抗病毒藥品 Treatment of Herpes simplex virus (HSV) infections and herpes zoster (shingles) in immunocompromised patients

Antiviral Agent
Acyclovir is converted to acyclovir monophosphate by virus-specific thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes. Acyclovir triphosphate inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA.

Distribution:
1. Widely (eg, brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, CSF); CSF acyclovir concentration is ~50% of plasma concentrations
2. Vdss: (Neonates to 3 months) 28.8 L/1.73 m2; (1-2 y/o) 31.6 L/1.73 m2; (2-7 y/o) 42 L/1.73 m2; (Adults) 0.8 L/kg
3. Protein binding: 9% to 33%
Metabolism:
1. Converted by viral enzymes to acyclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes
2. Half-life elimination, Terminal: (Neonates to 3 months) 3.8 ± 1.19 hours; (3 months to ≤12 years) 2.36 ± 0.97 hours; (Adults with normal renal function) ~2.5 hours; (ESRD) 20 hours; (Hemodialysis) ~5 hours
Excretion:
Urine (62% to 91% as unchanged drug and metabolite)

Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation

Acyclovir is recommended for the treatment of genital herpes simplex virus (HSV), varicella (chickenpox) in pregnant patients

Although the manufacturer recommends that caution be exercised when administering acyclovir to patients who are breastfeeding, acyclovir is considered compatible with breastfeeding.

Severe inflammation sometimes leading to ulceration has resulted from accidental infusion into the tissue extravascularly.

HSV, central nervous system infection (encephalitis or meningitis):
10 mg/kg/dose every 8 hours; duration for encephalitis is 14 to 21 days and for meningitis is 10 to 14 days
HSV, mucocutaneous infection:
5 to 10 mg/kg/dose every 8 hours; once clinically improved, may switch to oral therapy to complete >10 days of therapy
Herpes zoster (shingles):
10 mg/kg/dose every 8 hours
Varicella (chickenpox):
10 mg/kg/dose every 8 hours for 7 to 10 days

1. ClCr 25–50mL/min : 5mg/kg Q12H
2. ClCr 10-25mL/min : 5mg/kg Q24H
3. ClCr <10mL/min : 2.5mg/kg Q24H

There are no dosage adjustments provided in the manufacturer's labeling; use caution in patients with severe impairment.

In sterile water for injection at concentration 50mg/ml, the reconstituted solution is stable for 12 hours at 25℃. In NS or D5W solution when concentration less than 10mg/ml, the solution is remained its stablility for 24 hours at 25℃.