CHAPTER 49 Antiviral Chemotherapy & Prophylaxis

437

DRUG SUMMARY TABLE: Antivirals & Antiretrovirals

Drug Class

Mechanism
of Action

Clinical Applications

Pharmacokinetics &
Interactions

Activated by viral
thymidine kinase (TK) to
forms that inhibit viral
DNA polymerase

Treatment and
prophylaxis for HSV-I,
HSV-2, and VZV
None of these drugs is
active against TK strains

Acyclovir: Topical, oral,

and IV
Penciclovir: Topical
Famciclovir and
valcyclovir: Oral

Oral forms cause nausea,

diarrhea, and headache
IV acyclovir may cause
renal and CNS toxicity

Viral activation of
ganciclovir to form
inhibiting DNA
polymerase; no viral
bioactivation of cidofovir
and foscarnet

Treatment of CMV
infections in immunosuppression (eg, AIDS)
and organ
transplantation

Ganciclovir: Oral, IV,

intraocular forms
Valganciclovir: Oral Cidofovir,
foscarnet (IV)

Ganciclovir: Bone
marrow suppression,
hepatic and neurologic
dysfunction
Cidofovir and foscarnet:
Nephrotoxicity
Foscarnet: CNS effects
and electrolyte
imbalance

Degrades viral RNA via

activation of host cell
RNAase (IFN-)
inhibition of HBV
polymerase (others)
multiple antiviral
actions (ribavirin)

Suppressive treatment
of HBV (all drugs except
ribavirin) treatment of
HCV (ribavirin +/ IFN-)

IFN-: Parenteral
Adefovir, entacavir,
lamivudine, and ribavirin: Oral
Ribavirin: Inhalational

IFN-: Alopecia, myalgia,

depression, flu-like
syndrome
Adefovir: lactic acidosis,
renal and hepatic toxicity
Ribavirin: Anemia,
teratogen

Amantadine and
rimantidine: block of M2
proton channels
Oseletamivir and
zanamivir inhibit
neuraminidase

M2 blockers virtually
obsolete others
prophylaxis vs most
current flu strains and
shorten symptoms

Oral forms except zanamivir

(inhalational)

Oseltamivir:
Gastrointestinal effects
Zanamivir:
Bronchospasm in
asthmatics

Duration of action
usually longer than
half-life most undergo
renal elimination
especially, didanosine,
emtricitabine,
lamivudine, stavudine,
tenofovir, and
zidovudine

Zidovudine: Bone marrow

suppression
Abacavir: Hypersensitivity
Didanosine: Pancreatitis
Stavudine, zalcitabine:
Peripheral neuropathy

Most NRTIs are not

extensively metabolized
by hepatic enzymes such
as the CYP450 isoforms,
so they have few
interactions that concern
their pharmacokinetic
characteristics

All current NNRTIs are

metabolized via CYP450
isozymes etravirine
may induce formation
of CYP3A4, but inhibits
other CYP450s

Delavirdine, nevirapine: Rash,

increased liver enzymes
Efavirenz: Teratogenicity

Inducers of CYP450
isozymes (eg, phenytoin,
rifampin) and inhibitors
(eg, azoles, PIs) alter
NNRTI duration of action
note etravirine

Toxicities

Antiviral Drugs
Antiherpes drugs
Acyclovir
Valacyclovir (prodrug)
Penciclovir
Famciclovir (prodrug)

Drugs for cytomegalovirus

Ganciclovir
Valganciclovir
Cidofovir
Foscarnet

Antihepatitis drugs
Interferon- (IFN-)
Adefovir-dipivoxil
Entecavir
Lamivudine
Ribavirin

Anti-influenza drugs
Amantadine
Rimantadine
Oseltamivir
Zanamivir

Antiretroviral Drugs
Nucleoside/nucleotide reverse transcriptase inhibitor (NRTIs)a
Abacavir
Didanosine
Emtricitabine
Lamivudine
Stavudine
Tenofovir
Zalcitabine
Zidovudine

Inhibit HIV reverse

transcriptase after
phosphorylation by
cellular enzymes
cross-resistance
common, but
incomplete

Nonnucleoside reverse transcriptase inhibitors (NNRTIs)

Delavirdine
Efavirenz
Etravirine
Nevirapine

Inhibit HIV reverse

transcriptase no
phosphorylation
required crossresistance between
NNRTIs but not with
NRTIs

(Continued)

438

PART VIII Chemotherapeutic Drugs

DRUG SUMMARY TABLE: Antivirals & Antiretrovirals (Continued)

Drug Class

Mechanism
of Action

Clinical Applications

Pharmacokinetics &
Interactions

Inhibit viral protein

processing
cross-resistance
between PIs common

Elimination mainly via

metabolism by CYP450
isozymes they act as
substrates and inhibitors
of P450
Fosamprenavir is a
prodrug forming
amprenavir, a substrate
and inducer of CYP450

Atazanavir, fosamprenavir,
lopinavir, nelfinavir,
saquinavir: GI distress and
diarrhea
Atazanavir: Peripheral
neuropathy
Amprenavir: Rash
Indinavir: Hyperbilirubinemia
and nephrolithiasis

Ritonavirc and other

PIs can inhibit CYP450
metabolism of many
drugs including
antihistamines,
antiarrhythmics,
HMG-CoA reductase
inhibitors, oral
contraceptives and
sedative-hypnotics
Drugs known to induce
or inhibit CYP450
isoforms may alter the
plasma levels of PIs

Block fusion between

viral and cellular
membranes (enfuvirtide)
CCR5 receptor
antagonist (maraviroc)

Extrahepatic hydrolysis
of enfuvirtide
(subcutaneous
injection) P450
metabolism (maraviroc)

Enfuvirtide:
Hypersensitivity Maraviroc:
Muscle/joint pain, diarrhea,
and increased liver enzymes

Inducers and inhibitors

of CYP450 alter
elimination of maraviroc
no effects on
enfuvirtide

Toxicities

Protease inhibitors (PIs)b

Atazanavir
Darunavir
Fosamprenavir
Indinavir
Nelfinavir
Ritonavir
Saquinavir
Tipranavir

Entry inhibitors
Enfuvirtide
Maraviroc

NRTIs, nucleoside/nucleotide reverse transcriptase inhibitors: Risk of lactic acidosis with hepatic steatosis is characteristic of the group.
PIs, inhibitors: Risk of hyperlipidemia, fat maldistribution, hyperglycemia, and insulin resistance is characteristic of the group, with possible
exception of fosamprenavir.
c
Ritonavir is a potent inhibitor of the 3A4 isoform of CYP450, an action used to advantage in boosting effects of other PIs. Drugdrug
interactions between PIs and many other medications occur commonly.
b