McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 1 0  Antiviral agents

non-nucleoside antivirals; these combinations are often used, and the person needs to be monitored very closely. There have been reports of severe drowsiness and lethargy if zidovudine is combined with cyclosporin; warn the person to take appropriate safety precautions. P rotease inhibitors The protease inhibitors block protease activity within the HIV virus. The protease inhibitors that are avail- able for use include atazanavir ( Reyataz ), darunavir ( Prezista ), fosamprenavir ( Telzir ), indinavir ( Crixivan ), lopinavir ( Kaletra ), ritonavir ( Norvir ), saquinavir ( Invirase ) and tipranavir ( Aptivus ). Therapeutic actions and indications Protease is essential for the maturation of an infectious virus; without it, an HIV particle is immature and non- infective, unable to fuse with and inject itself into a cell. All of these drugs are used as part of combination therapy for the treatment of HIV infection (see Table 10.3). Pharmacokinetics Atazanavir is rapidly absorbed from the GI tract and can be taken with food. After metabolism in the liver, it is excreted in the urine and faeces with a half-life of 6.5 to 7.9 hours. It is not recommended for people with severe hepatic impairment; for those with moderate hepatic impairment, the dose should be reduced. Fosamprenavir is rapidly absorbed after oral admini­ stration, reaching peak levels in 1.5 to 4 hours. It is metabolised in the liver and excreted in urine and faeces. Indinavir is rapidly absorbed from the GI tract, reaching peak levels in 0.8 hour. Indinavir is metabo- lised in the liver by the cytochrome P450 system. It is excreted in the urine with a half-life of 1.8 hours. People with hepatic or renal impairment are at risk for increased toxic effects, necessitating a reduction in dose. Lopinavir is used as a fixed combination drug that combines lopinavir and ritonavir. The ritonavir inhibits the metabolism of lopinavir, leading to increased lopina- vir serum levels and effectiveness. It is readily absorbed from the GI tract, reaching peak levels in 3 to 4 hours, and undergoes extensive hepatic metabolism by the cytochrome P450 system. Lopinavir is excreted in urine and faeces. Tipranavir is used for the treatment of HIV infec- tion in adults in combination with 200 mg of ritonavir. It is taken orally with food, two 250-mg capsules each day with the ritonavir. It is slowly absorbed, reaching peak levels in 2.9 hours. It is metabolised in the liver with a half-life of 4.8 to 6 hours; excretion is through urine and faeces. Ritonavir is rapidly absorbed from the GI tract, reaching peak levels in 2 to 4 hours. Ritonavir undergoes

extensive metabolism in the liver and is excreted in faeces and urine. Saquinavir is slowly absorbed from the GI tract and is metabolised in the liver by the cytochrome P450 mediator, so it must be used cautiously in the presence of hepatic dysfunction. It is primarily excreted in the faeces with a short half-life. Because therapy for HIV infection involves the use of several different antiviral drugs, many are now avail- able as combination drugs, which reduces the number of tablets a person has to take each day. Box 10.4 discusses combination drugs. Contraindications and cautions Of the protease inhibitors listed, saquinavir is the only agent that has not been shown to be teratogenic; however, its use during pregnancy should be limited. Saquinavir crosses into breast milk, and women are advised not to breastfeed while taking this drug. For the People who are taking combination drug therapy for HIV infection may have to take a very large number of pills each day. Keeping track of these pills and swallowing such a large number each day can be an overwhelming task. In an effort to improve compliance and make it easier for some of these people, some anti- HIV agents are now available in combination products. Combivir is a combination of 150 mg lamivudine and 300 mg zidovudine. The person takes one tablet twice a day. Because this is a fixed combination drug, it is not the drug of choice for people who require a dose reduction owing to renal impairment or adverse effects that limit dose tolerance. Trizivir combines 300 mg abacavir, 150 mg lamivudine and 300 mg zidovudine. The person takes one tablet twice a day. Because this is a fixed combination drug, it is not the drug of choice for people who require a dose reduction owing to renal impairment or adverse effects that limit dose tolerance. People taking Trizivir should be warned at the time the prescription is filled about the potentially serious hypersensitivity reactions associated with abacavir and should be given a written list of warning signs to watch for. In 2005, a new combination product was approved to make compliance with an HIV drug regimen easier. Truvada (200 mg emtricitabine with 300 mg tenofovir) is a once-a-day tablet. People should be stabilised on each antiviral individually before being switched to the combination form. The year 2009 saw another combination product, Atripla —600 mg efavirenz, 200 mg emtricitabine and 300 mg tenofovir—which is recommended for people 18 years of age and older who have already been stabilised on each antiviral individually. ■■ BOX 10.4  Fixed combination drugs for treatment of HIV infection