Valacyclovir: Package Insert and Label Information

VALACYCLOVIR- valacyclovir hydrochloride tablet, film coated
McKesson Corporation dba SKY Packaging

1 INDICATIONS AND USAGE

1.1 Adult patients

Cold Sores (Herpes Labialis)
Valacyclovir tablets are indicated for treatment of cold sores (herpes labialis). The efficacy of valacyclovir tablets initiated after
the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established.


Genital Herpes
Initial Episode: Valacyclovir tablets are indicated for treatment of the initial episode of genital herpes in immunocompetent
adults. The efficacy of treatment with valacyclovir tablets when initiated more than 72 hours after the onset of signs and
symptoms has not been established.


Recurrent Episodes: Valacyclovir tablets are indicated for treatment of recurrent episodes of genital herpes in
immunocompetent adults. The efficacy of treatment with valacyclovir tablets when initiated more than 24 hours after the
onset of signs and symptoms has not been established.


Suppressive Therapy: Valacyclovir tablets are indicated for chronic suppressive therapy of recurrent episodes of genital
herpes in immunocompetent and in HIV-1–infected adults. The efficacy and safety of valacyclovir tablets for the suppression
of genital herpes beyond 1 year in immunocompetent patients and beyond 6 months in HIV-1–infected patients have not been
established.


Reduction of Transmission: Valacyclovir tablets are indicated for the reduction of transmission of genital herpes in
immunocompetent adults. The efficacy of valacyclovir tablets for the reduction of transmission of genital herpes beyond 8
months in discordant couples has not been established. The efficacy of valacyclovir tablets for the reduction of transmission
of genital herpes in individuals with multiple partners and non-heterosexual couples has not been established. Safer sex
practices should be used with suppressive therapy (see current Centers for Disease Control and Prevention [CDC] Sexually
Transmitted Diseases Treatment Guidelines).


Herpes Zoster
Valacyclovir tablets are indicated for the treatment of herpes zoster (shingles) in immunocompetent adults. The efficacy of
valacyclovir tablets when initiated more than 72 hours after the onset of rash and the efficacy and safety of valacyclovir
tablets for treatment of disseminated herpes zoster have not been established.

1.2 Pediatric Patients

Cold Sores (Herpes Labialis)
Valacyclovir tablets are indicated for the treatment of cold sores (herpes labialis) in pediatric patients aged greater than or
equal to 12 years. The efficacy of valacyclovir tablets initiated after the development of clinical signs of a cold sore (e.g.,
papule, vesicle, or ulcer) has not been established.


Chickenpox
Valacyclovir tablets are indicated for the treatment of chickenpox in immunocompetent pediatric patients aged 2 to less than
18 years. Based on efficacy data from clinical trials with oral acyclovir, treatment with valacyclovir tablets should be initiated
within 24 hours after the onset of rash [see Clinical Studies (14.4)].

1.3 Limitations of Use

The efficacy and safety of valacyclovir tablets have not been established in:
• Immunocompromised patients other than for the suppression of genital herpes in HIV-1–infected patients with a CD4+
cell count greater than or equal to 100 cells/mm3.
• Patients aged less than 12 years with cold sores (herpes labialis).
• Patients aged less than 2 years or greater than or equal to 18 years with chickenpox.
• Patients aged less than 18 years with genital herpes.
• Patients aged less than 18 years with herpes zoster.
• Neonates and infants as suppressive therapy following neonatal herpes simplex virus (HSV) infection.

2 DOSAGE & ADMINISTRATION

• Valacyclovir tablets may be given without regard to meals.
• Valacyclovir oral suspension (25 mg/mL or 50 mg/mL) may be prepared extemporaneously from 500 mg valacyclovir tablets for use in pediatric patients for whom a solid dosage form is not appropriate [see Dosage and Administration (2.3)].

2.1 Adult Dosing Recommendations

Cold Sores (Herpes Labialis)
The recommended dosage of valacyclovir tablets for treatment of cold sores is 2 grams twice daily for 1 day taken 12 hours
apart. Therapy should be initiated at the earliest symptom of a cold sore (e.g., tingling, itching, or burning).


Genital Herpes
Initial Episode: The recommended dosage of valacyclovir tablets for treatment of initial genital herpes is 1 gram twice daily for
10 days. Therapy was most effective when administered within 48 hours of the onset of signs and symptoms.


Recurrent Episodes: The recommended dosage of valacyclovir tablets for treatment of recurrent genital herpes is 500 mg
twice daily for 3 days. Initiate treatment at the first sign or symptom of an episode.


Suppressive Therapy: The recommended dosage of valacyclovir tablets for chronic suppressive therapy of recurrent genital
herpes is 1 gram 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 once daily.


In HIV-1–infected patients with a CD4+ cell count greater than or equal to 100 cells/mm3, the recommended dosage of
valacyclovir tablets for chronic suppressive therapy of recurrent genital herpes is 500 mg twice daily.


Reduction of Transmission: The recommended dosage of valacyclovir tablets for reduction of transmission of genital herpes in
patients with a history of 9 or fewer recurrences per year is 500 mg once daily for the source partner.


Herpes Zoster
The recommended dosage of valacyclovir tablets for treatment of herpes zoster is 1 gram 3 times daily for 7 days. Therapy
should be initiated at the earliest sign or symptom of herpes zoster and is most effective when started within 48 hours of the
onset of rash.

2.2 Pediatric Dosing Recommendations

Cold Sores (Herpes Labialis)
The recommended dosage of valacyclovir tablets for the treatment of cold sores in pediatric patients aged greater than orequal to 12 years is 2 grams twice daily for 1 day taken 12 hours apart. Therapy should be initiated at the earliest symptom
of a cold sore (e.g., tingling, itching, or burning).


Chickenpox
The recommended dosage of valacyclovir tablets for treatment of chickenpox in immunocompetent pediatric patients aged 2
to less than 18 years is 20 mg/kg administered 3 times daily for 5 days. The total dose should not exceed 1 gram 3 times
daily. Therapy should be initiated at the earliest sign or symptom [see Use in Specific Populations (8.4), Clinical Pharmacology
(12.3), Clinical Studies (14.4)].

2.3 Extemporaneous Preparation of Oral Suspension

Ingredients and Preparation per USP-NF
valacyclovir tablets 500 mg, cherry flavor, and Suspension Structured Vehicle USP-NF (SSV). Valacyclovir oral suspension
(25 mg/mL or 50 mg/mL) should be prepared in lots of 100 mL.


Instructions for Preparing Suspension at Time of Dispensing
• Prepare SSV according to the USP-NF.
• Using a pestle and mortar, grind the required number of valacyclovir 500-mg tablets until a fine powder is produced (5
valacyclovir tablets for 25-mg/mL suspension; 10 valacyclovir tablets for 50-mg/mL suspension).
• Gradually add approximately 5-mL aliquots of SSV to the mortar and triturate the powder until a paste has been produced.
Ensure that the powder has been adequately wetted.
• Continue to add approximately 5-mL aliquots of SSV to the mortar, mixing thoroughly between additions, until a
concentrated suspension is produced, to a minimum total quantity of 20 mL SSV and a maximum total quantity of 40 mL
SSV for both the 25-mg/mL and 50-mg/mL suspensions.
• Transfer the mixture to a suitable 100-mL measuring flask.
• Transfer the cherry flavor* to the mortar and dissolve in approximately 5 mL of SSV. Once dissolved, add to the measuring
flask.
• Rinse the mortar at least 3 times with approximately 5-mL aliquots of SSV, transferring the rinsing to the measuring flask
between additions.
• Make the suspension to volume (100 mL) with SSV and shake thoroughly to mix.
• Transfer the suspension to an amber glass medicine bottle with a child-resistant closure.
• The prepared suspension should be labeled with the following information “Shake well before using. Store suspension
between 2° to 8°C (36° to 46°F) in a refrigerator. Discard after 28 days.”
* The amount of cherry flavor added is as instructed by the suppliers of the cherry flavor.

2.4 Patients with Renal impairment

Dosage recommendations for adult patients with reduced renal function are provided in Table 1 [see Use in Specific Populations (8.5, 8.6), Clinical Pharmacology (12.3)]. Data are not available for the use of valacyclovir tablets in pediatric patients with a creatinine clearance <50 mL/min/1.73 m 2. Table 1. Valacyclovir Tablets Dosage Recommendations for Adults With Renal Impairment

Indications Normal Dosage Regimen (Creatinine Clearance ≥50 mL/min) Creatinine Clearance (mL/min)
30-49 10-29 <10
Cold sores (Herpes labialis) Do not exceed 1 day of treatment. Two 2 gram doses taken 12 hours apart Two 1 gram doses taken 12 hours apart Two 500 mg doses taken 12 hours apart 500 mg single dose
Genital herpes: Initial episode 1 gram every 12 hours no reduction 1 gram every 24 hours 500 mg every 24 hours
Genital herpes: Recurrent episode 500 mg every 12 hours no reduction 500 mg every 24 hours 500 mg every 24 hours
Genital herpes: Suppressive therapy
Immunocompetent patients 1 gram every 24 hours no reduction 500 mg every 24 hours 500 mg every 24 hours

Alternate dose for immunocompetent patients with less or equal to 9

recurrences/year

500 mg every 24 hours no reduction 500 mg every 48 hours 500 mg every 48 hours
HIV-1-infected patients 500 mg every 12 hours no reduction 500 mg every 24 hours 500 mg every 24 hours
Herpes zoster 1 gram every 8 hours 1 gram every 12 hours 1 gram every 24 hours 500 mg every 24 hours


Hemodialysis: Patients requiring hemodialysis should receive the recommended dose of valacyclovir tablets after hemodialysis. During hemodialysis, the half-life of acyclovir after administration of valacyclovir tablets is approximately 4 hours. About one third of acyclovir in the body is removed by dialysis during a 4-hour hemodialysis session.
Peritoneal Dialysis: There is no information specific to administration of valacyclovir tablets in patients receiving peritoneal dialysis. The effect of chronic 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 end-stage renal disease (ESRD) not receiving hemodialysis. Therefore, supplemental doses of valacyclovir tablets should not be required following CAPD or CAVHD.

3 DOSAGE FORMS & STRENGTHS

Tablets:
• 500 mg: blue, film-coated, capsule shaped tablets, debossed with ‘I’ on one side and ’86’ on other side.

4 CONTRAINDICATIONS

Valacyclovir tablets are contraindicated in patients who have had a demonstrated clinically significant hypersensitivity reaction (e.g., anaphylaxis) to valacyclovir, acyclovir, or any component of the formulation [see Adverse Reactions (6.3)].

5 WARNINGS AND PRECAUTIONS

5.1 Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome (TTP/HUS)


TTP/HUS, in some cases resulting in death, has occurred in patients with advanced HIV disease and also in allogeneic bone marrow transplant and renal transplant recipients participating in clinical trials of valacyclovir hydrochloride at doses of 8 grams per day. Treatment with valacyclovir hydrochloride should be stopped immediately if clinical signs, symptoms, and laboratory abnormalities consistent with TTP/HUS occur.

5.2 Acute Renal Failure

Cases of acute renal failure have been reported in:
• Elderly patients with or without reduced renal function. Caution should be exercised when administering valacyclovir to geriatric patients, and dosage reduction is recommended for those with impaired renal function [see Dosage and Administration (2.4), Use in Specific Populations (8.5)].
• Patients with underlying renal disease who received higher than recommended doses of valacyclovir for their level of renal function. Dosage reduction is recommended when administering valacyclovir to patients with renal impairment [see Dosage and Administration (2.4), Use in Specific Populations (8.6)].
• Patients receiving other nephrotoxic drugs. Caution should be exercised when administering valacyclovir to patients receiving potentially nephrotoxic drugs.
• Patients without adequate hydration. Precipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid. Adequate hydration should be maintained for all patients.
In the event of acute renal failure and anuria, the patient may benefit from hemodialysis until renal function is restored [see Dosage and Administration (2.4), Adverse Reactions (6.3)].

5.3 Central Nervous System Effects

Central nervous system adverse reactions, including agitation, hallucinations, confusion, delirium, seizures, and encephalopathy, have been reported in both adult and pediatric patients with or without reduced renal function and in patients with underlying renal disease who received higher than recommended doses of valacyclovir for their level of renal function. Elderly patients are more likely to have central nervous system adverse reactions. Valacyclovir should be discontinued if central nervous system adverse reactions occur [see Adverse Reactions (6.3), Use in Specific Populations (8.5, 8.6)].

6 ADVERSE REACTIONS

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:
• Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome [see Warnings and Precautions (5.1)].
• Acute Renal Failure [see Warnings and Precautions (5.2)].
• Central Nervous System Effects [see Warnings and Precautions (5.3)].
The most common adverse reactions reported in at least 1 indication by greater than 10% of adult subjects treated with valacyclovir and observed more frequently with valacyclovir compared with placebo are headache, nausea, and abdominal pain. The only adverse reaction reported in greater than 10% of pediatric subjects aged less than 18 years of age was headache.

DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.

As the leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. Our material is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2022. All Rights Reserved.