Acyclovir (Aciclovir)

What Is Acyclovir and What Is It Used For?

Acyclovir is a synthetic nucleoside analogue antiviral medication that selectively inhibits herpes virus replication. It is used to treat and prevent infections caused by herpes simplex virus types 1 and 2 (cold sores and genital herpes), varicella-zoster virus (chickenpox and shingles), and to prevent viral reactivation in immunocompromised patients.

Acyclovir belongs to a group of medicines known as nucleoside analogue antivirals. It was first synthesised in the late 1970s by Gertrude Elion and George Hitchings at Burroughs Wellcome (now GlaxoSmithKline), a discovery that contributed to their Nobel Prize in Physiology or Medicine in 1988. Since its introduction, acyclovir has become one of the most widely used antiviral agents worldwide and remains on the World Health Organization's Model List of Essential Medicines.

The drug works by a unique mechanism: once inside a virus-infected cell, acyclovir is phosphorylated by a viral enzyme called thymidine kinase (TK). This first phosphorylation step is highly specific to virus-infected cells, meaning the drug has minimal effect on uninfected host cells. The monophosphate form is then converted by cellular kinases to acyclovir triphosphate, which acts as a competitive inhibitor of viral DNA polymerase and causes premature chain termination of the viral DNA strand. This selective activation is what gives acyclovir its favourable safety profile compared to earlier antiviral agents.

Acyclovir is effective against the following viral infections:

• Herpes simplex virus type 1 (HSV-1): Causes cold sores (herpes labialis), herpetic keratitis (eye infections), and herpes encephalitis
• Herpes simplex virus type 2 (HSV-2): The primary cause of genital herpes, though HSV-1 can also cause genital infections
• Varicella-zoster virus (VZV): Causes chickenpox (varicella) on primary infection and shingles (herpes zoster) on reactivation
• Epstein-Barr virus (EBV): Some activity, though not a first-line treatment
• Cytomegalovirus (CMV): Used prophylactically in immunocompromised patients, though ganciclovir is more potent for active CMV disease

Acyclovir is available in several dosage forms to suit different clinical needs: oral tablets (200 mg, 400 mg, and 800 mg), a topical cream (5%) for localised skin lesions, and an intravenous formulation (25 mg/ml powder for solution for infusion) for severe or life-threatening infections requiring rapid systemic drug levels. The oral bioavailability of acyclovir is relatively low (approximately 15–30%), which is why the prodrug valacyclovir was later developed to improve oral absorption.

What Should You Know Before Taking Acyclovir?

Before starting acyclovir, inform your doctor if you have kidney problems, are over 65 years old, or are taking other medications. Ensure adequate hydration throughout treatment. Acyclovir should not be used if you are allergic to acyclovir or valacyclovir.

While acyclovir is generally well tolerated, there are important considerations before starting treatment. Your doctor needs to assess whether this medication is appropriate for you and may need to adjust the dose based on your individual circumstances. Being open about your medical history and current medications helps ensure safe and effective treatment.

Contraindications

You must not take acyclovir if you have a known allergy (hypersensitivity) to acyclovir, valacyclovir, or any of the other ingredients in the formulation. Valacyclovir is a prodrug that is converted to acyclovir in the body, so cross-reactivity between these two medications is expected. Allergic reactions can range from mild skin rashes to severe anaphylactic reactions, though the latter are very rare.

Warnings and Precautions

Talk to your doctor or pharmacist before taking acyclovir if any of the following apply to you:

• Kidney (renal) impairment: Acyclovir is primarily excreted by the kidneys. In patients with reduced kidney function, the drug can accumulate to potentially toxic levels. Dose adjustment is essential, and your doctor will likely check your kidney function (creatinine clearance) before and during treatment.
• Age over 65 years: Elderly patients are more likely to have age-related decline in kidney function, even if their serum creatinine appears normal. Dose reduction and careful monitoring are recommended.
• Dehydration risk: Acyclovir crystals can precipitate in the renal tubules if fluid intake is insufficient, potentially leading to acute kidney injury. This risk is particularly elevated in elderly patients, those receiving high intravenous doses, and patients with pre-existing renal compromise. Drinking plenty of water during treatment is strongly recommended.
• Immunocompromised state: While acyclovir is frequently used in immunocompromised patients, prolonged or repeated courses can lead to the development of acyclovir-resistant herpes strains. This is more common in patients with HIV/AIDS or those receiving chemotherapy.

Pregnancy and Breastfeeding

If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, seek advice from your doctor before taking acyclovir. While animal reproductive studies have not shown direct harmful effects, there are no adequate and well-controlled studies in pregnant women. Acyclovir should only be used during pregnancy when the potential benefit outweighs the potential risk to the foetus.

Post-marketing surveillance registries (such as the Acyclovir in Pregnancy Registry, which monitored outcomes of over 1,000 pregnancies) have not shown an increased risk of birth defects compared to the general population. However, the data are insufficient to draw definitive conclusions. Many international guidelines (including those from the CDC and RCOG) do support the use of acyclovir in late pregnancy to prevent neonatal herpes in women with active genital herpes.

Acyclovir is excreted in breast milk at concentrations approximately 0.6 to 4.1 times the corresponding plasma levels. However, the dose an infant would receive through breast milk is estimated to be less than 1% of a typical paediatric dose, which is generally considered clinically insignificant. The decision to continue or discontinue breastfeeding should be made in consultation with your doctor, weighing the benefits of breastfeeding against the potential exposure.

Driving and Using Machines

The effects of acyclovir on the ability to drive and use machines have not been formally studied. However, some side effects such as dizziness, drowsiness, and confusion may impair your ability to concentrate and react. Avoid driving or operating machinery until you know how acyclovir affects you. You are personally responsible for assessing whether you are fit to drive or perform tasks requiring alertness.

How Does Acyclovir Interact with Other Drugs?

Acyclovir has relatively few significant drug interactions. The most important interactions involve probenecid (which increases acyclovir levels), cimetidine (which may increase acyclovir exposure), and mycophenolate mofetil (used in transplant medicine). Always tell your doctor about all medications you are taking.

Compared to many other medications, acyclovir has a relatively clean drug interaction profile. This is partly because it is not significantly metabolised by the cytochrome P450 enzyme system, which is responsible for many drug-drug interactions. However, there are some clinically relevant interactions that your healthcare provider should be aware of.

The following table summarises the most important known drug interactions with acyclovir:

Important Considerations for Drug Interactions

Because acyclovir is primarily eliminated by the kidneys through both glomerular filtration and active tubular secretion, any drug that affects these processes can potentially alter acyclovir's pharmacokinetics. This is particularly important when treating patients who are already receiving multiple medications, such as transplant recipients or patients with HIV/AIDS.

It is also worth noting that while acyclovir itself has few interactions, patients receiving acyclovir often have conditions that require other treatments. For example, patients with herpes zoster (shingles) frequently take pain medications including opioids and gabapentinoids, and there is no clinically significant interaction between acyclovir and these commonly co-prescribed analgesics.

What Is the Correct Dosage of Acyclovir?

Acyclovir dosage varies significantly depending on the condition being treated. For oral herpes simplex treatment, the typical adult dose is 200 mg five times daily for 5 days. For shingles, the dose is 800 mg five times daily for 7 days. Always follow your doctor's instructions, as dose adjustments are required for kidney impairment and in elderly patients.

The dosage of acyclovir depends on several factors: the type of infection being treated, the severity of the condition, the patient's age, body weight (in children), and kidney function. Always take acyclovir exactly as prescribed by your doctor or pharmacist. Do not change your dose without consulting your healthcare provider.

Adult Dosage

For the treatment of herpes simplex infections, it is crucial to start treatment as early as possible, ideally at the first sign of prodromal symptoms such as tingling, itching, or burning. Early treatment can significantly reduce the duration and severity of an outbreak. In patients with frequently recurrent genital herpes (6 or more episodes per year), long-term suppressive therapy with acyclovir 400 mg twice daily may be recommended.

Children's Dosage

For children with chickenpox, the dose may be calculated more precisely as 20 mg per kg of body weight (up to a maximum of 800 mg per individual dose) given four times daily. A liquid formulation (oral suspension) of acyclovir is available and may be more suitable for young children who have difficulty swallowing tablets.

Elderly Patients and Renal Impairment

In elderly patients and in patients with impaired kidney function, the dose of acyclovir must be reduced. The kidney's ability to clear acyclovir decreases with age, and drug accumulation can lead to neurological side effects including confusion, tremors, and in severe cases, encephalopathy. Your doctor will calculate the appropriate dose based on your creatinine clearance (a measure of kidney function).

It is particularly important for elderly patients to maintain adequate fluid intake during acyclovir therapy. Dehydration increases the risk of acyclovir crystalluria (crystal deposits in the kidneys), which can cause acute kidney injury. Aim to drink at least 1.5 to 2 litres of water daily, unless your doctor has advised fluid restriction for another medical reason.

Missed Dose

If you forget to take a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a forgotten one. If you miss doses frequently, consider setting reminders or alarms to help you stay on schedule.

Overdose

If you or someone else has taken too much acyclovir, contact a poison control centre or seek emergency medical attention immediately. Symptoms of overdose may include nausea, vomiting, confusion, hallucinations, agitation, seizures, and kidney injury. Acyclovir is removed by haemodialysis, which may be considered in cases of severe overdose, particularly in patients with kidney failure.

What Are the Side Effects of Acyclovir?

Like all medicines, acyclovir can cause side effects, though not everyone experiences them. The most common side effects include headache, dizziness, nausea, diarrhoea, and skin rash. Serious side effects such as severe allergic reactions, kidney problems, and neurological symptoms are rare. Stop taking acyclovir and seek immediate medical attention if you develop signs of a severe allergic reaction.

Acyclovir is generally well tolerated, and serious adverse effects are uncommon at recommended oral doses. The risk of side effects increases with higher doses, intravenous administration, impaired kidney function, and dehydration. Below is a comprehensive overview of reported side effects organised by frequency, as defined by internationally standardised terminology.

Neurological Side Effects

Neurological side effects of acyclovir deserve special mention because, while rare, they can be serious. These effects are more likely to occur in elderly patients, those with impaired kidney function, and patients receiving high intravenous doses. Symptoms may include confusion, agitation, tremors, hallucinations, seizures, and in severe cases, encephalopathy or coma. These neurological effects are generally reversible upon discontinuation of acyclovir and correction of any underlying factors such as dehydration or renal impairment.

The mechanism behind acyclovir-induced neurotoxicity is thought to involve accumulation of the drug and its metabolite 9-carboxymethoxymethylguanine (CMMG) in patients with reduced renal clearance. Monitoring kidney function and maintaining adequate hydration are key preventive measures.

Kidney-Related Side Effects

Acyclovir-related nephrotoxicity primarily occurs through crystal precipitation in the renal tubules. Risk factors include rapid intravenous infusion, inadequate hydration, pre-existing renal disease, and concomitant use of other nephrotoxic drugs. When acyclovir is administered intravenously, it should be infused slowly over at least one hour to reduce the risk of renal crystal deposition. Oral acyclovir is much less likely to cause nephrotoxicity, provided adequate fluid intake is maintained.

Reporting Side Effects

If you experience any side effects, including those not listed here, talk to your doctor or pharmacist. You can also report side effects to your national medicines regulatory authority. Reporting helps improve knowledge about the safety of medications.

How Should You Store Acyclovir?

Store acyclovir tablets below 30°C (86°F) in a dry place. Keep out of sight and reach of children. Do not use after the expiry date printed on the packaging. Return unused medicines to your pharmacy for safe disposal.

Proper storage of medications is essential to maintain their effectiveness and safety. Acyclovir tablets should be stored at room temperature, not exceeding 30°C (86°F). Avoid storing them in bathrooms or near sinks where moisture levels are high, as humidity can degrade the tablets. Keep the blister packs in the original outer carton to protect from light exposure.

Always keep acyclovir and all medicines out of the sight and reach of children. The tablets should be stored in their original packaging until it is time to take them. Do not use acyclovir after the expiry date stated on the carton or blister pack – the expiry date refers to the last day of that month.

Do not dispose of medications via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines you no longer use. These measures help protect the environment and prevent accidental exposure.

What Does Acyclovir Contain?

Each acyclovir tablet contains the active substance aciclovir (available in 200 mg, 400 mg, and 800 mg strengths). The inactive ingredients include microcrystalline cellulose, povidone, sodium starch glycolate, and magnesium stearate. The tablets are sodium-free.

Understanding what your medication contains is important, particularly if you have known allergies or intolerances to specific excipients (inactive ingredients). Below is a detailed breakdown of what acyclovir tablets contain.

Active Ingredient

The active substance is aciclovir (also spelled acyclovir in American English). Each tablet contains either 200 mg, 400 mg, or 800 mg of aciclovir, depending on the prescribed strength. Aciclovir is a white crystalline powder with the molecular formula C₈H₁₁N₅O₃ and a molecular weight of 225.21 g/mol.

Inactive Ingredients (Excipients)

• Microcrystalline cellulose: A commonly used tablet filler and binder derived from plant cellulose
• Povidone: A binding agent that helps hold the tablet together
• Sodium starch glycolate (type A): A disintegrant that helps the tablet break down in the stomach for proper absorption
• Magnesium stearate: A lubricant used in tablet manufacturing to prevent sticking to equipment

Tablet Descriptions