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Valacyclovir: Drug information

Valacyclovir: Drug information
(For additional information see "Valacyclovir: Patient drug information" and see "Valacyclovir: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Special Alerts
Valacyclovir-Containing Products Safety Review June 2022

After a safety review, Health Canada has concluded that there may be a link between the use of valacyclovir-containing products and the potential risk of drug reaction with eosinophilia and systemic symptoms (DRESS). This safety review was triggered by updates made by the European Medicines Agency to the product safety information for valacyclovir-containing products to include the risk of DRESS. Health Canada will work with manufacturers to update the Canadian product safety information for valacyclovir-containing products to include the risk of DRESS.

Further information may be found at https://hpr-rps.hres.ca/reg-content/summary-safety-review-detail.php?lang=en&linkID=SSR00284.

Brand Names: US
  • Valtrex
Brand Names: Canada
  • AG-Valacyclovir;
  • APO-Valacyclovir;
  • Auro-Valacyclovir;
  • BIO-Valacyclovir [DSC];
  • DOM-Valacyclovir [DSC];
  • JAMP Valacyclovir;
  • JAMP-Valacyclovir;
  • Mar-Valacyclovir [DSC];
  • MYLAN-Valacyclovir;
  • PMS-Valacyclovir;
  • Priva-Valacyclovir [DSC];
  • PRO-Valacyclovir;
  • RIVA-Valacyclovir;
  • SANDOZ Valacyclovir;
  • TEVA-Valacyclovir;
  • Valtrex
Pharmacologic Category
  • Antiviral Agent;
  • Antiviral Agent, Oral
Dosing: Adult
Bell palsy, new onset

Bell palsy, new onset (adjunctive therapy) (off-label use): Oral: 1 g three times daily for 7 days in combination with corticosteroids; begin within 3 days of symptom onset (Ref). Note: Antiviral therapy alone is not recommended (Ref); some experts only recommend addition of an antiviral to steroid therapy in patients with severe Bell palsy (Ref).

Cytomegalovirus, prevention in allogeneic hematopoietic cell transplant recipients

Cytomegalovirus, prevention in allogeneic hematopoietic cell transplant recipients (alternative agent) (off-label use): Oral: 2 g three to four times daily, beginning at engraftment and continued to day 100 (Ref) or 2 g three times daily, started after initial therapy with IV ganciclovir from day −8 to day −2 prior to transplant, and continued until engraftment or longer in patients on glucocorticoids (Ref). Note: Combine with screening for CMV reactivation (due to weak activity) (Ref).

Herpes simplex virus, meningitis

Herpes simplex virus, meningitis (off-label use): Oral: 1 g three times daily, to complete a 10- to 14-day course following clinical improvement with IV acyclovir. Note: Not recommended for herpes simplex virus encephalitis, which requires treatment with IV acyclovir (Ref).

Herpes simplex virus, mucocutaneous infection

Herpes simplex virus, mucocutaneous infection:

Genital:

Patients who are immunocompetent:

Treatment, initial episode: Oral: 1 g twice daily for 7 to 10 days; extend duration if lesion has not healed completely after 10 days (Ref).

Treatment, recurrent episode: Oral: 500 mg twice daily for 3 days or 1 g once daily for 5 days. Note: Treatment is most effective when initiated during the prodrome or within 1 day of lesion onset (Ref).

Suppressive therapy (eg, for severe and/or frequent recurrences): Oral: 500 mg or 1 g once daily. Note: Reassess need periodically (eg, annually). The 500 mg daily dose may be less effective in patients who experience very frequent (≥10) recurrences per year (Ref).

Patients who are immunocompromised (including patients with HIV):

Treatment, initial or recurrent episode: Oral: 1 g twice daily for 5 to 10 days (7 to 10 days for initial episode in patients with HIV); extend treatment duration if lesions have not healed completely after 10 days. Note: Treat severe disease initially with IV acyclovir; may switch to valacyclovir when lesions begin to regress and continue for >10 days total and until lesions have resolved completely (Ref).

Suppressive therapy (eg, for severe and/or frequent recurrences): Oral: 500 mg twice daily. Note: Reassess need periodically (eg, annually) (Ref).

Pregnant patients:

Treatment, initial episode (alternative agent): Oral: 1 g twice daily for 7 to 10 days; extend duration if lesion has not healed completely after 10 days (Ref).

Treatment, recurrent episode (symptomatic) (alternative agent): Oral: 500 mg twice daily for 3 days or 1 g once daily for 5 days (Ref). Note: Some experts reserve treatment of recurrent episodes for patients with severe and/or frequent symptoms (Ref).

Suppressive therapy, for patients with a genital herpes simplex virus lesion anytime during pregnancy (alternative agent): Oral: 500 mg twice daily, beginning at 36 weeks' gestation and continued until delivery (Ref); some experts recommend discontinuing suppressive therapy at the onset of labor (Ref). Note: For patients with a primary infection during the third trimester, may consider suppressive therapy earlier than 36 weeks’ gestation (Ref).

Orolabial: Note: Initiate therapy at earliest symptom.

Patients who are immunocompetent:

Treatment, initial infection (eg, gingivostomatitis): Oral: 1 g twice daily for 7 to 10 days (Ref).

Treatment, recurrent infection (eg, cold sores): Oral: 2 g twice daily for 1 day (Ref).

Suppressive therapy (eg, for severe and/or frequent recurrences): Oral: 500 mg or 1 g once daily (Ref).

Patients who are immunocompromised (including patients with HIV):

Treatment, initial or recurrent infection: Oral: 1 g twice daily for 5 to 10 days and until complete lesion resolution (Ref).

Suppressive therapy (eg, for severe and/or frequent recurrences): Oral: 500 mg twice daily. Note: Reassess need periodically (eg, annually) (Ref).

Herpes simplex virus, prevention in patients who are immunocompromised

Herpes simplex virus, prevention in patients who are immunocompromised (off-label use):

Seropositive HCT recipients (allogeneic or autologous) or seropositive patients undergoing leukemia induction chemotherapy: Oral: 500 mg twice daily (Ref). Note: Initiate with the chemotherapeutic or conditioning regimen and continue until recovery of WBC count and resolution of mucositis; duration may be extended in patients with frequent recurrences or graft-vs-host disease (GVHD) (Ref).

Solid organ transplant recipients (patients who are HSV-seropositive who do not require CMV prophylaxis): Oral: 500 mg twice daily for ≥1 month (Ref); some experts recommend continuing for 3 to 6 months after transplantation and during periods of lymphodepletion associated with treatment of rejection (Ref).

Herpes zoster, treatment

Herpes zoster (shingles), treatment:

Note: Initiate at earliest sign or symptom. Antiviral treatment is most effective ≤72 hours after rash onset but may be initiated >72 hours in certain situations (eg, new lesions continue to appear); for patients who are immunocompromised, initiate treatment even if >72 hours after symptom onset unless all lesions have crusted (Ref).

Acute localized dermatomal lesion(s): Oral: 1 g three times daily for 7 to 10 days; for slowly improving lesions, may extend therapy until resolution (Ref). For select patients who are immunocompromised at high risk of dissemination (eg, recent transplant, graft-versus-host disease), some experts suggest regimens used for disseminated zoster (Ref).

Disseminated zoster (extensive cutaneous lesions or visceral involvement): Oral: Initial therapy with acyclovir IV may be switched to valacyclovir 1 g three times daily to complete a 10- to 14-day course when formation of new lesions has ceased and signs/symptoms of visceral infection are improving (Ref).

Herpes zoster ophthalmicus

Herpes zoster ophthalmicus (off-label use): Oral: 1 g three times daily for 7 days (Ref).

Varicella, uncomplicated, treatment

Varicella (chickenpox), uncomplicated, treatment: Oral: 1 g three times daily (Ref). Note: Ideally initiate therapy within 24 hours of symptom onset, but may start later if patient still has active skin lesions; continue treatment for at least 5 to 7 days and until all lesions have crusted (Ref). In patients who are immunocompromised (eg, solid organ transplant recipients), some experts recommend a minimum duration of 7 days (Ref). Patients who are immunocompromised generally require IV acyclovir; however, for patients with uncomplicated or mild disease (<50 lesions), some experts treat with valacyclovir (Ref).

Varicella zoster virus, acute retinal necrosis

Varicella zoster virus, acute retinal necrosis (off-label use): Oral: 1 g three times daily following initial treatment with IV acyclovir (Ref); in patients with HIV, duration is ≥14 weeks and intravitreal ganciclovir may be considered (Ref).

Varicella zoster virus, prevention in patients who are immunocompromised

Varicella zoster virus, prevention in patients who are immunocompromised (off-label use):

HCT recipients (allogeneic and autologous):

Postexposure prophylaxis: Oral: 1 g three times daily; initiate within 96 hours (preferably within 48 hours) of exposure and continue until 22 days after exposure. Note: Indicated following exposure if varicella-zoster immune globulin is unavailable in seronegative HCT recipients who are <24 months after HCT or >24 months after HCT and on immunosuppressive therapy or have chronic GVHD (Ref).

Prevention of VZV reactivation in seropositive patients: Oral: 500 mg twice daily for 1 year following transplantation; may extend duration in patients requiring ongoing immunosuppression (some experts continue prophylaxis in these patients until 6 months after discontinuation of all systemic immunosuppression) (Ref).

Solid organ transplant recipients (patients who are VZV-seropositive who do not require CMV prophylaxis): Oral: 500 mg twice daily for 3 to 6 months after transplantation and during periods of lymphodepletion associated with treatment of rejection (Ref).

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: The following adjustments are based on usual doses up to 4 g/day. There are no specific dosage adjustment recommendations for patients receiving >4 g/day (eg, cytomegalovirus prevention in allogeneic hematopoietic cell transplant recipients [off-label use]); consultation with nephrology and/or transplant specialists is recommended in patients with altered kidney function.

Altered kidney function:

Valacyclovir Dose Adjustments for Kidney Impairmenta

CrCl

If usual recommended dose is 500 mg every 24 hours

If usual recommended dose is 1 g every 24 hours or 500 mg every 12 hours

If usual recommended dose is 1 g every 12 hours

If usual recommended dose is 1 g every 8 hours

If usual recommended dose is 2 g every 12 hours for 2 doses

aManufacturer’s labeling.

≥50 mL/minute

No dosage adjustment necessary

No dosage adjustment necessary

No dosage adjustment necessary

No dosage adjustment necessary

No dosage adjustment necessary

30 to <50 mL/minute

No dosage adjustment necessary

No dosage adjustment necessary

No dosage adjustment necessary

1 g every 12 hours

1 g every 12 hours for 2 doses

10 to <30 mL/minute

500 mg every 48 hours

500 mg every 24 hours

1 g every 24 hours

1 g every 24 hours

500 mg every 12 hours for 2 doses

<10 mL/minute

500 mg every 48 hours

500 mg every 24 hours

500 mg every 24 hours

500 mg every 24 hours

500 mg as a single dose

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):

Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post-trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).

Use the indication-specific maximum allowable dose along with therapeutic drug monitoring of acyclovir to support valacyclovir dosing when available (Ref).

Hemodialysis, intermittent (thrice weekly): Dialyzable (33% removed during 4-hour session).

500 mg every 24 hours; give after dialysis when given on dialysis day (Ref).

Peritoneal dialysis: 500 mg every 24 hours (Ref).

CRRT:

Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.

Usual recommended dose: 500 mg to 1 g every 12 to 24 hours along with therapeutic drug monitoring of acyclovir to support valacyclovir dosing when available; for less severe infections, a maximum daily dose of 1.5 g/day is recommended (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration):

Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.

Usual recommended dose: 500 mg to 1 g every 12 to 24 hours along with therapeutic drug monitoring of acyclovir to support valacyclovir dosing when available; for less severe infections, a maximum daily dose of 1.5 g/day is recommended (Ref).

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Valacyclovir: Pediatric drug information")

Herpes simplex virus, orolabial infection

Herpes simplex virus (HSV), orolabial infection: Note: Initiate at earliest symptom onset.

Patients without HIV: Treatment:

Weight-directed dosing: Limited data available: Infants ≥3 months, Children, and Adolescents: Oral: 20 mg/kg/dose every 12 hours; maximum dose: 1,000 mg/dose. In immunocompetent patients, treat for 5 to 7 days; immunocompromised patients may require 10 to 14 days of therapy (Ref).

Fixed dosing: Children ≥12 years and Adolescents: Oral: 2,000 mg every 12 hours for 1 day (2 doses) (Ref).

Patients with HIV: Limited data available:

Treatment: Adolescents: Oral: 1,000 mg every 12 hours for 5 to 10 days (Ref).

Suppressive therapy (eg, for severe or frequent recurrences): Adolescents: Oral: 500 mg every 12 hours; reassess continued need annually (Ref).

Herpes simplex virus, genital infection

Herpes simplex virus (HSV), genital infection: Limited data available:

First episode; treatment: Children and Adolescents: Oral: 20 mg/kg/dose every 12 hours; maximum dose: 1,000 mg/dose. Treat for 7 to 10 days; some patients may need a longer duration if lesions are incompletely healed (Ref).

Recurrent episode; treatment: Note: Most effective if started during prodrome or within 1 day lesion appearance (Ref).

Children and Adolescents: Oral: 20 mg/kg/dose every 12 hours; maximum dose: 1,000 mg/dose. Treat for 5 to 10 days (Ref). Alternatively, adolescents who are not HIV infected may receive 500 mg every 12 hours for 3 days (Ref).

Suppressive therapy:

Patients without HIV: Adolescents: Oral: 20 mg/kg/dose once daily; maximum dose: 500 mg/dose. In adolescents with frequent recurrences (ie, ≥10 per year), doses of 1,000 mg/day may be more effective (Ref).

Patients with HIV: Adolescents: Oral: 500 mg every 12 hours; reassess continued need annually (Ref).

Herpes simplex virus, prophylaxis in immunocompromised patients

Herpes simplex virus (HSV), prophylaxis in immunocompromised patients (alternative agent): Limited data available:

Hematopoietic cell transplant (HCT) recipients, seropositive:

Children and Adolescents: Note: To prevent early reactivation, begin at initiation of conditioning and continue until engraftment or resolution of mucositis; to prevent late reactivation, continue throughout the first year following HCT (Ref).

<40 kg: Oral: 250 mg twice daily.

≥40 kg: Oral: 500 mg once or twice daily; use twice-daily dosing in highly suppressed patients (eg, high-dose steroids, T cell depletion).

Solid organ transplant recipients, seropositive: Note: Administer for ≥1 month after transplant and during treatment of rejection episodes.

Children and Adolescents: Oral: 20 mg/kg/dose twice daily; maximum dose: 500 mg/dose (Ref).

Herpes zoster, treatment

Herpes zoster (shingles; caused by varicella zoster virus [VZV]), treatment:

Note: In immunocompromised patients with extensive lesions, visceral involvement, disseminated disease, or who are <2 years of age, initial parenteral treatment is recommended.

Children ≥2 years and Adolescents: Oral: 20 mg/kg/dose every 8 hours; maximum dose: 1,000 mg/dose. Treat for at least 7 to 10 days and until lesions have crusted over; lesions resolving more slowly may require longer treatment (Ref).

Varicella zoster virus, prophylaxis in HCT recipients

Varicella zoster virus (VZV) (chickenpox), prophylaxis in HCT recipients (alternative agent): Limited data available:

Postexposure prophylaxis (Ref):

Children and Adolescents: Note: Begin within 48 hours if possible; continue for 22 days postexposure.

<40 kg: Oral: 500 mg every 8 hours.

≥40 kg: Oral: 1,000 mg every 8 hours.

Prevention of VZV reactivation in seropositive patients:

Children and Adolescents:

<40 kg: Oral: 250 or 500 mg every 12 hours (Ref).

≥40 kg: Oral: 500 mg every 12 hours (Ref).

Varicella zoster virus, treatment

Varicella zoster virus (VZV) (chickenpox), treatment:

Note: Treatment not routinely recommended in otherwise healthy younger children; consider treatment in individuals at high risk for moderate to severe disease (eg, unvaccinated adolescents, patients with chronic cutaneous or pulmonary conditions, patients on long-term salicylate therapy or receiving corticosteroids). Parenteral acyclovir is generally recommended for immunocompromised patients; oral therapy may be considered in select cases when outcome is expected to be good or as oral step-down therapy (Ref).

Infants ≥3 months, Children, and Adolescents <18 years: Limited data available in patients <2 years of age: Oral: 20 mg/kg/dose every 8 hours for 5 days; maximum dose: 1,000 mg/dose; initiate as soon as possible and within 24 hours of rash onset. In immunocompromised patients, treat for 7 to 14 days, dependent upon clinical response; patients with HIV may need 4 to 6 weeks of treatment (Ref).

Varicella zoster virus, acute retinal necrosis; step-down therapy

Varicella zoster virus, acute retinal necrosis; step-down therapy: Limited data available: HIV-infected: Adolescents: 1,000 mg every 8 hours for ≥14 weeks (following initial treatment with IV acyclovir) (Ref).

Dosing: Kidney Impairment: Pediatric

Note: There are no pediatric-specific dose adjustments provided in the manufacturer's labeling; however, the following adjustments are recommended for adults receiving similar initial dosages.

Herpes labialis: Adolescents: Based on usual dose of 2,000 mg every 12 hours for 2 doses.

CrCl 30 to 49 mL/minute: 1,000 mg every 12 hours for 2 doses.

CrCl 10 to 29 mL/minute: 500 mg every 12 hours for 2 doses.

CrCl <10 mL/minute: 500 mg as a single dose.

Genital herpes: Adolescents:

Initial episode: Based on usual dose of 1,000 mg every 12 hours.

CrCl 10 to 29 mL/minute: 1,000 mg every 24 hours.

CrCl <10 mL/minute: 500 mg every 24 hours.

Recurrent episode: Based on usual dose of 500 mg every 12 hours.

CrCl ≤29 mL/minute: 500 mg every 24 hours.

Suppressive therapy: CrCl ≤29 mL/minute:

For usual dose of 1,000 mg every 24 hours, decrease dose to 500 mg every 24 hours.

For usual dose of 500 mg every 24 hours, decrease dose to 500 mg every 48 hours.

HIV-infected patients: 500 mg every 24 hours.

Hemodialysis: Dialyzable (~33% removed during 4-hour session); administer dose postdialysis.

Dosing: Hepatic Impairment: Pediatric

Children ≥2 years and Adolescents: No dosage adjustment necessary.

Adverse Reactions (Significant): Considerations
Acute kidney injury

As a prodrug of acyclovir, valacyclovir may also cause acute kidney injury (Ref). Like acyclovir, this may result most often from obstructive nephropathy but may also be due to interstitial nephritis or renal tubular necrosis. Kidney injury is reversible in most cases after dosage reduction or discontinuation; however, some cases may not return to baseline (Ref).

Mechanism: Dose-related; not clearly established, multiple proposed mechanisms. Usually attributed to the formation of acyclovir crystals, which result in intrarenal obstruction and nephropathy (Ref). May also be due to glomerular hyperfiltration; injury may occur because kidneys have little reserve, resulting in an intolerance to nephrotoxic insult or increased filtrate delivery to the renal tubules (Ref). Other proposed mechanisms include an immune reaction that may contribute to interstitial nephritis and a major metabolite of acyclovir (9-carboxymethoxymethylguanine [CMMG]) that may be directly cytotoxic to cells of the renal tubule (Ref).

Onset: Varied; reported cases range from 1 to 9 days of initiation (Ref).

Risk factors:

Less established than with acyclovir, but may include:

• Higher doses (Ref)

• Older adults (Ref)

• Preexisting kidney impairment (Ref)

• Hypertension (Ref)

• Diabetes (Ref)

• Concurrent use of nephrotoxic agents (eg, nonsteroidal anti-inflammatory drugs, vancomycin) (Ref)

Neurotoxicity

As a prodrug of acyclovir, valacyclovir may also cause neurotoxicity. Acyclovir-induced neurotoxicity most commonly includes reported symptoms such as agitation, confusion, dysarthria, hallucination, and impaired consciousness (Ref). Other reported symptoms include aphasia, ataxia, myoclonus, tremor, and seizure (including status epilepticus) (Ref). Most cases of neurotoxicity are reversible after discontinuation with or without hemodialysis; however, some cases may not be fully reversible (Ref).

Mechanism: Dose-related; indirect, via metabolite 9-carboxymethoxymethylguanine (CMMG) accumulation (Ref).

Onset: Rapid; typically reported within 3 days of initiation (Ref).

Risk factors:

Less established than with acyclovir, but may include:

• Higher doses (Ref)

• Kidney impairment (Ref); however, some cases have been reported in normal kidney function (Ref)

• Advanced age (Ref)

Thrombotic microangiopathy

Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS), manifestations of thrombotic microangiopathy, have been reported with both acyclovir and valacyclovir (Ref). TTP/HUS may result in damage to the brain, heart, kidney, liver, and pancreas (Ref). Resolution has been reported with drug discontinuation and appropriate therapy (Ref).

Mechanism: Idiosyncratic; thrombotic microangiopathy (and resulting TTP and HUS) involves endothelial cell injury, intravascular platelet-fibrin thrombi, and vascular damage (Trachtman 2013).

Onset: Varied; has been reported within 3 days of initiation (Ref) and after 1 year of therapy (Ref).

Risk factors (largely unknown):

• Genetic susceptibility may play a role for drug-induced HUS (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Gastrointestinal: Abdominal pain (3% to 11%), nausea (8% to 15%)

Hematologic & oncologic: Neutropenia (HIV-1-infected patients: 18%) (table 1)

Valacyclovir: Adverse Reaction: Neutropenia

Drug ( Valacyclovir )

Placebo

Dose

Indication

Number of Patients ( Valacyclovir )

Number of Patients (Placebo)

18%

10%

500 mg twice daily

Suppression of recurrent genital herpes in HIV-1−infected subjects

194

99

Hepatic: Increased serum alanine aminotransferase (2%; HIV-1-infected patients: 14%), increased serum aspartate aminotransferase (≤4%; HIV-1-infected patients: 16%)

Nervous system: Headache (13% to 38%)

Respiratory: Nasopharyngitis (16%)

1% to 10%:

Dermatologic: Skin rash (HIV-1-infected patients: 8%)

Endocrine & metabolic: Dehydration (infants and children: 2%)

Gastrointestinal: Diarrhea (infants and children: 5%; adults: <1%), vomiting (3% to 6%)

Genitourinary: Dysmenorrhea (5% to 8%)

Hematologic & oncologic: Leukopenia (≤1%), thrombocytopenia (HIV-1-infected patients: 3%) (table 2)

Valacyclovir: Adverse Reaction: Thrombocytopenia

Drug (Valacyclovir)

Placebo

Dose

Indication

Number of Patients ( Valacyclovir )

Number of Patients (Placebo)

3%

0%

500 mg twice daily

Suppression of recurrent genital herpes in HIV-1−infected subjects

194

99

Hepatic: Increased serum alkaline phosphatase (HIV-1-infected patients: 4%)

Infection: Herpes simplex infection (infants and children: 2%)

Nervous system: Depression (7%), dizziness (2% to 4%), fatigue (HIV-1-infected patients: 8%)

Neuromuscular & skeletal: Arthralgia (5% to 6%)

Respiratory: Rhinorrhea (infants and children: 2%)

Miscellaneous: Fever (infants and children: 4%)

<1%:

Hematologic & oncologic: Decreased hemoglobin

Renal: Increased serum creatinine

Postmarketing:

Cardiovascular: Hypertension, tachycardia

Dermatologic: Alopecia, erythema multiforme, skin photosensitivity, urticaria (Singh 2015)

Genitourinary: Urinary urgency

Hematologic & oncologic: Aplastic anemia, hemolytic-uremic syndrome (Bell 1997), thrombotic thrombocytopenic purpura (Bukhari 2020)

Hepatic: Hepatitis (Renkes 1999)

Hypersensitivity: Anaphylaxis, angioedema (Ebo 2008), drug reaction with eosinophilia and systemic symptoms (Ingen-Housz-Oro 2019), hypersensitivity angiitis, hypersensitivity reaction (acute) (Lammintausta 2001)

Nervous system: Aggressive behavior, agitation (Rivkin 2003), ataxia (Helldén 2006), coma (Carlon 2005), confusion (Yoshimura 2018), delirium (Asahi 2009), delusion (Helldén 2006), dysarthria (Asahi 2009), emotional lability (Memon 2021), encephalopathy (Guramrinder 2017), hallucination (Helldén 2006; Strumia 2004), loss of consciousness (Carlon 2005), mania, myoclonus (Strumia 2004), neuritis (Pary 2004), psychosis, seizure (Hoskote 2016), tremor (Prasad 2017)

Renal: Acute kidney injury (Kitano 2015; Sugimoto 2008)

Contraindications

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

Warnings/Precautions

Disease-related concerns:

• Renal impairment: Use caution in patients with renal impairment; dosage adjustments may be required.

Other warnings/precautions:

• Appropriate use: For genital herpes, treatment should begin as soon as possible after the first signs and symptoms (within 72 hours of onset of first diagnosis or within 24 hours of onset of recurrent episodes).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Valtrex: 500 mg [contains fd&c blue #2 (indigo carm) aluminum lake]

Valtrex: 1 g [scored; contains fd&c blue #2 (indigo carm) aluminum lake]

Generic: 500 mg, 1 g

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (valACYclovir HCl Oral)

1 g (per each): $11.62 - $12.66

500 mg (per each): $3.97 - $7.23

Tablets (Valtrex Oral)

1 g (per each): $25.38

500 mg (per each): $16.11

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Valtrex: 500 mg [contains fd&c blue #2 (indigo carm) aluminum lake, polysorbate 80]

Valtrex: 1 g [contains polysorbate 80]

Generic: 500 mg, 1000 mg, 1 g

Administration: Adult

May administer with or without food; maintain adequate hydration.

Administration: Pediatric

Oral: May administer with or without food; maintain adequate hydration.

Use: Labeled Indications

Treatment of herpes zoster (shingles) in patients who are immunocompetent; treatment of first-episode and recurrent genital herpes in patients who are immunocompetent; suppression of recurrent genital herpes and reduction of transmission of genital herpes in patients who are immunocompetent; suppression of genital herpes in patients with HIV; treatment of herpes labialis (cold sores); treatment of chickenpox in children who are immunocompetent.

Use: Off-Label: Adult

Bell palsy, new onset; Cytomegalovirus, prevention in allogeneic hematopoietic cell transplant recipients; Herpes simplex virus, meningitis; Herpes simplex virus, prevention in patients who are immunocompromised; Herpes zoster ophthalmicus; Varicella zoster virus, acute retinal necrosis; Varicella zoster virus, prevention in patients who are immunocompromised

Medication Safety Issues
Sound-alike/look-alike issues:

Valtrex may be confused with Keflex, Valcyte, Zovirax

ValACYclovir may be confused with acyclovir, valGANciclovir, vancomycin

Metabolism/Transport Effects

Substrate of OAT1/3, OCT1; Inhibits CYP1A2 (weak)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Fezolinetant: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination

Foscarnet: May enhance the nephrotoxic effect of Acyclovir-Valacyclovir. Risk X: Avoid combination

Mycophenolate: Acyclovir-Valacyclovir may increase the serum concentration of Mycophenolate. Mycophenolate may increase the serum concentration of Acyclovir-Valacyclovir. Risk C: Monitor therapy

Talimogene Laherparepvec: Antiherpetic Antivirals may diminish the therapeutic effect of Talimogene Laherparepvec. Risk C: Monitor therapy

Tenofovir Products: Acyclovir-Valacyclovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Risk C: Monitor therapy

Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification

Varicella Virus Vaccine: Acyclovir-Valacyclovir may diminish the therapeutic effect of Varicella Virus Vaccine. Management: When possible, avoid use of acyclovir or valacyclovir within the 24 hours prior to administration of the varicella vaccine, and avoid use of these antiviral agents for 14 days after vaccination. Risk X: Avoid combination

Zoster Vaccine (Live/Attenuated): Acyclovir-Valacyclovir may diminish the therapeutic effect of Zoster Vaccine (Live/Attenuated). Risk X: Avoid combination

Pregnancy Considerations

Following maternal administration of valacyclovir, acyclovir is detectable in the cord blood and amniotic fluid (Jacquemard 2007; Kimberlin 1998).

The valacyclovir pregnancy registry included information from 28 pregnancies with first-trimester valacyclovir exposure. Data from the registry, which closed in 1999, did not find a statistically significant increase in the number of birth defects with exposure to valacyclovir; however, data were limited and there were insufficient data regarding miscarriage or adverse maternal or fetal outcomes. Valacyclovir is metabolized to acyclovir; data from the acyclovir pregnancy registry did not find an increase in the number of birth defects with exposure to acyclovir when compared to those expected in the general population (refer to the Acyclovir monograph for additional information). A population-based registry study conducted in Denmark had similar results. The study used data from 1996 to 2008 and included 229 pregnancies with first-trimester valacyclovir exposure; an increased risk of birth defects was not observed (Pasternak 2010). One study observed an increased risk of gastroschisis following use of antiherpetic medications such as valacyclovir during the first trimester to treat maternal genital herpes; this risk was also increased in the offspring of women with genital herpes not receiving treatment (Ahrens 2013).

In a pharmacokinetic study, maternal acyclovir serum concentrations were higher in pregnant patients receiving valacyclovir than those given acyclovir for the suppression of recurrent herpes simplex virus (HSV) infection late in pregnancy. Amniotic fluid concentrations were also higher; however, there was no evidence that fetal exposure differed between the groups (Kimberlin 1998).

Valacyclovir is recommended for the treatment of genital HSV in pregnant patients. Primary HSV infection during the first trimester may be associated with neonatal chorioretinitis, microcephaly, and skin lesions. The risk of perinatal transmission is greater when the primary infection occurs during pregnancy. Maternal treatment decreases duration and severity of disease and duration of viral shedding (ACOG 2020). Suppressive therapy is recommended for patients beginning at 36 weeks' gestation who have a history of genital lesions (ACOG 2020; CDC [Workowski 2021]; HHS [OI adult] 2023).

Valacyclovir has been studied for the treatment of congenital cytomegalovirus infection during pregnancy. Until additional data are available, use outside of a clinical trial is not currently recommended (Shahar-Nissan 2020; SMFM 2016; Zammarchi 2020).

Breastfeeding Considerations

Valacyclovir is rapidly metabolized to acyclovir. Following administration of valacyclovir, acyclovir is present in breast milk; unchanged valacyclovir has not been detected in breast milk.

Peak acyclovir milk concentrations (1.1 to 6.4 mcg/mL) occurred 4 hours (range: 2 to 4 hours) following maternal administration of a single oral dose of valacyclovir 500 mg to 5 postpartum females; the half-life of acyclovir in breast milk was ~2 hours (range: 1.3 to 12.2 hours). Peak breast milk concentrations were 0.5 to 2.3 times the concentration of acyclovir in the maternal serum. Acyclovir was detected in the urine of breastfeeding infants following 5 days of maternal treatment with valacyclovir 500 mg twice daily. Authors of this study calculated the acyclovir exposure to a breastfed infant to be ~2% of a standard acyclovir IV neonatal dose (Sheffield 2002). A second study tested acyclovir breast milk concentrations following maternal administration of valacyclovir 500 mg twice daily to women 2 weeks postpartum. Acyclovir was detectable in 35 of 44 samples obtained. Median acyclovir concentrations were 2.62 mcg/mL (range: 0.15 to 10.15 mcg/mL). Authors of this study calculated the acyclovir exposure from breast milk to an infant breastfeeding for 1 year following a maternal dose of valacyclovir to be 79% lower than a neonatal acyclovir IV dose given over 14 to 21 days for the treatment of neonatal herpes (Drake 2012).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. However, valacyclovir is considered compatible with breastfeeding. Patients with herpes simplex virus infection taking valacyclovir may breastfeed as long as there are not lesions on the breast, body lesions are covered, and strict hand hygiene is practiced; patients with herpetic lesions near or on the breast should not breastfeed (ACOG 2020). Patients with breast lesions can pump and discard milk to maintain milk supply until lesions are healed and breastfeeding can be resumed (D’Andrea 2019).

Monitoring Parameters

Urinalysis, BUN, serum creatinine, liver enzymes, CBC, hydration status, signs and symptoms of neurotoxicity.

Mechanism of Action

Valacyclovir is rapidly and nearly completely converted to acyclovir by intestinal and hepatic metabolism. Acyclovir is converted to acyclovir monophosphate by virus-specific thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes. Acyclovir triphosphate inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Rapid.

Distribution: Acyclovir is widely distributed throughout the body including brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, and CSF.

Vd: Acyclovir: Children ≥3 years and Adolescents: Mean: 1.34 ± 0.65 L/kg (Bomgaars 2008).

Protein binding: Valacyclovir: 13.5% to 17.9%; Acyclovir: 9% to 33%.

Metabolism: Hepatic; valacyclovir is rapidly and nearly completely converted to acyclovir and L-valine by first-pass effect; acyclovir is hepatically metabolized to a very small extent by aldehyde oxidase and by alcohol and aldehyde dehydrogenase (inactive metabolites).

Bioavailability: Acyclovir:

Children and Adolescents: Tablet, extemporaneously prepared oral suspension: Mean range: 44% to 64%; varies based on formulation and age from 27.7% to 87% (Bomgaars 2008; Eksborg 2002; Kimberlin 2010; Nadal 2002).

Adults (healthy volunteers): Tablet: 54.5% ± 9.1%.

Half-life elimination: Acyclovir:

Infants 1 to <3 months: 2 hours (Kimberlin 2010).

Infants 3 to <6 months: 1.8 hours (Kimberlin 2010).

Infants ≥6 months: 1.3 hours (Kimberlin 2010).

Children and Adolescents: Mean range: 1.3 to 2.51 hours (Bomgaars 2008; Eksborg 2002; Kimberlin 2010; Nadal 2002).

Adults: Normal renal function: 2.5 to 3.3 hours, Valacyclovir: ~30 minutes; End-stage renal disease: 14 to 20 hours; During hemodialysis: 4 hours.

Time to peak: Acyclovir:

Children ≥2 years and Adolescents: Mean range: 1.41 to 2.62 hours (Bomgaars 2008; Eksborg 2002; Nadal 2002).

Adults: 1.5 hours.

Excretion: Urine, primarily as acyclovir (89%); Note: Following oral administration of radiolabeled valacyclovir, 46% of the label is eliminated in the feces (corresponding to nonabsorbed drug), while 47% of the radiolabel is eliminated in the urine.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Pediatric: Cmax (Acyclovir): Oral valacyclovir suspension (extemporaneously compounded): Single dose, 20 mg/kg (manufacturer's labeling):

Children <2 years: 4.03 ± 1.37 mg/L.

Children 2 to <6 years: 3.75 ± 1.14 mg/L.

Children 6 to <12 years: 4.71 ± 1.2 mg/L.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Valabin | Valtrex | Virico;
  • (AR) Argentina: Rapivir | Valtrex | Viramixal | Viranet;
  • (AT) Austria: Valaciclovir actavis | Valaciclovir Arcana | Valaciclovir bluefish | Valaciclovir pfizer | Valaciclovir Stada | Valtrex | Viropel;
  • (AU) Australia: Apo valaciclovir | Apx valaciclovir | Chemmart valaciclovir | Noumed valaciclovir | Shilova | Terry white chemist valaciclovir | Vaclovir | Valaciclovir | Valaciclovir actavis | Valaciclovir an | Valaciclovir ga | Valaciclovir generic health | Valaciclovir rbx | Valaciclovir sandoz | Valaciclovir sz | Valacor | Valnir | Valtrex | Valvala | Zelitrex;
  • (BD) Bangladesh: Alaclov | Revira | Valarux | Valovir | Zostiva;
  • (BE) Belgium: Valaciclovir Apotex | Valaciclovir mylan | Valaciclovir sandoz | Zelitrex;
  • (BF) Burkina Faso: Zelitrex;
  • (BG) Bulgaria: Valtrex;
  • (BR) Brazil: Cloridrato de valaciclovir | Dazek | Herpstal | Valtrex;
  • (CH) Switzerland: Valaciclovir actavis | Valaciclovir Helvepharm | Valaciclovir Mepha | Valaciclovir sandoz | Valaciclovir Spirig | Valaciclovir Streuli | Valaciclovir teva | Valaciclovir therica | Valaciclovir zentiva | Valacivir mepha | Valtrex;
  • (CI) Côte d'Ivoire: Alyvir | Zelitrex;
  • (CL) Chile: Pervioral | Vacper | Vadiral | Valtrex | Virmax;
  • (CN) China: A mai xin | Li ke fen | Li zhu wei | Ming zhu xin | Valacyclovir hydrochloride | Valtrex;
  • (CO) Colombia: Clovirax | Hetval | Vadiral | Valaciclovir | Valclomed | Valclovir | Valcyclor | Valtrex | Valtrois | Valyc | Virentel;
  • (CR) Costa Rica: Valvirex;
  • (CZ) Czech Republic: Valaciclovir +pharma | Valaciclovir mylan | Valtrex;
  • (DE) Germany: Valaciclovir 1 a pharma | Valaciclovir AL | Valaciclovir amneal | Valaciclovir aurobindo | Valaciclovir bluefish | Valaciclovir Hexal | Valaciclovir Orifam | Valtrex | Valtrex s;
  • (DO) Dominican Republic: Vadiral | Valtrex;
  • (EC) Ecuador: Pervioral | Vadiral | Valaciclovir | Valaciclovir mk | Valtrex;
  • (EE) Estonia: Valaciclovir actavis | Valaciclovir Portfarma | Valtrex;
  • (EG) Egypt: Cicloherp | Herpacut | Valtrex | Valtrovir | Valysernex | Viroclear;
  • (ES) Spain: Tridiavir | Valaciclovir almus | Valaciclovir amneal | Valaciclovir arrow | Valaciclovir aurobindo | Valaciclovir Combix | Valaciclovir Kern | Valaciclovir Pharmacia | Valaciclovir Stada | Valaciclovir stada genericos | Valaciclovir tecnigen | Valaciclovir teva | Valherpes | Valpridol | Valtrex | Virval;
  • (FI) Finland: Flushnil | Valaciclovir actavis | Valaciclovir bluefish | Valaciclovir mylan | Valaciclovir orifarm | Valaciclovir pfizer | Valaciclovir Ratiopharm | Valaciclovir sandoz | Valaciclovir teva | Valavir | Valtrex | Zelitrex;
  • (FR) France: Valaciclovir actavis | Valaciclovir almus | Valaciclovir Alter | Valaciclovir Arrow generiques | Valaciclovir biogaran | Valaciclovir bluefish | Valaciclovir Bouchara Recordati | Valaciclovir Cristers | Valaciclovir EG | Valaciclovir evolugen | Valaciclovir isomed | Valaciclovir Mylan pharma | Valaciclovir pfizer | Valaciclovir phr | Valaciclovir Qualimed | Valaciclovir Ranbaxy | Valaciclovir Ratiopharm | Valaciclovir sandoz | Valaciclovir teva | Valaciclovir Teva pharma | Valaciclovir Winthrop | Valaciclovir zentiva | Valaciclovir Zydus France | Zelitrex;
  • (GB) United Kingdom: Valaciclovir | Valtrex;
  • (GR) Greece: Solvaprent | Valaciclovir/actavis | Valomed | Valtrex | Vociflon;
  • (HK) Hong Kong: Apo valacyclovir | Valaciclovir actavis | Valaciclovir sandoz | Valtra | Valtrex;
  • (HU) Hungary: Rivacir | Valtrex;
  • (ID) Indonesia: Cloviar | Herclov | Iclofar | Inclovir | Valaciclovir | Valciron | Valtrex | Valvir | Vandavir | Zostavir;
  • (IE) Ireland: Myval | Valaciclovir | Valaciclovir actavis | Valaciclovir bluefish | Valaciclovir teva | Valherp | Valotix | Valtrex;
  • (IL) Israel: Valtrex;
  • (IN) India: Herpival | Valamac | Valanext | Valanix | Valcet | Valcivir | Valtoval | Zimivir;
  • (IS) Iceland: Valablis;
  • (IT) Italy: Crevir | Talavir | Valaciclovir aurobindo | Valaciclovir EG | Valaciclovir generics mylan | Valaciclovir San | Valaciclovir tecnigen | Zelitrex;
  • (JO) Jordan: Valtrex;
  • (JP) Japan: Valaciclovir | Valaciclovir aspen | Valaciclovir dk | Valaciclovir ffp | Valaciclovir meek | Valaciclovir sanwa | Valtrex;
  • (KE) Kenya: Valovir | Valtrex | Viraval;
  • (KR) Korea, Republic of: Balrasi | Herpozi | Newvalaclov | Pms valacyclovir | Vaciclovir | Valacil | Valaclor | Valarex | Valaxy | Valcicol | Valcivir | Valclex | Valclovior | Valclovir | Valex | Valraci | Valtavics | Valtcro | Valtllis | Valtmax | Valtra | Valtran | Valtrex | Valtris | Valtvala | Valvirus;
  • (KW) Kuwait: Valtrex;
  • (LB) Lebanon: Valaciclovir arrow | Valcyk | Valtrex;
  • (LT) Lithuania: Valaciclovir 1 a pharma | Valaciclovir actavis | Valaciclovir actiofarma | Valaciclovir bluefish | Valaciclovir Hexal | Valaciclovir Portfarma | Valaciclovir puren | Valaciclovir teva | Valtrex;
  • (LU) Luxembourg: Zelitrex;
  • (LV) Latvia: Valaciclovir actavis | Valaciclovir Combix | Valaciclovir Portfarma | Valtrex;
  • (MA) Morocco: Alyvir | Valex | Zelitrex;
  • (MX) Mexico: Asfina | Rapivir | Valaciclovir | Valextra | Valinir | Vijay | Zelitrex | Zoclorida;
  • (MY) Malaysia: Axcel Valacyclovir | Valovir | Valtrex | Valvir;
  • (NG) Nigeria: Valtrex;
  • (NL) Netherlands: Valaciclovir | Valaciclovir actavis | Valaciclovir aurobindo | Valaciclovir bluefish | Valaciclovir focus | Valaciclovir mylan | Valaciclovir PCH | Valaciclovir sandoz | Valtrex | Zelitrex;
  • (NO) Norway: Valaciclovir actavis | Valaciclovir bluefish | Valaciclovir orifarm | Valaciclovir sandoz | Valtrex;
  • (NZ) New Zealand: Vaclovir;
  • (PA) Panama: Valvicic;
  • (PE) Peru: Alyvir | Bagovir | Cephaming | Vadiral | Valtero | Valtrex | Valyc;
  • (PH) Philippines: Valtrex;
  • (PK) Pakistan: Nexvalor | Vaclovir | Valahep | Valavir | Valtrex;
  • (PL) Poland: Vaciclor | Valtrex;
  • (PR) Puerto Rico: Valacyclovir | Valacyclovir hcl | Valacyclovir hydrochloride | Valtrex;
  • (PT) Portugal: Azel | Crotax | Valaciclovir actavis | Valaciclovir amex | Valaciclovir aurobindo | Valaciclovir azevedos | Valaciclovir ciclum | Valaciclovir daquimed | Valaciclovir labesfal | Valavir | Valtrex;
  • (PY) Paraguay: Clotie | Vadiral | Valtrex;
  • (QA) Qatar: Valtrex;
  • (RO) Romania: Valtrex;
  • (RU) Russian Federation: Vacirex | Valaciclovir | Valaciclovir canon | Valaciclovir obl | Valacitek | Valacyclovir | Valacyclovir velpharm | Valavir | Valcycon | Valmik | Valtrex | Valvir | Vayrova | Virdel;
  • (SA) Saudi Arabia: Apo valacyclovir | Herptrex | Pms valacyclovir | Valtrex;
  • (SE) Sweden: Valaciclovir | Valaciclovir abacus medicine | Valaciclovir actavis | Valaciclovir alternova | Valaciclovir amneal | Valaciclovir arrow | Valaciclovir bluefish | Valaciclovir CC pharma | Valaciclovir mylan | Valaciclovir orifarm | Valaciclovir orion | Valaciclovir sandoz | Valaciclovir teva | Valaciklovir Ebb | Valtrex | Zeltrex;
  • (SG) Singapore: Vaciclor | Valovir | Valtrex;
  • (SI) Slovenia: Valaciklovir | Valaciklovir Teva | Valdacir | Valtrex;
  • (SK) Slovakia: Valtrex;
  • (TH) Thailand: Valtrex;
  • (TN) Tunisia: Aviral | Cyvaltex | Valcyvir | Zelitrex | Zelivir;
  • (TR) Turkey: Valtrex | Vaxvire | Viromed;
  • (TW) Taiwan: Vacyless | Valacyclovir mylan | Valtrex | Vibox;
  • (UA) Ukraine: Herpeval | Valacyclovir hetero | Valavir | Valtrex;
  • (UG) Uganda: Valovir;
  • (UY) Uruguay: Kalfed | Rapivir | Valaciclovir;
  • (VE) Venezuela, Bolivarian Republic of: Vadiral | Valaciclovir | Valtrex;
  • (ZA) South Africa: Actiprez | Anviro | Hevitrex | Mylan valaciclovir | Shilova | Valatrex | Vavirex | Vorior | Zelitrex | Zelivire;
  • (ZM) Zambia: Alyvir;
  • (ZW) Zimbabwe: Vaclovir | Valovir | Zelitrex
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