Aciclovir (Zovirax)

Generic Name

Aciclovir

Brand Names

Zovirax

Acyclovir (alternative spelling in the US and other countries)

Acivir

Herpex

Acivirax

Many generics available globally

Drug Class

Antiviral agent

Synthetic purine nucleoside analogue

DNA polymerase inhibitor

Mechanism of Action

Aciclovir is selectively phosphorylated by viral thymidine kinase into aciclovir monophosphate

Host enzymes further convert it to aciclovir triphosphate, the active form

This metabolite inhibits viral DNA polymerase and incorporates into viral DNA, leading to premature chain termination

It acts selectively on herpesvirus-infected cells due to their viral kinase activity, sparing normal host cells

Effective particularly against herpes simplex virus type 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), and, to a lesser extent, Epstein–Barr virus (EBV) and cytomegalovirus (CMV)

Indications

Topical and Oral

Genital herpes (initial and recurrent episodes)

Herpes labialis (cold sores)

Herpes zoster (shingles)

Varicella (chickenpox)

Prophylaxis in immunocompromised patients

Suppression of recurrent genital herpes

HSV encephalitis (IV formulation)

Herpetic keratitis (ophthalmic formulations)

Dosing and Administration

Oral for Genital Herpes

Initial episode: 200 mg five times daily for 5 to 10 days or 400 mg three times daily

Recurrent: 200 mg five times daily for 5 days or 800 mg twice daily for 5 days

Suppressive therapy: 400 mg twice daily

Oral for Herpes Zoster

800 mg five times daily for 7 to 10 days

Oral for Chickenpox

800 mg four times daily for 5 days

IV for Severe Infections

5–10 mg/kg every 8 hours for HSV encephalitis or disseminated infection

Dosing based on ideal body weight and renal function

Topical

Apply thin film to affected area 5 times daily for 4 to 5 days

Begin at earliest sign (tingling, redness) for maximal effect

Ophthalmic (not available in all markets)

Aciclovir 3% eye ointment used in herpetic keratitis

Pediatric Use

Dosing is weight-based for varicella and HSV infections

Used in neonates and immunocompromised children with severe disease

Elderly

Dose adjustment may be required due to age-related decline in renal function

Renal Impairment

Dosage modification essential to avoid accumulation and neurotoxicity

CrCl <10 mL/min: reduce frequency or dose significantly

Hepatic Impairment

No adjustment typically required

Monitor liver function in long-term or high-dose therapy

Contraindications

Hypersensitivity to aciclovir or valaciclovir

Topical forms should not be applied to mucous membranes or eyes unless specifically formulated for such use

Precautions

Maintain adequate hydration during systemic use to reduce risk of renal crystalluria

Monitor for neurotoxicity in high doses or renal dysfunction

Use caution in immunocompromised patients or those on other nephrotoxic agents

Topical forms are less effective for systemic infections

May not prevent viral shedding and transmission, especially in asymptomatic carriers

Resistance may occur in immunosuppressed populations due to mutations in viral thymidine kinase

Adverse Effects

Oral

Nausea

Vomiting

Diarrhea

Abdominal pain

Headache

Fatigue

Rash

Topical

Mild stinging or burning

Dryness or flaking at application site

Rarely contact dermatitis

Intravenous

Phlebitis at injection site

Renal impairment

Neurotoxicity (agitation, tremors, confusion, hallucinations, seizures)

Encephalopathy in overdose or renal impairment

Rare but Serious

Thrombotic thrombocytopenic purpura

Hemolytic uremic syndrome

Severe hypersensitivity reactions

Crystalluria leading to renal tubular obstruction

Pregnancy and Lactation

Pregnancy

Classified as low risk in pregnancy

Extensively used without increased risk of congenital anomalies

May be used to treat primary genital herpes in pregnancy

Used as prophylaxis in women with recurrent herpes near term

Lactation

Compatible with breastfeeding

Minimal amounts detected in breast milk

No adverse effects expected in breastfed infants

Use in Special Populations

Pediatrics

Approved for use in neonates and older children with appropriate dosing

IV aciclovir standard in neonatal HSV infections

Elderly

Increased risk of nephrotoxicity and neurotoxicity

Careful dose adjustment based on renal function essential

Immunocompromised Patients

Used for treatment and prophylaxis of HSV and VZV infections

Higher doses and longer durations may be needed

Resistance is more common in this population

Drug Interactions

Probenecid

Inhibits renal excretion of aciclovir, increasing plasma levels

Cimetidine

May reduce renal clearance of aciclovir

Nephrotoxic Drugs (e.g., aminoglycosides, ciclosporin, tacrolimus)

Increased risk of nephrotoxicity

Zidovudine

Possible additive CNS depression or lethargy

Mycophenolate Mofetil

Combined use may increase systemic exposure of both drugs

Monitoring Parameters

Renal function (baseline and periodically during IV therapy or in renal impairment)

Neurologic status in high doses or renal insufficiency

Hydration status during IV treatment

Hepatic enzymes if on long-term or high-dose therapy

CBC in long-term use or if clinically indicated

Formulations

Tablets: 200 mg, 400 mg, 800 mg

Oral suspension: 200 mg/5 mL

Topical cream and ointment: 5%

Ophthalmic ointment: 3%

IV injection: 25 mg/mL and 50 mg/mL concentrations

Patient Counseling Points

Begin therapy at first sign of symptoms for best results

Take oral tablets with or without food, but drink plenty of fluids

Do not skip doses; maintain regular dosing interval

Topical cream should be applied using clean hands and should not be rubbed into lesions

Avoid sexual contact when genital lesions are active

Use condoms consistently to reduce transmission risk

Report signs of confusion, agitation, or reduced urine output immediately

Complete full course even if symptoms improve

Store oral forms at room temperature and topical in cool, dry places