Generic Name

Valtrex

Mechanism

• Cell‑entry: Valacyclovir is rapidly converted by intestinal *haptocorrin* to acyclovir.
• Viral inhibition: Acyclovir is phosphorylated by viral thymidine kinase to acyclovir monophosphate. Viral UL23 (HSV) or UL30 (VZV) kinases further phosphorylate it to the active triphosphate form.
• DNA chain termination: Acyclovir‑triphosphate competitively inhibits viral DNA polymerase (UL30) and incorporates into growing viral DNA, causing chain termination without affecting host DNA synthesis.

Pharmacokinetics

• Absorption: Oral bioavailability ≈ 55 % (≈ 100 % for acyclovir). Peak plasma concentrations reached within 1–2 h.
• Distribution: Widely distributes into skin, mucosa, cerebrospinal fluid, and ocular tissues. Protein binding < 5 %.
• Metabolism: Valacyclovir → acyclovir by intestinal esterase. Acyclovir is not further metabolized.
• Excretion: Primarily renal via glomerular filtration and tubular secretion.
• Half‑life: ~2–3 h (acyclovir); ~3–4 h for valacyclovir.
• Renal dependence: Clearance decreases linearly with reduced GFR.

Indications

• Herpes simplex (HSV‑1/HSV‑2): primary or recurrent mucocutaneous lesions, genital herpes, neonatal herpes prophylaxis.
• Herpes zoster (VZV): acute zoster rash and post‑herpetic neuralgia.
• Immunocompromised patients: prophylaxis in post‑transplant or HIV‑infected individuals.
• Adjunctive therapy for other HSV‑related conditions: e.g., cold sores preventive regimens in high‑frequency outbreaks.

Contraindications

• Absolute contraindication: Hypersensitivity to valacyclovir or acyclovir.
• Renal impairment: Dose adjustment required; avoid in severe renal failure unless specific guidelines are followed.
• Pregnancy category B – use only if benefits outweigh potential risks.
• Breastfeeding: Limited data; consider alternative agents.
• Drug interactions: Caution with other nephrotoxic drugs (e.g., aminoglycosides, NSAIDs).
• Caution: Use in elderly or those on concurrent immunosuppressants; monitor for breakthrough HSV disease.

Dosing

• Take with food to improve tolerability.
• Suspend if vomiting < 30 min after dose (prevent absorption loss).

Adverse Effects

• Common (≥ 1–5 %): Nausea, vomiting, diarrhea, headache, dizziness, rash.
• Serious (≤ 0.5 %): Nephrotoxicity (renal impairment, proteinuria), hypersensitivity reactions, CNS effects (confusion, seizures), pancreatitis, rare bone marrow suppression.
• Long‑term use risks: Rarely, secondary malignancies (rarely reported).

Monitoring

• Renal function: Serum creatinine, BUN, eGFR before initiation; every 1–2 weeks in at‑risk patients.
• Liver enzymes: ALT/AST if hepatic disease suspected.
• Serum electrolytes: Especially in patients on concurrent diuretics.
• Signs of systemic HSV: Persistent lesions, fever, or new rash should prompt evaluation for drug resistance.
• If prolonged use (> 3 months): Consider periodic CBC and urinalysis.

Clinical Pearls

• Early initiation of Valtrex within 48 h of prodrome significantly reduces lesion duration and transmission risk.
• Renal adjustment is critical: For GFR 30–59 mL/min, dose 2 × 250 mg BID; for GFR 15–29 mL/min, 1 × 250 mg BID; for GFR < 15 mL/min, 1 × 250 mg Q12 h.
• Prophylaxis in transplant: 2 g daily has shown 90 % reduction in HSV recurrences; adjust for renal function.
• Intravenous vs oral: Oral Valtrex is bioequivalent to IV acyclovir for most indications; thus, outpatient management is feasible for mild‑to‑moderate disease.
• Adverse effect mitigation: Administer with meals to lessen GI upset; hydration improves renal clearance.
• Drug‑drug interactions: Concomitant use of foscarnet or cidofovir may compound nephrotoxicity – monitor renal function closely.
• Pregnancy and lactation: Though category B, opt for HSV‑specific therapy only when clinically warranted versus patient‑centered risk assessment.

*These high‑yield points align with current AHA/IDSA guidelines and optimize patient safety and therapeutic efficacy in clinical practice.*