Aciclovir


Generic Medicine Info
Indications and Dosage
Buccal
Recurrent herpes labialis
Adult: In immunocompetent patients: As delayed-release buccal tab: Apply 1 tab (50 mg) as a single dose to the upper gum region (canine fossa) within 1 hour following the onset of prodromal symptoms and before the appearance of any signs of herpes labialis lesions. Place the tab on the upper gum on the same side of the mouth as the herpes labialis symptoms. Do not apply the tab on the inside of the cheek or lip.

Intravenous
First episodes of genital herpes
Adult: For severe initial episodes in immunocompetent patients: 5 mg/kg 8 hourly via slow IV infusion over 1 hour for 5-7 days.
Child: ≥12 years Same as adult dose. Treatment recommendations may vary among countries and individual products (refer to specific local or product guidelines).

Intravenous
Varicella-zoster virus infection
Adult: Immunocompetent patients: 5 mg/kg 8 hourly via slow IV infusion over 1 hour for 5 days. Immunocompromised patients: 10 mg/kg 8 hourly via slow IV infusion over 1 hour for 5-7 days.
Child: 3 months to 12 years Immunocompetent patients: 250 mg/m2 8 hourly. Immunocompromised patients: 500 mg/m2 8 hourly. Treatment duration: 5 days. Alternative dosing for immunocompromised patients: <12 years 20 mg/kg 8 hourly; ≥12 years 10 mg/kg 8 hourly. Treatment duration: 7 days. All doses are given via slow IV infusion over 1 hour. Dosage recommendations may vary among countries and individual products (refer to specific local or product guidelines).

Intravenous
Mucocutaneous herpes simplex in immunocompromised patients
Adult: 5 mg/kg 8 hourly via slow IV infusion over 1 hour for 5-7 days.
Child: 3 months to 12 years 250 mg/m2 8 hourly for 5 days. Alternative dosing: <12 years 10 mg/kg 8 hourly for 7 days; ≥12 years Same as adult dose. All doses are given via slow IV infusion over 1 hour. Dosage recommendations may vary among countries and individual products (refer to specific local or product guidelines).

Intravenous
Herpes simplex encephalitis
Adult: 10 mg/kg 8 hourly via slow IV infusion over 1 hour for 10 days.
Child: 3 months to 12 years 500 mg/m2 8 hourly, or 20 mg/kg 8 hourly; ≥12 years Same as adult dose. All doses are given via slow IV infusion over 1 hour. Treatment duration: 10 days. Dosage recommendations may vary among countries and individual products (refer to specific local or product guidelines).

Ophthalmic
Herpes simplex keratitis
Adult: As 3% eye ointment: Apply 1 cm ribbon of ointment inside the lower conjunctival sac 5 times daily at approx 4-hourly intervals. Continue treatment for at least 3 days after healing is complete.
Child: Same as adult dose.

Oral
Herpes zoster (shingles)
Adult: 800 mg 5 times daily at approx 4-hourly intervals (omit the night-time dose). Initiate therapy as early as possible following onset of rash. Treatment duration: 7-10 days. Consider IV dosing in severely immunocompromised patients or patients with impaired gut absorption.

Oral
Varicella
Adult: 800 mg 5 times daily at approx 4-hourly intervals (omit the night-time dose). Alternatively, 800 mg 4 times daily. Initiate therapy within 24 hours following onset of rash. Treatment duration: 5-7 days. Consider IV dosing in severely immunocompromised patients or patients with impaired gut absorption.
Child: ≥2 years weighing ≤40 kg: 20 mg/kg (Max: 800 mg) 4 times daily; >40 kg: Same as adult dose. Alternative dosing: <2 years 200 mg 4 times daily; 2-5 years 400 mg 4 times daily; ≥6 years 800 mg 4 times daily. Treatment duration: 5 days.

Oral
Herpes simplex infections of skin and mucous membranes
Adult: 200 mg 5 times daily at approx 4-hourly intervals (omit the night-time dose). Treatment duration: 5-10 days. Initiate therapy as early as possible after the start of infection. In severely immunocompromised patients or patients with impaired gut absorption: 400 mg 5 times daily for 5 days or consider IV dosing. Treatment or dosage recommendations may vary among countries and individual products (refer to specific local or product guidelines).
Child: <2 years Half the adult dose; ≥2 years Same as adult dose.

Oral
Suppression of recurrent herpes simplex
Adult: In immunocompetent patients: 400 mg bid at approx 12-hourly intervals, or 200 mg 4 times daily at approx 6-hourly intervals. Interrupt treatment every 6-12 months to reassess the condition. Episodic treatment of recurrent episodes: 200 mg 5 times daily at approx 4-hourly intervals for 5 days, preferably initiated during the prodromal period. Dosage recommendations may vary among countries and individual products (refer to specific local or product guidelines).

Oral
Prophylaxis of herpes simplex in immunocompromised patients
Adult: 200 mg 4 times daily at approx 6-hourly intervals. In severely immunocompromised patients or patients with impaired gut absorption: 400 mg 4 times daily or consider IV dosing.
Child: <2 years Half the adult dose; ≥2 years Same as adult dose.

Topical/Cutaneous
Herpes labialis
Adult: As 5% cream: Apply onto the affected area(s) 5 times daily at approx 4-hourly intervals for 4-10 days. Start treatment as soon as possible, preferably during the prodromal period.
Child: As 5% cream: Same as adult dose. Treatment recommendations may vary among countries and individual products (refer to specific local or product guidelines).

Topical/Cutaneous
Mucocutaneous herpes simplex in immunocompromised patients
Adult: For limited non-life-threatening infections: As 5% ointment: Apply sufficient amount to cover all lesions 6 times daily at approx 3-hourly intervals for 7 days. Start treatment as early as possible after the onset of signs and symptoms.

Topical/Cutaneous
Genital herpes
Adult: As 5% cream: Apply onto the affected area(s) 5 times daily at approx 4-hourly intervals for 5-10 days. As 5% ointment: For management of initial episodes: Apply sufficient amount to cover all lesions 6 times daily at approx 3-hourly intervals for 7 days. Start treatment as soon as possible, preferably during the prodromal period. Treatment recommendations may vary among countries and individual products (refer to specific local or product guidelines).
Special Patient Group
Intravenous:
Obese patients: Dose reduction may be required. Calculate the dose based on the ideal body weight.
Renal Impairment
Oral:
Herpes simplex infections of skin and mucous membranes; Suppression of recurrent herpes simplex:
CrCl (mL/min) Dosage
<10 200 mg bid at approx 12-hourly intervals.

Herpes zoster; Varicella:
CrCl (mL/min) Dosage
<10 800 mg bid at approx 12-hourly intervals.
10-25 800 mg tid at approx 8-hourly intervals.

Intravenous:
Mucocutaneous herpes simplex in immunocompromised patients; First episodes of genital herpes; Herpes simplex encephalitis; Varicella-zoster virus infection:
Patients undergoing CAPD: Reduce the recommended dose to half given 24 hourly. Patients undergoing haemodialysis: Reduce the recommended dose to half given 24 hourly, then an additional half dose given after haemodialysis.
CrCl (mL/min) Dosage
<10 Reduce the recommended dose to half given 24 hourly.
10-24 Give the full recommended dose 24 hourly.
25-50 Give the full recommended dose 12 hourly.
Administration
May be taken with or without food. May be taken w/ meals to reduce GI discomfort.
Reconstitution
Powder for solution for IV infusion: Reconstitute vial with an appropriate volume of sterile water for inj or NaCl 0.9% inj to make a solution containing 25 mg/mL or 50 mg/mL. Further dilute the reconstituted solution with a compatible IV fluid (e.g. dextrose 5% in water, NaCl 0.9%) to a final concentration of ≤5 mg/mL or ≤7 mg/mL, respectively. Reconstitution and dilution recommendations may vary among local guidelines (refer to specific country guidelines).
Incompatibility
IV: Incompatible with foscarnet, ciclosporin, diphenhydramine, gentamicin, granisetron, and metoclopramide.
Contraindications
Hypersensitivity to aciclovir and valaciclovir.
Special Precautions
Patients receiving high doses; those with underlying neurological abnormalities, significant hypoxia, and serious electrolyte or hepatic abnormalities (IV); volume depletion. Maintain adequate hydration during therapy, particularly with high doses or IV infusion. Avoid extravasation during IV infusion. Topical cream or ointment is not recommended to be applied to the mucous membranes (e.g. eyes, vagina, mouth). Immunocompromised and obese patients. Renal impairment. Neonates, children, and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Acute kidney injury, neurotoxicity (e.g. confusion, agitation, lethargy, hallucination, impaired consciousness); skin irritation and contact sensitisation (topical cream).
Blood and lymphatic system disorders: Thrombocytopenia, anaemia, leucopenia.
Eye disorders: Superficial punctate keratopathy, conjunctivitis, transient mild burning or stinging in the eye after ophthalmic application. Rarely, blepharitis.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain; gingival pain, aphthous stomatitis (buccal tab).
General disorders and administration site conditions: Malaise, fatigue, fever, peripheral oedema; inj site inflammation and phlebitis (IV).
Hepatobiliary disorders: Rarely, jaundice, hepatitis.
Immune system disorders: Rarely, anaphylaxis, angioedema.
Investigations: Increased serum transaminases, serum bilirubin, BUN, and serum creatinine.
Musculoskeletal and connective tissue disorders: Myalgia.
Nervous system disorders: Headache, dizziness, dysarthria, somnolence.
Skin and subcutaneous tissue disorders: Pruritus, rash, photosensitivity reaction, urticaria; mild local pain (including transient burning or stinging sensation), mild drying or flaking of the skin, erythema (topical).
Vascular disorders: Hypotension.
Potentially Fatal: Thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome (particularly in immunocompromised patients); renal failure.
Buccal/IV/Parenteral/PO/Topical: B
Patient Counseling Information
Oral/IV: Ensure to maintain adequate hydration (especially when taking high doses). Ophthalmic: This drug may interfere with visual ability, if affected, do not drive or operate machinery. Avoid wearing contact lenses when using the eye ointment.
Monitoring Parameters
Monitor CBC, urinalysis, BUN, serum creatinine, urine output, hydration status, and liver enzymes. Obtain neutrophil count at least twice weekly in neonates receiving 60 mg/kg daily via IV. Closely assess for signs of neurotoxicity and nephrotoxicity (particularly in children receiving high doses, elderly and patients with renal impairment).
Overdosage
Symptoms: Oral: Nausea, vomiting, headache and confusion. IV: Elevated serum creatinine and BUN and subsequent renal failure; neurological effects (e.g. confusion, hallucinations, agitation, seizures, coma). Management: Consider haemodialysis until renal function is restored.
Drug Interactions
Increased risk of renal dysfunction with other nephrotoxic agents. May increase the serum concentration of theophylline. Probenecid and cimetidine may increase the plasma exposure and reduce the renal clearance of aciclovir. Increases in plasma concentrations of both aciclovir and inactive metabolite of mycophenolate mofetil when the drugs are administered concurrently. Concomitant use of high-dose IV aciclovir and lithium may increase the risk of lithium toxicity.
Action
Description:
Mechanism of Action: Aciclovir, a synthetic purine nucleoside analogue derived from guanine, is converted by virus-specific thymidine kinase to aciclovir monophosphate, then further converted to aciclovir triphosphate by other cellular enzymes. Aciclovir triphosphate competes with deoxyguanosine triphosphate for viral DNA polymerase and incorporates into viral DNA to inhibit DNA synthesis and viral replication.
Synonym(s): Acyclovir.
Pharmacokinetics:
Absorption: Poorly absorbed from the gastrointestinal tract; minimal systemic absorption after topical application; rapidly absorbed by the corneal epithelium and superficial ocular tissues. Bioavailability: Oral: 10-20% (decreases with increasing dose).
Distribution: Widely distributed into body tissues (e.g. brain, lungs, kidneys, liver, spleen, muscles, uterus, vagina), including CSF (approx 50% of plasma concentrations). Crosses the placenta and enters the breast milk. Volume of distribution: 0.8 ± 0.18 L/kg. Plasma protein binding: 9-33%.
Metabolism: Converted by viral enzymes into aciclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by other cellular enzymes.
Excretion: Via urine (62-91% as unchanged drug; 10-15% as 9-carboxymethoxymethylguanine metabolite). Elimination half-life: Approx 2-3 hours.
Chemical Structure

Chemical Structure Image
Aciclovir

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 135398513, Acyclovir. https://pubchem.ncbi.nlm.nih.gov/compound/Acyclovir. Accessed Aug. 16, 2023.

Storage
Conventional or dispersible tab: Store below 30°C. Protect from light and moisture. Oral susp: Store between 15-25°C. Protect from light. Cap/Buccal tab: Store between 20-25°C. Protect from light (cap) and moisture (cap; buccal tab). Powder and solution for IV infusion: Store intact vials between 15-25°C. Do not refrigerate reconstituted solution or solutions diluted for infusion. Topical cream or ointment/Ophthalmic ointment: Store below 25°C. Storage recommendations may vary between individual products or countries (refer to detailed product guidelines).
MIMS Class
Antivirals / Eye Anti-Infectives & Antiseptics / Topical Antivirals
ATC Classification
J05AB01 - aciclovir ; Belongs to the class of nucleosides and nucleotides excluding reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.
D06BB03 - aciclovir ; Belongs to the class of topical antivirals used in the treatment of dermatological diseases.
S01AD03 - aciclovir ; Belongs to the class of antiinfectives, antivirals. Used in the treatment of eye infections.
References
Kimberlin DW, Whitley RJ, Wan W et al. Oral Acyclovir Suppression and Neurodevelopment after Neonatal Herpes. New England Journal of Medicine. 2011 Oct;365(14):1284-1292. doi: 10.1056/NEJMoa1003509. Accessed 07/06/2023

Sampson MR, Bloom BT, Lenfestey RW et al. Population Pharmacokinetics of Intravenous Acyclovir in Preterm and Term Infants. Pediatr Infect Dis J. 2014 Jan;33(1):42-49. doi: 10.1097/01.inf.0000435509.75114.3d. Accessed 07/06/2023

Committee on Infectious Diseases, American Academy of Pediatrics, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH. "Non-HIV Antiviral Drugs", Red Book: 2021-2024 Report of the Committee on Infectious Diseases. American Academy of Pediatrics [online]. Accessed 02/06/2023.

Aciclovir 200 mg/5 mL Oral Suspension (Syri Limited, Trading as Thame Laboratories). MHRA. https://products.mhra.gov.uk. Accessed 02/06/2023.

Aciclovir 400 mg Tablets (Crescent Pharma Limited). MHRA. https://products.mhra.gov.uk. Accessed 02/06/2023.

Aciclovir 800 mg Dispersible Tablets (Wockhardt UK Ltd). MHRA. https://products.mhra.gov.uk. Accessed 02/06/2023.

Aciclovir Agepha 30 mg/g Eye Ointment (Agepha Pharma s.r.o). MHRA. https://products.mhra.gov.uk. Accessed 02/06/2023.

Acyclovir Capsule and Tablet (Chartwell RX, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/06/2023.

Acyclovir Cream (Padagis Israel Pharmaceuticals Ltd). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/06/2023.

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AFT Pharmaceuticals Ltd. Virupos Eye Ointment data sheet 03 August 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 02/06/2023.

Anon. Aciclovir [Acyclovir] (Ophthalmic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/06/2023.

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Anon. Aciclovir [Acyclovir] (Topical). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/06/2023.

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Baxter Healthcare Ltd. Aciclovir‐Baxter 25 mg/mL Solution for Infusion data sheet 8 February 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 02/06/2023.

Buckingham R (ed). Aciclovir. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/06/2023.

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Sitavig Tablet, Delayed Release (EPI Health, Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 02/06/2023.

Vicide Cream 5% (Noripharma Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 02/06/2023.

Zovirax Cold Sore Cream (GlaxoSmithKline Consumer Healthcare [UK] Trading Limited). MHRA. https://products.mhra.gov.uk. Accessed 02/06/2023.

Zovirax Cream (The Wellcome Foundation Ltd., Trading as GlaxoSmithKline UK). MHRA. https://products.mhra.gov.uk. Accessed 02/06/2023.

Zovirax Dispersible Tablets (GlaxoSmithKline Pharmaceutical Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 02/06/2023.

Zovirax IV 250 mg and 500 mg (The Wellcome Foundation Ltd., Trading as GlaxoSmithKline UK). MHRA. https://products.mhra.gov.uk. Accessed 02/06/2023.

Zovirax Oral Suspensions (GlaxoSmithKline Pharmaceutical Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 02/06/2023.

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Disclaimer: This information is independently developed by MIMS based on Aciclovir from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2024 MIMS. All rights reserved. Powered by MIMS.com
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