Antiviral Drugs Table

ANTI-HERPES AGENTS
Drug MOA Pharmacokinetics Adverse Effect Precaution/Drug Interaction Resistance

 Not affected by food
 Widely distributed in CSF,  Well-tolerated  Alteration in viral
Acyclovir to acyclovir breast milk, amniotic fluid,  Oral > topical thymidine kinase or
triphosphate (require viral placenta  Oral: nausea, diarrhea, DNA polymerase
ACYCLOVIR
 HSV-I > HSV II > VZV and EBV
kinases) competitively  IV more effective for rash, headache Crystalluria due to IV infusion:  Cross-resistance to
inhibits herpes virus DNA primary HSV infection  Topical: mucosal irritation, give adequate hydration valacyclovir,
 CMV not affected
polymerase to incorporate (CNS HSV) burning sensation famciclovir,
dGTP into viral DNA  Oral: genital herpes,  Renal insufficiency ganciclovir
varicella, post-organ  CNS side effects
transplant
VALACYCLOVIR  Zoster associated pain
(L-valyl ester prodrug of acyclovir) (herpetic neuralgia): High dose lead to:
 Genital herpes Converted to acyclovir via  Oral: 54-70% valacyclovir > acyclovir  Thrombotic
 Varicella zoster first pass metabolism  CSF: 50% of plasma  Nausea, vomiting, rash thrombocytopenic purpura
 Prevent CMV after transplant  Confusion, hallucination,  Hemolytic uremic syndrome
 Prevent VZV reactivation seizures at high doses
 Similar to acyclovir
FAMCICLOVIR/PENCICLOVIR  Headache, diarrhea,
(penciclovir triphosphate)
(acyclic guanosine analog)  Oral penciclovir: low nausea, burning sensation
 Famciclovir – oral drug Cross-resistance to
 HSV-1, HSV-2, VZV, HBV for bioavailability  Testicular toxicity with no
metabolized to acyclovir and
both  Oral famciclovir: higher changes in sperm
penciclovir famciclovir
 Add EBV for famciclovir bioavailability morphology or motility
 Penciclovir – no chain
 Genital herpes, herpes labialis  Mammary adenocarcinoma
termination
Inhibition of fusion between
DOCOSANOL
host cell plasma membrane
(long chain saturated 22 carbon
and HSV envelope 
aliphatic alcohol)
prevent viral entry and
 Orolabial herpes (topical)
replication
TRIFLURIDINE  Irreversible inhibition of

(fluorinated pyrimidine nucleoside) thymidylate synthase
 HSV-1, HSV-2, CMV  Trifluridine triphosphate  Hypersensitivity reactions
 Adenoviruses as competitive inhibitor
 Eye irritation
of thymidine triphosphate
 Primary keratoconjunctivitis
for incorporation into
 Recurrent epithelial keratitis DNA
ANTI-CYTOMEGALOVIRUS AGENTS
 Myelosuppression
GANCICLOVIR (neutropenia)
(acyclic guanosine analog)  CNS side effects  Probenecid and
 Mutation in UL97
 Infusion-related phlebitis trimethoprim increase
 CMV infection (retinitis, organ  Same as acyclovir  Poor oral absorption and UL54 in DNA
ganciclovir and didanosine
transplant, colitis, esophagitis,  Competitively inhibit viral  Bioavailability: IV > oral  Azotemia, anemia, rash polymerase
levels
pneumonitis) DNA polymerase  Clearance linearly related  Liver function abnormalities  Cross-resistance
 Cyclosporine and
 HSV, VZV, EBV, HHV-6, HHV-8  Cause chain termination with creatinine clearance  Diarrhea with cidofovir and
amphotericin B reduce
 Reduce risk for Kaposi sarcoma  Insomnia foscarnet
clearance
in AIDS  Peripheral neuropathy
 Pregnancy category C
VALGANCICLOVIR
(L-valyl ester prodrug of
ganciclovir)
 Metabolized to ganciclovir Overdose can result to renal
 CMV retinitis Myelosuppression
 60% oral bioavailability toxicity
 Prophylaxis in high risk solid
organ
 Prevent CMV in transplant
FOSCARNET  Inhibits viral nucleic acid  Not require activation by  Nephrotoxicity
/trisodium phosphonoformate synthesis by interacting phosphorylation  Electrolyte imbalance  CMV UL54 gene
(inorganic pyrophosphate analog) directly with DNA  Not undergo significant  Infusion-related nausea  Point mutation in
 All herpesvirus and HIV polymerase or reverse intracellular metabolism  Elevate liver transaminases Prevent toxicity by using DNA polymerase
 HSV, VZV, CMV, EBV, HHV-6 transcriptase  Only in IV  Anemia, leukopenia infusion pump to control rate of gene
and 8, HIV 1 and 2  Reversibly binds with  Dose adjustment in renal  Ca and PO4 imbalances infusion  Mutations in HIV-1
 End-organ CMV disease (retinitis, pyrophosphate binding failure  Low K and Mg reverse
colitis, esophagitis) site  Large volumes required  CNS toxic transcriptase gene
 Acyclovir resistant HSV and VZV since poorly soluble  Genital ulcerations
 Given via IV  Dose-dependent  Administer with high dose
CIDOFOVIR Competitive inhibitor of
 2 metabolites: cidofovir proximal tubule probenecid to block active  Cross-resistant with
(cytidine nucleoside analog) deoxycytidine triphosphate
diphosphate and cidofovir nephrotoxicity tubular secretion and ganciclovir
 CMV retinitis, HSV-1 and 2, VZV, (dCTP) into viral DNA
phosphocholine  Eyes: uveitis, ocular decrease nephrotoxicity  Mutation in viral
EBV, HHV-6 and 8 polymerase and becomes
hypotony  Avoid administering with DNA polymerase
 Poxvirus, polyomavirus, HPV alternative substrate
 Neutropenia nephrotoxic drugs
ANTI-INFLUENZA DRUGS – NEURAMINIDASE INHBITORS
Interfere with the release of
NEURAMINIDASE INHIBITORS Low level of
progeny influenza virus
 Influenza A and B resistance
from infected host cells
 H7N9 avian virus
 Nausea  Used in
 Activated by hepatic  Probenecid reduces renal
 Vomiting uncomplicated acute
esterases clearance
OSELTAMIVIR  Headache influenza in patients
 80% bioavailable  Dose adjustment in renal
 Diarrhea >1
 Not impaired by food failure
 Neuropsychiatric events  Prophylaxis of
influenza in >13
 Cough
 Inhaled Not recommended if with
 Bronchospasm
ZANAMIVIR  Renally eliminated with no underlying respiratory disease
 Transient nasal and throat (asthma or COPD)
dose adjustment
discomfort
ANTI-INFLUENZA DRUGS – ADAMANTANES
Drug MOA  Pharmacokinetics Adverse Effect Precaution/Drug Interaction Resistance
 High level of
ADAMANTANES Inhibitory to 3 antigenic
resistance
 Uniquely configured tricyclic subtypes of influenza A
 Treatment of influenza A2  High rates of
amines (H1N1, H2N2, H3N2)
 Parkinsonism resistant strains of
 Influenza A
H1N1 and H3N2
Dose adjustment in:

Mediated by single
Inhibit early step in viral  Well-absorbed CNS side effects: anxiety,  Patients >65 years
nucleotide changes
replication viral uncoating  Excreted unchanged in insomnia, impaired thinking,  Creatinine clearance <50
AMANTADINE involving
by acting on M2 protein urine confusion, lightheadedness, mL/min transmembrane
hallucinations Contraindicated in untreated portion of molecule
angle closure glaucoma
 Oral well-absorbed
Dosage adjustment in elderly
RIMANTADINE  Extensive metabolism:
and renal and hepatic
 4x to 10x more active in vitro hydroxylation, conjugation, impairments
glucuronidation
ANTI-HEPATITIS B AGENTS – NUCLEOSIDE ANALOGS (HBV+HIV: Tenofovir, Lamivudine, Adefovir dipivoxil)
Inhibits HBV DNA  Lactic acidosis
Resistance with long
NUCLEOSIDE ANALOGS polymerase and suppress  Hepatomegaly
term treatment
HBV replication  Steatosis
 Headache
Inhibits all three function of
 Fatigue  Higher barrier to
HBV DNA polymerase:
ENTACAVIR  Dizziness resistance: entecavir
 Base priming  100% bioavailable Interaction with drugs that
 For HBV DNA: entecavir >  Nausea > lamivudine
 Reverse transcription of  Glomerular filtration reduce renal function
lamivudine or adefovir  Upper abdominal pain  Weak anti-HIV 
(-) strand
 Lung adenomas and M148V variant
 Synthesis of (+) strand
carcinomas in mice
 Renal, excreted unchanged
Inhibit HIV reverse  Headache  Discontinuation: flare of
 Rapidly absorbed Emergence of
transcriptase and HBV DNA  Nausea hepatitis in HBV+HIV co-
LAMIVUDINE  Poor CSF penetration lamivudine-resistant
polymerase with  Vomiting infection
 Increased bioavailability HBV isolates
deoxycytidine triphosphate  Skin rash  Prolonged treatment: HCC
with TMP-SMX
 Fatigue
Phosphorylated by cellular  Headache
Resistance with
kinases to active  Oral bioavailability  Cough
duration of therapy
TELBIVUDINE triphosphate to  Unaffected by food  Nausea
exceeding 1 year 
competitively inhibit HBV  Diarrhea virologic rebound
DNA polymerase  Myopathy
 Myalgia
ANTI-HEPATITIS B AGENTS – NUCLEOTIDE ANALOGS
 Headache  29% after more than
ADEFOVIR DIPIVOXIL Phosphorylated by cellular  Glomerular filtration  Reversible increase in serum
 Diarrhea 5 years use
(diester prodrug kinases to active  59% bioavailable creatinine after 4-5 years of
 Asthenia  No cross-resistance
acyclic phosphonated adenine diphosphate metabolite and  Hydrolyzed to parent treatment
nucleotide analog)  Abdominal pain between adefovir
competitively inhibits HBV compound by intestinal and  Pivalic acid causes
 Dose-dependent and lamivudine or
 Chronic HBV infections DNA polymerase blood esterases decreased carnitine levels
nephrotoxicity entecavir
TENOFOVIR DISOPROXIL  Inhibits replication of Renal  Nausea No resistance
 Used in pregnancy HBV by inhibiting HBV  Abdominal pain
polymerase  Diarrhea
 Tenofovir > adefovir  Dizziness Dose adjustment with renal
 Fatigue impairment
ANTI-HEPATITIS B AGENTS – INTERFERON
INTERFERONS
 Alpha & beta
- All cells
- Anti-viral and anti-proliferative  Decompensated cirrhosis
- Stimulate cytokine activity  Immune pathway  Flu-like symptoms  Increase theophylline and
modulation  Transient hepatic enzyme methadone levels
- Upregulate class 1 MHC
 MHC complex antigen elevations  Increase risk of hepatic Absence or lack of
 Alpha – hepatitis, tumors
expression  Neurologic toxicities (mood failure with didanosine resistance
 Beta – multiple sclerosis
 Enhanced phagocytic disorders, depression,  Increase risk of BM
 Gamma
activity somnolence, confusion, suppression with zidovudine
- T-lymphocytes and NK cells seizures)
- Less antiviral activity
- More potent
immunoregulatory effects
 Increased theophylline and
 Route of elimination:
methadone levels
undergoes rapid proteolytic
 Flu-like symptoms  With didanosine: hepatic
 Inhibits HBV replication degradation during tubular
absorption  Transient hepatic failure
INTERFERON-ALPHA  Induces Apobec3G
 Liver metabolism
elevations  With zidovudine:
protein expression
 Neurotoxicity exacerbate cytopenia
 Biliary excretion
 Abortifacient in primates
 SQ or IM
(not used in pregnancy)
PEGYLATED INTERFERON Definite treatment duration and
Improves pharmacokinetics
(polyethylene glycol) higher rates of HBsAg and
and prolongs drug half-life Renal elimination
 Superior efficacy but more HBeAg conversion but greater
(1x/week administer)
expensive adverse effects
ANTI-HEPATITIS C AGENTS – NS5A INHIBITORS
Plays a role in both viral
All oral
NS5A INHIBITORS replication and assembly of
Elimination: all fecal
hepatitis C
DACLATASVIR  Headache
Used in combination with  Fatigue  Dose adjustments (reduction
sofosbuvir (HCV genotypes 1,2,3)  Symptomatic bradycardia or increase) when given with
with sofosbuvir CYP3 inhibitors or inducers
 Inhibitor of P-gp, OATP 1B1
and 1B3, BCRP (breast
cancer resistance protein)
ANTI-HEPATITIS C AGENTS – NS5A INHIBITORS (-ASVIR)
 Not given with moderate
 Elimination: partially and strong inducers or
 Fatigue
ELBASVIR eliminated by oxidative strong inhibitors of CYP3A
 Headache
Only a fixed dose combination with metabolism; primary in  Contraindicated in px with
 Nausea
protease inhibitor Grazoprevir for feces hepatic impairment
 Elevations in serum
genotype 1, 4  Extensively bound to  Interactions: OATP1B/13,
plasma aminotransferases
CYP3A, Efavirenz,
Elbasvir+Grazoprevir
 No dose adjustments
 Interaction: inhibitor of drug
 Fatigue transporters P-gp and
LEDIPASVIR
 Headache BCRP
Available as part of fixed-dose Present in feces
 Asthenia  Increase intestinal
combination with Sofosbuvir
 Symptomatic bradycardia absorption of co-
administered substrates for
transporters
OMBITASVIR Pharmacologic booster to
 Dosage precautions
Fixed dose combination with: increase plasma conc of  Nausea
 Contraindicated in patients
 Paritaprevir + Ritonavir for HCV 4 Paritaprevir -  Pruritus
 Effect on CYP3A with moderate or severe
 Add Dasabuvir to ^3 for HCV 1  Insomnia
hepatic impairment
 No activity against HCV
VELPATASVIR First once-daily single tablet Headache and fatigue
Adjustment when given with
Fixed dose combination with regimen with pangenotypic
CYP3A and CYP2 inhibitors
sofosbuvir activity
ANTI-HEPATITIS C AGENTS – NS5B RNA POLYMERASE INHIBITORS (-BUVIR)
NS5B RNA POLYMERASE Involved in post-
INHIBITORS translational processing
All oral
necessary for replication of
HCV
 No adjustments; not be used
 Headache
 Direct acting against HCV with other antivirals
 Fatigue
NUCLEOSIDE/NUCLEOTIDE  Prodrug converted to  Potential intestinal P-gp
Renal elimination  Asthenia
ANALOGS – SOFOSBUVIR active form via inducers
 Symptomatic bradycardia
intracellular metabolism  May decrease sofosbuvir
with amiodarone
levels
NON-NUCLEOSIDE ANALOGS – Fecal elimination  Nausea
DASASBUVIR in combination with:
 Pruritus
Ombitasvir, Paritaprevir, Ritonavir
 Insomnia
ANTI-HEPATITIS C AGENTS – NS3/4 INHIBITORS (-PREVIR)
Inhibitors of NS3/4A serine
protease (involved in post-
NS3/4 INHIBITORS
translational processing and
replication of HCV)
 Potent, pangenotypic  Not administered to px with
protease inhibitor hepatic impairment
GRAZOPREVIR
 Reversibly binds to HCV  Not given with:
In combination with NS5A inhibitor
N53/4A  OATP1B1/3 inhibitors
Elbasvir
Fecal elimination  CYP3
inducers/inhibitors
 Nausea
PARITAPREVIR +Ombitasvir: HCV 4 Drug-drug interactions due to
 Pruritus
+ Dasabuvir: HCV 1 CYP3A system
 Insomnia
 Enhanced binding affinity
and specificity to NS3/4A
SIMEPREVIR  HCV 1: Simeprevir +  Photosensitivity
 Take meals to maximize  Not recommended in px with Resistance
First available 2nd generation either:  Rash (sulfa moiety)
absorption hepatic impairment associated with Q80K
protease inhibitor - Peginterferon +  Pruritus
 Biliary excretion  Interaction: CYP3A substrate mutations
Ribavirin  Nausea
- Sofosbuvir w/ or w/o
Ribavirin
ANTIRETROVIRAL (HIV) AGENTS – NRTIS
Risk factors for lactic acidosis Mutations
NUCELOSIDE/NUCLEOTIDE  Women
REVERSE TRANSCRIPTASE  Premature chain M184V
termination due to:  Mitochondrial toxicity  Alcoholics abacavir, didanosine,
INHIBITORS (NRTIs)
 Phosphorylated to (inhibition of mitochondrial  Obesity zalcitabine,
 Backbone of antiretroviral therapy
triphosphates + lack of DNA polymerase gamma)  Prolonged nucleoside lamivudine,
 Used in combination with other
3’OH group =>  Lactic acidosis exposure emtricitabine
ART agents in pairs to decrease
incorporated into DNA =>  Hepatomegaly Stop treatment if: K65R/N
pill burden
inhibits binding of  Hepatic necrosis  Inc aminotransferase levels Tenofovir, abacavir,
 Competitive inhibition of HIV-1 lamivudine,
incoming nucleotide  Progressive hepatomegaly
reverse transcriptase emtricitabine
 Metabolic acidosis
ABACAVIR  Undergoes hepatic  Nausea, vomiting, diarrhea  Elevates transaminases and Requires 2-3
(synthetic carbocyclic guanosine glucuronidation and  Headache, dyspnea creatinine kinase concomitant
analog) carboxylation  Pancreatitis  Screening for HLA-B*5701: mutations
 Active against HIV-1  Elimination: Renal > Feces  Fatal hypersensitivity abacavir-associated
 FDC: Abacavir + Lamivudine syndrome (fever, abdomen
hypersensitivity reaction
 A + L + Zidovudine pain, rash, respi, musculo)
Buffer interferes with
DIDANOSINE absorption
(synthetic analog of  Indinavir
 Dose-dependent pancreatitis
deoxyadenosine)  Delavirdine
 Distal peripheral sensory
 Active against HIV-1 and 2,  Atazanavir
neuropathy
HTLV-1
 Retinal changes, optic  Dapsone
Decreased levels with didanosine  30-40% oral bioavailable  Itraconazole
neuritis
 Ciprofloxacin, Ketoconazole,  Enteric coated to avoid  Fluoroquinolone
 Hepatotoxicity
Itraconazole inactivation by gastric acid Avoid concurrent use with
 Hyperuricemia, lipoatrophy
Increases Didanosine levels  Pancreatitis: Zalcitabine,
 Diarrhea
 Allopurinol, Tenofovir, Ganciclovir Stavudine, Ribavirine,
Decreases Didanosine levels  Cardiomyopathy
Hydroxyurea
 Methadone, Atazanavir,  CNS toxicity
 Peripheral neuropathy:
Delavirdine, Ritonavir, Tipranavir Stavudine, INH, Vincristine,
Ribavirin
EMTRICITABINE  High oral bioavailability Oral prep has propylene glycol
 One of the least toxic NRTIs
(cytosine analog with 2 chiral  Low CSF penetration which is contraindicated in
 Headache, diarrhea, nausea,
centers)  Renal elimination  Young children Resistance most
asthenia
 Fluorinated analog of lamivudine  Tenofovir + Emtricitabine:  Women common: M184V/1
 Hyperpigmentation of skin
 Active against HIV-1 and 2,, HBV pre-exposure prophylaxis to  Patients with renal and
 Hepatitis flare
 Recommended for pregnancy reduce HIV acquisition hepatic failure
 Unaffected by food
LAMIVUDINE  Neutropenia
 Increase bioavailability with
(cytosine analog)  Headache
TMP-SXT
 Active against HIV-1 and 2, HBV  Nausea Avoid lamivudine + zalcitabine:
 Renal elimination
 Recommended in pregnant  Dizziness may inhibit intracellular
 Freely crosses placenta
women  GI discomfort phosphorylation of one another
 Poor CSF penetration
 FDC: Lamivudine + Zidovudine or  Dry mouth
Abacavir  Higher conc in male genital
 Hepatitis flare
tract
STAVUDINE  High oral bioavailability  Peripheral neuropathy Zidovudine may reduce
(synthetic thymidine analog)  Readily crosses placenta  Pancreatitis (stavudine + intracellular phosphorylation of
 Active against HIV-1 and 2  Renal elimination didanosine) stavudine
 Arthralgia
 Elevated serum
transaminases
 Lactic acidosis
 Hepatic steatosis
 Lipodystrophy
Orally administered as
TENOFOVIR Tenofovir + Emtricitabine: pre-
prodrug:
(acyclic nucleotide phosphonate exposure prophylaxis to reduce
 Tenofovir Disoproxil  GI complaints (nausea,
analog of adenosine) HIV acquisition
Fumarate (TDF) diarrhea, vomiting,
 Derivative of adenosine 5’
 Tenofovir Alafenamide flatulence)
monophosphate lacking a Produces less mitochondrial
(TAF)  Headache
complete ribose ring toxicity than NRTIs Mutation in K65R/N
Both converted intracellularly  Asthenia
 Active against HIV-1 and 2, HBV and K70E gene
to active moiety:  Dizziness Increases tenofovir levels:
 FDC: Tenofovir +Emtricitabine
 Tenofovir Diphosphate  Renal failure (Fanconi’s  Atazanavir
 Tenofovir +Efavirenz, Rilpivirine,
syndrome)  Lopinavir
Elvitegravir+Cobicistat
- Water-soluble prodrug  Osteomalacia
 Tenofovir Disoproxil Fumarate for  Ritonavir
- Low plasma-protein binding
pregnancy
- Not a substrate or inhibitor of
ZIDOVUDINE CYPs
(deoxythymidine analog)  More active in  Myelosuppression –
Increases zidovudine levels
 Active against HIV-1 and 2, lymphocytes due to  Oral bioavailable: 63% macrocytic anemia
 Probenecid
HTLV-1 and 2 enhanced cellular  Rapid first pass hepatic  GI intolerance
 Phenytoin Resistance:
 HIV-associated dementia and proliferation metabolism  Headache, insomnia,
 Methadone  M41L
thrombocytopenia  Decreases rate of clinical  Absorbed regardless food lipoatrophy
 Fluconazole  D67N
 Reduce rate of vertical progression and prolongs intake  Fatigue, malaise, myalgia,
 Atovaquone  K70R
transmission (first line agent for survival  Detectable in breast milk, anorexia
 Valproic acid  T215F
pregnant)  FDC: Zidovudine + semen, fetal tissue  Nail hyperpigmentation
 HIV infection in children and  Lamivudine  K219Q
Lamivudine  High conc in male genital  Muscle myopathy
adults  Zidovudine + Lamivudine - Decreased when given with
tract  Anxiety, confusion
 Post-exposure prophylaxis in + Abacavir zidovudine: Phenytoin
 Vaginal neoplasm
HIV-exposed healthcare workers - Competitive inhibition with
stavudine
ZALCITABINE More antiretroviral activity in  High oral bioavailability  Dose-dependent peripheral Increases zalcitabine levels
(synthetic cytosine analog) monocyte-macrophage cell  Food has negligible effect neuropathy  Probenecid
 Active against HIV-1 and 2, HBV lines  Oral and esophageal  Cimetidine
ulcerations
 Headache, nausea, rash,
arthralgia
 Cardiomyopathy
 Erythematous maculopapular
rash
 Elevated hepatic
transaminases
ANTIRETROVIRAL (HIV) AGENTS – NNRTIS
 Metabolized and induced
by CYP450  2-8% primary
 Bind directly to HIV-1  First generation NNRTI resistance rates
NON-NUCLEOSIDE REVERSE reverse transcriptase  (efavirenz, and nevirapine)  K103N and Y181C:
TRANSCRIPTASE INHIBITORS allosteric inhibition of RNA All substrates are for CYP3A4 resistance to first
- Low barrier to  Fat accumulation
(NNRTI) and DNA-dependent DNA  Inducers (nevirapine) generation NNRTI
resistance  Fatal hepatitis
 Do not compete with nucleoside polymerase  Inhibitors (delavirdine)  L1001, Y188C,
- Require single mutation  GI intolerance
triphosphates  Non-competitively inhibits  Mixed inducers-inhibitors G190A: cross-
 Second generation NNRTI  Skin rash (SJS)
 Do not require phosphorylation viral reverse transcriptase (efavirenz, etravirine) resistance
(etravirine and rilpivirine)
for activation by binding its active site  No cross-resistance
- Higher potency
 enzyme inactivation between NRTI and
- Longer half-lives
NNRTI
- Reduced side effects
 Skin rash (trunk and
Decreases delavirdine levels
dermatitis)
 Fosamprenavir
 Headache
 High oral bioavailability  Rifabutin
 Fatigue
DELAVIRDINE  Efficacy reduced by  Didanosine
 Nausea, diarrhea
(bisheteroarylpieperazine NNRTI) antacids, PPI, and H2  Lopinavir
 Elevated serum
 Active against HIV-1 blockers  Nelfinavir
transaminases
 Low CSF penetration  Ritonavir
 Severe dermatitis
Prolongs elimination half-life of
 Neutropenia
indinavir or saquinavir
 Teratogenic
 Inducer and inhibitor of
CYP3A4
 Rash  Decreased levels when given
EFAVIRENZ  Moderately absorbed in with efavirenz
 Neural tube defects
(dihydrobenzoxazinone NNRTI) GIT (take on empty
 CNS toxicity  Phenobarbital
 Active against HIV-1 stomach)
 Nausea, vomiting, diarrhea  Phenytoin
 Recommended for pregnancy  High fat meal improves
 Crystalluria  Carbamazepine
but should be initiated after first bioavailability
 Elevated liver enzymes and  Methadone
8 weeks  Fecal elimination
serum cholesterol  Indinavir
 Saquinavir
 Amprenavir
ETRAVIRINE  Taken with meals  Rash, nausea, diarrhea  Substrate and inducer of Resistance to 1st gen
 Alternative drug in patients with  Highly protein-bound  Increased levels of CYP3A4 NNRTIs d/t mutations
resistance to 1st gen NNRTI  Fecal elimination cholesterol, glucose,  Inhibitor of CYP2C9 and (efavirenz, nevirapine,
liver enzymes CYP2C19 delavirdine)
 Not given with other NNRTI  K103N
and NRTI (-navir)  Y181C
ANTIRETROVIRAL (HIV) AGENTS – NNRTIS
NEVIRAPINE Moderate inducer of CYP3A
(dipyridodiazepinone NNRTI) system
 Active against HIV-1  Well-absorbed  Dose-limiting toxicity: rash
 Lipophilic sparing the palms and soles Decreased levels when given
Decreases nevirapine  Readily crosses placenta  Pruritus, hepatitis with nevirapine
 Rifampin  Renal elimination  Elevated transaminases  Amprenavir
 Rifabutin  Metabolized by CYP3A  Fever, headache, fatigue  Indinavir
Increases nevirapine: isoform to hydroxylated  SJS  Lopinavir
 Fluconazole metabolites  Toxic epidermal necrolysis  Saquinavir
 Ketoconazole  Efavirenz
 Clarithromycin  Methadone
RILPIVIRINE 
Rash
 Naïve patients with HIV-1 RNA 
Depression
<100,000 copies/mL  Preferably taken with high 
Headache  Caution when taking antacids
 Used in combination with 2 other fat or >400 kcal meal 
Insomnia and H2 receptor antagonist EI38K and M184I
ART agents  Fecal elimination 
Increased liver enzymes  Contraindicated when taking substitution
 FDC: Rilpivirine + Emtricitabine + and cholesterol PPI
Tenofovir  Fat redistribution
 Prolonged QT interval
ANTIRETROVIRAL (HIV) AGENTS – PROTEASE INHIBITORS
 GI intolerance Ritonavir: most pronounced
 Substitutions at 10,
 Not need intracellular inhibitory effect
PROTEASE INHIBITOR  Lipodystrophy 46, 54, 82, 84, 90
activation  Act as pharmacokinetic
 Peptide-like chemicals that Competitively inhibits  PR and QT interval codons
 High plasma protein enhancer
competitively inhibit aspartyl cleavage of Gag-Pol prolongation  Atazanavir: I50L
binding  Increases drug exposure and
protease required for production polyproteins in HIV-infected  Drug-induced hepatitis  Darunavir and
 Limited CNS penetration prolong drug’s half life and
of mature infective virus cells  Spontaneous bleeding tipranavir: used in
 Active against HIV-1 and 2  Metabolized by CYP3A4 barrier to resistance
 Sulfa allergy Saquinavir: least pronounced
px that are HIV-1
resistant to other PIs
inhibitory effect
ATAZANAVIR Other adverse effects:  Increased absorption in an  Central obesity/buffalo hump  PPIs contraindicated
(azapeptide PI)  GI disturbance, headache, acidic medium (pH-  Peripheral and facial wasting  CYP3A4, CYP2C9, and
 Safe for pregnancy  Peripheral neuropathy dependent solubility)  Breast enlargement UGT1A1 inhibitor
 Kidney stones, gallstones  Taken with meals  Not associated with  Tenofovir and Efavirenz not
 PR prolongation  Antacids taken 12 hours dyslipidemia or given together unless
 Decreased bone density apart hyperglycemia ritonavir is added I50L substitution
 SJS  Metabolism: liver  Indirect hyperbilirubinemia  Px with hepatic insufficiency
 Elimination: Biliary

DARUNAVIR  Diarrhea, nausea
 Increased bioavailability  Contains sulfonamide moiety
 Best tolerated PI in randomized  Headache
when taken with meals (inc risk for hypersensitivity
studies  Inc amylase and hepatic
 Metabolism: liver rxn)
 Given with ritonavir or cobicistat aminotransferase levels
 Elimination: feces and urine  CYP3A enzyme system
 Darunavir/Ritonavir: safe for  Liver toxicity
 Highly protein bound (many drug-drug int)
pregnancy  Hypersensitivity reaction
FOSAMPRENAVIR Amprenavir: disubstituted  Can be taken with or  Headache  With sulfonamide moiety
(phosphonooxy prodrug of hydroxyethyl without food  Nausea  CYP3A4 inducer and inhibitor
amprenavir) aminosulfonamide  High fat meals decrease  Diarrhea  Oral suspension contains
 Given with low dose ritonavir nonopeptide protease absorption  Perioral paresthesias propylene glycol
inhibitor  Metabolism: liver  Depression contraindicated in children,
 Highly protein bound  Rash (sulfonamide moiety) women, etc
 Unconjugated
hyperbilirubinemia
 Needs acidic environment  Nephrolithiasis
for optimum solubility  CYP3A4 inhibitor
 Acute renal failure
INDINAVIR  Consumed on empty  If given with ritonavir:
 Interstitial fibrosis
(peptidomimetic hydroxyethylene stomach or with small, low- increased risk for
 Nausea, diarrhea, headache
protease inhibitor) fat low-protein meal nephrolithiasis (give high
 Sicca syndrome
 More potent against HIV-1  Liver metabolism fluid)
 Blurred vision
 Fecal elimination
 Insulin resistance
 High level CSF
 Higher risk for MI
 Acute hemolytic anemia
 GI disturbance
 Rapidly absorbed after oral  Increased serum lipids  Contains propylene glycol
LOPINAVIR
administration  Increased serum If given with lopinavir
(peptidomimetic protease inhibitor)
 Liver metabolism aminotransferases (common  Dec levels of lamotrigine and
 Given with low-dose ritonavir
 Low CSF penetration in HBV or HCV co-infection) methadone
 Safe for pregnant women
 Highly protein bound  Prolonged PR or QT interval  Inc levels of bosentant
 Pancreatitis
NELFINAVIR  Increased absorption in fed  GI disturbance  Inc dose of nelfinavir if given
(nonpeptidic protease inhibitor) state  Glucose intolerance with rifabutin
 Liver metabolism  Hypercholesterolemia  Dec dose of nelfinavir if given
 Fecal elimination  Hypertriglyceridemia with saquinavir
 Highly protein bound  Contraindicated if given with
drugs that contain
phenylalanine
Full-dose ritonavir
 Asthenia
 GI disturbance Saquinavir/ritonavir:
RITONAVIR  Hepatitis contraindicated due to
 Increased bioavailability
(peptidomimetic protease inhibitor) Others increased risk of QT
with food intake
 Safe for pregnant women  Altered taste prolongation
 Low doses of ritonavir + other PIs  Paresthesia, headache
 Biliary elimination
for lower dosing with greater  Inc serum
 Highly protein bound
tolerability and efficacy aminotransferase
 Inc lipid levels
 Inc serum creatine kinase
 Pancreatitis
 Taken 2 hours after a fatty
SAQUINAVIR meal for enhanced  GI discomfort  Increased saquinavir levels:
(peptidomimetic hydroxyethylamine absorption  Low dose ritonavir: less omeprazole
protease inhibitor)  Liver metabolism dyslipidemia or GI toxicity  Saquinavir/delavirdine or
 Reformulated and combined with  Fecal elimination  Increased risk for QT or PR rifampin: liver tests monitored
ritonavir  Large Vd but negligible prolongation  Not given with darunavir
CSF penetration  Torsades de pointes
 Highly protein bound
 GI disturbance
 Urticarial or maculopapular
rash  Sulfonamide moiety – not
 Liver toxicity given if with sulfa allergy
 Poor absorption but
TIPRANAVIR  Tipranavir/ritonavir:  CYP3A4 system inducer and
increased when taken with
 For those resistant to other PIs increased risk for inhibitor
high fat meal
 Give with ritonavir intracranial hemorrhage  Induces P-gp transporter
 Depression  Contraindicated use of
 Elevated serum amylase supplemented vitamin E
 Increased serum lipids
 Decreased WBC
ANTIRETROVIRAL (HIV) AGENTS – FUSION INHIBITORS
FUSION INHIBITORS Inhibits viral attachment by
 Inhibits HIV-1 entry into preventing binding of viral
host cells envelope glycoprotein
complex gp160 (gp120 and
gp41) to its cellular receptor
CD4
ANTIRETROVIRAL (HIV) AGENTS – FUSION INHIBITORS
ENFURVITIDE
(synthetic 36-amino acid peptide  Local injection site reactions
FI) Binds gp41 subunit of  Insomnia
 SQ injection (only one
 Only available HIV entry glycoprotein to prevent  Headache
parenteral)
inhibitor conformational changes  Dizziness No drug-drug interactions Mutations in gp41
 Active only against HIV-1 required for fusion of viral  Nausea
 Given with other ART in px and cellular membrane  Eosinophilia
with viral replication despite  Bacterial pneumonia
ART
ANTIRETROVIRAL (HIV) AGENTS – ENTRY INHIBITORS (CCR5 ANTAGONISTS)
 Upper respiratory tract infect
 Cough, pyrexia  Dose varies according to
 Rash, dizziness renal function and use of
 Muscle and joint pain CYP3A inducers or inhibitors
 Rapid but variable  Diarrhea, sleep disturbance  Substrate for P-glycoprotein
MARAVIROC
absorption  Elevated serum  Decrease dose of maraviroc:
 Given with other ART in Blocks entry of CCR5-tropic Mutations in V3 loop
 Liver metabolism aminotransferases when given with strong
adult px infected only with viruses into CD4 T-cell of gp120
 Fecal > renal elimination  Hepatotoxicity CYP3A inhibitors
CCR5-tropic HIV-1
 Excellent tissue penetration  Myocardial ischemia  Increase dose of maraviroc:
 Postural hypotension when given with CYP3A
 No evidence of increased inducers
risk of malignancy or  Not given with rifampin
infection
ANTIRETROVIRAL (HIV) AGENTS - INTEGRASE STRAND INHIBITORS (INSTIs)
INTEGRASE STRAND Prevent binding of pre-  Well-tolerated Combination with cobicistat =
INHIBITORS integration complex to host  Favorable effects upon lipid additional adverse events and
 Active against HIV-1 and 2 cell DNA  terminate metabolism drug-drug interactions
integration step of HIV  Headache
replication  GI effects
 Systemic hypersensitivity
 Rhadomyolysis
ANTIRETROVIRAL (HIV) AGENTS - INTEGRASE STRAND INHIBITORS (INSTIs)
Drug MOA  Pharmacokinetics Adverse Effect Precaution/Drug Interaction Resistance
 Not prescribed to any person
 Taken 2 hours before or 6 of childbearing potential who
hours after  Insomnia is sexually active and not
- cation-containing  Headache using birth control method
DOLUTEGRAVIR antacids  Increased serum  Inhibits renal organic cation
 Used in raltegravir and - laxatives aminotransferase levels transporter OCT2 
elvitegravir resistance - sucralfate  Fat redistribution syndrome increase plasma conc of
- oral iron and calcium  Rash drugs eliminated via OCT2
supplements  Hypersensitivity (dofetilide and metformin)
 Taken with food  Increased serum creatinine  Not given with metabolic
(elvitegravir) inducers (oxcarbazepine,
 Liver metabolism phenytoin, phenobarbital)
ELVITEGRAVIR  Fecal elimination  Not given with azole
 Diarrhea
 Used in treatment-naïve or (dolutegravir) antifungal drugs
 Rash
treatment-experienced px  Highly protein bound  Increases rifabutin levels
 Elevated hepatic
 Given with a boosting agent  Efavirenz or nevirapine
aminotransferases
(cobicistat or ritonavir) decreases elvitegravir
 Nausea
 Headache  UGT1A1 inducers or
 Fatigue inhibitors (rifampin or
 Not food-dependent
RALVITEGRAVIR  Muscle aches rifapentine) -> dosage
 Taken at least 4 hours Single point mutatioin
(pyriminidone analog)  Increased serum amylase adjustment
before antacids (codons 148 or 155)
 Safe for pregnancy and aminotransferase levels  Chewable tablets contain

 SJS phenylalanine (harmful if with
 Hypersensitivity phenylketonuria)
 Toxic epidermal necrolysis
OTHER ANTIVIRAL AGENTS
INTERFERON Condyloma acuminate
IMIQUIMOD Topical agent of external genital warts
Nebulizing agents for infants and children w/ severe respiratory syncytial virus (RSV) bronchiolitis or pneumonia to reduce severity & duration of illness
RIBAVIRIN
Teratogenic and Embryotoxic
PALIZIVUMAN Prevents RSV infection in high-risk infants and children (premature infants and those with bronchopulmonary dysplasia or congenital heart disease)
SPECIAL CONSIDERATIONS
PHARMACOKINETIC BOOSTING Usually wth low-dose ritonavir or cobicistat
TROUBLE SWALLING PILLS Some are available in liquid preparations (some are crushed or dissolved w/ or w/o losing potency)
TIMING OF DOSES IN
Take soon after dialysis
HEMODIALYSIS PATIENTS

Antiviral Drugs Table

Încărcat de

Informații document

Titlu original

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

Antiviral Drugs Table

Încărcat de

Drepturi de autor:

Formate disponibile

ANTI-HERPES AGENTS

Drug MOA Pharmacokinetics Adverse Effect Precaution/Drug Interaction Resistance

TRIFLURIDINE  Irreversible inhibition of

Dose adjustment in:

ANTIRETROVIRAL (HIV) AGENTS – PROTEASE INHIBITORS

S-ar putea să vă placă și