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
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: 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).
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.
