Valacyclovir: uses, appearance and warnings

Valacyclovir tablets are a deoxynucleoside analogue DNA polymerase inhibitor indicated for: Adult Patients ( 1.1 ) Cold Sores (Herpes Labialis) Genital Herpes Treatment in immunocompetent patients (initial or recurrent episode) Suppression in immunocompetent or HIV-1-infected patients Reduction of transmission Herpes Zoster Pediatric Patients ( 1.2 ) Cold Sores (Herpes Labialis) Chickenpox Limitations of Use ( 1.3 ) 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. 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, USP 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, USP when initiated more than 72 hours after the onset of rash and the efficacy and safety of valacyclovir tablets, USP 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/mm 3 . 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. …

Tablets: 500 mg: blue colored, capsule-shaped, film-coated tablets, debossed with "RX 904" on one side and plain on the other side. 1 gram: blue colored, capsule-shaped, film-coated tablets, debossed with "RX 905" on one side and partial score bar on both sides. Tablets: 500 mg (unscored), 1 gram (partially scored) (3)

Valacyclovir tablets, USP (blue colored, capsule-shaped, film-coated tablets) containing 556.2 mg of valacyclovir hydrochloride, USP (hydrous) equivalent to 500 mg valacyclovir and debossed with "RX 904" on one side and plain on the other side. NDC 63304-904-03 Bottles of 10 NDC 63304-904-30 Bottles of 30 NDC 63304-904-90 Bottles of 90 NDC 63304-904-05 Bottles of 500 NDC 63304-904-77 Blister pack of 100 Valacyclovir tablets, USP (blue colored, capsule-shaped, film-coated tablets) containing 1.112 grams of valacyclovir hydrochloride, USP (hydrous) equivalent to 1 gram valacyclovir and debossed with "RX 905" on one side and partial score bar on both sides. NDC 63304-905-03 Bottles of 10 NDC 63304-905-30 Bottles of 30 NDC 63304-905-90 Bottles of 90 NDC 63304-905-05 Bottles of 500 NDC 63304-905-77 Blister pack of 100 Storage: Store at 20° C to 25° C (68° F to 77° F) [See USP Controlled Room Temperature]. Dispense in a well-closed container as defined in the USP.

Valacyclovir hydrochloride is contraindicated in patients who have had a demonstrated clinically significant hypersensitivity reaction [e.g., anaphylaxis, severe cutaneous adverse reactions (SCARs)] to valacyclovir, acyclovir, or any component of the formulation [see Warnings and Precautions (5.4) , Adverse Reactions (6.3) ] . Hypersensitivity to valacyclovir (e.g., anaphylaxis), acyclovir, or any component of the formulation. ( 4 )

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS): Has occurred in patients with advanced HIV-1 disease and in allogenic bone marrow transplant and renal transplant patients receiving 8 grams per day of valacyclovir hydrochloride in clinical trials. Discontinue treatment if clinical symptoms and laboratory findings consistent with TTP/HUS occur. ( 5.1 ) Acute renal failure: May occur in elderly patients (with or without reduced renal function), patients with underlying renal disease who receive higher-than-recommended doses of valacyclovir hydrochloride for their level of renal function, patients who receive concomitant nephrotoxic drugs, or inadequately hydrated patients. Use with caution in elderly patients and reduce dosage in patients with renal impairment. ( 2.4 , 5.2 ) Central nervous system adverse reactions (e.g., agitation, hallucinations, confusion, and encephalopathy): May occur in both adult and pediatric patients (with or without reduced renal function) and in patients with underlying renal disease who receive higher-than-recommended doses of valacyclovir hydrochloride for their level of renal function. Elderly patients are more likely to have central nervous system adverse reactions. Use with caution in elderly patients and reduce dosage in patients with renal impairment. ( 2.4 , 5.3 ) Severe cutaneous adverse reactions (SCARs): Including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), toxic epidermal necrolysis (TEN), and Stevens-Johnson syndrome (SJS) have been reported during the postmarketing experience with valacyclovir. Discontinue valacyclovir hydrochloride immediately if a painful rash with mucosal involvement or a progressive severe rash develops, and closely monitor clinical status. ( 5.4 ) 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-1 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 hydrochloride 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 hydrochloride for their level of renal function. Dosage reduction is recommended when administering valacyclovir hydrochloride 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 hydrochloride 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 hydrochloride for their level of renal function. Elderly patients are more likely to have central nervous system adverse reactions. Valacyclovir hydrochloride should be discontinued if central nervous system adverse reactions occur [see Adverse Reactions (6.3) , Use in Specific Populations (8.5 , 8.6) ]. 5.4 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions (SCARs), including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been reported during postmarketing experience with valacyclovir [see Contraindications (4) and Adverse Reactions (6.3) ] . Discontinue valacyclovir hydrochloride immediately if a painful rash with mucosal involvement or a progressive severe rash develops. Closely monitor clinical status and initiate appropriate therapy. Valacyclovir hydrochloride is contraindicated in patients who have developed SCARs with the use of valacyclovir or acyclovir, or any component of the formulation [see Contraindications (4) , Adverse Reactions (6.3) ] .

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) ] . Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.4) ] . The most common adverse reactions reported in at least 1 indication by greater than 10% of adult subjects treated with valacyclovir hydrochloride and observed more frequently with valacyclovir hydrochloride 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 was headache. …

No clinically significant drug-drug or drug-food interactions with valacyclovir hydrochloride are known [see Clinical Pharmacology (12.3) ].