McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 1 0  Antiviral agents

Pharmacokinetics Most of the agents for herpes and cytomegalovirus are readily absorbed in the body and excreted in the urine. Although cidofovir has been proven to be embryotoxic in animals, no adequate studies have been completed for the other agents. Aciclovir, which can be given orally and paren- terally or applied topically, reaches peak levels within 1 hour and has a half-life of 2.5 to 5 hours. It is excreted unchanged in the urine. It crosses into breast milk, which exposes the neonate to high levels of the drug. Cidofovir, which is given by intravenous (IV) infusion, reaches peak levels at the end of the infusion and in studies was cleared from the system within 15 minutes after the infusion. It is excreted unchanged in the urine and must be given with probenecid to increase renal clearance of the drug. The dose must be titrated according to renal function and creatinine clear- ance; renal function tests must be done before each dose and the dose planned accordingly. Famciclovir, an oral drug, is well absorbed from the GI tract, reaching peak levels in 2 to 3 hours. Famciclo- vir is metabolised in the liver and excreted in the urine and faeces. It has a half-life of 2 hours and is known to cross the placenta. Foscarnet is available in IV form only. It reaches peak levels at the end of the infusion and has a half- life of 4 hours. About 90% of foscarnet is excreted unchanged in the urine, making it highly toxic to the kidneys. Use caution and at reduced dose in individuals with renal impairment. Ganciclovir is available in IV and oral forms. It has a slow onset and reaches peak levels at 1 hour if given IV and 2 to 4 hours if given orally. This drug is primar- ily excreted unchanged in the faeces with some urinary excretion, with a half-life of 2 to 4 hours. Valaciclovir is an oral agent and is rapidly absorbed from the GI tract and metabolised in the liver to aci- clovir. Excretion occurs through the urine, so caution should be used in individuals with renal impairment. Valganciclovir is the oral prodrug, that is, it is imme- diately converted to ganciclovir once it is in the body. It is rapidly absorbed and reaches peak levels in 3 hours. It is primarily excreted unchanged in the faeces with some urinary excretion, with a half-life of 2.5 to 3 hours. Contraindications and cautions Drugs indicated for the treatment of herpes and CMV are highly toxic and should not be used during preg- nancy or breastfeeding to prevent adverse effects on the fetus or infant ; use only if the benefits clearly outweigh the potential risks to the fetus or infant. Avoid use in people with known allergies to antiviral agents to prevent serious hypersensitivity reactions ; in indi- viduals with renal disease, which could interfere with

excretion of the drug ; or in people with severe CNS disorders because the drug can affect the CNS, causing headache, neuropathy, paraesthesias, confusion and hallucinations. Cidofovir has been proven to be embryotoxic in animals. Use cidofovir with caution in children with AIDS because of the potential carcinogenic effects and effects on fertility. If no other treatment option is avail­ able, monitor the child very closely. For famciclovir, safety of use in children younger than 18 years of age has not been established. Foscarnet has been shown to affect bone develop- ment and growth. Foscarnet, as well as ganciclovir and valganciclovir, should not be used in children unless the benefit clearly outweighs the risk and the child is moni- tored very closely. Adverse effects The adverse effects most commonly associated with these antiviral agents include nausea and vomiting, headache, depression, paraesthesias, neuropathy, rash and hair loss. Rash, inflammation and burning often occur at sites of IV injection and topical application. Renal dysfunction and renal failure also have been reported. Cidofovir is associated with severe renal toxicity and granulocytopenia. Ganciclovir and valganciclovir have been associated with bone marrow suppression. Fos- carnet has been associated with seizures, especially in individuals with electrolyte imbalance. Clinically important drug–drug interactions The risk of nephrotoxicity increases when agents indi- cated for the treatment of herpes and CMV are used in Prototype summary: Aciclovir Indications: Treatment of herpes simplex virus (HSV) 1 and 2 infections; treatment of severe genital HSV infections; treatment of HSV encephalitis; acute treatment of shingles and chickenpox; ointment for the treatment of genital herpes infections; cream for the treatment of cold sores (herpes labialis). Actions: Inhibits viral DNA replication. Pharmacokinetics: Route Onset Peak Duration Oral Varies 1.5–2 hours Not known IV Immediate 1 hour 8 hour Topical Not generally absorbed systemically T 1/2 : 2.5–5 hours; excreted unchanged in the urine. Adverse effects: Headache, vertigo, tremors, nausea, vomiting, rash.