VALTREX (valacyclovir hydrochloride) caplets are indicated:

• For the treatment of herpes zoster (shingles).

  
  

• For the treatment or suppression of genital herpes in immunocompetent individuals and for the suppression of recurrent genital herpes in HIV infected individuals.

  
  

• To reduce the risk of transmission of genital herpes with the use of suppressive therapy. Safer sex practices should be used with suppressive therapy.

  
  

• For the treatment of cold sores (herpes labialis).

  
  

 

Use in the geriatric population may be associated with differences in safety due to age-related changes in renal function and a brief discussion can be found in the appropriate sections (see Warnings and Precautions).

No data is available.

VALTREX (valacyclovir hydrochloride) caplets are contraindicated in patients with a known hypersensitivity or intolerance to valacyclovir, acyclovir, or any component of the formulation. For a complete listing of ingredients, see Dosage Forms, Composition and Packaging.

Care should be taken to ensure adequate fluid intake in patients who are at risk of dehydration particularly in the elderly.

In patients with advanced HIV disease (CD4 cell counts <100 cells/mm³), allogenic bone marrow transplant and renal transplant recipients receiving VALTREX (valacyclovir hydrochloride) at a dose of 8000 mg per day, there have been reports of Thrombotic Thrombocytopenia Purpura/Hemolytic Uremic Syndrome (TTP/HUS), in some cases resulting in death.

The safety and efficacy of valacyclovir hydrochloride have not been established for the treatment of disseminated herpes zoster.

The safety and efficacy of VALTREX have not been established in immunocompromised patients other than for the suppression of ano-genital herpes in HIV-infected patients. The safety and efficacy of valacyclovir hydrochloride for the suppression of recurrent ano-genital herpes in patients with advanced HIV disease (CD4 cell count <100 cells/mm³) have not been established.

Patients should be informed that valacyclovir hydrochloride is not a cure for genital herpes.

Safer sex practices should be used in combination with suppressive therapy. VALTREX alone should not be used for reducing the risk of transmitting genital herpes. Because genital herpes is a sexually transmitted infection, patients should, in order to further reduce the risk of infecting partners, avoid contact with lesions, damaged skin/mucosa, and also avoid intercourse when lesions and/or symptoms are present. Genital herpes is frequently transmitted in the absence of symptoms through asymptomatic viral shedding therefore patients should be counseled to use safer sex practices. The effect of VALTREX on transmission of sexually transmitted infections other than herpes (including HIV, gonorrhea, syphilis and Chlamydia) is unknown.

The efficacy of VALTREX for reducing transmission of genital herpes has not been established in individuals with multiple partners, non-heterosexual couples, and couples not counseled to use safer sex practices.

Dose modification is not required in patients with mild or moderate cirrhosis (hepatic synthetic function maintained). Pharmacokinetic data in patients with advanced cirrhosis (impaired hepatic synthetic function and evidence of portal-systemic shunting) do not indicate the need for dosage adjustment. However, clinical experience is limited.

Acyclovir, the active metabolite of valacyclovir, is eliminated by renal clearance, therefore the dose of valacyclovir must be reduced in patients with renal impairment (see Dosage and Administration, Patients with Acute or Chronic Renal Impairment). Elderly patients are likely to have reduced renal function and therefore the need for dose reduction must be considered in this group of patients. Both elderly patients and patients with a history of renal impairment are at increased risk of developing neurological side effects and should be closely monitored for evidence of these effects. In the reported cases, these reactions were generally reversible on discontinuation of treatment (see Adverse Reactions).

Caution should be exercised when administering VALTREX to patients with significant renal impairment or those receiving potentially nephrotoxic agents, since this may increase the risk of renal dysfunction (see Dosage and Administration, Patients with Acute or Chronic Renal Impairment) and/or the risk of reversible central nervous system symptoms such as those that occur infrequently in patients treated with intravenous acyclovir.

Given the dosage recommendations for treatment of cold sores, special attention should be paid when prescribing VALTREX for cold sores in patients who are elderly or who have impaired renal function (see Dosage and Administration, Patients with Acute or Chronic Renal Impairment, Table 8). Treatment should not exceed 1 day (2 doses of 2000 mg in 24 hours). Therapy beyond 1 day does not provide additional clinical benefit.

There are no adequate and well-controlled studies with either acyclovir or VALTREX in pregnant women. In a study of the pharmacokinetics of valacyclovir and acyclovir during late pregnancy, the steady-state daily acyclovir AUC (area under plasma concentration-time curve) following valacyclovir 1000 mg was approximately 2 times greater than that observed with oral acyclovir at 1200 mg daily. Valacyclovir hydrochloride caplets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pregnancy registries have documented the pregnancy outcomes in women exposed to VALTREX or to any formulation of acyclovir (the active metabolite of valacyclovir); 111 and 1246 outcomes (29 and 756 exposed during the first trimester of pregnancy), respectively, were obtained from women prospectively registered. The findings of the acyclovir pregnancy registry have not shown an increase in the number of birth defects amongst acyclovir-exposed subjects compared with the general population, and any birth defects showed no uniqueness or consistent pattern to suggest a common cause. Given the small number of women enrolled into the valacyclovir pregnancy registry, reliable and definitive conclusions could not be reached regarding the safety of VALTREX in pregnancy.

Valacyclovir hydrochloride was not teratogenic in rats or rabbits given 400 mg/kg (which results in 10 and 7 times human plasma levels, respectively) during the period of major organogenesis. However, in a non-standard test in rats given three subcutaneous doses of 100 mg/kg acyclovir (20 times human plasma levels) on gestation day 10, there were fetal abnormalities, such as head and tail anomalies, and maternal toxicity.

Acyclovir, the principal metabolite of valacyclovir, is excreted in breast milk. Following oral administration of a 500 mg dose of valacyclovir, peak acyclovir concentrations (C_max) in breast milk ranged from 0.5 to 2.3 (median 1.4) times the corresponding maternal acyclovir serum concentrations. The acyclovir breast milk to maternal serum AUC ratios ranged from 1.4 to 2.6 (median 2.2).

The median acyclovir concentration in breast milk was 2.24 μg/mL (9.95 μM). With a maternal valacyclovir dosage of 500 mg twice daily, this level would expose a nursing infant to a daily oral acyclovir dosage of about 0.61 mg/kg/day. The elimination half-life of acyclovir from breast milk was similar to that for serum.

Unchanged valacyclovir was not detected in maternal serum, breast milk, or infant urine.

Caution should be exercised when valacyclovir hydrochloride is administered to a nursing woman. Consideration should be given to temporary discontinuation of nursing, as the safety of valacyclovir hydrochloride has not been established in infants.

Safety and efficacy in children have not been established.

Of the total number of patients included in clinical studies of valacyclovir hydrochloride, more than 800 were age 65 or older, and more than 300 were age 75 or older. A total of 34 volunteers age 65 or older completed a pharmacokinetic trial of valacyclovir hydrochloride. The pharmacokinetics of acyclovir following single- and multiple-dose oral administration of valacyclovir hydrochloride caplets in geriatric volunteers varied with renal function. The possibility of renal impairment in the elderly must be considered and the dosage should be adjusted accordingly (see Warnings and Precautions, Renal and Dosage and Administration, Patients with Acute or Chronic Renal Impairment). Adequate hydration should be maintained.

The most frequent adverse reactions associated with the use of VALTREX (valacyclovir hydrochloride) are headache and nausea.

Neurological side effects have also been reported in rare instances. Elderly patients and patients with a history of renal impairment are at increased risk of developing these effects. In the reported cases, these reactions were generally reversible on discontinuation of treatment (see Warnings and Precautions and Adverse Reactions, Post-Market Adverse Drug Reactions).

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

Adverse drug reactions were not significantly different in recipients of VALTREX compared to placebo or acyclovir in the two double-blind, randomized clinical trials of treatment of herpes zoster (shingles) in immunocompetent patients. The most frequent adverse drug reactions reported in recipients of valacyclovir hydrochloride are listed in Table 1.

Table 1: VALTREX

Incidence (%) of Drug-Related Adverse Reactions Occurring in ≥1% of Patients Receiving VALTREX in Two Clinical Trials of Treatment of Herpes Zoster

Adverse Drug Reaction	Herpes Zoster
	18–50 Years		>50 Years
	VALTREX (n=202)	Placebo (n=195)	VALTREX (n=765)	Acyclovir (n=376)
Nausea	8	6	12	14
Headache	11	8	8	7
Diarrhea	4	4	4	4
Vomiting	2	2	4	3
Asthenia	1	3	3	2
Constipation	<1	<1	3	3
Abdominal Pain	<1	1	2	1
Anorexia	<1	2	2	2
Dizziness	1	1	2	2
Dry Mouth	<1	0	2	1
Dyspepsia	0	<1	2	1
Flatulence	0	0	1	1
Pruritus	1	0	<1	0

In two double-blind, randomized trials of treatment of recurrent genital herpes in immunocompetent patients, adverse drug reactions were not significantly different in recipients of valacyclovir hydrochloride compared to placebo. The most frequent adverse reactions are listed in Table 2.

Table 2: VALTREX

Incidence (%) of Drug-Related Adverse Reactions Occurring in ≥1% of Patients Receiving VALTREX in Two Clinical Trials of Treatment of Recurrent Genital Herpes

Adverse Event	VALTREX (n=1235)	Placebo (n=439)
Headache	11	9
Nausea	5	6
Diarrhea	4	4
Dizziness	2	2
Abdominal Pain	2	1
Asthenia	1	3

In two recurrent genital herpes suppression studies of immunocompetent patients, adverse drug reactions were not significantly different, in recipients of VALTREX 1000 mg once daily, VALTREX 500 mg once daily compared to placebo or ZOVIRAX (acyclovir) 400 mg twice daily. The most frequent adverse reactions are reported in Table 3.

Table 3: VALTREX

Incidence (%) of Drug-Related Adverse Reactions Occurring in ≥1% of Patients Receiving VALTREX in Two Clinical Trials for Suppression of Recurrent Genital Herpes

In one multicenter, double-blind, randomized study of immunocompetent patients for the treatment of an initial episode of genital herpes, the frequency of adverse events, regardless of attributability to study medication, was similar in both treatment groups: VALTREX 1000 mg twice daily (n=318) compared to acyclovir 200 mg five times a day (n=318). The most frequent adverse events were headache (13% with valacyclovir versus 10% with acyclovir) and nausea (6% with both treatments). All other adverse events were reported by 3% or less of patients.

In a 6-month study of suppression of recurrent genital herpes in HIV-infected patients, adverse drug reactions were similar in nature and incidence in the groups receiving VALTREX 500 mg twice daily and placebo when duration of exposure was considered. Adverse reactions reported with an incidence ≥1% during the double-blind phase are detailed in Table 4.

Table 4: VALTREX

Incidence (%) of Drug-Related Adverse Reactions Occurring in ≥1% of Patients Receiving VALTREX in a Clinical Trial for Suppression of Recurrent Genital Herpes in HIV-Infected Patients

Adverse Drug Reaction	Valacyclovir 500 mg b.i.d. (n=194)	Placebo (n=99)
Headache	5	3
Diarrhea	3	2
Nausea	2	5
Constipation	1	0
Dizziness	1	0

Adverse reactions reported by patients receiving VALTREX 500 mg once daily (n=743) or placebo once daily (n=741) in a clinical study for the reduction of transmission of genital herpes are listed below in Table 5.

Table 5: VALTREX

Incidence (%) of Drug-Related Adverse Reactions Occurring in ≥1% of Patients Receiving VALTREX in a Clinical Trial for the Reduction of Transmission of Genital Herpes

Adverse Drug Reaction	VALTREX (n=743)	Placebo (n=741)
Headache	6	4
Diarrhea	2	1
Nausea	2	2
Dyspepsia	1	1

Adverse drug reactions reported by patients receiving VALTREX 2000 mg twice daily for one day (n=609) or placebo (n=609) in clinical studies for the treatment of cold sores are listed in Table 6.

Table 6: VALTREX

Incidence (%) of Drug-Related Adverse Reactions Occurring in ≥1% of Patients Receiving VALTREX in Two Clinical Trials for the Treatment of Cold Sores

Adverse Drug Reaction	VALTREX (n=609)	Placebo (n=609)
Headache	9	5
Nausea	4	5
Diarrhea	3	3
Dyspepsia	1	1

In herpes zoster trials, the frequencies of white blood cells abnormality (<0.75 times the lower limit of normal) were 1.3% for patients receiving VALTREX compared with 0.6% for patients receiving placebo. This difference was not clinically or statistically significant.

In studies of suppression of genital herpes in HIV-infected patients and of reduction of transmission of genital herpes, there were no clinically significant changes from baseline in laboratory parameters in patients receiving VALTREX compared to placebo.

In clinical studies for the treatment of cold sores, the frequencies of abnormal ALT values (>2 times the upper limit of normal) were 1.8% for patients receiving VALTREX at the recommended clinical dose and 0.8% for placebo. Other laboratory abnormalities (hemoglobin, white blood cells, alkaline phosphatase, and serum creatinine) occurred with similar frequencies in the 2 groups.

The following events have been reported voluntarily during post-approval use of VALTREX in clinical practice. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, causal connection to VALTREX, or a combination of these factors. Reported rates determined on the basis of spontaneously reported post-marketing adverse events are generally presumed to underestimate the risks associated with drug treatment.

facial edema, hypertension, tachycardia.

nausea, abdominal discomfort, vomiting and diarrhea.

rare reports of thrombocytopenia, aplastic anemia, leukocytoclastic vasculitis, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Leukopenia, mainly reported in immunocompromised patients.

acute hypersensitivity reactions including anaphylaxis, angioedema, dyspnea, pruritus, rash and urticaria.

erythema multiforme, rashes including photosensitivity.

rare reports of renal impairment, elevated creatinine. Very rare reports of acute renal failure.

rare reports of reversible increases in liver function test, occasionally described as hepatitis.

headache. Uncommonly, reports of neurological reactions including dizziness, confusion, hallucinations (auditory and visual), aggressive behaviour, rarely decreased consciousness, and very rarely tremor, ataxia, dysarthria, convulsions, encephalopathy, coma. Agitation and psychotic symptoms have also been reported. These events are generally reversible and usually seen in patients with renal impairment or with other predisposing factors (see Warnings and Precautions).

There have been reports of renal insufficiency, microangiopathic hemolytic anemia and thrombocytopenia (sometimes in combination) in severely immunocompromised patients, particularly those with advanced HIV disease, receiving high doses (8000 mg daily) of valacyclovir for prolonged periods in clinical trials. These findings have also been observed in patients not treated with valacyclovir who have the same underlying or concurrent conditions.

No clinically significant interactions have been identified.

No dosage adjustment is recommended when VALTREX (valacyclovir hydrochloride) is co-administered with digoxin, antacids, thiazide diuretics, cimetidine, or probenecid in subjects with normal renal function.

Acyclovir is eliminated primarily unchanged in the urine via active renal tubular secretion. Any drugs administered concurrently that compete with this mechanism may increase acyclovir plasma concentrations following valacyclovir administration.

Following administration of valacyclovir 1000 mg, cimetidine and probenecid increase the area under the curve (AUC) of acyclovir by this mechanism, and reduce acyclovir renal clearance. However, no dosage adjustment is necessary at this dose because of the wide therapeutic index of acyclovir.

There is no known interaction with food.

Interactions with herbal products have not been established.

Interactions with laboratory tests have not been established.

• The dosage of VALTREX (valacyclovir hydrochloride) should be reduced in patients with impaired renal function.

  
  

• Therapy should be initiated as soon as possible after a diagnosis of herpes zoster, or at the first sign or symptoms of an outbreak of oral or genital herpes.

  
  

• The recommended dose and duration of use is dependent on the indication.

  
  

VALTREX caplets may be given without regard to meals.

The recommended dosage of VALTREX caplets for the treatment of herpes zoster is 1000 mg orally three times daily for 7 days. Treatment with valacyclovir hydrochloride should be initiated within 72 hours of the onset of rash.

The recommended dosage of VALTREX caplets for the treatment of an initial episode of genital herpes is 1000 mg orally twice daily for 10 days. There are no data on the effectiveness of treatment with VALTREX when initiated more than 72 hours after the onset of signs and symptoms. Therapy was most effective when administered within 48 hours of the onset of signs and symptoms.

The recommended dosage of VALTREX caplets for the treatment of recurrent episodes of genital herpes is 500 mg orally twice daily for 3 days. Therapy should be initiated at the earliest sign or symptom of recurrence. Valacyclovir hydrochloride can prevent lesion development when taken at the first signs and symptoms of a genital herpes recurrence.

The recommended dosage of VALTREX caplets for chronic suppressive therapy of recurrent genital herpes is 1000 mg orally once daily in patients with normal immune function. In patients with a history of 9 or fewer recurrences per year, an alternative dose is 500 mg orally once daily. The safety and efficacy of therapy with VALTREX beyond 1 year have not been established.

In patients with HIV infection with CD4 cell count >100 cells/mm³, the recommended dosage of VALTREX caplets for chronic suppressive therapy of recurrent genital herpes is 500 mg orally twice daily. The safety and efficacy of therapy with VALTREX beyond 6 months in patients with HIV infection have not been established.

The recommended dosage of VALTREX caplets for reduction of transmission of genital herpes in patients with a history of 9 or fewer recurrences per year is 500 mg orally once daily for the source partner. The efficacy of reducing transmission beyond 8 months in couples discordant for HSV-2 infection has not been established.

The recommended dosage of VALTREX for the treatment of cold sores (herpes labialis) is 2000 mg orally twice daily for 1 day (24-hour period). The second dose should be taken approximately 12 hours after the first dose, but not less than 6 hours after the first dose. Therapy should be initiated at the earliest symptom of a cold sore (e.g., tingling, itching, or burning). There are no data on the efficacy of treatment initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle or ulcer).

Caution is advised when administering valacyclovir to patients with impaired renal function. Adequate hydration should be maintained.

Pharmacokinetic and safety evaluations following administration of oral valacyclovir hydrochloride have been performed in patients with renal impairment and volunteers with end-stage renal disease (ESRD) managed by hemodialysis. Based on these studies and extensive experience with acyclovir, the following dosage adjustments are recommended (see Table 7 and Table 8).

Table 7: VALTREX

Dosage Adjustments for Renal Impairment

Creatinine Clearance (mL/min)	Dosage for Herpes Zoster	Dosage for Recurrent Episodes of Genital Herpes	Dosage for Suppression of Genital Herpes			Dosage for Initial Episode of Genital Herpes
			500 mg (9 or fewer recurrences/year)	1000 mg (chronic suppressive therapy)	HIV-infected adults
>30	1000 mg every 8 hoursa	500 mg every 12 hoursa	500 mg every 24 hoursa	1000 mg every 24 hoursa	500 mg every 12 hoursa	1000 mg every 12 hoursa
15 to 30	1000 mg every 12 hours	500 mg every 12 hoursa	500 mg every 24 hoursa	500 mg every 24 hoursa	500 mg every 24 hours	1000 mg every 24 hours
<15	1000 mg every 24 hours	500 mg every 24 hours	500 mg every 48 hours	500 mg every 24 hours	500 mg every 24 hours	500 mg every 24 hours

^a. Standard dose—adjustment not necessary.



Table 8: VALTREX

Dosage Adjustments for Renal Impairment

Creatinine Clearance (mL/min)	Dosage for Cold Sores (Herpes Labialis)a
>50	Two 2000 mg doses within 24 hoursb , c
30 to 49	Two 1000 mg doses within 24 hoursc
10 to 29	Two 500 mg doses within 24 hoursc
<10	500 mg single dose

^a. Do not exceed one day of treatment.
^b. Standard dose—adjustment not necessary.
^c. Doses should be taken about 12 hours apart (not less than 6 hours apart).

During hemodialysis, the half-life of acyclovir after administration of valacyclovir hydrochloride is approximately 4 hours. About 1/3 of acyclovir in the body is removed by dialysis during a 4-hour hemodialysis session. These patients should receive the daily dose of valacyclovir hydrochloride recommended for patients with creatinine clearance of <15 mL/min, with the dose administered after hemodialysis on the days it is performed.

There is no information specific to administration of valacyclovir hydrochloride. The effect of continuous ambulatory peritoneal dialysis (CAPD) and continuous arteriovenous hemofiltration/dialysis (CAVHD) on acyclovir pharmacokinetics has been studied. The removal of acyclovir after CAPD and CAVHD is less pronounced than with hemodialysis, and the pharmacokinetic parameters closely resemble those observed in patients with ESRD not receiving hemodialysis. Therefore, supplemental doses of valacyclovir hydrochloride should not be required following CAPD or CAVHD.

If a dose of VALTREX is missed, the patient should be advised to take it as soon as he/she remembers, and then continue with the next dose at the proper time interval.

Acute renal failure and neurological symptoms, including confusion, hallucinations, agitation, decreased consciousness and coma, have been reported in patients receiving overdoses of VALTREX (valacyclovir hydrochloride). Nausea and vomiting may also occur. Caution is required to prevent inadvertent overdose. Many of the reported cases involved renally impaired and elderly patients receiving repeated overdoses, due to lack of appropriate dosage reduction (see Warnings and Precautions, Renal and Adverse Reactions).

Patients should be observed closely for signs of toxicity. Hemodialysis significantly enhances the removal of acyclovir from the blood and may, therefore be considered a management option in the event of symptomatic overdose. However, it is known that precipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid. In the event of acute renal failure and anuria, the patient may benefit from hemodialysis until renal function is restored (see Dosage and Administration).

Although no data are available, administration of activated charcoal may be used to aid in the removal of unabsorbed drug.

VALTREX (valacyclovir hydrochloride) is the L-valyl ester and a pro-drug of the antiviral drug acyclovir. Valacyclovir hydrochloride is rapidly converted to acyclovir, which has in vitro and in vivo inhibitory activity against human herpes viruses including herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), and varicella-zoster virus (VZV).

The inhibitory activity of acyclovir is highly selective due to its unique affinity for the thymidine kinase (TK) encoded by HSV, and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In vitro, acyclovir triphosphate terminates growing chains of viral DNA. Once incorporated, acyclovir irreversibly binds to viral DNA polymerase, effectively inactivating the enzyme. Acyclovir triphosphate is a potent inhibitor of all of the human herpes virus DNA polymerases studied.

Acyclovir is virtually inactive in uninfected cells, since it is preferentially taken up and selectively converted to the active triphosphate form by herpes virus-infected cells. Additionally, the enzyme thymidine kinase of uninfected cells does not effectively use acyclovir as a substrate and cellular α-DNA polymerase is less sensitive than viral DNA polymerase to the effects of acyclovir.

A combination of the thymidine kinase specificity, competitive inhibition of DNA polymerase and incorporation and termination of the growing viral DNA chain results in inhibition of herpes virus replication. No effect on latent non-replicating virus has been demonstrated. Inhibition of viral replication reduces the period of viral shedding, limits the degree of spread and level of pathology, and thereby facilitates healing. The pain of shingles is related to viral damage to neurons which takes place during viral replication.

Acyclovir pharmacokinetics are unaltered after multiple-dose administration.

After oral administration, valacyclovir hydrochloride is rapidly absorbed from the gastrointestinal tract. The absolute bioavailability of acyclovir after administration of valacyclovir hydrochloride is 54.5%±9.1% as determined following a 1000 mg oral dose of valacyclovir hydrochloride and a 350 mg intravenous acyclovir dose to 12 healthy volunteers.

The binding of valacyclovir to human plasma proteins ranged from 13.5% to 17.9%.

Following absorption, valacyclovir is rapidly and nearly completely hydrolyzed to acyclovir and L-valine, an essential amino acid, by first-pass metabolism. This hydrolysis is mediated primarily by the enzyme valacyclovir hydrolase, and occurs predominantly in the liver.

The pharmacokinetic disposition of acyclovir delivered by valacyclovir is consistent with previous experience from intravenous and oral acyclovir. Acyclovir is eliminated primarily by urinary excretion of unchanged drug. In all studies of valacyclovir hydrochloride, the half-life of acyclovir typically averages 2.5 to 3.3 hours in subjects with normal renal function.

The pharmacokinetics of valacyclovir hydrochloride have not been evaluated in pediatric patients.

The pharmacokinetics of acyclovir following single- and multiple-dose oral administration of valacyclovir hydrochloride caplets in geriatric volunteers varied with renal function. Dosage reduction may be required in geriatric patients with reduced renal function (see Dosage and Administration).

The half-life and total body clearance of acyclovir are dependent on renal function. A dosage adjustment is recommended for patients with reduced renal function (see Dosage and Administration).

VALTREX caplets should be stored between 15 and 30°C and protected from light.

Valtrex.

Each blue, film-coated, capsule-shaped tablet (caplet), printed with edible white ink with “VALTREX 500 mg”, contains: valacyclovir HCl equivalent to 500 mg valacyclovir. Nonmedicinal ingredients: carnauba wax, cellulose, crospovidone, hydroxypropyl methylcellulose, Indigotine Aluminum Lake, magnesium stearate, polyethylene glycol, polysorbate 80, povidone, silicon dioxide and titanium dioxide. Bottles of 42.

Each white, film-coated, capsule-shaped tablet (caplet), printed with edible blue ink with “GX CF2”, contains: valacyclovir HCl equivalent to 1000 mg valacyclovir. Nonmedicinal ingredients: carnauba wax, cellulose, crospovidone, hydroxypropyl methylcellulose, magnesium stearate, polyethylene glycol, polysorbate 80, povidone, silicon dioxide and titanium dioxide. Blister packs of 21.