McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 1 0  Antiviral agents

CCR5 coreceptor antagonist In 2007, another new class of drugs was introduced for the treatment of HIV. Maraviroc ( Celsentri ) is a CCR5 coreceptor antagonist. It blocks the receptor site to which the HIV virus needs to interact to enter the cell. It is indicated for the treatment of HIV in adults as part of combination therapy with other antiviral agents. Mara- viroc is rapidly absorbed from the GI tract, metabolised in the liver and excreted primarily through the faeces. It has a half-life of 14 to 18 hours. Maraviroc should not be used with known hypersensitivity to any component of the drug or by breastfeeding women. Caution should be used in the presence of liver disease or co-infection with hepatitis B because of the risk of serious hepatic toxicity. People at increased risk for cardiovascular events or with hypotension should be monitored very closely if this is the drug of choice for them. As with other antiviral agents, it should be used in pregnancy only if the benefit outweighs the potential risk to the fetus. Severe hepatotoxicity has been reported with this drug, often preceded by a systemic allergic reaction with eosinophilia and rash. Regular monitoring of liver function should be routine when using this drug. CNS effects including dizziness and changes in consciousness have been reported; people experiencing these should be cautioned to take measures to assure safety. People may also be at increased risk of infections because of the way the drug affects the cell membrane of the CD4 cells. Appropriate precautions are necessary. There is a risk of increased serum levels and toxicity when combined with cytochrome P450 CYP3A Prototype summary: Maraviroc Indications: Combination antiretroviral treatment of adults infected with CCR5-tropic HIV-1 who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents. Actions: Selectively binds to the human chemokine receptor CCR5 on the cell membrane, preventing interaction of HIV-1 and CCR5, which is necessary for the HIV to enter the cell; HIV cannot enter the cell and cannot multiply. Pharmacokinetics: Route Onset Peak Oral Slow 0.5–4 hours T 1/2 : 14 to 28 hours; metabolised in the liver, excreted in the faeces and urine. Adverse effects: Dizziness, paraesthesias, nausea,

inhibitors (ketoconazole, lopinavir/ritonavir, ritonavir, saquinavir, atazanavir), and the maraviroc dose should be adjusted accordingly. Decreased serum levels and loss of effectiveness may occur if maraviroc is combined with CYP3A inducers (rifampicin, efavirenz), and the maraviroc dose should be adjusted accordingly. Individ- uals should not use St John’s wort while on this drug because there is a loss of antiviral effects when the two are combined. I ntegrase inhibitor In late 2007, another class of drugs—integrase inhibi- tors—was introduced to treat HIV infection. The drug raltegravir ( Isentress ) belongs to this class. Raltegravir inhibits the activity of the virus-specific enzyme inte- grase, an encoded enzyme needed for viral replication. Blocking this enzyme prevents the formation of the HIV-1 provirus and leads to a decrease in viral load and increase in active CD4 cells. It is reserved for use in people who have been treated with other antiviral agents and have evidence of a return to viral replication. Raltegravir is rapidly absorbed from the GI tract and metabolised in the liver. It has a half-life of 3 hours and is excreted primarily in the faeces. Raltegravir is contraindicated with known hyper- sensitivity to any component of the drug, as initial treatment in adults, for use in children and for breast- feeding women. Caution should be used if the person is at risk for rhabdomyolysis or myopathy and during preg- nancy. People taking this drug must be very careful to Prototype summary: Raltegravir Indications: In combination with other antiviral agents for the treatment of HIV-1 infection in treatment-experienced adults who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents. Actions: Inhibits the activity of the virus-specific enzyme integrase, an encoded enzyme needed for viral replication. Blocking this enzyme prevents the formation of the HIV-1 provirus and leads to a decrease in viral load and an increase in active CD4 cells. Pharmacokinetics: Route Onset Peak Oral Rapid 3 hours T 1/2 : 9 hours; metabolised in the liver, excreted in the faeces and urine. Adverse effects: Headache, dizziness, nausea, vomiting, diarrhoea, fever, rhabdomyolysis.

vomiting, diarrhoea, cough, URI, fever, musculoskeletal symptoms, hepatotoxicity.