Generic Name: Valacyclovir Hydrochloride
Class: Nucleosides and Nucleotides
VA Class: AM800
Chemical Name: 2-[(2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxyl]ethyl ester-l-valine monohydrochloride
Molecular Formula: C13H20N6O4•ClH
CAS Number: 124832-27-5

Introduction

Antiviral; prodrug of acyclovir, a nucleoside.1

Uses for Valtrex

Genital Herpes

Treatment of initial episodes of genital herpes in immunocompetent1 24 29 30 or HIV-infected24 adults and adolescents.

Episodic treatment of recurrent episodes of genital herpes in immunocompetent1 24 29 30 or HIV-infected24 adults and adolescents.

Chronic suppressive therapy of recurrent episodes of genital herpes in immunocompetent or HIV-infected adults and adolescents.1 24 29 30 33 When used for suppressive therapy in immunocompetent individuals, the risk of heterosexual transmission of genital herpes to susceptible partners is reduced;1 35 efficacy for reducing transmission not established in those with multiple partners or in non-heterosexual couples.1

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CDC and others recommend oral acyclovir, oral famciclovir, or oral valacyclovir as drug of choice for treatment of initial episodes of genital herpes and for episodic treatment or chronic suppressive therapy of recurrent genital herpes.24 29 30

Herpes Labialis

Treatment of herpes labialis (perioral herpes, cold sores, fever blisters) in adults and adolescents.1 34

Safety and efficacy not established in immunocompromised patients.1

Mucocutaneous Herpes Simplex Virus (HSV) Infections

Treatment of recurrent mucocutaneous HSV infections in HIV-infected adults.26

Chronic suppressive or maintenance therapy (secondary prophylaxis) against recurrence of HSV infections in HIV-infected individuals who have frequent or severe recurrences.25 26

Herpes Zoster

Treatment of acute, localized herpes zoster (shingles, zoster) in adults and adolescents.1 4 10 11

Treatment of localized dermatomal herpes zoster in HIV-infected adults or adolescents.38 If cutaneous lesions are extensive or there is clinical evidence of visceral involvement, IV acyclovir should be used for initial treatment.38

Safety and efficacy not established in immunocompromised patients.1

Safety and efficacy not established for treatment of disseminated herpes zoster.1

Prevention of Cytomegalovirus (CMV) Disease in Transplant Recipients

Prevention of CMV disease in kidney transplant recipients at high risk (CMV-seropositive donor).27

Not recommended for prevention of CMV disease in hematopoietic stem cell transplant (HSCT) recipients because the drug is presumed to be less effective than ganciclovir.31

Not recommended for primary prevention of CMV disease in HIV-infected individuals because of an unexplained trend toward increased mortality in clinical studies.25 28

Valtrex Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals.1

Patients should maintain adequate hydration during treatment.1

Dosage

Available as valacyclovir hydrochloride;1 dosage expressed in terms of valacyclovir.1

Pediatric Patients

Genital Herpes, Herpes Labialis, Mucocutaneous Herpes Simplex Virus (HSV) Infections, and Herpes Zoster
Oral

Adolescents should receive dosage recommended for adults.24 (See Adults under Dosage and Administration.)

Adults

Genital Herpes
Treatment of First Episodes
Oral

Immunocompetent adults: 1 g twice daily for 7–10 days.1 24 29 30 CDC suggests duration of treatment may be extended if healing is incomplete after 10 days.24

HIV-infected adults: 1 g twice daily for 7–14 days recommended by CDC and others.38

Initiate therapy within 48 hours of onset of signs and symptoms;1 efficacy not established if initiated >72 hours after onset of signs or symptoms.1

Episodic Treatment of Recurrent Episodes
Oral

Immunocompetent adults: 500 mg twice daily for 3 days.1 24 29 30 Alternatively, CDC recommends 1 g once daily for 5 days.24

HIV-infected adults: CDC recommends 1 g twice daily for 5–10 days;24 may be continued for 7–14 days.38

Initiate therapy at first sign or symptom of an episode;1 efficacy not established if initiated >24 hours after onset of signs or symptoms.1

Suppressive Therapy of Recurrent Episodes
Oral

Immunocompetent adults: 1 g once daily.1 24 30 Alternatively, 500 mg once daily for those with a history of ≤9 recurrences per year.1 24 30

HIV-infected adults: 500 mg twice daily.1 24

Manufacturer states safety and efficacy not established beyond a duration of 1 year in immunocompetent or 6 months in HIV-infected individuals.1

Because frequency of recurrent episodes diminishes over time in many patients, CDC and others recommend suppressive antiviral therapy be discontinued periodically (e.g., once yearly) to assess the need for continued therapy.24 29 30

Reduction of Transmission
Oral

500 mg once daily in source partner with a history of ≤9 recurrences per year.1

Efficacy for reducing transmission not established beyond a duration of 8 months in discordant couples.1

Herpes Labialis
Oral

Immunocompetent adults: 2 g every 12 hours for 1 day;1 treatment for cold sores should not exceed 1 day.1

Initiate treatment at earliest symptom of cold sore (e.g., tingling, itching, burning);1 efficacy not established if initiated after development of clinical signs of cold sore (e.g., papule, vesicle, ulcer).1

Mucocutaneous Herpes Simplex Virus (HSV) Infections
Chronic Suppression of Recurrent Episodes
Oral

HIV-infected adults: 500 mg twice daily for chronic suppressive or maintenance therapy (secondary prophylaxis) of HSV infections in those who have frequent or severe recurrences.25

Herpes Zoster
Oral

Immunocompetent adults: 1 g 3 times daily for 7 days.1

Local dermatomal herpes zoster in HIV-infected adults or adolescents: 1 g 3 times daily for 7–10 days recommended by CDC and others.38

Initiate therapy at earliest sign or symptom (preferably within 48 hours of rash onset);1 efficacy not established if initiated >72 hours after rash onset.1

Special Populations

Hepatic Impairment

Dosage adjustments not recommended for patients with cirrhosis.1

Renal Impairment

Genital Herpes
Oral
Table 1. Dosage for Treatment of Genital Herpes in Renal Impairment1

Clcr (mL/min)

Daily Dosage

First Episodes

 

≥50

1 g every 12 hours

30–49

1 g every 12 hours

10–29

1 g once every 24 hours

<10

500 mg once every 24 hours

Episodic Treatment of Recurrent Episodes

 

≥50

500 mg every 12 hours

30–49

500 mg every 12 hours

10–29

500 mg once every 24 hours

<10

500 mg once every 24 hours

Suppressive Therapy of Recurrent Episodes (Immunocompetent with >9 Episodes/Year)

 

≥50

1 g once every 24 hours

30–49

1 g once every 24 hours

10–29

500 mg once every 24 hours

<10

500 mg once every 24 hours

Suppressive Therapy of Recurrent Episodes (Immunocompetent with <9 Episodes/Year)

 

≥50

500 mg once every 24 hours

30–49

500 mg once every 24 hours

10–29

500 mg once every 48 hours

<10

500 mg once every 48 hours

Suppressive Therapy of Recurrent Episodes (HIV-infected Individuals)

 

≥50

500 mg every 12 hours

30–49

500 mg every 12 hours

10–29

500 mg once every 24 hours

<10

500 mg once every 24 hours

Herpes Labialis
Oral
Table 2. Dosage for Treatment of Herpes Labialis in Renal Impairment1

Clcr (mL/min)

Daily Dosage

≥50

2 g every 12 hours for 1 day

30–49

1 g every 12 hours for 1 day

10–29

500 mg every 12 hours for 1 day

<10

A single dose of 500 mg

Herpes Zoster
Oral
Table 3. Dosage for Treatment of Herpes Zoster in Renal Impairment1

Clcr (mL/min)

Daily Dosage

≥50

1 g every 8 hours

30–49

1 g every 12 hours

10–29

1 g once every 24 hours

<10

500 mg once every 24 hours

Hemodialysis

Usual dose should be administered after hemodialysis.23

Peritoneal Dialysis

Supplemental doses unnecessary following CAPD or CAVHD.1

Geriatric Patients

No dosage adjustments except those related to renal impairment.1 23

Cautions for Valtrex

Contraindications

  • Known hypersensitivity or intolerance to valacyclovir, acyclovir, or any component of the formulation.1

Warnings/Precautions

Warnings

Hematologic Effects

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (sometimes fatal) reported in patients with advanced HIV infection and in allogeneic bone marrow or renal transplant recipients receiving high dosages (8 g daily).1 23

General Precautions

Renal Effects

Use of inappropriately high dosage for the level of renal function has resulted in acute renal failure in patients with underlying renal disease.1

Acyclovir may precipitate in renal tubules if solubility (2.5 mg/mL) is exceeded in intratubular fluid.1 Maintain adequate hydration.1

If acute renal failure and anuria occur, hemodialysis recommended until normal renal function returns.1

CNS Effects

Use of inappropriately high dosage for the level of renal function has resulted in CNS symptoms in patients with underlying renal disease.1

Genital Herpes

Valacyclovir is not a cure for genital herpes.1

Avoid sexual contact while lesions and/or symptoms are present due to risk of infecting sexual partners.1 Infection can be transmitted in the absence of symptoms through asymptomatic viral shedding.1

Although use for suppressive therapy in immunocompetent individuals with genital herpes decreases the risk for heterosexual transmission, safer sex practices also should be used.1 Efficacy for reducing transmission not established in individuals with multiple partners or in non-heterosexual couples.1

Type-specific serologic testing of asymptomatic partners of individuals with genital herpes can determine whether risk for HSV-2 acquisition exists.1

Valacyclovir has not been shown to reduce transmission of sexually transmitted infections other than HSV-2.1

Recommended by CDC and others for episodic treatment of genital herpes or chronic suppressive therapy of recurrent episodes in HIV-infected adults and adolescents,1 25 26 but manufacturer says efficacy not established for treatment of genital herpes in HIV-infected individuals and safety and efficacy not established for chronic suppressive therapy in those with advanced HIV disease (CD4+ T-cell count <100/mm3).1

Herpes Labialis

Valacyclovir is not a cure for cold sores.1

Treatment should not exceed a single day;1 therapy beyond 1 day does not provide additional clinical benefits.1

Because of high dosage, use caution when prescribing valacyclovir for treatment of cold sores in geriatric individuals or those with renal impairment.1 (See Special Populations under Dosage and Administration.)

Safety and efficacy not established for treatment of cold sores in immunocompromised individuals.1

Herpes Zoster

Safety and efficacy not established for treatment of disseminated herpes zoster or for treatment of herpes zoster in immunocompromised individuals.1

Specific Populations

Pregnancy

Category B.1

Lactation

Acyclovir distributed into human milk following oral administration of valacyclovir.1 Use valacyclovir with caution.1

Pediatric Use

Safety and efficacy not established in prepubertal children.1

Geriatric Use

Increased risk of adverse renal or CNS effects.1 CNS effects reported more frequently in geriatric adults than in younger adults include agitation, hallucinations, confusion, delirium, and encephalopathy.1

In herpes zoster, longer duration of pain after healing (post-herpetic neuralgia) than in younger adults.1

Consider age-related decreases in renal function when selecting dosage and adjust dosage if necessary.1 23 (See Renal Impairment under Dosage and Administration.)

Renal Impairment

Decreased clearance; increased risk of adverse renal and CNS effects in patients with underlying renal disease receiving high dosages.1

Adjust dosage as necessary.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Headache, nausea, vomiting.1

Interactions for Valtrex

Neither valacyclovir nor acyclovir metabolized by CYP isoenzymes.1

Specific Drugs

Drug

Interaction

Comments

Antacids (aluminum- or magnesium-containing)

No effect on acyclovir pharmacokinetics1

Use usual dosages1

Cimetidine

Potential increased peak plasma concentrations and AUC of acyclovir1

Not considered clinically important if renal function normal;1 use usual dosages1

Digoxin

No effect on pharmacokinetics of acyclovir or digoxin1

Use usual dosages1

Probenecid

Potential increased peak plasma concentrations and AUC of acyclovir1

Not considered clinically important if renal function normal;1 use usual dosage1

Thiazide diuretics

No effect on acyclovir pharmacokinetics1

Use usual dosages1

Valtrex Pharmacokinetics

Absorption

Bioavailability

Valacyclovir hydrochloride, a prodrug of acyclovir, is rapidly absorbed following oral administration and almost completely converted to acyclovir andl-valine by first-pass intestinal and/or hepatic metabolism.1 36

Absolute bioavailability of acyclovir approximately 54% following oral administration of valacyclovir hydrochloride;1 36 peak acyclovir plasma concentrations attained within 1.7 hours.36

Food

Administration of valacyclovir with food does not alter acyclovir bioavailability.1

Distribution

Extent

Although there are no adequate studies using valacyclovir, acyclovir crosses the placenta.1

Following oral administration of valacyclovir to the mother, acyclovir is distributed into milk.1

Plasma Protein Binding

13.5–17.9% bound to plasma proteins.1

Elimination

Metabolism

Valacyclovir hydrochloride rapidly converted to acyclovir and l-valine by first-pass intestinal and/or hepatic metabolism.1 Acyclovir converted to acyclovir monophosphate, diphosphate, and triphosphate in cells infected with herpesviruses.1

Neither valacyclovir nor acyclovir metabolized by CYP enzymes.1

Elimination Route

Valacyclovir principally eliminated as acyclovir;1 46 and 47% of an oral dose eliminated in urine and feces, respectively.1 36

Half-life

Plasma elimination half-life of acyclovir after oral administration of valacyclovir averages 2.5–3.3 hours.1 36

Special Populations

Renal clearance and elimination half-life decreased in patients with renal impairment;1 half-life averages 14 hours in end-stage renal disease.1

Pharmacokinetics in geriatric patients vary depending on renal function.1

Stability

Storage

Oral

Tablets

15–25°C.1

Actions and Spectrum

  • Valacyclovir is thel-valine ester of acyclovir.1 2 3 4 5 6 7 8 9 Prodrug with no antiviral activity until converted in vivo to acyclovir and subsequently to the active acyclovir triphosphate.1 2 5 6 7

  • GI absorption of valacyclovir substantially greater than absorption of oral acyclovir resulting in plasma acyclovir concentrations comparable to those achieved with IV acyclovir.36

  • Active against Herpesviridae including herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), and cytomegalovirus (CMV).1

  • Acyclovir highly selective for thymidine kinase encoded by HSV and VZV, which converts acyclovir into acyclovir monophosphate, which is further converted to the diphosphate and then to the active triphosphate via other cellular enzymes.1 Also exhibits activity against viruses that do not code for this enzyme.12 13 14 15 16 17 18 19 20

  • Inhibits viral DNA replication by competitive inhibition of viral DNA polymerase, incorporation and termination of the growing viral DNA chain, and inactivation of the viral DNA polymerase.1

  • Resistant strains of HSV and VZV reported.1

Advice to Patients

  • Advise patients that valacyclovir is not a cure for genital herpes or herpes labialis (cold sores).1

  • Importance of avoiding sexual contact with uninfected partners while genital herpes lesions and/or symptoms are present since there is a risk of transmission.1 Genital herpes can be transmitted in the absence of symptoms.1

  • Importance of using safer sex practices in conjunction with use of valacyclovir for suppressive therapy of genital herpes.1

  • Importance of initiating treatment of genital herpes recurrence as soon as possible following onset of signs and symptoms.1

  • For treatment of herpes labialis, importance of initiating treatment immediately following onset of symptoms (tingling, itching, burning) and importance of not using valacyclovir for longer than 1 day.1

  • Importance of maintaining adequate hydration during treatment.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Valacyclovir Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

500 mg (of valacyclovir)

Valtrex Caplets (with povidone)

GlaxoSmithKline

1 g (of valacyclovir)

Valtrex Caplets (with povidone)

GlaxoSmithKline

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Valacyclovir HCl 1GM Tablets (AUROBINDO PHARMA): 30/$340.99 or 90/$975.97

Valacyclovir HCl 500MG Tablets (MYLAN): 30/$185.99 or 90/$525.97

Valtrex 1GM Tablets (GLAXO SMITH KLINE): 30/$365.99 or 90/$1,050.46

Valtrex 500MG Tablets (GLAXO SMITH KLINE): 30/$235.98 or 90/$660.00

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. GlaxoSmithKline. Valtrex (valacyclovir hydrochloride) caplets prescribing information. Research Triangle Park, NC; 2006 Jul.

2. Jacobson MA, Gallant J, Wang LH et al. Phase I trial of valaciclovir, the l-valyl ester of acyclovir, in patients with advanced human immunodeficiency virus disease. Antimicrob Agents Chemother. 1994; 38:1534-40. [IDIS 332383] [PubMed 7979285]

3. Darby G. Acyclovir—and beyond. J Int Med Res. 1994; 22(Suppl 1):33-42A. [PubMed 8187942]

4. Beutner KR, Friedman DJ, Forszpaniak C et al. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1995; 39:1546-53. [IDIS 350497] [PubMed 7492102]

5. Gnann JW Jr. New antivirals with activity against varicella-zoster virus. Ann Neurol. 1994; 34(Suppl):S69-72.

6. Easterbrook P, Wood MJ. Successors to acyclovir. J Antimicrob Chemother. 1994; 34:307-11. [IDIS 336425] [PubMed 7829405]

7. Weller S, Blum MR, Doucette M et al. Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers. Clin Pharmacol Ther. 1993; 54:595-605. [IDIS 324231] [PubMed 8275615]

8. Lampkin TA. Valacyclovir HCl (Valtrex) administration achieves increased acyclovir concentration in multiple populations. Int Pharm Abst. 1994; 31:2291.

9. Shaefer MS. Valacyclovir HCl (Valtrex) provides simplified dosing and increased efficacy in the treatment of herpes virus infections. Int Pharm Abst. 1994; 31:2244-5.

10. The International Valaciclovir Zoster Study Group, Smiley ML. The efficacy and safety of valaciclovir for the treatment of herpes zoster. Proceedings of ICAAC New Orleans 1993. Abstract No. 1203.

11. The International Valaciclovir Zoster Study Group, Smiley ML. Valaciclovir and acyclovir for the treatment of recurrent genital herpes simplex virus infections. Proceedings of ICAAC New Orleans 1993. Abstract No. 1210.

12. Koch-Weser J, Hirsch MS, Swartz MN. Drug therapy: antiviral agents (second of two parts). N Engl J Med. 1980; 302:949-53. [IDIS 113597] [PubMed 6244492]

13. Lerner AM. Acyclovir reaches clinical trial. Ann Intern Med. 1982; 96:370-2. [IDIS 146189] [PubMed 7036819]

14. Weller IV, Carreno V, Fowler MJ et al. Acyclovir inhibits hepatitis B virus replication in man. Lancet. 1982; 1:273. [IDIS 144926] [PubMed 6120286]

15. Colby BM, Furman PA, Shaw JE et al. Phosphorylation of acyclovir [9-(2-hydroxyethoxymethyl)-guanine] in Epstein-Barr virus infected lymphoblastoid cell lines. J Virol. 1981; 38:606-11. [PubMed 6264131]

16. St. Clair MH, Furman PA, Lubbers CM et al. Inhibition of cellular α and virally induced deoxyribonucleic acid polymerases by the triphosphate of acyclovir. Antimicrob Agents Chemother. 1980; 18:741-5. [PubMed 7192534]

17. Tyms AS, Scamans EM, Naim HM. The in vitro activity of acyclovir and related compounds against cytomegalovirus infections. J Antimicrob Chemother. 1981; 8:65-72. [PubMed 6265430]

18. Burns WH, Wingard JR, Bender WJ et al. Thymidine kinase not required for antiviral activity of acyclovir against mouse cytomegalovirus. J Virol. 1981; 30:889-93.

19. McCarthy P (Burroughs Wellcome Co, Research Triangle Park, NC): Personal communication; 1982 Aug.

20. Mar E, Patel PC, Huang E. Effect of 9-(2-hydroxyethoxymethyl) guanine on viral-specific polypeptide synthesis in human cytomegalovirus-infected cell. Am J Med. 1982; 73(Acyclovir symposium):82-5. [IDIS 154027] [PubMed 6285739]

21. Lang DJ, Cheung K. Effectiveness of acycloguanosine and trifluorothymidine as inhibitors of cytomegalovirus infection in vitro. Am J Med. 1982; 73(Acyclovir symposium):49-53. [IDIS 154025] [PubMed 6285732]

22. Pagano JS, Datta AK. Perspectives on interactions of acyclovir with Epstein-Barr and other herpes viruses. Am J Med. 1982; 73(Acyclovir symposium):18-26. [IDIS 156729] [PubMed 6285710]

23. Glaxo Wellcome, Inc, Research Triangle Park, NC: Personal communication.

24. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006; 55(RR-11):1-95.

25. US Public Health Service (USPHS) and Infectious Diseases Society of America (IDSA) Prevention of Opportunistic Infections Working Group. 2001 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons with human immunodeficiency virus. From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website ().

26. Balfour HH. Antiviral drugs. N Engl J Med. 1999; 340:1255-68. [IDIS 423356] [PubMed 10210711]

27. Lowance D, Neumayer HH, Legendre CM et al. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. N Engl J Med. 1999; 340:1462-70. [IDIS 427339] [PubMed 10320384]

28. Feinberg JE, Hurwitz S, Cooper D et al. A randomized, double-blind trial of valaciclovir prophylaxis for cytomegalovirus disease in patients with advanced human immunodeficiency virus infection. J Infect Dis. 1998; 177:48-56. [IDIS 399239] [PubMed 9419169]

29. Anon. Drugs for sexually transmitted infections. Treat Guidel Med Lett. 2004; 2:67-74. [PubMed 15529116]

30. Anon. Drugs for non-HIV viral infections. Treat Guidel Med Lett. 2005; 3:23-32.

31. Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: recommendations of CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation. MMWR Recomm Rep. 2000; 49(RR-10):1-125.

32. Leone P, Trottier S, Miller JM. Valacyclovir for episodic treatment of genital herpes: a shorter 3-day treatment course compared with 5-day treatment. Clin Infect Dis. 2002; 34:958-62. [IDIS 480416] [PubMed 11880962]

33. DeJesus E, Wald A, Warren T et al. Valacyclovir for suppression of recurrent genital herpes in human immunodeficiency virus-infected subjects. J Infect Dis. 2003; 188:1009-16. [IDIS 516503] [PubMed 14513421]

34. Spruance SL, Jones TM, Blatter MM et al. High-dose, short-duration, early valacyclovir therapy for episodic treatment of cold sores: results of two randomized, placebo-controlled, multicenter studies. Antimicrob Agents Chemother. 2003; 47:1072-80. [IDIS 495732] [PubMed 12604544]

35. Corey L, Wald A, Patel R et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004; 350:11-20. [IDIS 508984] [PubMed 14702423]

36. Soul-Lawton J, Seaber E, On N et al. Absolute bioavailability and metabolic disposition of valaciclovir, the L-valyl ester of acyclovir, following oral administration to humans. Antimicrob Agents Chemother. 1995; 39:2759-64. [IDIS 358708] [PubMed 8593015]

37. Soul-Lawton J, Seaber E, On N et al. Absolute bioavailability and metabolic disposition of valaciclovir, the L-valyl ester of acyclovir, following oral administration to humans. Antimicrobial Agents and Chemotherapy. 1995; 39:2759-64. [IDIS 358708] [PubMed 8593015]

38. 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.

39. Centers for Disease Control and Prevention. Treating opportunistic infections among HIV-exposed and infected children: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. MMWR Recomm Rep. 2004; 53( RR-14):1-92.

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