McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 1 0  Antiviral agents

TABLE 10.3

DRUGS IN FOCUS Agents for HIV and AIDS continued

Drug name

Dosage/route

Usual indications

Protease inhibitors (continued) tipranavir (Aptivus)

Adults: 500 mg PO b.d. with ritonavir 200 mg PO b.d. Paediatric >2 years: 375 mg/m 2 b.d. with ritonavir 150 mg/m 2 b.d.

Treatment of adults and children with HIV in combination with ritonavir

Fusion inhibitor

Adult: 90 mg PO b.d. by SC injection Paediatric 6–16 years: 2 mg/kg b.d. by SC injection

Part of combination therapy in treatment of people with HIV with evidence of HIV replication despite antiretroviral therapy

enfuvirtide (Fuzeon)

CCR5 coreceptor antagonist maraviroc (Celsentri)

Adult: 150 mg PO b.d.

Part of combination therapy for treatment of HIV-1 infections

Integrase inhibitor

Adult: 400 mg PO b.d.

Part of combination therapy for treatment of HIV-1 infections

raltegravir (Isentress)

treat HIV infections. These are drugs that compete with the naturally occurring nucleosides within a human cell that the virus would need to develop. The nucleoside reverse transcriptase inhibitors include the following agents: abacavir ( Ziagen ), didanosine ( Videx ), emtrici­ tabine ( Emtriva ), lamivudine ( Combivir, 3TC, Zeffix ), stavudine ( Zerit ), tenofovir ( Viread ) and zidovudine ( Retrovir ). Therapeutic actions and indications Nucleoside reverse transcriptase inhibitors compete with the naturally occurring nucleosides within the cell that the virus would use to build the DNA chain. These nucleosides, however, lack a substance needed to extend the DNA chain. As a result, the DNA chain cannot lengthen and cannot insert itself into the host DNA. Thus the virus cannot reproduce. They are used as part of com- bination therapy for the treatment of HIV infection. See Table 10.3 for usual indications for each of these agents. Pharmacokinetics Abacavir is an oral drug that is rapidly absorbed from the GI tract. It is metabolised in the liver and excreted in faeces and urine with a half-life of 1 to 2 hours. Didanosine is rapidly destroyed in an acid environ- ment and therefore must be taken in a buffered form. It reaches peak levels in 15 to 75 minutes. Didanosine undergoes intracellular metabolism with a half-life of 8 to 24 hours. It is excreted in the urine. Emtricitabine has the advantage of being a one- capsule-a-day therapy. Emtricitabine has a rapid onset and peaks in 1 to 2 hours. It has a half-life of 10 hours, and after being metabolised in the liver is excreted in the urine and faeces. Dose needs to be reduced in indi- viduals with renal impairment. It has been associated

with severe and even fatal hepatomegaly with steatosis, a fatty degeneration of the liver. Lamivudine is rapidly absorbed from the GI tract and is excreted primarily unchanged in the urine. It peaks within 4 hours and has a half-life of 5 to 7 hours. Because excretion depends on renal function, dose reduction is recommended in the presence of renal impairment. The drug is available as an oral solution, Epivir-HBV ; it is also recommended for the treatment of chronic hepatitis B. Stavudine is rapidly absorbed from the GI tract, reaching peak levels in 1 hour. Most of the drug is excreted unchanged in the urine, making it important to reduce dose and monitor people carefully in the presence of renal dysfunction. It can be used for adults and children and is only available in an extended-release form, allowing for once-a-day dosing. Tenofovir is a newer drug that affects the virus at a slightly different point in replication—a nucleotide that becomes a nucleoside. It is used only in combination with other antiretroviral agents. It is rapidly absorbed from the GI tract, reaching peak levels in 45 to 75 minutes. Its metabolism is not known, but it is excreted in the urine. Zidovudine was one of the first drugs found to be effective in the treatment of AIDS. It is rapidly absorbed from the GI tract, with peak levels occurring within 30 to 75 minutes. Zidovudine is metabolised in the liver and excreted in the urine, with a half-life of 1 hour. Contraindications and cautions Of the nucleosides, zidovudine is the only agent that has been proven to be safe when used during pregnancy. Of the other agents, there have been no adequate studies in pregnancy, so use should be limited to situations in which the benefits clearly outweigh any risks. Women