Valarux

Approved Indications:

• Herpes Zoster (Shingles):
  Treatment of herpes zoster in immunocompetent adults to reduce pain and rash duration.
• Genital Herpes Simplex Virus (HSV-2):
  • Initial episode in adults and adolescents ≥12 years
  • Recurrent episodes
  • Chronic suppressive therapy in patients with frequent recurrences
  • Suppressive therapy to reduce HSV-2 transmission in discordant couples
• Herpes Labialis (Cold Sores):
  Treatment of recurrent herpes labialis in immunocompetent adults and adolescents ≥12 years
• Varicella (Chickenpox):
  Treatment of varicella in immunocompetent pediatric patients aged 2 to <18 years
• Cytomegalovirus (CMV) Prophylaxis:
  Prevention of CMV disease in adult renal transplant recipients at high risk (especially CMV-seronegative recipients of CMV-seropositive donors)

Off-label / Clinically Accepted Uses:

• HSV Prophylaxis in Immunocompromised Patients (e.g., post-transplant or HIV-positive)
• Bell’s Palsy (when HSV involvement is suspected)
• Adjunctive systemic antiviral therapy in Herpes Simplex Keratitis

Route of Administration: Oral
Formulations Available: Tablets – 500 mg, 1000 mg

Adults:

• Herpes Zoster: 1000 mg orally every 8 hours for 7 days
• Initial Genital Herpes: 1000 mg orally twice daily for 10 days
• Recurrent Genital Herpes: 500 mg orally twice daily for 3 days
• Suppressive Therapy for Recurrent Genital HSV:
  • 500 mg once daily (≤9 recurrences/year)
  • 1000 mg once daily (≥10 recurrences/year or HIV-infected)
• Reduction of Transmission in Discordant Couples: 500 mg orally once daily
• Cold Sores (Herpes Labialis): 2000 mg every 12 hours for 1 day (total 2 doses)

Pediatrics:

• Herpes Labialis (≥12 years): 2000 mg every 12 hours for 1 day
• Varicella (2–<18 years): 20 mg/kg orally three times daily for 5 days (max 1000 mg/dose)

Elderly Patients:

• Use lowest effective dose; ensure adequate hydration

Renal Impairment:

• Dose Adjustment Required
  • CrCl 30–49 mL/min: 1000 mg every 12 hours (for herpes zoster)
  • CrCl 10–29 mL/min: 1000 mg every 24 hours
  • CrCl <10 mL/min: 500 mg every 24 hours
  • Post-hemodialysis: Administer dose after dialysis session

Hepatic Impairment:

• No adjustment needed in mild-to-moderate hepatic disease; caution in severe impairment

Valacyclovir is a prodrug of acyclovir. After oral administration, valacyclovir is rapidly converted by first-pass intestinal and hepatic metabolism into acyclovir. Inside virus-infected cells, acyclovir is phosphorylated by viral thymidine kinase to acyclovir monophosphate, then by host cell kinases to its active form, acyclovir triphosphate. This active triphosphate inhibits viral DNA polymerase and incorporates into viral DNA, resulting in premature chain termination and inhibition of viral replication. The drug is selectively activated in infected cells, limiting toxicity to host cells.

• Absorption: Rapid and nearly complete; converted to acyclovir; oral bioavailability of acyclovir from valacyclovir is ~54%
• Peak Plasma Time: Acyclovir peaks ~1.5–2 hours after valacyclovir dosing
• Distribution: Widely distributed in body tissues and fluids, including CSF; protein binding 13–22%
• Metabolism: Valacyclovir is rapidly hydrolyzed to acyclovir and L-valine
• Half-life (Acyclovir): ~2.5–3.3 hours in healthy adults
• Excretion: Primarily renal (glomerular filtration and tubular secretion); ~89% as unchanged acyclovir
• Onset of Action: Generally within hours; clinically observable within 1–2 days depending on indication

• Pregnancy:
  • Former FDA Category B
  • Animal studies show no teratogenic effects; human data indicate low fetal risk
  • Used in pregnancy for suppressive therapy in recurrent genital herpes, especially during the third trimester
• Lactation:
  • Acyclovir is excreted in human milk in low concentrations
  • Generally considered safe; monitor breastfed infants for potential effects (e.g., diarrhea, rash)
• Recommendations:
  • Use during pregnancy or breastfeeding only if clearly needed
  • Avoid high-dose therapy unless benefit outweighs risk

• Primary Class: Antiviral
• Subclass: Nucleoside analogue antiviral
• Prodrug: L-valyl ester of acyclovir

• Known hypersensitivity to valacyclovir, acyclovir, or any formulation components
• Severe renal impairment without appropriate dose adjustment
• History of severe allergic reaction to nucleoside analogues

• Renal Impairment:
  • Risk of acute kidney injury, especially in dehydrated patients or those on nephrotoxic agents
  • Ensure adequate hydration; monitor renal function during treatment
• Neurological Effects:
  • Hallucinations, confusion, agitation, tremors, and seizures, particularly in elderly or renally impaired patients
  • Discontinue immediately if neurotoxicity develops
• TTP/HUS:
  • Rare but life-threatening; reported in immunocompromised patients on high-dose valacyclovir
  • Monitor for signs of thrombocytopenia or hemolysis
• Immunocompromised Status:
  • Prolonged therapy may result in resistance; careful virologic monitoring recommended

Common (≥1%):

• Neurologic: Headache, dizziness
• Gastrointestinal: Nausea, abdominal pain
• Dermatologic: Rash, pruritus
• General: Fatigue

Less Common / Serious:

• Renal: Acute renal failure, elevated serum creatinine
• Neurologic: Encephalopathy, hallucinations, delirium (mostly in elderly or renally impaired)
• Hematologic: Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS)
• Hypersensitivity: Anaphylaxis, angioedema (rare)

Onset & Severity:

• Most side effects occur within the first few days of therapy and are usually mild to moderate in intensity

• Nephrotoxic Drugs:
  • Cyclosporine, tacrolimus, NSAIDs – ↑ risk of renal toxicity
• Probenecid & Cimetidine:
  • Reduce renal clearance of acyclovir → ↑ systemic exposure
• Zidovudine (AZT):
  • ↑ risk of neurotoxicity when combined

Metabolic Enzymes:

• Valacyclovir is not a CYP450 substrate
• No known inhibition or induction of CYP450 enzymes

Food Interaction:

• Food does not significantly affect absorption

• CDC Guidelines (2021):
  Valacyclovir remains first-line therapy for initial and recurrent genital herpes. Suppressive therapy recommended to reduce transmission in serodiscordant couples.
• Pregnancy Use Guidelines:
  Third-trimester suppressive therapy is now standard in women with recurrent HSV to reduce neonatal herpes risk.
• Organ Transplantation:
  Continued recommendation for CMV prophylaxis in high-risk kidney transplant recipients

• Storage Temperature: 20°C to 25°C (68°F to 77°F)
• Allowed Excursion: 15°C to 30°C (59°F to 86°F)
• Humidity: Store in a dry place, away from excessive moisture
• Light: Protect from light; store in original packaging
• Handling: Do not break or crush tablets; swallow whole
• Refrigeration: Not required