjustment

Renal insufficiency:

  • CrCl 25—50 ml/min: extend IV dosing interval to every 12 hours.
  • CrCl 10—24 ml/min: extend IV dosing interval to every 24 hours. Extend 800 mg oral dosage interval to every 8 hours.
  • CrCl < 10 ml/min: reduce recommended IV dose by 50% and extend dosing interval to every 24 hours. For patients receiving 200 mg orally five times per day or 400 mg orally every 12 hours, reduce dose to 200 mg every 12 hours. For patients receiving 800 mg orally five times per day, reduce dose to 800 mg every 12 hours.

Hemodialysis: the intravenous dosing interval should be extended to every 24 hours and the schedule adjusted so that a dose is administered after each dialysis session. For patients receiving 200 mg orally five times per day or 400 mg orally every 12 hours, reduce dose to 200 mg every 12 hours. For patients receiving 800 mg orally five times per day, reduce dose to 800 mg every 12 hours.
Geriatric: no age specific data available, however renal function should be considered.
Pediatric: no data available.

Dosage Limits

  • Adults: 60 mg/kg/day IV; 4000 mg/day PO
  • Elderly: 60 mg/kg/day IV; 4000 mg/day PO (may need to be renally adjusted)
  • Adolescents and children ≥10 years: 60 mg/kg/day IV; 4000 mg/day PO
  • Children <10 years: 60 mg/kg/day IV; 80 mg/kg/day PO or 4000 mg/day PO, whichever is less


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Administration

  • Route: Oral
  • Method:
    • May be taken without regard to meals.
    • If GI upset occurs, take with a meal.
    • Measure the suspension with a calibrated oral dosing device to give accurate dosage.
  • Route: IV
  • Method:
    • For IV infusion only.
    • Powder requires mixing and dilution.
    • Infuse over 1 hour to prevent renal damage. Avoid rapid infusion.
    • Maintain adequate hydration of patient. Check for phlebitis and rotate injection sites.
  • Route: Topical
  • Method:
    • Apply using a finger cot or rubber glove to avoid transmission to other parts of the body or to other people.
    • If not using finger cot or glove, wash hands thoroughly after administration.
    • Not for ophthalmic use. For external use only.

Monitoring Parameters

  • Serum creatinine/BUN: at baseline
  • Urinalysis
  • Liver enzymes
  • CBC

Contraindications/Precautions

Contraindications

  • Hypersensitivity to valacyclovir, acyclovir, or any component of the formulation.

Precautions

  • Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has occurred in advanced HIV patients as well as allogeneic bone marrow transplant and renal transplant recipients who were receiving high doses (8 g/day) of valacyclovir. This is potentially fatal.
  • Dosage reduction is recommended when administering acyclovir to patients with renal impairment.
  • Use with caution in the elderly due to decreased renal function.
  • Use with caution in patients who receive nephrotoxic drugs.
  • Use caution when administering via IV in those with pre-existing neurologic abnormalities, serious hepatic or electrolyte abnormalities, or hypoxia.

Pregnancy indications

Category B

There are no adequate well-controlled trials in pregnant women. Acyclovir does cross the placenta, however, it was not shown to increase birth defects during a review of a pregnancy registry that was established in 1984 and studied until 1999. The manufacterer suggests using during pregnancy with caution and only when absolutely needed.

Breast-feeding indications

Secretion into breast milk: acyclovir should be administered to a nursing mother with caution and only when indicated. Data suggests that the exposure to the infant is 0.3 mg/kg/day following oral administration to the mother.

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Drug-Drug, -Food, -Herb Interactions

Click the link above to go to the drug interactions page.

Adverse Reactions/Side Effects

Acyclovir Adverse Reactions Chart[1][6]
Incidence Body System Adverse Reactions
>10% All Mild pain, burning, or stinging (topical formulation, 30%), malaise (oral, 12%)
1-10% CNS Headache (oral, 2%)
Dermatologic Hives (IV, 2%), itching (IV, 2%), rash (IV, 2%), pruritus (topical, 4%)
GI Vomiting (oral, 3%), nausea (oral, 2-5%), diarrhea (oral, 2-3%)
Misc Liver function tests increased (IV, 1-2%), BUN increased (IV, 5-10%), creatinine increased (IV, 5-10%), injection site reactions or phlebitis (IV, 9%), acute renal failure (IV)
<1% All Abdominal pain, aggression, agitation, alopecia, anaphylaxis, anemia, angioedema, anorexia, ataxia, coma, confusion, consciousness decreased, delirium, desquamation, diarrhea, disseminated intravascular coagulopathy, dizziness, dry lips, dysarthria, encephalopathy, erythema multiforme, fatigue, fever, GI distress, hallucinations, hematuria, hemolysis, hepatitis, hyperbilirubinemia, hypotension, insomnia, jaundice, leukocytoclastic vasculitis, leukocytosis, leukopenia, local tissue necrosis, lymphadenopathy, mental depression, myalgia, neutrophilia, paresthesia, peripheral edema, photosensitization, pruritis, psychosis, renal failure, seizure, somnolence, sore throat, Stevens-Johnson syndrome, thrombocytopenia, thrombocytopenic purpura/hemolytic uremic syndrome, thrombocytosis, toxic epidermal necrolysis, tremor, urticaria, visual disturbances

Overdosage Measures

Precipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid.
Treatment (in the event of acute renal failure and anuria):

  • Hemodialysis should be considered until renal function is restored.
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Product Information and Distribution

Note: appearance only available for brand-name product
Dose/form Drug color(s) Drug shape Markings or odor/flavor
200 mg capsule blue capsule Zovirax 200/Wellcome
400 mg tablet white shield Zovirax/triangle imprint
800 mg tablet blue oval Zovirax 800
200 mg/5 mL suspension white - banana flavor
500 mg powder for injection white - -
5% ointment white - -
5% cream white - -
  • Inactive ingredients for capsules: corn starch, edible black ink, FD&C Blue No. 2, gelatin, lactose, magnesium stearate, parabens, sodium lauryl sulfate, titanium dioxide
  • Inactive ingredients for tablets: FD&C Blue No. 2 (800 mg tablet only), magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate
  • Inactive ingredients for suspension: carboxymethylcellulose, glycerin, microcrystalline cellulose, parabens, sorbitol
  • Inactive ingredients for ointment: polyethylene glycol
  • Inactive ingredients for cream: cetostearyl alcohol, mineral oil, petrolatum, poloxamer 407, propylene glycol, sodium lauryl sulfate, water

Patient Information

  • Take as directed, with or without food.
  • Maintain adequate hydration unless otherwise restricted.
  • Begin use at the first sign of a herpes outbreak.
  • Remember that this is not a cure for herpes, and spread is possible even when no symptoms are present.
  • May cause dizziness (use caution while driving or operating heavy machinery)
  • May cause headache, nausea, vomiting, and abdominal pain. If GI upset occurs, take with a meal.
  • Immediately report difficulty of breathing or swallowing, hives or rash, or changes in menses.
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References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 GlaxoSmithKline. Zovirax (acyclovir) Package Insert. Research Triangle Park, NC 2004.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Blum MR, Liao SH, de Miranda P. Overview of acyclovir pharmacokinetic disposition in adults and children. Am J Med 1982;73(1A):186-92.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 de Miranda P, Blum MR. Pharmacokinetics of acyclovir after intravenous and oral administration. J Antimicrob Chemother 1983;12 Suppl B:29-37.
  4. ↑ 4.0 4.1 4.2 Lietman PS. Acyclovir clinical pharmacology. An overview. Am J Med 1982;73(1A):193-6.
  5. ↑ Whitley RJ, Blum MR, Barton N, de Miranda P. Pharmacokinetics of acyclovir in humans following intravenous administration. A model for the development of parenteral antivirals. Am J Med 1982;73(1A):165-71.
  6. ↑ 6.0 6.1 Fiddian AP, Halsos AM, Kinge BR, Nilsen AE, Wikstrom K. Oral acyclovir in the treatment of genital herpes. Preliminary report of a multicenter trial. Am J Med 1982;73(1A):335-7.
  7. ↑ Nilsen AE, Aasen T, Halsos AM, Kinge BR, Tjotta EA, Wikstrom K, et al. Efficacy of oral acyclovir in the treatment of initial and recurrent genital herpes. Lancet 1982;2(8298):571-3.
  8. ↑ Spruance SL, Nett R, Marbury T, Wolff R, Johnson J, Spaulding T. Acyclovir cream for treatment of herpes simplex labialis: results of two randomized, double-blind, vehicle-controlled, multicenter clinical trials. Antimicrob Agents Chemother 2002;46(7):2238-43.
  9. ↑ Kinghorn GR, Jeavons M, Rowland M, Abeywickreme I, Barton IG, Potter CW, et al. Acyclovir prophylaxis of recurrent genital herpes: randomised placebo controlled crossover study. Genitourin Med 1985;61(6):387-90.
  10. ↑ 10.0 10.1 10.2 Gold D, Corey L. Acyclovir prophylaxis for herpes simplex virus infection. Antimicrob Agents Chemother 1987;31(3):361-7.
  11. ↑ Meyding-Lamade UK, Oberlinner C, Rau PR, Seyfer S, Heiland S, Sellner J, et al. Experimental herpes simplex virus encephalitis: a combination therapy of acyclovir and glucocorticoids reduces long-term magnetic resonance imaging abnormalities. J Neurovirol 2003;9(1):118-25.
  12. ↑ Hato N, Matsumoto S, Kisaki H, Takahashi H, Wakisaka H, Honda N, et al. Efficacy of early treatment of Bell's palsy with oral acyclovir and prednisolone. Otol Neurotol 2003;24(6):948-51.
  13. ↑ 13.0 13.1 Moreno J, Montero JL, Gavilan F, Costan G, Herrero C, Cardenas M, et al. [Open clinical trial with oral acyclovir for the prophylaxis of disease by Cytomegalovirus in low risk liver transplant recipients]. Enferm Infecc Microbiol Clin 1999;17(8):382-5.
  14. ↑ 14.0 14.1 Vila A, Guirado LL, Balius A, Diaz M, Baro E, Olaya M, et al. Acyclovir prophylaxis of cytomegalovirus disease in kidney transplant recipients. Transplant Proc 1999;31(6):2335-6.
  15. ↑ Andersson J, Skoldenberg B, Ernberg I, Britton S, Henle W, Andersson U. Acyclovir treatment in primary Epstein-Barr virus infection. A double-blind placebo-controlled study. Scand J Infect Dis Suppl 1985;47:107-15.
  16. ↑ Ernberg I, Andersson J. Acyclovir efficiently inhibits oropharyngeal excretion of Epstein-Barr virus in patients with acute infectious mononucleosis. J Gen Virol 1986;67 ( Pt 10):2267-72.
  17. ↑ Pagano JS, Sixbey JW, Lin JC. Acyclovir and Epstein-Barr virus infection. J Antimicrob Chemother 1983;12 Suppl B:113-21.
  18. ↑ Kurahara K, Aoyagi K, Nakamura S, Kuwano Y, Yamamoto C, Iida M, et al. Treatment of herpes simplex esophagitis in an immunocompetent patient with intravenous acyclovir: a case report and review of the literature. Am J Gastroenterol 1998;93(11):2239-40.
  19. ↑ Glick M, Pliskin ME. Regression of oral hairy leukoplakia after oral administration of acyclovir. Gen Dent 1990;38(5):374-5.
  20. ↑ Resnick L, Herbst JS, Ablashi DV, Atherton S, Frank B, Rosen L, et al. Regression of oral hairy leukoplakia after orally administered acyclovir therapy. Jama 1988;259(3):384-8.
  21. ↑ Gibson JR, Klaber MR, Harvey SG, Tosti A, Jones D, Yeo JM. Prophylaxis against herpes labialis with acyclovir cream--a placebo-controlled study. Dermatologica 1986;172(2):104-7.
  22. ↑ Uchoa UB, Rezende RA, Carrasco MA, Rapuano CJ, Laibson PR, Cohen EJ. Long-term acyclovir use to prevent recurrent ocular herpes simplex virus infection. Arch Ophthalmol 2003;121(12):1702-4.
  23. ↑ Pancheva S, Shishkov S, Ilieva D. Effect of combined acyclovir and ribavirin on experimental herpes simplex virus type 1 keratoconjunctivitis in rabbits. Acta Microbiol Bulg 1993;29:61-4.
  24. ↑ El-Daher N, Magnussen R, Betts RF. Varicella pneumonitis: clinical presentation and experience with acyclovir treatment in immunocompetent adults. Int J Infect Dis 1998;2(3):147-51.
  25. ↑ Pasqualucci A, Pasqualucci V, Galla F, De Angelis V, Marzocchi V, Colussi R, et al. Prevention of post-herpetic neuralgia: acyclovir and prednisolone versus epidural local anesthetic and methylprednisolone. Acta Anaesthesiol Scand 2000;44(8):910-8.
  26. ↑ Rompalo AM, Mertz GJ, Davis LG, Benedetti J, Critchlow C, Stamm WE, et al. Oral acyclovir for treatment of first-episode herpes simplex virus proctitis. Jama 1988;259(19):2879-81.
  27. ↑ Latysheva SV, Andreeva OT, Darevskii VI. [Effectiveness of acyclovir in the therapy of recurrent herpetic stomatitis]. Stomatologiia (Mosk) 1988;67(2):22-4.
  28. ↑ Legge RH, Thompson AB, Linder J, Woods GL, Robbins RA, Moulton AL, et al. Acyclovir-responsive herpetic tracheobronchitis. Am J Med 1988;85(4):561-3.
  29. ↑ Lin TY, Huang YC, Ning HC, Hsueh C. Oral acyclovir prophylaxis of varicella after intimate contact. Pediatr Infect Dis J 1997;16(12):1162-5.

PUBMED References

Efficacy Trial Articles

  1. Fiddian AP, Halsos AM, Kinge BR, Nilsen AE, Wikstrom K. Oral acyclovir in the treatment of genital herpes. Preliminary report of a multicenter trial. Am J Med 1982;73(1A):335-7.
  2. Nilsen AE, Aasen T, Halsos AM, Kinge BR, Tjotta EA, Wikstrom K, et al. Efficacy of oral acyclovir in the treatment of initial and recurrent genital herpes. Lancet 1982;2(8298):571-3.
  3. Kinghorn GR, Jeavons M, Rowland M, Abeywickreme I, Barton IG, Potter CW, et al. Acyclovir prophylaxis of recurrent genital herpes: randomised placebo controlled crossover study. Genitourin Med 1985;61(6):387-90.
  4. Spruance SL, Nett R, Marbury T, Wolff R, Johnson J, Spaulding T. Acyclovir cream for treatment of herpes simplex labialis: results of two randomized, double-blind, vehicle-controlled, multicenter clinical trials. Antimicrob Agents Chemother 2002;46(7):2238-43.
  5. Meyding-Lamade UK, Oberlinner C, Rau PR, Seyfer S, Heiland S, Sellner J, et al. Experimental herpes simplex virus encephalitis: a combination therapy of acyclovir and glucocorticoids reduces long-term magnetic resonance imaging abnormalities. J Neurovirol 2003;9(1):118-25.
  6. Hato N, Matsumoto S, Kisaki H, Takahashi H, Wakisaka H, Honda N, et al. Efficacy of early treatment of Bell's palsy with oral acyclovir and prednisolone. Otol Neurotol 2003;24(6):948-51.
  7. Moreno J, Montero JL, Gavilan F, Costan G, Herrero C, Cardenas M, et al. Open clinical trial with oral acyclovir for the prophylaxis of disease by Cytomegalovirus in low risk liver transplant recipients. Enferm Infecc Microbiol Clin 1999;17(8):382-5.
  8. Andersson J, Skoldenberg B, Ernberg I, Britton S, Henle W, Andersson U. Acyclovir treatment in primary Epstein-Barr virus infection. A double-blind placebo-controlled study. Scand J Infect Dis Suppl 1985;47:107-15.
  9. Ernberg I, Andersson J. Acyclovir efficiently inhibits oropharyngeal excretion of Epstein-Barr virus in patients with acute infectious mononucleosis. J Gen Virol 1986;67 ( Pt 10):2267-72.
  10. Pagano JS, Sixbey JW, Lin JC. Acyclovir and Epstein-Barr virus infection. J Antimicrob Chemother 1983;12 Suppl B:113-21.
  11. Kurahara K, Aoyagi K, Nakamura S, Kuwano Y, Yamamoto C, Iida M, et al. Treatment of herpes simplex esophagitis in an immunocompetent patient with intravenous acyclovir: a case report and review of the literature. Am J Gastroenterol 1998;93(11):2239-40.
  12. Resnick L, Herbst JS, Ablashi DV, Atherton S, Frank B, Rosen L, et al. Regression of oral hairy leukoplakia after orally administered acyclovir therapy. Jama 1988;259(3):384-8.
  13. Gibson JR, Klaber MR, Harvey SG, Tosti A, Jones D, Yeo JM. --a placebo-controlled study. Dermatologica 1986;172(2):104-7.
  14. Uchoa UB, Rezende RA, Carrasco MA, Rapuano CJ, Laibson PR, Cohen EJ. Long-term acyclovir use to prevent recurrent ocular herpes simplex virus infection. Arch Ophthalmol 2003;121(12):1702-4.
  15. Pancheva S, Shishkov S, Ilieva D. Effect of combined acyclovir and ribavirin on experimental herpes simplex virus type 1 keratoconjunctivitis in rabbits. Acta Microbiol Bulg 1993;29:61-4.
  16. El-Daher N, Magnussen R, Betts RF. Varicella pneumonitis: clinical presentation and experience with acyclovir treatment in immunocompetent adults. Int J Infect Dis 1998;2(3):147-51.
  17. Pasqualucci A, Pasqualucci V, Galla F, De Angelis V, Marzocchi V, Colussi R, et al. Prevention of post-herpetic neuralgia: acyclovir and prednisolone versus epidural local anesthetic and methylprednisolone. Acta Anaesthesiol Scand 2000;44(8):910-8.
  18. Rompalo AM, Mertz GJ, Davis LG, Benedetti J, Critchlow C, Stamm WE, et al. Oral acyclovir for treatment of first-episode herpes simplex virus proctitis. Jama 1988;259(19):2879-81.
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Therapeutic Class Comparison Articles

  1. Tyring SK, Douglas JM, Jr., Corey L, Spruance SL, Esmann J. A randomized, placebo-controlled comparison of oral valacyclovir and acyclovir in immunocompetent patients with recurrent genital herpes infections. The Valaciclovir International Study Group. Arch Dermatol 1998;134(2):185-91
  2. Balfour HH, Jr. Antiviral drugs. N Engl J Med 1999; 340 (16):1255-68.

Pharmacokinetics Articles

  1. Blum MR, Liao SH, de Miranda P. Overview of acyclovir pharmacokinetic disposition in adults and children. Am J Med 1982;73(1A):186-92.
  2. de Miranda P, Blum MR. Pharmacokinetics of acyclovir after intravenous and oral administration. J Antimicrob Chemother 1983;12 Suppl B:29-37.
  3. Whitley RJ, Blum MR, Barton N, de Miranda P. Pharmacokinetics of acyclovir in humans following intravenous administration. A model for the development of parenteral antivirals. Am J Med 1982;73(1A):165-71.
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Drug Interaction Articles

  1. DeBony F, Tod M, Bidault M, et al. Multiple interactions of cimetidine and probenecid with valacyclovir and its metabolite acyclovir. Antimicrob Agents Chemother 2002;46:458—63
  2. Parmeggiani A, Riva R, Posar A, et al. Possible interaction between acyclovir and antiepileptic treatment. Ther Drug Monit 1995;17:312—5

Adverse Effects Articles

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Compliance Articles

Pharmacoeconomic Articles

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External Links

Clinical treatment guidelines

Patient information pages

Other resources

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