Acyclovir (brand: Zovirax) is a synthetic nucleoside analogue with potent antiviral activity against herpes simplex virus (HSV) types 1 and 2 and varicella-zoster virus (VZV). It is the gold standard for managing genital herpes, herpes labialis (cold sores), herpes zoster (shingles), chickenpox (varicella), and herpes simplex encephalitis. Acyclovir works by selectively inhibiting viral DNA polymerase after being activated by viral thymidine kinase, terminating viral DNA chain elongation. It is a prescription-only medication available in multiple formulations (oral, topical, intravenous) with important considerations: renal toxicity risk with IV administration or high oral doses, neurotoxicity (especially in elderly or renally impaired), drug interactions with nephrotoxic agents, and probenecid interaction that reduces renal excretion.

Drug Name	Dosage Forms & Strengths	Best Price	Shipment	Where to Buy
Acyclovir (Zovirax) – Oral	200mg, 400mg, 800mg tablets; 200mg/5mL suspension	$0.55 per tablet	Worldwide Shipping – Discreet Packaging – Prescription Required	Visit Shop

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Zovirax at a Glance

Generic	Acyclovir
Brand (examples)	Zovirax® (oral, topical, IV), Sitavig® (buccal tablet)
Class	Nucleoside analogue antiviral (guanosine derivative)
Core indications	HSV-1, HSV-2 (genital herpes, cold sores); VZV (shingles, chickenpox); HSV encephalitis; herpes simplex keratitis
Typical dose (adult)	Genital herpes (primary): 200mg 5x/day or 400mg TID x 7-10 days; Suppression: 400mg BID; Shingles: 800mg 5x/day x 7 days
Onset	Peak plasma levels ~1.5-2 hours (oral); topical effect within days
Half-life	~2.5-3.5 hours (normal renal); prolonged in renal impairment (up to 20 hours)
Metabolism	Minimal hepatic; primarily excreted unchanged renally
Key interactions	Probenecid (↑ levels), nephrotoxic agents (additive renal risk), tenofovir, NSAIDs, contrast dye
Control status	Prescription-only; not a controlled substance

Why Zovirax (and When Not)

• Pros: Highly selective for infected cells (minimal host toxicity); established safety profile (decades of use); multiple formulations for flexible administration; effective for acute outbreaks and chronic suppression; pregnancy category B (generally considered safe).
• Trade-offs: Frequent dosing (5x/day for some indications); renal toxicity risk with high doses; neurotoxicity in elderly/renal impairment; lower bioavailability (~15-30%) requiring higher oral doses; valacyclovir offers improved convenience.
• Modern approach: Use early in prodrome for maximal efficacy; consider valacyclovir for less frequent dosing; monitor renal function in at-risk patients; use suppression therapy for frequent recurrences (≥6 episodes/year).

Mechanism of Action

Acyclovir’s selectivity is its hallmark. The drug is activated through a three-step phosphorylation process:

1. Viral thymidine kinase (TK): Selectively phosphorylates acyclovir to acyclovir monophosphate in infected cells (uninfected cells have minimal activation).
2. Host cellular kinases: Convert monophosphate to diphosphate then triphosphate (the active form).
3. DNA polymerase inhibition: Acyclovir triphosphate competitively inhibits viral DNA polymerase and incorporates into viral DNA, causing chain termination.

This mechanism results in 1000-3000x greater activity in infected cells compared to uninfected cells, explaining the favorable safety profile.

Pharmacokinetics & Clinical Implications

Aspect	Detail	Clinical implication
Absorption	Oral: ~15-30% bioavailability; Tmax 1.5-2h; food has minimal effect	Frequent dosing required (5x/day); valacyclovir (prodrug) has 3-5x higher bioavailability
Distribution	Wide distribution; CSF levels 50% of plasma; penetrates skin vesicles	Effective for CNS infections (encephalitis) at IV doses
Metabolism	Minimal hepatic metabolism; primarily unchanged	Safe in liver disease; dose adjustment not needed for hepatic impairment
Elimination	Renal excretion (glomerular filtration + tubular secretion); half-life 2.5-3.5h	Dose adjustment essential in renal impairment; maintain hydration to prevent crystallization in tubules

Evidence-Based Indications

Herpes Simplex Virus (HSV) Infections

• Genital herpes (primary): Reduces lesion duration, viral shedding, and new lesion formation; 200mg 5x/day or 400mg TID x 7-10 days.
• Genital herpes (recurrent): Shortens episode duration if started during prodrome or within 24h of lesion onset; 200mg 5x/day or 800mg TID x 5 days.
• Suppression therapy: Reduces recurrence frequency by 70-80%; 400mg BID (or 200mg 3-4x/day).
• Herpes labialis (cold sores): Topical cream 5x/day x 5 days; oral for severe or immunocompromised patients.
• Herpes simplex keratitis (ocular): Topical ophthalmic ointment; refer to ophthalmologist.
• Herpes simplex encephalitis: IV acyclovir (10 mg/kg q8h) x 14-21 days; reduces mortality from 70% to <20%.
• Neonatal herpes: IV acyclovir; emergency treatment.

Varicella-Zoster Virus (VZV) Infections

• Herpes zoster (shingles): 800mg 5x/day x 7 days; reduces acute pain, lesion duration, and risk of postherpetic neuralgia. Initiate within 72h of rash onset.
• Varicella (chickenpox): 20 mg/kg (max 800mg) 4x/day x 5 days; for immunocompromised, severe cases, or secondary household transmission. Healthy children: treatment optional.

Other Indications

• Immunocompromised patients: Higher doses and IV formulations for severe HSV/VZV infections.
• Eczema herpeticum: Severe disseminated HSV in atopic dermatitis; IV therapy often required.
• Prophylaxis in transplant recipients: Prevents HSV reactivation during immunosuppression.

Formulations & Strengths

Formulation	Strengths	Indications	Key notes
Oral tablets	200 mg, 400 mg, 800 mg	Genital herpes, shingles, chickenpox, suppression	Scored; can be split; take with food if GI upset
Oral suspension	200 mg/5 mL (400 mg/5 mL in some formulations)	Pediatric, dysphagia	Shake well; refrigerate; use within 10 days
Topical cream (Zovirax)	5% (50 mg/g) – 2g, 5g, 15g tubes	Herpes labialis (cold sores), mild genital herpes	Apply 5x/day for 5 days; not for ophthalmic use
Topical ointment	5% – 30g tube	Herpes labialis, herpes simplex mucocutaneous	Petrolatum base; apply 6x/day
Ophthalmic ointment	3% (10g tube)	Herpes simplex keratitis	Prescription only; apply 5x/day
Intravenous (IV)	500 mg, 1000 mg vials	Encephalitis, neonatal herpes, severe infections in immunocompromised	Hospital administration; requires hydration monitoring
Buccal tablet (Sitavig®)	50 mg	Herpes labialis (single-dose adhesive tablet)	Apply to upper gum; releases drug locally over hours

Dosing & Duration Strategies

Follow your prescriber and local labeling. Ranges below are educational, not personal medical advice.

Indication	Adult dose (oral)	Duration	Renal adjustment (CrCl <10 mL/min)
Genital herpes – primary	200 mg 5x/day OR 400 mg TID	7-10 days	200 mg 2x/day (or per guidance)
Genital herpes – recurrent	200 mg 5x/day OR 800 mg TID	5 days	200 mg 2x/day
Suppression therapy	400 mg BID	Chronic	200 mg BID (or 400 mg daily)
Herpes zoster (shingles)	800 mg 5x/day (every 4h while awake)	7 days	800 mg 2x/day
Chickenpox (varicella)	800 mg 4x/day	5 days	Dose per renal function
Herpes simplex encephalitis (IV)	10 mg/kg IV q8h	14-21 days	Adjust per CrCl; monitor hydration

Special Populations & Comorbidities

• Renal impairment: Critical dose reduction required. CrCl <10 mL/min: 200 mg BID (oral); IV: reduce frequency to q24h. Monitor creatinine, BUN, and urine output.
• Elderly: Increased risk of nephrotoxicity and neurotoxicity; start at lower doses; assess renal function before and during therapy; maintain hydration.
• Pregnancy: Category B; considered safe; used for primary genital herpes to reduce neonatal transmission risk. Acyclovir Pregnancy Registry shows no increased risk of birth defects.
• Breastfeeding: Excreted in breast milk (peak ~2.5 mg/L after 200mg dose); considered compatible; monitor infant for rash or GI effects.
• Pediatric: Weight-based dosing (varicella: 20 mg/kg/dose 4x/day; herpes: 10-20 mg/kg/dose 3-4x/day). Neonatal herpes: IV therapy only.
• Immunocompromised: Higher doses and IV often required; extended duration; monitor for resistance.
• Dehydration/volume depletion: Correct before initiating high-dose therapy; risk of crystal nephropathy.

Drug Interactions

Interaction	Effect	Action
Probenecid	Reduces renal tubular secretion → increased acyclovir levels (up to 50% AUC increase)	Monitor for toxicity; dose adjustment may be needed
Nephrotoxic agents (aminoglycosides, amphotericin B, contrast dye, NSAIDs, tenofovir)	Additive nephrotoxicity risk	Avoid combination if possible; monitor renal function closely; maintain hydration
Mycophenolate mofetil	Potential additive neurotoxicity (both metabolize to mycophenolic acid glucuronide)	Monitor for confusion, tremors
Zidovudine (AZT)	Potential additive neurotoxicity and hematologic toxicity	Monitor CBC, neurological status
Live vaccines (varicella, zoster)	Acyclovir may reduce vaccine efficacy (antiviral activity against vaccine strain)	Discontinue acyclovir ≥24h before live varicella/zoster vaccination; restart ≥14 days after

Adverse Effects & Warning Signs

Common	Less common	Serious (seek care immediately)
Nausea, vomiting Diarrhea Headache Dizziness Malaise Topical: burning/stinging, dry skin	Rash, urticaria Fatigue Elevated LFTs Alopecia (rare) Local irritation (IV site)	Acute kidney injury (oliguria, flank pain, edema) Neurotoxicity (confusion, agitation, hallucinations, tremors, seizures, lethargy) Thrombotic thrombocytopenic purpura (TTP) / hemolytic uremic syndrome (HUS) – rare, especially in immunocompromised Anaphylaxis (rash, dyspnea, angioedema) Hepatotoxicity (jaundice, dark urine)

• Neurotoxicity risk factors: Elderly, renal impairment, high IV doses, concurrent nephrotoxic drugs, dehydration. Symptoms typically reversible within 24-72h of dose adjustment/discontinuation.
• Nephrotoxicity prevention: Hydration (≥1.5-2 L/day), slow IV infusion (≥1 hour), dose adjustment for CrCl <50 mL/min, avoid concurrent nephrotoxins.
• Topical reactions: Usually mild; discontinue if severe irritation or allergic reaction.

Nephrotoxicity & Renal Monitoring

Acyclovir can cause crystal nephropathy due to precipitation of acyclovir crystals in renal tubules, particularly with:

• High oral doses (e.g., 800 mg 5x/day for shingles).
• IV administration (especially rapid infusion).
• Dehydration or volume depletion.
• Pre-existing renal impairment.
• Concurrent nephrotoxic medications.

Prevention strategies:

• Assess baseline creatinine and estimate CrCl before initiation.
• Maintain adequate hydration (≥1.5-2 L/day oral fluids).
• For IV: dilute to ≤7 mg/mL, infuse over ≥1 hour, monitor urine output.
• Adjust dose based on CrCl (see dosing table).
• Monitor creatinine every 1-2 days during high-dose or IV therapy.

Neurotoxicity Recognition

Acyclovir neurotoxicity is dose-dependent and more common in:

• Elderly patients.
• Renal impairment (accumulation of metabolite CMMG).
• High IV doses.
• Concurrent use of other neurotoxic drugs.

Symptoms (onset 1-5 days after initiation):

• Confusion, disorientation.
• Agitation, aggression.
• Hallucinations (visual, auditory).
• Tremors, myoclonus.
• Lethargy, somnolence.
• Seizures (generalized or focal).
• Coma (severe cases).

Management: Discontinue acyclovir; adjust dose based on renal function; provide supportive care. Symptoms typically resolve within 24-72 hours. Hemodialysis may accelerate clearance in severe cases.

Antiviral Resistance

Resistance to acyclovir occurs primarily through thymidine kinase (TK) deficiency or alteration (most common) or DNA polymerase mutations. Risk factors:

• Prolonged or repeated courses in immunocompromised patients (e.g., transplant recipients, HIV).
• Incomplete treatment courses.
• Severe immunosuppression.

Management of resistance:

• Foscarnet: Active against TK-deficient HSV/VZV; nephrotoxic, requires IV administration.
• Cidofovir: Broad-spectrum; nephrotoxic.
• Higher-dose acyclovir: May overcome some resistant strains (limited).
• Valacyclovir: Not effective against TK-deficient strains.
• Consult infectious disease specialist for confirmed resistance.

Comparison with Valacyclovir & Famciclovir

Agent	Key features	Pros	Trade-offs
Acyclovir (Zovirax)	Nucleoside analogue; low bioavailability (15-30%)	Decades of safety data; lowest cost; multiple formulations (topical, IV)	Frequent dosing (5x/day); lower convenience; requires dose adjustment in renal impairment
Valacyclovir (Valtrex)	Prodrug of acyclovir; 3-5x higher bioavailability	Less frequent dosing (BID or daily); better compliance; improved plasma levels	Higher cost; still requires renal adjustment; same resistance profile
Famciclovir	Prodrug of penciclovir; similar efficacy	Good bioavailability; less frequent dosing; active against acyclovir-resistant HSV (some strains)	Higher cost; less experience in pregnancy; renal adjustment

Suppression Therapy for Recurrent Herpes

Chronic suppressive therapy reduces recurrence frequency by 70-80% and reduces transmission risk. Indications:

• ≥6 recurrences per year (genital herpes).
• Severe or psychologically distressing recurrences.
• Immunocompromised patients.
• HSV-2 serodiscordant couples (to reduce transmission).

Regimens:

• Acyclovir: 400 mg BID.
• Valacyclovir: 500 mg daily (or 1g daily for high-frequency recurrences).
• Famciclovir: 250 mg BID.

Monitoring: Assess renal function every 6-12 months; reassess need for suppression annually; evaluate for breakthrough recurrences (may require dose adjustment).

Use in Pregnancy & Lactation

Pregnancy category: B (US FDA). Acyclovir is considered safe based on:

• Acyclovir Pregnancy Registry: No increased risk of birth defects compared to general population (over 1,500 first-trimester exposures).
• No evidence of teratogenicity in animal studies.
• Used for primary genital herpes near term to reduce neonatal transmission risk.

Indications in pregnancy:

• Primary genital herpes (especially third trimester): IV or oral acyclovir to reduce cesarean delivery and neonatal transmission.
• Recurrent genital herpes at term: Suppression therapy from 36 weeks to delivery.
• Severe VZV infection (pneumonia).

Breastfeeding: Acyclovir excreted in breast milk (peak ~2.5 mg/L after 200mg dose). Milk:plasma ratio ~1-2. Considered compatible; monitor infant for rash, diarrhea, or lethargy.

Performance, Driving & Safety

Acyclovir may cause dizziness, confusion, or hallucinations in some patients, particularly with high doses, renal impairment, or elderly patients. If neurotoxicity occurs, driving and hazardous activities should be avoided. Topical formulations do not impair driving.

Legal/Regulatory Status (Rx-Only)

Acyclovir is a prescription-only medication in most countries. It is not a controlled substance. Topical over-the-counter availability varies by country (US: prescription only for Zovirax cream; some countries OTC). Oral formulations always require prescription. Valacyclovir and famciclovir are also prescription-only. Dispensing restrictions may apply for suppressive therapy quantities (up to 90-day supply).

Safe Access via Clinicians & Licensed Pharmacies

1. Clinical diagnosis: Visual inspection (lesions), viral culture, PCR, or serology for HSV/VZV.
2. Timing: Initiate as early as possible (prodrome or within 48h of lesion onset) for maximal efficacy.
3. Renal assessment: Baseline creatinine and estimated CrCl before high-dose or suppressive therapy.
4. Prescription: From licensed clinician to licensed pharmacy; pharmacist counseling on hydration, dosing frequency, and adverse effect monitoring.
5. Hydration counseling: Emphasize importance of adequate fluid intake, especially with high-dose regimens.
6. Follow-up: Reassess if lesions not improving after 5-7 days; consider resistance, immunocompromised status, or alternate diagnosis.

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FAQ – Practical Questions

1. How quickly does acyclovir work? Lesions begin healing within 2-3 days; pain and viral shedding reduced within 24-48 hours if started early.
2. When should I start treatment? At first sign of prodrome (tingling, burning, itching) or within 24-48 hours of lesion onset.
3. Can I take acyclovir for cold sores? Yes, topical cream (5x/day) or oral for severe cases.
4. Does acyclovir cure herpes? No – it manages acute episodes and suppresses recurrences but does not eliminate latent virus.
5. How often do I take it for shingles? 800 mg 5 times daily for 7 days (every 4 hours while awake).
6. Can I drink alcohol while taking acyclovir? No direct interaction, but alcohol may worsen nausea and dehydration (risk for nephrotoxicity).
7. What if I miss a dose? Take when remembered; if close to next dose, skip; do not double.
8. How much water should I drink? ≥1.5-2 L/day, especially with high-dose therapy.
9. What are signs of kidney problems? Decreased urination, flank pain, swelling, nausea → stop and seek care.
10. Can acyclovir cause confusion? Yes, especially in elderly or renal impairment; stop and contact prescriber if confusion, hallucinations, or agitation occur.
11. Is acyclovir safe during pregnancy? Yes, category B; used for primary genital herpes to reduce neonatal transmission.
12. Can I take acyclovir while breastfeeding? Yes; levels in breast milk are low; considered compatible.
13. How long does suppression therapy last? Often 6-12 months, then reassess; may continue indefinitely for frequent recurrences.
14. Will acyclovir prevent transmission to my partner? Suppression therapy (valacyclovir 500 mg daily) reduces transmission risk by ~50% in HSV-2 discordant couples.
15. Can I use topical and oral acyclovir together? Not typically needed; oral covers systemic; topical for mild localized lesions.
16. What if acyclovir doesn’t work? Consider resistance (especially in immunocompromised), alternative antivirals (foscarnet), or incorrect diagnosis.
17. Can I take acyclovir for postherpetic neuralgia? No – acyclovir treats acute shingles but does not prevent or treat postherpetic neuralgia; pain management requires other agents.
18. Does acyclovir interact with birth control? No significant interaction.
19. Can I take acyclovir with ibuprofen? Yes, but both may affect kidneys; maintain hydration and monitor renal function.
20. What is the difference between acyclovir and valacyclovir? Valacyclovir is a prodrug with better absorption (3-5x higher bioavailability) and less frequent dosing.
21. How long should I take acyclovir for recurrent genital herpes? 5 days (oral) or valacyclovir 2g BID x 1 day.
22. Can acyclovir cause hair loss? Rare, reversible alopecia reported.
23. Is acyclovir safe for children? Yes, weight-based dosing for varicella or HSV.
24. What if I have a rash while taking acyclovir? Stop and contact prescriber; rule out allergic reaction.
25. Can I take acyclovir with food? Yes, may reduce GI upset.
26. How should I store acyclovir? Room temperature; protect from moisture; suspension refrigerated.
27. Does acyclovir cause sun sensitivity? No.
28. Can I use expired acyclovir? No; efficacy and safety not guaranteed.
29. What is the half-life? ~2.5-3.5 hours (normal renal); prolonged in renal impairment.
30. Can acyclovir cause depression? Rare; neurotoxicity may present as mood changes.
31. Is IV acyclovir painful? Can cause local irritation; dilute appropriately and infuse slowly.
32. How long after starting acyclovir am I contagious? Viral shedding reduced within 24-48 hours; lesions remain infectious until fully crusted.
33. Can I get acyclovir over the counter? Oral: prescription only; topical: varies by country (US: prescription).
34. What should I tell my doctor before taking acyclovir? Kidney disease, elderly, pregnancy/breastfeeding, dehydration, allergies, other medications (especially nephrotoxic).

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Printable Safe-Use Checklist

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Disclaimer: This educational document does not replace personalized medical advice. Acyclovir (Zovirax) is a prescription antiviral with important renal and neurotoxicity risks, especially with high doses, IV administration, and in patients with renal impairment or advanced age. Use only under licensed clinician supervision and according to local laws and product labeling. Acyclovir does not cure herpesvirus infections.