Acyclovir is a synthetic antiviral drug. It is the foundational treatment for infections caused by herpes simplex viruses (HSV-1 and HSV-2), varicella-zoster virus (VZV) and Epstein-Barr virus. Acyclovir is one of the most widely prescribed antivirals globally. Acyclovir is available in tablet, injection, cream, ointment and eye ointment formulations.

Drug Class

Acyclovir belongs to the nucleoside analogue antiviral class that mimics the chemical building blocks of viral DNA to interfere with viral replication. Unlike antibiotics, which target bacteria, antivirals target viral enzymes and replication machinery. Acyclovir is a virostatic that stops the virus from multiplying but does not eliminate the virus from the body. Acyclovir reduces the severity and duration of outbreaks but does not cure latent herpesvirus infection.

Viral Infections Acyclovir Treats 

Doctors prescribe acyclovir to treat:

• Herpes simplex virus type 1 (HSV-1): Oral herpes (cold sores, herpes labialis), herpes simplex encephalitis, and neonatal herpes

• Herpes simplex virus type 2 (HSV-2): Genital herpes; used for acute episodes and suppressive therapy 

• Varicella-zoster virus (VZV): Chickenpox and shingles (herpes zoster) - acyclovir reduces pain duration and rash severity when started within 72 hours of rash onset

• Herpes simplex keratitis: Treated with acyclovir ophthalmic ointment

• Herpes simplex encephalitis: A life-threatening CNS infection requiring intravenous acyclovir

• Neonatal herpes: HSV infection in newborns acquired during delivery from a mother with active genital herpes; treated with intravenous acyclovir

Forms of Acyclovir

Acyclovir is available as:

• Tablets: 200 mg, 400 mg and 800 mg; used for oral herpes, genital herpes, chickenpox and shingles

• Intravenous injection: 250 mg and 500 mg vials for IV infusion; used for herpes simplex encephalitis, neonatal herpes and severe herpes zoster in immunocompromised patients

• Cream (5%): For topical application to cold sores (herpes labialis) on the lips and face

• Ophthalmic ointment (3%): For herpes keratitis.

• Oral suspension: 200 mg per 5 mL for children.

Acyclovir Cream vs Ointment - When to Use Which?

Acyclovir 5% cream is formulated for application to the skin specifically cold sores on the lips and face. It should not be applied inside the mouth, eyes, genitals or on broken skin. Acyclovir 3% ophthalmic ointment is a sterile formulation designed for application inside the lower eyelid for herpes simplex keratitis (corneal herpes infection). It is not interchangeable with the skin cream - acyclovir skin cream should never be applied to the eye and the ophthalmic ointment is not used on skin.

How Acyclovir Stops the Virus from Multiplying

Acyclovir's mechanism involves selective activation by a viral enzyme. Viral thymidine kinase (TK) phosphorylates acyclovir into acyclovir monophosphate; cellular enzymes then convert it to acyclovir triphosphate (the active form). Acyclovir triphosphate is incorporated into the growing viral DNA chain by the viral DNA polymerase. Because acyclovir lacks the chemical group needed to extend the DNA chain, this incorporation terminates viral DNA replication. Acyclovir requires viral thymidine kinase for activation so its effects are largely selective for virus-infected cells - explaining the drug's favourable safety profile.

Common Side Effects of Each Form

• Oral tablets: Nausea, headache, and diarrhoea are most common; rarely, neurological effects (confusion, agitation, hallucinations) occur with high doses or renal impairment.

• Intravenous acyclovir: Nephrotoxicity is the most important adverse effect; phlebitis at the infusion site; neurological effects including tremor, confusion and encephalopathy at high doses.

• Cream (topical): Mild local reactions including burning, stinging, or tingling at the application site; dryness and flaking; allergic contact dermatitis is rare.

• Ophthalmic ointment: Mild transient stinging on application; punctate keratopathy with prolonged use.

Who Should Use Acyclovir Cautiously?

Certain group of people should use acyclovir cautiously. They are:

• Patients with renal impairment

• Elderly patients as reduced renal clearance with age increases the risk of neurological side effects and nephrotoxicity

• Patients with neurological conditions 

• Immunocompromised patients.

Drug Interactions to Be Aware Of

Key interactions are:

• Aminoglycosides 

• Contrast agents

• Ciclosporin

• Methotrexate

• Mycophenolate mofetil

• NSAIDs like ibuprofen, naproxen  

• Probenecid

• Tacrolimus

• Zidovudine (AZT).

How Long Before Acyclovir Starts Working?

Oral acyclovir for cold sores begins to reduce viral shedding within 24 hours; visible improvement typically occurs within 2 to 3 days; complete healing takes 4 to 8 days. For shingles, oral acyclovir (800 mg five times daily) started within 72 hours of rash onset reduces the duration of rash and pain by approximately 2 days and reduces the risk of post-herpetic neuralgia. For genital herpes, acute episodes resolve within 5 to 10 days with a 5-day or 10-day course; suppressive therapy (400 mg twice daily) is required to reduce outbreak frequency.

Does Acyclovir Cure Herpes Permanently?

No this is the most important limitation of acyclovir and all herpesvirus antivirals. After primary infection, HSV and VZV establish lifelong latency in sensory nerve ganglia, where they are inaccessible to antiviral drugs because no active viral replication occurs. Acyclovir can only suppress replication during active outbreaks or during suppressive therapy. There is currently no cure for herpes simplex infection. Suppressive therapy with acyclovir 400 mg twice daily substantially reduces the frequency and severity of recurrences and reduces asymptomatic viral shedding and transmission risk.

FAQs

1. What is acyclovir cream used for on the skin?

   Acyclovir 5% cream is used for herpes labialis - cold sores on the lips and face caused by HSV-1. It reduces the duration of cold sore episodes by approximately 12 to 18 hours when applied at the first sign of tingling or burning, before a visible blister forms. The cream should be applied five times daily for 4 to 5 days. It is not effective for cold sores that have fully crusted over. 

2. Can acyclovir cure herpes completely?

   No acyclovir suppresses HSV replication during active outbreaks and reduces outbreak frequency during suppressive therapy but does not eliminate the virus from the body. HSV establishes permanent latency in nerve ganglia, where it is inaccessible to antiviral drugs. There is currently no cure for herpes simplex infection. Recurrences are significantly reduced with suppressive therapy but the virus remains present and can reactivate if treatment is stopped.

3. How long does acyclovir take to clear a cold sore?

   With topical acyclovir cream applied at the earliest sign of tingling, the cold sore episode typically resolves within 4 to 5 days. Oral acyclovir (400 mg three times daily for 5 days) produces faster and more complete suppression than cream. Treatment should begin at the prodromal stage (tingling, itching, or burning) before a blister appears as the drug is most effective when viral replication is highest.

4. Is acyclovir safe to use during pregnancy?

   Acyclovir is generally considered safe in pregnancy. The Acyclovir Pregnancy Registry, which followed over 1,000 women exposed in the first trimester, did not find an increased rate of birth defects. It is used for severe primary genital herpes, herpes simplex encephalitis and from 36 weeks gestation for suppression of recurrent genital herpes to reduce neonatal HSV risk. All use in pregnancy should be under medical supervision.

5. Can acyclovir tablets be used for chickenpox in adults?

   Yes oral acyclovir is recommended for chickenpox in adults, adolescents above 12 years, immunocompromised individuals, pregnant women and those with chronic skin or lung disease. The standard adult dose is 800 mg five times daily for 7 days, started within 24 to 48 hours of rash onset. Intravenous acyclovir is preferred in immunocompromised patients. Acyclovir is not routinely recommended for uncomplicated chickenpox in healthy children.

6. Can acyclovir stop the virus from spreading to others?

   Acyclovir reduces but does not eliminate the risk of transmission. By reducing viral shedding during active outbreaks and asymptomatic shedding during suppressive therapy acyclovir lowers the risk of transmitting herpes to sexual partners. Suppressive valacyclovir reduces transmission risk by approximately 50%. Condom use combined with suppressive antiviral therapy provides greater protection than either alone, but neither completely eliminates transmission risk.

7. What is the difference between acyclovir and valacyclovir?

   Valacyclovir is the L-valyl ester prodrug of acyclovir and when taken orally, it is converted to acyclovir in the gut and liver. The critical difference is bioavailability: oral acyclovir has a bioavailability of only 10 to 20%, requiring five daily doses; valacyclovir achieves three to five times higher acyclovir blood levels and requires only two to three doses daily. Valacyclovir has largely replaced acyclovir for systemic indications in adults due to improved convenience. 

8. Is it safe to use acyclovir ointment near the eyes?

   Acyclovir ophthalmic ointment (3%) is specifically designed for use inside the lower eyelid for herpes simplex keratitis and must only be used under ophthalmological supervision. Acyclovir skin cream (5%) should never be applied near the eye as it is not sterile and can cause irritation and corneal damage. 

References

1. Elion GB. The purine path to chemotherapy. Science. 1989;244(4900):41–7. https://doi.org/10.1126/science.2649222

2. Corey L, Benedetti J, Critchlow C, et al. Treatment of primary first-episode genital herpes simplex virus infections with acyclovir: results of topical, intravenous and oral therapy. J Antimicrob Chemother. 1983;12(Suppl B):79–88. https://doi.org/10.1093/jac/12.suppl_B.79

3. Whitley RJ, Gnann JW Jr. Acyclovir: a decade later. N Engl J Med. 1992;327(11):782–9. https://doi.org/10.1056/NEJM199209103271108

4. Stone KM, Reiff-Eldridge R, White AD, et al. Pregnancy outcomes following systemic prenatal acyclovir exposure. BMJ. 2004;328(7445):880. https://doi.org/10.1136/bmj.38082.563542.AE

5. Corey L, Wald A, Patel R, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350(1):11–20. https://doi.org/10.1056/NEJMoa023144