McKenna's Pharmacology for Nursing, 2e

140

P A R T 2  Chemotherapeutic agents

other agents, there are no adequate studies in pregnancy, so use should be limited to situations in which the benefits clearly outweigh any risks. It is suggested that women not breastfeed if they are infected with HIV. People with mild to moderate hepatic dysfunction should receive a lower dose of fosamprenavir, and people with severe hepatic dysfunction should not receive this drug because of its toxic effects on the liver. People receiving tipranavir must have liver function monitored regularly because of the possibility of potentially fatal liver dysfunction. Saquinavir must also be used cau- tiously in the presence of hepatic dysfunction. The safety of indinavir for use in children younger than 12 years has not been established. Adverse effects As with the other antiviral agents, people taking these drugs often experience GI effects, including nausea, vomiting, diarrhoea, anorexia and changes in liver function. Elevated cholesterol and triglyceride levels may occur. There is often a redistribution of fat to a buffalo hump with thinning of arms and legs. Rashes, pruritus and the potentially fatal Steven–Johnson syndrome have also occurred. Clinical significant drug–drug interactions Fosamprenavir should not be used in people who are receiving ritonavir if they have used protease inhibitors to treat their disease because of a risk of serious adverse effects. Tipranavir and fosamprenavir have been shown to interact with many other drugs. Before administering these drugs, it is important to check a drug guide to Prototype summary: Fosamprenavir Indications: Management of adults with symptomatic HIV infection in combination with other antiretrovirals. Actions: Inhibits protease activity, leading to the formation of immature, non-infectious virus particles. Pharmacokinetics: Route Onset Peak Oral Varies 1.5–4 minutes T 1/2 : 7.7 hours; metabolised in the liver and excreted in the faeces and urine. Adverse effects: Headache, mood changes, nausea, diarrhoea, fatigue, rash, Stevens–Johnson syndrome, redistribution of body fat (buffalo hump, thin arms and legs).

assess for potential interactions with other drugs being given. Many potentially serious toxic effects can occur when ritonavir is taken with non-sedating antihista- mines, sedative/hypnotics or antiarrhythmics because of the activity of ritonavir in the liver. Individuals with hepatic dysfunction are at increased risk for serious effects when taking ritonavir and require a reduced dose

and close monitoring. F usion inhibitor

A new class of drug called a fusion inhibitor (Table 10.3) was introduced in 2003. This agent acts at a different site than do other HIV antiviral agents. The fusion inhibitor prevents the fusion of the virus with the human cellular membrane, which prevents the HIV-1 virus from entering the cell. Enfuvirtide ( Fuzeon ) is used in combination with other antiretroviral agents to treat adults and children older than 6 years who have evidence of HIV-1 replication despite ongoing antiretro- viral therapy. Enfuvirtide is given by subcutaneous injection and peaks in effect in 4 to 8 hours. After metabolism in the liver, it is recycled in the tissues and not excreted. The half-life of enfuvirtide is 3.2 to 4.4 hours. Enfuvirtide is contraindicated with hypersensitivity to any compo- nent of the drug and in breastfeeding women. It should be used with caution in the presence of lung disease or pregnancy. The drug has been associated with insomnia, depression, peripheral neuropathy, nausea, diarrhoea, pneumonia and injection-site reactions. There are no reported drug interactions, but caution should be used when it is combined with any other drug. Prototype summary: Enfuvirtide Indications: Treatment of HIV-1–infected individuals who have experienced clinical or immunological deterioration after treatment with other agents, in combination with other antiretrovirals. Actions: Prevents the entry of the HIV-1 virus into cells by inhibiting the fusion of the virus membrane with the cellular membrane. Pharmacokinetics: Route Onset Peak Subcutaneous Slow 4–8 hours T 1/2 : 3.2 to 4.4 hours; metabolised in the liver, tissues recycle the amino acids, not excreted. Adverse effects: Headache, nausea, vomiting, diarrhoea, rash, anorexia, pneumonia, chills, injection-site reactions.