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Antivirals (book)

22 January 08

ANTIVIRAL DRUGS - serious HSV or VZV infections

 Antiviral agents must either block viral entry into or exit from - Nausea, diarrhea, and headache
the cell or be active inside the host cell. - reversible renal dysfunction (due to crystalline nephropathy)
- neurologic toxicity (eg, tremors, delirium, seizures)
(1) attachment of the virus to the host cell 2. VALACYCLOVIR
(2) entry of virus through the host cell membrane - L-valyl ester of acyclovir
(3) uncoating viral nucleic acid - rapidly converted to acyclovir after oral administration via
(4) synthesis of early regulatory protein eg, nucleic acid intestinal and hepatic first-pass metabolism
polymerases; CLINICAL USES
(5) synthesis of RNA DNA; - Tx of first or recurrent genital herpes
(6) synthesis of late, structural proteins - suppression of frequently recurring genital herpes
(7) assembly (maturation) of viral particles - 1-day treat ment for orolabial herpes
(8) release from the cell - associated with a shorter duration of zoster-associated pain
- effective in preventing cytomegalovirus disease after organ
- nausea, vomiting, or rash occasionally
• oral nucleoside analogs:
- Agitation, dizziness, headache, liver enzyme elevation,
 acyclovir anemia, and neutropenia
 valacyclovir - confusion, hallucinations, and seizures
 famciclovir - increased incidence of gastrointestinal intolerance as well as
thrombotic microangiopathies (thrombotic thrombocytopenic
1. ACYCLOVIR purpura and hemolytic-uremic syndrome in AIDS px.
- an acyclic guanosine derivative with clinical activity against
- weaker in vitro activity against Epstein-Barr virus (EBV), - the diacetyl ester prodrug of 6-deoxypenciclovir, an acyclic
cytomegalovirus (CMV), and human herpesvirus-6 (HHV-6) guanosine analog
- Requires three phosphorylation steps for activation: - rapidly converted by first-pass metabolism to penciclovir.
• It is converted first to the mono phosphate derivative by - active in vitro against HSV-1, HSV-2, VZV, EBV, and HBV.
the virus-specified THYMIDINE KINASE then to the di- - activation by phosphorylation is catalyzed by the virus-
and triphosphate compounds by host enzymes specified thymidine kinase in infected cells, followed by
- Selectively activated, and the active metabolite accumulates, competitive inhibition of the viral DNA polymerase to block
only in infected cells. DNA synthesis.
MOA - penciclovir does not cause chain termination.
- inhibits viral DNA synthesis by two mechanisms: Penciclovir triphosphate
1. competition with deoxyGTP for the viral DNA - lower affinity for the viral DNA polymerase than acyclovir
polymerase., resulting in binding to the DNA template as triphosphate, bur it achieves higher intracellular
an irreversible complex concentrations and has a more prolonged intracellular effect
2. chain termination, following incorporation into the viral in experimental systems.
DNA - cross resistant to acyclovir and famciclovir
- In first episodes of genital herpes - treatment of first d recurrent genital herpes
• oral acyclovir shortens the duration of symptoms by - chronic daily suppression of genital herpes
approximately 2 days - treatment of acute zoster
• the time to lesion healing by 4 days - accelerates herpes labial healing time
• the duration of viral shedding by 7 days ADR
- In recurrent genital herpes - headache, diarrhea, and nausea
• the time course is shortened by 1-2 days - testicular toxicity has been demonstrated in animals receiving
- modestly beneficial in recurrent herpes labia repeated doses
- in varicella (if begun within 24 hours after the onset of rash) - incidence of mammary adenocarcinoma was increased
or in cutaneous zoster (if begun within 72 hours) female rats receiving famciclovir for 2 years
• decreases the total number of lesions
• duration of symptoms 4. PENCICLOVIR
• viral shedding - guanosine analog penciclovir, the active metabolite of
- in patients undergoing organ transplantation famciclovir
• prevents reactivation of HSV infection - available for topical use
IV FORM DOC - 1% effective for the treatment of current herpes labialis in
- in herpes simplex encephalitis immunocompetent
- neonatal HSV infection - Side effects are uncommon

Elyu, Brim, Virna 1 of 6

Pharmacology – Antiviral Agents by Dra Biag Page 2 of 6

- saturated 22-carbon aliphatic alcohol that inhibits fusion 2. VALGANCICLOVIR
between the plasma membrane and the HSV envelope - an L-valyl ester prodrug of ganciclovir that exists as a mixture
- prevent viral entry into cells and subsequent viral replication of two
- After oral administration, both diastereomers are rapidly
6. TRIFLURIDINE hydrolyzed to ganciclovir by intestinal and hepatic esterases.
- fluorinated pyrimidine nucleoside that inhibits viral DNA CLINICAL USE
synthesis in HSV-l, HSV-2, vaccinia, and some adenoviruses - indicated for the treatment of CMV retinitis in patients with
- phosphorylated intracellularly to its active form by host cell AIDS and for the prevention of CMV disease in high-risk
enzymes, and then competes with thymidine tri phosphate for kidney, heart, and kidney-pancreas transplant patients
incorporation by the viral DNA polymerase ADR, drug interactions, and resistance patterns are the same
- Incorporation of trifluridine tri phosphate into both viral and those associated with ganciclovir.
host DNA prevents its systemic use.
- keratoconjunctivitis - an inorganic pyrophosphate compound that inhibits viral DNA
- recurrent epithelial keratitis due to HSV-l and HSV-2 polymerase, RNA polymerase, and HIV reverse transcriptase
- Topical application of trifluridine solution, alone or in directly without requiring activation by phosphorylation
combination with interferon alfa, has been used successfully - has in vitro activity against HSV, ZV, CMV, EBV, HHV-6,
in the treatment of acyclovir-resistant HSV infections KSHV, and HIV-1
- DOC: Herpetic Keratitis CLINICAL USES
- treatment for CMV retinitis
- also used treatment of CMV colitis, CMV esophagitis,
AGENTS TO TREAT CYTOMEGALOVIRUS (CMV) INFECTIONS acyclovir-resistant HSV infection, and acyclovir-resistant VZV
• CMV infections occur primarily in the setting of advanced infection
immunosuppression and are typically due to reactivation of - a decrease in the incidence of Kaposi's sarcoma has been
latent infection observed in patients who have received long-term foscarnet.
• dissemination of infection results in end-organ disease, ADR
including retinitis, colitis, esophagitis, central nervous system - renal impairment, hypo- or hypercalcemia, hypo- or hyper
disease, and pneumonitis phosphatemia, hypokalemia, and hypomagnesemia
- Penile ulcerations associated with foscarnet therapy may be
due to high levels of ionized drug in the urine
1. GANCICLOVIR - Nausea, vomiting, anemia, elevation of liver enzymes, and
- An acyclic guanosine analogthat requires activation by
triphosphorylation before inhibiting the viral DNA polymerase
- the risk of anemia may be additive in patients receiving
- Initial phosphorylation is catalyzed by the virus-specified
concurrent zidovudine
protein kinase phosphotransferase UL97 in CMV-infected
- Central nervous system toxicities include headache,
hallucinations, and seizures; seizures may be increased with
- The activated compound competitively inhibits viral DNA
concurrent use of imipenem
polymerase and causes termination of viral DNA elongation
- caused chromosomal damage in preclinical studies
- Its activity against CMV is up to 100 times greater than that of
- IV, oral or intraocular implant
- Cytosine nucleotide analog with in vitro activity against CMV,
HSV-l, HSV-2, VZV, EBV, HHV-6, KSHV, adenovirus,
- delay progression of CMV retinitis in patients with AIDS when
poxviruses, polyoma viruses, and human papillomavirus.
compared with no treatment
- phosphorylation of cidofovir to the active diphos- phate is
- Dual therapy with foscarnet and ganciclovir has been shown
independent of viral enzymes (
to be more effective in delaying progression of retinitis than
- After phosphorylation, cidofovir acts both as a potent inhibitor
either drug administered alone
of and as an alternative substrate for viral DNA polymerase,
- treat CMV colitis and esophagitis
competitively inhibiting DNA synthesis and becom ing
- The risk of Kaposi's sarcoma is reduced in AIDS patients
incorporated into the viral DNA chain.
receiving long-term ganciclovir.
- CMV pneumonitis in immunocompromised patients may be
- treatment of CMV retinitis and is used experimentally to treat
beneficial, particularly in combination with intravenous cyto-
adenovirus infections
megalovirus immunoglobulin
- indicated for prevention of end-organ CMV disease in AIDS
- renal insufficiency
patients and as maintenance therapy of CMV retinitis after
- Direct intravitreal administration of cidofovir is not
recommended because of ocular toxicity.
- myelosuppression.
- dose-dependent nephrotoxicity
- nausea, diarrhea, fever, rash, headache, insomnia, and
- uveitis, ocular hypotony, neutropenia (15%), and metabolic
peripheral neuropathy and retinal detachment in patients with
CMV retlllltIs
- Gastrointestinal intolerance, fever, and rash due to
- central nervous system toxicity (confusion, seizures,
probenecid may occur
psychiatric disturbance) and hepatotoxicity
- mammary adenocarcinomas in rats and is embryotoxic.
- mitogenic in mammalian cells and carcinogenic and
embtyotoxic at high doses in aniimals and causes ANTIRETROVIRAL AGENTS
aspermatogenesis Highly active anti- retroviral therapy (HAART)
Pharmacology – Antiviral Agents by Dra Biag Page 3 of 6

- Combination therapy with maximally efficacious and potent - Tenofovir disopoxilfumarate - water-soluble pro drug
agents will reduce viral replication to the lowest possible level - ADR: gastrointestinal complaints (eg, nausea, diarrhea,
and decrease the likelihood of emergence resistance.
vomiting, flatulence)
- Typically comprising combination of 3-4 antiretroviral agents,
nucleoside reverse transcriptase inhibitors (NRTI),
nonnucleoside reverse transcriptase inhibitors (NNRTI),
- Zalcitabine (ddC) is a cytosine analog
protease inhibitors (PI), and a fusion inhibitor.
- ADR: dose-dependent peripheral neuropathy, oral and
Nucleoside & Nucleotide Reverse Transcriptase Inhibitors esophageal ulcerations
NRTI - CI: stavudine, didanosine, and isoniazid
- Act by competitive inhibition of HIV reverse transcriptase and
can also be incorporated into the growing viral DNA chain to 8. ZIDOVUDINE (azidothymidine; AZT)
cause termination. - A deoxythymidine analog
- Each requires intracytoplasmic activation via phosphorylation - The first antiretroviral agent to be approved and has been
by cellular enzymes to the triphosphate form. well studied
- Decreases the rate of clinical disease progression and
Nucleoside Analogs prolong survival in HIV-infected individuals
- inhibition mitochondrial DNA polymerase gamma - Treatment of HIV-associated dementia and thrombocytopenia
- ADR: mitochondrial toxicity, lactic acidosis with hepatic - Reduces the rate of vertical (mother-to newborn)
steatosis transmission of HI V by up to 23%.
- ADR: myelosuppression, resulting in macrocytic anemia or
1. ABACAVIR neutropenia
- A guanosine analog
Nonnucleoside Reverse Transcriptase Inhibitors
- Binds directly to HIV -1 reverse transcriptase, resulting in
- Synthetic analog of deoxyadenosine
blockade of RNA- and DNA-dependent DNA polymerase.
- Dosing on an empty stomach is required - Neither compete with nucleoside triphosphates nor require
- Major Clinical Toxicity: dose-dependent pancreatitis phosphorylation to be active
- Fluoroquinolones and tetracyclines should be administered at - Limitation: metabolism by the CYP450 system, leading to
least 2 hours before or after didanosine to avoid decreased innumerabIe potential drug-drug interactions
antibiotic plasma concentrations due to chelation. - substrates for CYP3A4 and can act as inducers (nevirapine),
inhibitors (delavirdine), mixed inducers and inhibitors
3. EMTRICITABINE (FTC) (efavirenz)
- A fluorinated analog of lamivudine
- Long intracellular half-life (> 39 hours), allowing for once-daily
dosing - Has an oral bioavailability of about 85%, but this is reduced
- The oral solution, which contains propylene glycol, is by antacids or H2-blockers.
contraindicated in young children, pregnant women, patients - Extensively metabolized to inactive metabolites by the
with renal or hepatic failure; and those using metronidazole or CYP3A and CYP2D6 enzymes and also inhibits CYP3A4 and
disulfiram. 2C9.
- Has in vitro activity against HBV likelihood of hepatitis
flares. 2. EFAVIRENZ
- ADR: headache, diarrhea, nausea, and asthenia; - Given once daily because of its long half-life (40-55 hours)
hyperpigmentation of the palms and/or soles - Toxicity increases owing to increased bioavailability after a
high-fat meal
4. LAMIVUDINE (3TC) - ADR: involve the CNS
- A cytosine analog
- Has in vitro activity against HIV-1 that is synergistic with a
- Both an inducer and an inhibitor of CYP3A4, thus inducing its
own metabolism and inter acting with the metabolism of many
variety of antiretroviral nucleoside analogs including
other drugs
zidovudine and stavudine
- A thymidine analog - A single dose of nevirapine (200 mg) has been shown to be
- Major dose-limiting toxicity: dose-related peripheral effective in the prevention of transmission of HIV from mother
to newborn when administered to women at the onset of
sensory neuropathy
labor and followed by a 2-mg/kg oral dose to the neonate
- Rare side effect: rapidly progressive ascending within 3 days after delivery.
neuromuscular weakness
- An acyclic nucleoside phosphonate (ie, nucleotide) analog of - By preventing cleavage of the Gag Pol polyprotein, protease
adenosine inhibitors (PIs) result in the production of immature,
noninfectious viral particles.
- MOA: Competitively inhibits HIV reverse transcriptase and
causes chain termination after incorporation into DNA.
Pharmacology – Antiviral Agents by Dra Biag Page 4 of 6

- ADR: A syndrome of redistribution and accumulation of body - Lopinavir 100/rironavir 400 is a licensed combination in which
fat that results in central obesity, dorsocervical fat subtherapeutic doses of ritonavir inhibit the CYP3A-mediated
enlargement (buffalo hump), peripheral and facial wasting, metabolism of lopinavir, thereby resulting in increased
breast enlargement, and a cushingoid appearance exposure to lopinavir.
- Associated with increased spontaneous bleeding in patients - Ritonavir is acting as a pharmacokinetic enhancer rather than
with hemophilia A or B. an antiretroviral agent.
- All are substrates and inhibitors of CYP3A4, with ritonavir - ADR: diarrhea, abdominal pain, nausea, vomiting, and
having the most pronounced inhibitory effect and saquinavir asthenia
the least
1. AMPRENAVIR - Has higher absorption in the fed state
- High-fat meals decrease absorption and should be avoided.
- The most common adverse effects: diarrhea and flatulence.
- ADR: nausea, diarrhea, vomiting, perioral paresthesias,
- An inhibiror of the CYP3A system
depresion, and rash.
- Has a favorable safety and pharmacokinetic profile for
- The oral solution which contains propylene glycol, is
pregnant women compared with that of other PIs
contraindicated in young children, pregnant women, patients
with renal or hepatic failure, and those using metronidazole or
- An inhibitor of HIV -1 and HIV-2 proteases with high
- Supplemental vitamin E should b avoided
bioavailability (about 75%) that increases when the drug is
- CI: patients with a history of sulfa allergy because it is itself a given with food.
sulfonamide. - The most common adverse effects: gastrointestinal
disturbances, paresthesias (circumoral and peripheral),
elevated serum aminotransferase levels, altered taste, and
- A newer azapeptide PI with a pharmacokinetic profile that hyperrriglyceridemia.
allows once-daily dosing. - Potent inhibitor of CYP3A4
- Requires an acidic medium for absorption and exhibits pH-
dependent aqueous solubility 8. SAQUINAVIR
- The primary route of elimination is biliary - In its original formulation as a hard gel capsule (saquinavir-H;
- ADR: Indirect hyperbilirubinemia with overt jaundice may Invirase), oral saquinavir is poorly bioavailable (only about
occur, in all likelyhood owing to inhibition of the UGT1A1 4% after food).
enzyme - It was therefore largely replaced in clinical use by a soft gel
- In contrast to the other PIs, it does not appear to be capsule formula (saquinavir-S; Fortovase) in which
associated with dyslipidemias, fat redistribution, or the absorption was increased approximately threefold.
metabolic syndrome - ADR: gastrointestinal discomfort (nausea, diarrhea,
- May be associated with electrocardiographic PR interval abdominal discomfort, dyspepsia; these are more common
prolongation, which is usually inconsequential but may be with saquinavir-S) and rhinitis.
exacerbated by other causative agents such as calcium - Subject to extensive first-pass metabolism by CYP3A4, and
channel blockers. functions as a CYP3A4 inhibitor; as well as a substrate.
- Also, a possible concentration-dependent increase in the QTc
interval may occur in patients receiving atazanavir in dosages 9. PRANAVIR
greater than 400 mg/d or in conjunction with the CYP3A4 - Another newer PI.
inhibitor clarithromycin. - Bioavailabiliry is increased when taken with a high-fat meal
- An inhibitor of CYP3A4 and CYP2C9, - CI: patients with hepatic insufficiency.
- Contains sulfonamide moiety and should not be administered
3. FOSAMPRENAVIR patients with known sulfa allergy.
- A prodrug of amprenavir that is rapidly hydrolyzed by - ADR: diarrhea, nausea, vomiting, abdominal pain, and rash;
enzymes in the intestinal epithelium. the latter is more common in women.
- Significantly lower daily pill burden, replaced amprenavir - Liver toxicity, including life threatening hepatic
capsules for adults decompensation, has been observed and is more common in
patients with chronic hepatitis B or C.
4. INDINAVIR - Both inhibits and induces the CYP3A4 system
- Must be consumed on an empty stomach for maximal
absorption; however, if co-administered with ritonavir, it may FUSION INHIBITORS
be taken without regard to food.
- ADR: indirect hyperbilirubinemia and nephrolithiasis due to
crystallization of the drug.
- Formerly called T-20, is the first representative
- Consumption of at least 48 ounces of water daily is important
- A fusion inhibitor that blocks entry into the cell
to maintain adequate hydration and prevent nephrolithiasis, - A synthetic 36-amino-acid peptide, binds to the gp41 subunit
- an inhibitor of CYP3A4 of the viral envelope glycoprotein, preventing the
conformational changes required for the fusion of the viral
5. LOPINAVIR/RITONAVIR and cellular membranes.
- Adminisrered by subcutaneous injection.
Pharmacology – Antiviral Agents by Dra Biag Page 5 of 6

- ADR: local injection site reactions. Eosinophilia has also been - As with other NRTI agents, lactic acidosis and hepatic
noted. steatosis are considered a risk owing to mitochondrial

- Treatment is suppressive rather than curative
- An orally administered guanosine nucleoside analog
- MOA: competitively inhibits all three functions of HBV DNA
1. INTERFERON ALFA polymerase, including base priming, reverse transcription of
- Host cytokines that exert complex antiviral, the negative strand, and synthesis of the positive strand of
immunomodulatory, and antiproliferative activities
- MOA: induction of intracellular signals following binding to
- Should be taken on an empty stomach
specific cell membrane receptors, resulting in inhibition of - Higher rates of HBV DNA viral suppression, normalization of
viral penetration, translation, transcription, protein processing, serum alanine aminotransferase levels, and histologic
maturation, and release, as well as increased expression of improvement in the liver
major histocompatibility complex antigens, enhanced - Well tolerated.
phagocytic activity of macrophages, and augmentation of the
proliferation and survival of cytotoxic T cells. TREATMENT OF HEPATITIS C INFECTION
- Injectable preparations - The primary goal of treatment in patients with HCV infection
- Pegylated interferon alfa-2a and pegylated interferon is viral eradication.
alfa-2b - The primary efficacy end point is typically achievement of
o Slower clearance, longer terminal half-lives and steadier sustained viral response (SVR), defined as the absence
detectable viremia for 6 months after completion therapy.
drug concentrations, allowing for less frequent dosing.
- In patients with chronic HBV infection, treatment with - In acute hepatitis C  interferon alfa-2b, in doses higher than
interferon alfa is associated with a higher incidence of those used for chonic HCV infection
hepatitis e antigen (HBeAg) seroconversion and undetectable - In chronic HCV infection  once-weekly pegylated interferon
HBV DNA levels than placebo. alfa in combination with daily oral ribavirin
- ADR: flu-like syndrome, neurotoxicities, myelosuppression,
profound fatigue, weight loss, rash, cough, myalgia, alopecia, 1. RIBAVIRIN
tinnitus, reversible hearing loss, retinopathy, pneumonitis, - A guanosine analog that is phosphorylated intracellularly by
and possibly cardiotoxicity. host cell enzymes
- CI: hepatic decompensation, autoimmune disease, and - MOA: Interfere with the synthesis of guanosine triphosphate,
history of cardiac arrhythmia to inhibit capping of viral messenger RNA, and to inhibit the
viral RNA-dependent polymerase of certain viruses.
TREATMENT OF HEPATITIS B VIRUS INFECTION - Influenza A and B, parainfluenza, respiratory syncytial virus,
- The most common efficacy end points: seroconversion from paramyxoviruses, HCV, and HIV-l.
HBeAg from positive to negative and suppression of HBV - ADR: dose-dependent hemolytic anemia
DNA to undetectable levels. - CI: uncorrected anemia, end-stage renal failure, ischemic
vascular disease, and pregnancy.
- The more prolonged intracellular half-life in HBV cell lines
(17-19 hours) than in HIV-infected cell lines (10.5-15.5 hours) ANTI-INFLUENZA AGENTS
allows for lower doses and less frequent administration - Influenza A, the only strain that causes pandemics, is
- Can be safely administered to patients with decompensated classified into 16H (hemagglutinin) and 9N (neuraminidase)
liver disease known subtypes based on surface proteins.
- MOA: inhibits HBV DNA polymerase and HIV reverse - Current influenza A subtypes that are circulating among
transcriptase by competing with deoxycytidine triphosphate people worldwide include H1N1, H1N2, and H3N2.
for incorporation into the viral DNA, resulting in chain - Of particular concern is the H5N1 virus, which first caused
termination human infection (including severe disease and death) in 1997
- Has an excellent safety profile. and has become endemic in Southeast Asia poultry since
- Co-infection with HIV may increase the risk of pancreatitis 2003.


- The diester prodrug of adefovir, an acyclic phosphonated - Amantadine (1-aminoadamantane hydrochloride) and its α-
adenine nucleotide analog methyl derivative, rimantadine, are cyclic amines of the
- Phosphorylated by cellular kinases to the active diphosphate adamantine family
metabolite and then competitively inhibits HBV DNA - MOA: block the M2 proton ion channel of the virus particle
polymerase to result in chain termination after incorporation and inhibit uncoating of the viral RNA within infected host
into the viral DNA. Well tolerated. cells, thus preventing its replication.
- ADR: dose-dependent nephrotoxicity, headache, diarrhea, - Active against influenza A only.
asthenia, and abdominal pain. - Rimantadine is four to ten times more active than amantadine
in vitro. Amantadine is more toxic.
Pharmacology – Antiviral Agents by Dra Biag Page 6 of 6

- ADR: gastrointestinal (nausea, anorexia) and central nervous

system (nervousness., difficulty in concentrating, insomnia,
light-headedness, peripheral edema.


- The neuraminidase inhibitors, analogs of sialic acid
- MOA: Interfere with release of progeny influenza virus from
infected to new host cells, thus halting the spread of infection
within the respiratory tract.
- Have activity against both influenza A and influenza B viruses
- Early administration is crucial because replication of influenza
virus peaks at 24-72 hours after the onset of illness.
- Oseltamivir
o FDA-approved for patients 1 year and older
o An orally administered prodrug that is activated by
hepatic esterases and widely distributed throughout the
o ADR: nausea, vomiting, and abdominal pain,
- Zanamivir
o approved in patients 7 years or older.
o delivered directly co the respiratory tract via inhalation.
o ADR: cough, bronchospasm (occasionally severe),
reversible decrease in pulmonary function, and transient
nasal and throat discomfort.


- intralesional injection of interferon alfa-2b or alfa-n3 may be
used for treatment of condylomata acuminata

- Aerosolized ribavirin is administered by nebulizer (20
mg/mL for 12-18 hours per day) to children and infants with
severe respiratory syncytial virus (RSV) bronchiolitis or
pneumonia to reduce the severity and duration of illness.
- generally well tolerated
- ADR: conjunctival or bronchial irritation
- Intravenous ribavirin decreases mortality in patients with
Lassa fever and other viral hemorrhagic fevers if started

- A humanized monoclonal antibody directed against an
epitope in the A antigen site on the F surface protein of RSV.
- For high-risk infants and children such as premature infants
and those with bronchopulmonary dysplasia or congenital
heart disease.
- ADR: upper respiratory tract infeerion, fever, rhinitis, rash,
diarrhea, vomiting, cough, otitis media, and elevation in
serum aminotransferase levels

- An immune response modifier shown to be effective in the
topical treatment of external genital and perianal warts
- Also effective against actinic keratoses.
- ADR: Local skin reactions, pigmentary skin changes, fatigue
and influenza-like syndrome