ANTI VIRAL AGENTS.pptx

Overview of Antiviral Agents
• The conventional approach to control of viral diseases is to
develop effective vaccines, but this is not always possible.
• The objective of antiviral activity is to eradicate the virus while
minimally impacting the host and to prevent further viral
invasion. However, because of their method of replication,
viruses present a greater therapeutic challenge than do
bacteria.
• Viruses cause a variety of conditions, ranging from warts, to the
common cold and “flu,” to diseases such as chickenpox and measles.
• A single virus particle is composed of a piece of DNA or RNA inside a
protein coat. To carry on any metabolic processes, including
replication, a virus must enter a cell.

•Once a virus has fused with a cell wall and injected its
DNA or RNA into the host cell, that cell is altered—
that is, it is “programmed” to control the metabolic
processes that the virus needs to survive. The virus,
including the protein coat, replicates in the host cell.
•When the host cell can no longer carry out its own
metabolic functions because of the viral invader, the
host cell dies and releases the new viruses into the
body to invade other cells.

• Interferons are released by the host in response to viral invasion of a cell and act to
prevent the replication of that particular virus.
• Interferons are a group of signalling proteins made and released by host cells in
response to the presence of several viruses. In a typical scenario, a virus-infected
cell will release interferons causing nearby cells to heighten their anti-viral
defenses.
• Other drugs that are used in treating viral infections are not natural substances and
have been effective against only a limited number of viruses.
• Viruses that respond to some antiviral therapy include influenza A and some
respiratory viruses, herpes viruses, cytomegalovirus (CMV), the human
immunodeficiency virus (HIV) that causes acquired immune deficiency syndrome
(AIDS), hepatitis B, hepatitis C, and some viruses that cause warts and certain eye
infections.

AGENTS FOR INFLUENZA AND
RESPIRATORY VIRUSES

THERAPEUTIC ACTIONS
✔The exact mechanism of action of drugs that combat Influenza A and
respiratory viruses is not known.
✔The belief is that these agents prevent shedding of the viral protein
coat and entry of the virus into the cell.
✔This action prevents viral replication, causing viral death.
✔These agents for influenza A and respiratory viruses are especially
important for health care workers and other high-risk individuals and
for reducing the severity of infection if it occurs.
✔Oseltamivir is the only antiviral agent that has been shown to be
effective in treating H1N1 and avian flu.

PHARMACOKINETICS
✔Amantadine is slowly absorbed from the gastrointestinal (GI)
tract, reaching peak levels in 4 hours.
✔Excretion occurs unchanged through the urine, with a half-life of
15 hours.
✔Oseltamivir is readily absorbed from the GI tract, extensively
metabolized in the urine, and excreted in the urine with a half-life
of 6 to 10 hours.
✔Ribavirin, an inhaled drug, is slowly absorbed through the
respiratory tract. It is metabolized at the cellular level and is
excreted in the feces and urine with a half-life of 9.5 hours.

PHARMACOKINETICS
✔It is teratogenic and is rated pregnancy category X.
✔Rimantadine is absorbed from the GI tract with peak levels
achieved in 6 hours. This drug is extensively metabolized in the
liver and excreted in the urine.
✔Zanamivir must be delivered by a Diskhaler device, which comes
with every prescription of zanamivir. It is absorbed through the
respiratory tract and excreted unchanged in the urine with a half-
life of 2.5 to 5.1 hours.

CONTRAINDICATIONS &
CAUTIONS
✔Amantadine must be used at reduced doses and with caution in
patients who have any renal impairment to avoid altered metabolism
and excretion of the drug.
✔Amantadine should be used during pregnancy and lactation only if
the benefits clearly outweigh the risks to the fetus or neonate.
✔Oseltamivir require reduced doses and close monitoring to avoid
altered metabolism and excretion of the drug.
✔Oseltamivir should be used during pregnancy and lactation only if
the benefits clearly outweigh the risks to the fetus or neonate
because there are no adequate studies in pregnancy and lactation.

ADVERSE EFFECTS
✔Use of these antiviral agents' effects include light-headedness,
dizziness, and insomnia; nausea; orthostatic hypotension; and
urinary retention.

DRUG- DRUG
INTERACTIONS
✔Patients who receive amantadine or rimantadine may experience increased
atropine-like effects if either of these drugs is given with an anticholinergic drug.
✔Patients taking rimantadine may also experience a loss of effectiveness of aspirin
and acetaminophen if these are also being used.
✔Ribavirin levels may be reduced if it is given with antacids.
✔The use of ribavirin should be avoided if the patient is also receiving a nucleoside
reverse transcriptase inhibitor (NRTI).
✔Rifampin is known to decrease the effectiveness of many drugs, including
antiarrhythmics, digoxin, hormonal contraceptives, corticosteroids, antifungals,
and central nervous system (CNS) depressants. Patients should be monitored
closely for loss of effectiveness of these drugs if this combination is used.
✔There is an increased incidence of rifampin-related hepatitis if it is used
concurrently with isoniazid. This combination should be avoided.

AGENTS FOR HERPES AND
CYTOMEGALOVIRUS

AGENTS FOR HERPES AND
CYTOMEGALOVIRUS
• Herpes viruses account for a broad range of conditions,
including cold sores, encephalitis, shingles, and genital
infections.
• Cytomegalovirus (CMV), although slightly different from the
herpes virus, can affect the eye, respiratory tract, and liver
and reacts to many of the same drugs.
• Antiviral drugs used to combat these infections include
acyclovir (Zovirax), cidofovir (Vistide), famciclovir (Famvir),
foscarnet (Foscavir), ganciclovir (Cytovene), valacyclovir
(Valtrex), and valganciclovir (Valcyte)

Therapeutic Actions and Indications
• Drugs that combat herpes and CMV inhibit viral DNA replication by
competing with viral substrates to form shorter, noneffective DNA
chains.
• This action prevents replication of the virus, but it has little effect on
the host cells of humans because human cell DNA uses different
substrates.
• These antiviral agents are indicated for treatment of the DNA viruses
herpes simplex, herpes zoster, and CMV.

Pharmacokinetics
• Most of the agents for herpes and CMV (Cytomegalovirus)
are readily absorbed and excreted through the kidney.
• Acyclovir, which can be given orally and parenterally or
applied topically, reaches peak levels within 1 hour and has a
half-life of 2.5 to 5 hours. It is excreted unchanged in the
urine. It crosses into breast milk, which exposes the neonate
to high levels of the drug.

Pharmacokinetics
• Cidofovir, which is given by intravenous (IV) infusion,
reaches peak levels at the end of the infusion and in studies
was cleared from the system within 15 minutes after the
infusion. It is excreted unchanged in the urine and must be
given with probenecid to increase renal clearance of the
drug. The dose must be decreased according to renal
function and creatinine clearance; renal function tests must
be done before each dose and the dose planned accordingly.

Pharmacokinetics
• Famciclovir, an oral drug, is well absorbed from the GI tract,
reaching peak levels in 2 to 3 hours. Famciclovir is
metabolized in the liver and excreted in the urine and feces.
It has a half-life of 2 hours and is known to cross the
placenta.
• Foscarnet is available in IV form only. It reaches peak levels
at the end of the infusion and has a half-life of 4 hours.
About 90% of foscarnet is excreted unchanged in the urine,
making it highly toxic to the kidneys. Use caution and at
reduced dose in patients with renal impairment.

Pharmacokinetics
• Ganciclovir is available in IV and oral forms. It has a slow
onset and reaches peak levels at 1 hour if given IV and 2 to 4
hours if given orally. This drug is primarily excreted
unchanged in the feces with some urinary excretion, with a
half-life of 2 to 4 hours.

Pharmacokinetics
• Valacyclovir is an oral agent and is rapidly absorbed from the
GI tract and metabolized in the liver to acyclovir. Excretion
occurs through the urine, so caution should be used in
patients with renal impairment.
• Valganciclovir is the oral prodrug, that is, it is immediately
converted to ganciclovir once it is in the body. It is rapidly
absorbed and reaches peak levels in 3 hours. It is primarily
excreted unchanged in the feces with some urinary
excretion, with a half-life of 2.5 to 3 hours.

Contraindications and Cautions
• Drugs indicated for the treatment of herpes and CMV (Cytomegalovirus) are highly toxic
and should not be used during pregnancy or lactation to prevent adverse effects on the
fetus or infant; use only if the benefits clearly outweigh the potential risks to the fetus or
infant.
• Avoid use in patients with known allergies to antiviral agents to prevent serious
hypersensitivity reactions.
• Avoid use in patients with renal disease, which could interfere with excretion of the drug.
• Avoid use in patients with severe CNS disorders because the drug can affect the CNS,
causing headache, neuropathy, paresthesias, confusion, and hallucinations

• Cidofovir has been proven to be embryotoxic in animals. Use cidofovir with caution in
children with AIDS because of the potential carcinogenic effects and effects on fertility. If
no other treatment option is available, monitor the child very closely.
• For famciclovir, safety of use in children younger than 18 years of age has not been
established.
• Foscarnet has been shown to affect bone development and growth. Foscarnet, as well as
ganciclovir and valganciclovir, should not be used in children unless the benefit clearly
outweighs the risk and the child is monitored very closely.

Adverse Effects
• The adverse effects most commonly associated with these antivirals
include nausea and vomiting, headache, depression, paresthesias,
neuropathy, rash, and hair loss.
• Rash, inflammation, and burning often occur at sites of IV injection and
topical application.
• Renal dysfunction and renal failure also have been reported.
• Cidofovir is associated with severe renal toxicity and granulocytopenia.
• Ganciclovir and valganciclovir have been associated with bone marrow
suppression.
• Foscarnet has been associated with seizures, especially in patients with
electrolyte imbalance.

NONNUCLEOSIDE REVERSE
TRANSCRIPTASE INHIBITORS
•The nonnucleoside reverse transcriptase inhibitors
have direct effects on the HIV virus activities within
the cell.
•The nonnucleoside reverse transcriptase inhibitors
available include delavirdine (Rescriptor), efavirenz
(Sustiva), etravirine (Intelence), and nevirapine
(Viramune) and rilpivirine (Edurant).

• The nonnucleoside reverse transcriptase inhibitors bind
directly to HIV reverse transcriptase, blocking both RNA- and
DNA-dependent DNA polymerase activities.
• They prevent the transfer of information that would allow
the virus to carry on the formation of viral DNA. As a result,
the virus is unable to take over the cell and reproduce.
• These antiviral agents are indicated for the treatment of
patients with documented AIDS or ARC who have decreased
numbers of helper T cells and evidence of increased
opportunistic infections in combination with other antiviral
drugs.

Pharmacokinetics
• Delavirdine is rapidly absorbed from the GI tract, with peak levels occurring
within 1 hour. Delavirdine is extensively metabolized by in the liver and is
excreted through the urine.
• Efavirenz is absorbed rapidly from the GI tract, reaching peak levels in 3 to 5
hours. Efavirenz is metabolized in the liver and is excreted in the urine and feces
with a half-life of 52 to 76 hours.
• Etravirine is rapidly absorbed from the GI tract, reaching peak levels in 2.5 to 4
hours. Etravirine is metabolized in the liver and is excreted in feces and urine
with a half-life of 21 to 61 hours.
• Nevirapine is recommended for use in adults and children older than 2 months.
After rapid GI absorption with a peak effect occurring at 4 hours, nevirapine is
metabolized in the liver. Excretion is through the urine with a half-life of 45
hours.
• Rilpivirine (Edurant) is the newest drug in this class. It is rapidly absorbed from
the GI tract, reaching peak levels in 4 to 5 hours. It is metabolized in the liver and
excreted in feces and urine with a half-life of 50 hours.

• There are no adequate studies of nonnucleoside reverse
transcriptase inhibitors 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.
• Safety for the use of delavirdine in children has not been
established.

Adverse Effects
• The adverse effects most commonly experienced with these
drugs are GI related—dry mouth, constipation or diarrhea,
nausea, abdominal pain, and dyspepsia.
• Dizziness, blurred vision, and headache have also been
reported.
• A flu-like syndrome of fever, muscle aches and pains,
fatigue, and loss of appetite often occurs with the anti-HIV
drugs, but these signs and symptoms may also be related to
the underlying disease.

Clinically Important Drug–Drug Interactions
• Life-threatening effects can occur if delavirdine is combined with
antiarrhythmics, clarithromycin, dapsone, antituberculosis drugs,
calcium-channel blockers, warfarin, quinidine, indinavir, saquinavir,
or dapsone. These combinations should be avoided if at all possible.
• There is a risk of serious adverse effects if efavirenz is combined with
midazolam, rifabutin, triazolam, or ergot derivatives; these
combinations should be avoided.
• There may be a lack of effectiveness if nevirapine is combined with
hormonal contraceptives or protease inhibitors.
• St. John’s wort should not be used with these drugs; a decrease in
antiviral effects can occur.

NUCLEOSIDE REVERSE TRANSCRIPTASE
INHIBITORS
• The nucleoside reverse transcriptase inhibitors were the first
class of drugs developed to 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 NRTIs include the following agents: abacavir (Ziagen),
didanosine (Videx), emtricitabine (Emtriva), lamivudine
(Epivir), stavudine (Zerit XR), tenofovir (Viread), and
zidovudine (Retrovir).

NUCLEOSIDE REVERSE TRANSCRIPTASE
INHIBITORS

• NRTIs 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
combination therapy for the treatment of HIV infection.

Pharmacokinetics
• Abacavir is an oral drug that is rapidly absorbed from the GI
tract. It is metabolized in the liver and excreted in feces and
urine.
• Didanosine is rapidly destroyed in an acid environment and
therefore must be taken in a buffered form.
• 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 and being metabolized in the liver is excreted in the
urine and feces. Dose needs to be reduced in patients with
renal impairment.

Pharmacokinetics
• Lamivudine is rapidly absorbed from the GI tract and is
excreted primarily unchanged in the urine
• 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.

Pharmacokinetics
• 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 fi rst 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 metabolized in the liver and excreted in the
urine, with a half-life of 1 hour.

• 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 infected with HIV are urged not to breast-feed.
• Tenofovir, zidovudine, and emtricitabine should be used with caution in
the presence of hepatic dysfunction or severe renal impairment because of
their effects on the liver and kidneys.
• Zidovudine should also be used with caution with any bone marrow
suppression because it could aggravate the suppression.

Adverse Effects
• Serious-to-fatal hypersensitivity reactions have occurred with abacavir, and it must be
stopped immediately at any sign of a hypersensitivity reaction (fever, chills, rash,
fatigue, GI upset, flu-like symptoms).
• Serious pancreatitis, hepatomegaly, and neurological problems have been reported
with didanosine, which is why its use is limited to the treatment of advanced
infections.
• Emtricitabine has been associated with severe and even fatal hepatomegaly with
steatosis.
• Severe hepatomegaly with steatosis has been reported with tenofovir, so it must be
used with extreme caution in any patient with hepatic impairment or lactic acidosis.
• Patients also need to be alerted that the drug may cause changes in body fat
distribution, with loss of fat from arms, legs, and face and deposition of fat on the
trunk, neck, and breasts.
• Severe bone marrow suppression has occurred with zidovudine.

Drug–Drug Interactions
• Tenofovir can cause large increases in the serum level of didanosine. If both of these
drugs are given, tenofovir should be given 2 hours before or 1 hour after didanosine.
• Lamivudine and zalcitabine inhibit the effects of each other and should not be used
together.
• Severe toxicity can occur if abacavir is combined with alcohol; this combination should
be avoided.
• Didanosine can cause decreased effects of several antibiotics and antifungals; any
antibiotic or antifungal started with didanosine should be evaluated carefully.
• There is an increased risk of potentially fatal pancreatitis if stavudine is combine with
didanosine and increased risk of severe hepatomegaly if it is combined with other
nonnucleoside antivirals; these combinations are often used, and the patient needs to
be monitored very closely.
• There have been reports of severe drowsiness and lethargy if zidovudine is combined
with cyclosporine; warn the patient to take appropriate safety precautions.

PROTEASE INHIBITORS
• The protease inhibitors block protease activity within the HIV virus. The
protease inhibitors that are available for use include atazanavir
(Reyataz), darunavir (Prezista). fosamprenavir (Lexiva), indinavir
(Crixivan), lopinavir (Kaletra), nelfi navir (Viracept), ritonavir (Norvir),
saquinavir (Fortovase), and tipranavir (Aptivus).

•Protease is essential for the maturation of an
infectious virus; without it, an HIV particle is
immature and noninfective, 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

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 feces. It is not recommended for patients
with severe hepatic impairment; for those with moderate
hepatic impairment, the dose should be reduced.
• Darunavir is well absorbed from the GI tract. It is
metabolized in the liver and excreted in the urine and feces.
It is not recommended for patients with severe hepatic
impairment.

Pharmacokinetics
• Fosamprenavir is rapidly absorbed after oral administration. It is
metabolized in the liver and excreted in urine and feces.
• Indinavir is rapidly absorbed from the GI tract, metabolized in the
liver and is excreted in the urine. Patients 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 lopinavir serum levels and
effectiveness. It is readily absorbed from the GI tract and
undergoes extensive hepatic metabolism. Lopinavir is excreted in
urine and feces.

Pharmacokinetics
• Tipranavir is the treatment of HIV infection 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
metabolized in the liver and excretion is through urine and feces.
• Nelfinavir is well absorbed from the GI tract, reaching peak levels
in 2 to 4 hours. Nelfinavir is metabolized in the liver. Caution
must be used in patients with any hepatic dysfunction. It is
primarily excreted in the feces. Because there is little renal
excretion, this is considered a good drug for patients with renal
impairment.
• Ritonavir is rapidly absorbed from the GI tract and undergoes
extensive metabolism in the liver and is excreted in feces and

Pharmacokinetics
• Saquinavir is slowly absorbed from the GI tract and is
metabolized in the liver, so it must be used cautiously in the
presence of hepatic dysfunction. It is primarily excreted in the
feces with a short half-life.

• 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 breast-feed
while taking this drug.
• For the 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 breast-feed if they are infected with HIV.
• Patients with mild to moderate hepatic dysfunction should receive a lower dose
of fosamprenavir, and patients with severe hepatic dysfunction should not
receive this drug or darunavir because of their toxic effects on the liver.

• Patients receiving tipranavir must have liver function monitored regularly
because of the possibility of potentially fatal liver dysfunction.
• Saquinavir must also be used cautiously in the presence of hepatic dysfunction.
• Patients receiving darunavir may also be at risk for developing diabetes mellitus
or hyperglycemia and may require dosage adjustments if being treated with
antidiabetic drugs. Darunavir is also associated with mild to severe dermatologic
reactions including Steven Johnson syndrome and the drug should be stopped if
a severe reaction develops.
• The safety of indinavir for use in children younger than 12 years has not been
established. Darunavir should not be used in children younger than 3 years of age
because of the potential for toxic effects.

Adverse Effects
• As with the other antivirals, patients taking these drugs
often experience GI effects, including nausea, vomiting,
diarrhea, 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.

• Fosamprenavir should not be used in patients who are receiving
ritonavir if they have used protease inhibitors to treat their disease
because of a risk of serious adverse effects.
• If nelfinavir is combined with pimozide, rifampin, triazolam, or
midazolam, severe toxic effects and life threatening arrhythmias may
occur. Such combinations should be avoided.
• Indinavir and nevirapine interact to cause severe toxicity. If these two
drugs are given in combination, the doses should be adjusted and the
patient should be monitored closely.

• Tipranavir, darunavir, 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 antihistamines, sedative/hypnotics, or
antiarrhythmics because of the activity of ritonavir in the liver.
• Patients with hepatic dysfunction are at increased risk for serious
effects when taking ritonavir and require a reduced dose and close
monitoring.

FUSION INHIBITOR
• This agent acts at a different site than do other HIV antivirals. 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 antiretroviral therapy.
• Enfuvirtide is given by subcutaneous injection. After metabolism in
the liver, it is recycled in the tissues and not excreted.

FUSION INHIBITOR
• Enfuvirtide is contraindicated with hypersensitivity to any component
of the drug and in nursing mothers.
• 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, diarrhea, pneumonia, and injection-site
reactions.
• There are no reported drug interactions, but caution should be used
when it is combined with any other drug.

CCR5 CORECEPTOR ANTAGONIST
• Maraviroc (Selzentry) is a CCR5 coreceptor antagonist.
• It blocks the receptor site on the cell membrane 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 antivirals.
• Maraviroc is rapidly absorbed from the GI tract, metabolized
in the liver, and excreted primarily through the feces.
• 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 nursing mothers.
• The safety and efficacy of maraviroc in children has not been
established.
• Caution should be used in the presence of liver disease or
coinfection with hepatitis B, because of the risk of serious
hepatic toxicity.
• Patients 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 antivirals, 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.
• Maraviroc has a Black Box Warning regarding the risk for
serious hepatotoxicity. Regular monitoring of liver function
should be routine when using this drug.

• CNS effects including dizziness and changes in consciousness
have been reported; patients experiencing these should be
cautioned to take measures to assure safety.
• Patients may also be at increased risk of infections because of
the way the drug affects the cell membrane of the CD4 cells.
• There is a risk of increased serum levels and toxicity when
combined with cytochrome P450 CYP3A inhibitors
(ketoconazole, lopinavir/ritonavir, ritonavir, saquinavir,
atazanavir, delavirdine), and the maraviroc dose should be
adjusted accordingly.

• Decreased serum levels and loss of effectiveness may occur
if maraviroc is combined with CYP3A inducers (nevirapine,
rifampin, efavirenz), and the maraviroc dose should be
adjusted accordingly.
• Patients should not use St. John’s wort while on this drug
because there is a loss of antiviral effects when the two are
combined.

INTEGRASE INHIBITOR
• Raltegravir 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 increase in active CD4 cells.
• Raltegravir is rapidly absorbed from the GI tract and metabolized in
the liver.
• It has a half-life of 3 hours and is excreted primarily in the feces.
• Raltegravir is contraindicated with known hypersensitivity to any
component of the drug, as initial treatment in adults, for use in
children, and for nursing mothers.

INTEGRASE INHIBITOR
• Caution should be used if the patient is at risk for rhabdomyolysis or
myopathy and during pregnancy.
• Patients taking this drug must be very careful to continue the drug
regimen to help decrease the development of resistant strains of the
virus.
• Common adverse effects include headache, dizziness, and an
increased risk for the development of rhabdomyolysis and myopathy.
There is a risk of decreased serum levels of raltegravir if it is
combined with rifampin; the patient should be monitored and the
dose adjusted if this combination must be used. Patients should avoid
the use of St. Johns wort, which can interfere with the drug’s
effectiveness.

ANTI–HEPATITIS B AGENTS
• Hepatitis B is a serious-to-potentially fatal viral infection of the liver.
The hepatitis B virus can be spread by blood or blood products,
sexual contact, or contaminated needles or instruments.
• Health care workers are at especially high risk for contracting
hepatitis B due to needle sticks. Hepatitis B has a higher mortality
than other types of hepatitis.
• Individuals infected may also develop a chronic condition or become
a carrier.

• All three of these antiviral drugs are indicated for the treatment of
adults with chronic hepatitis B who have evidence of active viral
replication and either evidence of persistent elevations in serum
aminotransferases or histologically active disease.
• The drugs inhibit reverse transcriptase in the hepatitis B virus and
cause DNA chain termination, leading to blocked viral replication and
decreased viral load.

Pharmacokinetics
• These drugs are rapidly absorbed from the GI tract, with peak effects
occurring in 0.5 to 1.5 hours (entecavir), 0.5 to 4 hours (adefovir), and
1 to 4 hours (telbivudine).
• Entecavir and adefovir are metabolized in the liver and excreted in
the urine.
• Telbivudine is excreted unchanged in the urine.
• Adefovir has a half-life of 7.5 hours; entecavir has a half-life of 128 to
149 hours; and telbivudine has a half-life of 40 to 49 hours.
• It is not known whether any of these drugs crosses the placenta or
enters breast milk.

•These drugs are contraindicated with any known
allergy to the drugs to prevent hypersensitivity
reactions and with lactation because of potential
toxicity to the infant.
•Use caution when administering these drugs to
patients with renal impairment and severe liver
disease because of increased toxicity with these drugs
and those who are pregnant because the effects on
the fetus are not known.

Adverse Effects
• The adverse effects most frequently seen with these drugs are
headache, dizziness, nausea, diarrhea, and elevated liver enzymes.
• Severe hepatomegaly with steatosis, sometimes fatal, has been
reported with adefovir and telbivudine use.
• Lactic acidosis and renal impairment have been reported with
entecavir and adefovir.
• A potential risk for hepatitis B exacerbation could occur when the
drugs are stopped. Therefore, teach patients the importance of not
running out of their drugs and use extreme caution when
discontinuing these drugs.

•There is an increased risk of renal toxicity if these
drugs are taken with other nephrotoxic drugs.
•If such a combination is used, monitor the patient
closely.
•An evaluation of risks versus benefits may be
necessary if renal function begins to deteriorate.

ANTI–HEPATITIS C AGENTS
• In 2011, two new drugs were approved for the treatment of hepatitis
C, boceprevie (Victrelis) and telaprevir (Incivek).
• The new drugs approved for treating this disease are protease
inhibitors.
• They are oral drugs that must also be taken with peginterferon and
ribavirin.
• Neither should be used in pregnancy because of risk to the fetus.
• Safety has not been established for use in patients who also have
hepatitis B and/or HIV infections.

Adverse Effects
•The most common adverse effects are headache,
fatigue, nausea and diarrhea.
•Bone marrow suppression and severe skin reactions
can occur.

LOCALLY ACTIVE ANTIVIRAL AGENTS
•Some antiviral agents are given locally to treat
local viral infections.
•These agents include docosanol (Abreva),
ganciclovir (Vitrasert), imiquimod (Aldara),
penciclovir (Denavir), and trifl uridine (Viroptic).

•These antiviral agents act on viruses by interfering
with normal viral replication and metabolic processes.
•They are indicated for specific, local viral infections.

•Locally active antiviral drugs are not absorbed
systemically, but caution must be used in patients
with known allergic reactions to any topical drugs.

Adverse Effects
•Because these drugs are not absorbed systemically,
the adverse effects most commonly reported are local
burning, stinging, and discomfort.
•These effects usually occur at the time of
administration and pass with time.

ANTI VIRAL AGENTS.pptx

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