Acyclovir

Indications

Oral
Primary herpes simplex infections
Adult: 200 mg 5 times daily every 4 hr for 5-10 days; for severely immunocompromised patients and those with impaired absorption: 400 mg 5 times daily for 5 days.

CrCl (ml/min)	Dosage Recommendation
<10	200 mg every 12 hr.

Oral
Suppression of recurrent herpes simplex
Adult: 800 mg daily in 2-4 divided doses. May reduce to 400-600 mg daily if necessary. Reassess the condition every 6-12 mth. For mild or infrequent recurrences: Episodic treatment may be used: 200 mg 5 times daily for 5 days, preferably begun during the prodromal period.

CrCl (ml/min)	Dosage Recommendation
<10	200 mg every 12 hr.

Oral
Prophylaxis of herpes simplex in immunocompromised patients
Adult: 200-400 mg 4 times daily.
Child: ≥2 yr: 200-400 mg 4 times daily; <2 yr: 100-200 mg 4 times daily.

CrCl (ml/min)	Dosage Recommendation
<10	200 mg every 12 hr.

Oral
Varicella zoster
Adult: >40 kg: 800 mg 4 times daily for 5 days.
Child: ≥2 yr and ≤40 kg: 20 mg/kg (up to 800 mg) 4 times daily for 5 days.

CrCl (ml/min)	Dosage Recommendation
10-25	800 mg tid.
<10	800 mg every 12 hr.

Oral
Herpes zoster (shingles)
Adult: 800 mg 5 times daily for 7-10 days.
Child: ≥6 yr: 800 mg 4 times daily; 2-5 yr: 400 mg 4 times daily; <2 yr: 200 mg 4 times daily.

CrCl (ml/min)	Dosage Recommendation
<10	800 mg every 12 hr.
10-25	800 mg tid.

Intravenous
Mucocutaneous herpes simplex in immunocompromised patients
Adult: 5 mg/kg every 8 hr for 7 days. Dose to be given as IV infusion over 1 hr.
Child: 10 mg/kg every 8 hr for 7 days.
Renal impairment: Peritoneal dialysis: Half the usual dose once daily. Haemodialysis: Half the usual dose every 24 hr and an additional half-dose after haemodialysis.

CrCl (ml/min)	Dosage Recommendation
25-50	Increase dose interval to 12 hr.
10-25	Increase dose interval to 24 hr.

Intravenous
Herpes simplex encephalitis
Adult: 10 mg/kg every 8 hr for 10 days.
Child: ≥3 mth: 20 mg/kg every 8 hr for 10 days.
Renal impairment: Peritoneal dialysis: Half the usual dose once daily. Haemodialysis: Half the usual dose every 24 hr and an additional half-dose after haemodialysis.

CrCl (ml/min)	Dosage Recommendation
25-50	Increase dose interval to 12 hr.
10-25	Increase dose interval to 24 hr.

Intravenous
Genital herpes
Adult: 5 mg/kg every 8 hr for 5-7 days.
Renal impairment: Peritoneal dialysis: Half the usual dose once daily. Haemodialysis: Half the usual dose every 24 hr and an additional half-dose after haemodialysis.

CrCl (ml/min)	Dosage Recommendation
25-50	Increase dose interval to 12 hr.
10-25	Increase dose interval to 24 hr.

Intravenous
Neonatal herpes simplex virus infections
Child: Birth - 3 mth: 10 mg/kg every 8 hr for 10 days.
Renal impairment: Peritoneal dialysis: Half the usual dose once daily. Haemodialysis: Half the usual dose every 24 hr and an additional half-dose after haemodialysis.

CrCl (ml/min)	Dosage Recommendation
25-50	Increase dose interval to 12 hr.
10-25	Increase dose interval to 24 hr.

Intravenous
Herpes zoster in immunocompromised patients
Adult: ≥12 yr: 10 mg/kg every 8 hr for 7 days.
Child: 20 mg/kg every 8 hr for 7 days.
Renal impairment: Peritoneal dialysis: Half the usual dose once daily. Haemodialysis: Half the usual dose every 24 hr and an additional half-dose after haemodialysis.

CrCl (ml/min)	Dosage Recommendation
25-50	Increase dose interval to 12 hr.
10-25	Increase dose interval to 24 hr.

Ophthalmic
Herpes simplex keratitis
Adult: Apply a 3% ointment 5 times daily until the 3rd day of complete healing.
Topical/Cutaneous
Herpes simplex infections of skin
Adult: Apply a 5% ointment/cream 5-6 times daily every 3-4 hr for 5-10 days.

Special Populations: Reduce dose in patients with renal impairment.

Reconstitution: Remove the calculated dose and add it to any appropriate IV solution at a volume selected for admin during each 1-hr infusion. Recommended infusion concentrations: About 7 mg/mL or lower. Higher concentrations (e.g. 10 mg/mL) may cause phlebitis or inflammation at the inj site if there is extravasation. Standard, commercially available electrolyte and glucose solutions are suitable for IV admin; biologic or colloidal fluids (e.g. blood products, protein solutions) are not recommended.
Incompatibility: Y-site incompatibility: Ondansetron, piperacillin/tazobactam, sargramostim, tacrolimus, vinorelbine, amifostine, amsacrine, aztreonam, cefepime, dobutamine, dopamine, fludarabine, foscarnet, gemcitabine, idarubicin, levofloxacin. Syringe incompatibility: Pantoprazole, caffeine citrate. Admixture incompatibility: Dobutamine, dopamine.

Contraindications

Hypersensitivity.

Warnings / Precautions

Renal impairment. Pregnancy, lactation. Neurological abnormalities with significant hypoxia, serious hepatic or electrolyte abnormalities. Maintain adequate hydration.

Adverse Reactions

Nausea, vomiting, headache, diarrhoea, rash, haematological changes (occasional), increase in liver enzymes, burning, itching or erythema (topical use). Eye application may produce stinging, superficial punctate keratopathy, blepharitis or conjunctivitis. IV administration: Local reaction, pain, inflammation, phlebitis, extravasation leads to ulceration. Increase in BUN and/or creatinine. Rarely, renal failure.
Potentially Fatal: Occasionally neurotoxicity after IV use: Lethargy, confusion, agitation, tremors, seizures, coma.

Drug Interactions

Probenecid decreases urinary excretion and increases half-life. Risk of renal impairment increased by other nephrotoxic drugs.
See Below for More aciclovir Drug Interactions

Mechanism of Actions

Activity against HSV types I and II and varicella-zoster virus is due to intracellular conversion of aciclovir to the monophosphate by viral thymidine kinase with subsequent conversion to the diphosphate and active triphosphate by cellular enzymes. This active form inhibits viral DNA synthesis and replication by interfering with viral DNA polymerase enzyme and being incorporated into viral DNA.
Absorption: 15-30% is absorbed from the GI tract (oral), slightly absorbed from the skin (topical), absorbed from the eye (ophthalmic).
Distribution: CSF (50% of conc is similar to those in plasma); crosses the placenta and enters breast milk (concentrations 3 times higher than in maternal serum). Protein-binding: 9-33%.
Excretion: Via kidney by glomerular filtration and tubular secretion (14% as unchanged), via faeces (2%); elimination half-life: 2-3 hr (normal renal function), 19.5% (anuric patients), 5-7% (haemodialysis patients).

Administration

May be taken with or without food. (May be taken w/ meals to reduce GI discomfort.)

Storage Conditions

Intravenous: Vial: Store between 15-25°C. Once diluted for admininstration, solution should be used within 24 hr. Ophthalmic: Store at 15-25°C. Oral: Store at 15-25°C. Topical/Cutaneous: Store at 15-25°C.

ATC Classification

D06BB03 - aciclovir ; Belongs to the class of topical antivirals used in the treatment of dermatological diseases.
J05AB01 - aciclovir ; Belongs to the class of nucleosides and nucleotides excluding reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.
S01AD03 - aciclovir ; Belongs to the class of antiinfectives, antivirals. Used in the treatment of eye infections.