A Review of Commonly Prescribed Antiviral and ... · a competitive irreversible chain terminator of...

Many common viruses (eg, influenza, rhinoviruses) arecontrolled or cleared by an individual’s immune systemwith few long-term sequelae. However, certain viral or hostfactors—viral type (and subtype), duration of infection, ageat time of acquisition, immunosuppressive conditions ormedications, and duration of the infection—increase thepathogenicity of viruses.1 In these situations, antiviral orantiretroviral agents may be prescribed for treatment of ac-tive disease, prevention, or preemptive therapy.

Because viral replication relies on a host cell for its lifecycle, most antiviral and antiretroviral agents interruptthe viral replication within the host cell.2 However; inter-feron augments the host’s immune response and assistswith viral clearing.3 Both mechanisms decrease the clini-cal manifestations of a virus.

Herpes Simplex Virus

Herpes simplex virus (HSV), a double-stranded DNAvirus, exists as 2 subtypes, HSV-1 and HSV-2. Infectionoccurs by mucus membrane contact with HSV. Viral par-ticles are secreted from active lesions and genital secre-tions of infected individuals. HSV-1 is primarily associat-ed with infections of the mouth (cold sores), whereasgenital herpes is predominately HSV-2. HSV acquisitionresults in lifelong infection that presents as alternatingepisodes of painful lesions and asymptomatic periods.Symptomatic reactivation may occur as a result of localtissue injury, acute illness, immunosuppression, or fever.4

Acyclovir, valacyclovir, and famciclovir are used in themanagement of HSV-1 and HSV-2.4,5

HANINE MANSOUR PharmD BCPS, Clinical Assistant Professor, Department of Pharmacotherapy and Translational Research,College of Pharmacy, University of Florida, St. Petersburg Campus, St. Petersburg, FL; LISA DEVITO INGE PharmD BCPS AAHIVE,Assistant Director, Jacksonville Campus; Clinical Assistant Professor, Department of Pharmacotherapy and Translational Re-search, College of Pharmacy, University of Florida; JASON FERREIRA PharmD, PGY1 Pharmacy Practice Resident, CharlestonArea Medical Center, Charleston, WV; and NATHAN R UNGER PharmD, PGY1 Pharmacy Practice Resident, James A Haley Vet-erans Hospital, Tampa, FL. Correspondence: Dr. Mansour, [email protected]

Reprints/Online Access: https://www.hwbooks.com/jpt/abstracts/volume27/may-june/order_article.html

Conflict of interest: Authors reported none

JPHARMTECHNOL.COM MAY/JUNE 2011 � VOLUME 27 � J PHARM TECHNOL 99

A Review of Commonly Prescribed Antiviraland Antiretroviral Agents

HANINE MANSOUR, LISA DEVITO INGE, JASON FERREIRA, AND NATHAN R UNGER

Objective: To review the pharmacologic properties of and uses for the most commonly prescribed antiviralagents.

Data Sources: A MEDLINE/PubMed search (1966-September 2010) was conducted for English-languagearticles using the terms HIV, hepatitis, cytomegalovirus (CMV), herpes simplex virus (HSV), antiviral agents,antiretroviral agent, acyclovir, valganciclovir, valacyclovir, interferon, ribavirin, ritonavir, efavirenz,zidovudine, darunavir, lopinavir, tenofovir, raltegravir, lamivudine, atazanavir, and emtricitabine. Bookchapters and recent guidelines pertaining to the pathophysiology or pharmacologic properties of antiviralagents were also reviewed.

Study Selection and Data Extraction: Articles, chapters, and guidelines pertaining to the relevantpharmacologic agents were collected for review.

Data Synthesis: Viral pathogens affect multiple organs, causing direct and indirect damage by activating animmune response. Unlike bacterial infections, which can be eradicated from the host system, viral infectionsare not curable. Antiviral treatments are prescribed to reduce morbidity and mortality. There are manyantiviral and more than 20 antiretroviral agents currently approved by the FDA. These include acyclovir,valacyclovir, and famciclovir for HSV; ganciclovir, valganciclovir, foscarnet, and cidofovir for CMV;interferon and ribavirin for hepatitis; and efavirenz, tenofovir, emtricitabine, atazanavir, darunavir, lopinavir,ritonavir, raltegravir, zidovudine, and lamivudine as first-line agents for HIV.

Conclusions: Viral illnesses affect a large portion of the population. Given the multitude of drugs available,pharmacists and pharmacy technicians should be educated about common treatment options. Having astrong knowledge of commonly prescribed antiviral drugs allows these frontline professionals to make asignificant impact on the quality of care that they provide to their patients and community.

J Pharm Technol 2011;27:99-110.

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Acyclovir, an acyclic guanine nucleoside analogue, re-quires tri-phosphorylation by the thymidine kinase inHSV, Epstein-Barr virus (EBV), and varicella-zoster virus(VZV) for activation. Once activated, acyclovir serves asa competitive irreversible chain terminator of viral DNAreplication. Although most effective for treatment ofHSV-1 and HSV-2, it offers some benefit in VZV and lim-ited benefit in cytomegalovirus (CMV) suppression.

Acyclovir’s poor oral bioavailability (10-30%) requiresthat large doses be administered. Valacyclovir, a prodrugL-valyl ester, was developed to overcome this limitation.Valacyclovir is converted to acyclovir by first-pass andhepatic metabolism, reaching an oral bioavailability ofabout 55%. Nonmetabolized acyclovir and any metabo-lites are eliminated through the renal system; therefore,dosing adjustments are necessary for patients with renaldysfunction. Treatment formulations, doses, and admin-istration frequencies for FDA-approved indications in vi-ral conditions are listed in Table 1.6,7

Adverse effects of both acyclovir and valacyclovir in-clude headaches, nausea, and diarrhea. Central nervoussystem (CNS) adverse effects, including lethargy, confu-sion, delirium, and hallucinations, are occasionally seen inpatients with renal dysfunction and those receiving the in-travenous formulation.8 Severe or fatal thrombocytopenicsyndromes have been reported in immunocompromisedpatients.9 Reversible neurotoxicity has also been reportedwith high serum acyclovir levels and is likely associatedwith a particular acyclovir metabolite.8 Renal dysfunction,obstruction, and renal tubular damage as a result of acy-clovir crystallization have also been reported.

The intravenous formulation should be administeredover 1 hour and accompanied by adequate hydration pre-and postinfusion as a precaution.10 Both oral formulationsshould be taken with plenty of water. Other adverse ef-fects include local irritation with topical formulations andrare phlebitis with intravenous extravasation.10,11

Nephrotoxicity may be increased when acyclovir is ad-ministered with other nephrotoxic drugs or when it isadministered with zidovudine or probenecid, which in-crease acyclovir concentrations.

Famciclovir, a prodrug of penciclovir, requires meta-bolism in the gastrointestinal tract, blood, and liver forconversion to its active form. It is a competitive inhibitorof viral DNA polymerase and is as effective as acyclovir

against herpes.8 Dosage adjustments are necessary in se-vere renal dysfunction. Like acyclovir and valacyclovir,rare adverse effects include headache, nausea, and diar-rhea. Data on use of famciclovir in pregnancy are limitedbut animal studies with very high doses found that thedrug may have mutagenic potential. To date, no drug in-teractions have been identified.12

Cytomegalovirus

CMV, a DNA virus in the herpes family, is also trans-mitted by bodily fluids. Acute infection is a result ofmouth-to-mouth transmission (ie, kissing), intimate sex-ual contact, perinatal transmission, and blood transfu-sion.1,2 Although 50-80% of chronic adult CMV infectionsare asymptomatic, acute exposure often begins as a mildillness with symptoms of fever, sore throat, swollenglands, and fatigue.13 Occasionally, CMV complicationsoccur during the chronic viral carrier state, particularly inpatients with immunosuppressive conditions (eg, HIV,malignancy, transplant recipients, neonates) or those re-ceiving immunosuppressive medications. Manifestationsof active viral replication can involve a variety of organs,including the eyes, lungs, CNS, and digestive tract. Thecorresponding symptoms include blindness or visual im-pairment, pneumonia, digestive tract ulceration,polyradiculopathies, and coma or seizures in the brain.13

Antiviral agents active against CMV are often prescribedfor immunocompromised persons to prevent or treatthese complications. Ganciclovir, foscarnet, and cidofovirare all approved for CMV treatment.13

Ganciclovir, a deoxyguanosine analogue, is an irre-versible DNA-chain terminator. It is extremely activeagainst CMV because the CMV phosphotransferase has agreater affinity for ganciclovir than for acyclovir. This affini-ty, in addition to its longer intracellular half-life, makes gan-ciclovir the treatment of choice for CMV, as opposed to acy-clovir. It is prescribed for CMV retinitis, as well astreatment and prevention of other CMV organ-specific dis-eases in immunosuppressed or transplant patients.14-16

As a result of ganciclovir’s poor bioavailability (8-9%),valganciclovir, another L-valyl ester prodrug, was devel-oped.17 Valganciclovir is converted to ganciclovir in theintestine and the liver, offering great bioavailability(60%).8 It also possesses good penetration into the cere-brospinal fluid and brain tissue. Elimination of this un-metabolized drug occurs by renal excretion, making re-nal dosing necessary.

Adverse effects of ganciclovir include reversiblemyelosuppression, specifically neutropenia (15-40%) andthrombocytopenia (5-20%).18 This risk increases 2 weeksinto therapy, but is reversible upon drug discontinuationor with cell line stimulation administration (ie, granulo-cyte stimulating factor). Five percent to 15% of patientsalso experience CNS adverse effects ranging fromheadaches to behavior changes or coma as a result ofCNS penetration.

100 J PHARM TECHNOL � VOLUME 27 � MAY/JUNE 2011 JPHARMTECHNOL.COM

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Most antiviral and antiretroviralagents interrupt the viral

replication within the host cell.

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COMMONLY PRESCRIBED ANTIVIRAL AND ANTIRETROVIRAL AGENTS


Table 1. Antiviral Agents

COMMON ADVERSEDRUG DOSAGE/FORM STANDARD ADULT DOSE EFFECTS/COMMENTS

Valganciclovira 450-mg tablet, 50-mg/mL CMV retinitis: 900 mg twice daily for 14-21 Diarrhea, nausea, GI disturbances, fever, (Valcyte) powder for solution days followed by 900 mg once daily for graft rejection, bone marrow suppression,

small peripheral lesions; in combination birth defectswith intraocular ganciclovir implant for sight-threatening lesions

Prevention of CMV infection in solid organ transplant: 900 mg once daily started within 10 days of transplantation and continued for 100 days after transplantation

Acyclovira 200-mg capsule, 400- Immunocompetent pts.: Nausea, vomiting, diarrhea (Zovirax) and 800-mg tablets, Initial genital herpes episode: 400 mg 3 times

200-mg/5-mL oral daily or 200 mg 5 times daily for 7-10 dayssuspension, 50-mg/mL Recurrent genital herpes episode: 400 mg byinjection, 100- and mouth 3 times daily for 5 days, 800 mg by500-mg/vial as powder mouth for 5 days or 800 mg by mouthfor injection, 5% (15-g 3 times daily for 2 daystube) topical ointment, Herpes zoster: 800 mg by mouth 5 times daily5% (2- and 5-g tubes) for 7-10 daystopical cream HSV encephalitis: 20 mg/kg iv every 8 h

Immunocompromised pts.:Herpes or varicella zoster: 10 mg/kg/dose ivor 500 mg/m2/dose by mouth every 8 h for7 days

Mucocutaneous HSV: 5 mg/kg/dose iv every 8 h for 7 days or 400 mg 5 times daily for 7-14 days

Valacyclovira 500-mg and 1-g caplets Initial genital herpes episode: 1 g by mouth Headache, nausea, abdominal pain(Valtrex) twice daily for 7-10 days

Recurrent genital herpes episode: 500 mg by mouth twice daily for 3 days or 1 g by mouth daily

Herpes zoster: 1 g by mouth 3 times daily for 7 days

Famciclovira (Famvir) 125-, 250-, and 500-mg Herpes labialis (cold sores): 1500 mg as a Headache, nausea, diarrheatablets single dose

Immunocompetent pts.:Initial genital herpes episode: 250 mg by mouth 3 times daily for 7-10 days

Recurrent genital herpes episode: 125 mg by mouth twice daily for 5 days or 1 g by mouthtwice daily for 1 day

Chronic suppressive therapy: 250 mg by mouthtwice daily

Immunocompromised pts.:Recurrent genital herpes episode: 500 mg by mouth twice daily for 5-10 days

Chronic suppressive therapy: 500 mg by mouthtwice daily

Peginterferon alfa-2a 180-mg/0.5- mL prefilled Chronic hepatitis C: 180 μg injected Flu-like syndrome, nausea, vomiting, diarrhea,(Pegasys) syringes, 180-μg/mL subcutaneously once weekly in combination worsening of psychosis, psychiatric effects,

solution for injection with ribavirin for 24-48 h insomnia, irritability, cardiovascular effects,Chronic hepatitis B: 180 μg injected increased risk of stroke or myocardialsubcutaneously for 48 wk infarction, bone marrow suppression;

contraindicated in pts. with estimated creatinine clearance <50 mL/min; not for use in pts. with severe hepatic impairment

Ribavirina 200-mg tablets Genotypes 1 and 4: Hemolytic anemia, hypersensitivity reactions,(Copegus) In combination with peginterferon alfa-2a for headache

48 wk: weight <75 kg, 1000 mg; weight Pregnancy category X≥75 kg, 1200 mg Contraindicated in hepatic impairment:

Genotypes 2 and 3: Child-Pugh classes B and CIn combination with peginterferon alfa-2afor 24 wk: 800 mg

CMV = cytomegalovirus; GI = gastrointestinal; HSV = herpes simplex virus.aDose adjustment needed in renal insufficiency.



When ganciclovir and zidovudine are combined, theeffectiveness of both agents decreases. If used with di-danosine, the risk of didanosine toxicity is increased.8

Valganciclovir also has major interactions with pro-benecid, mycophenolate mofetil, phenytoin, entecavir, ortenofovir.10,19 Concomitant use of ganciclovir with theseagents may enhance the adverse effects of thymine ana-logues or may potentiate renal problems.12

Foscarnet and cidofovir are also effective against CMVinfections, but are administered by intravenous routeonly. Their dose-limiting adverse effects include leukope-nia and neutropenia with cidofovir and renal impair-ment with foscarnet.

Hepatitis

Hepatitis may be caused by hepatitis A, B, C, D, and Eviruses.20 Hepatitis A and E viruses are transmitted byoral and fecal routes, while hepatitis B virus (HBV), hep-atitis C virus (HCV), and hepatitis D virus are transmit-ted by blood and bodily fluids.20 Perinatal transmissionof HBV and HCV are also possible.20

Viral hepatitis exhibits both an acute and chronic dis-ease course. After acute infection, some patients enterinto a noninfectious phase, referred to as remission.20 Al-ternatively, others enter into a chronic phase with long-term inflammation that results in extensive liver damage.Viral hepatitis is a common cause of liver failure and themost common cause of hepatocellular carcinoma and liv-er failure requiring transplantation.20,21 The goal of treat-ment is to prevent chronic sequelae.

Therapeutic choices vary depending on the hepatitissubtype, tolerability of indicated drugs, and treatment re-sponse. Interferon products, with and without the addi-tion of ribavirin, are prescribed for use in treatment ofHCV and HBV, respectively.20,21 HBV can also be treatedwith oral tenofovir, emtricitabine, or lamivudine. Patientscoinfected with HIV and HBV are often prescribed acombination of tenofovir and emtricitabine as part oftheir antiretroviral regimen.20 These nucleoside ana-logues are reviewed under antiretroviral agents.

Peginterferon alfa-2a (PIA2a) mimics the body’s naturalinterferon by activating natural proteins that provide an an-

tiviral effect.3 PIA2a binds viral infected cells, stimulatinggenes that have many biological effects including inhibitingviral replication, increasing cellular production, and in-creasing immune system function. It can be used alone as asingle agent for treatment of HBV or in combination withribavirin for the treatment of chronic HCV.3,20 Interferon in-jection is performed via an intramuscular or a subcuta-neous route. The attachment of polyethylene glycol slowsabsorption and decreases drug clearance, allowing onceweekly dosing. Dosing adjustments are necessary for pegy-lated interferon in severe renal disease.3

Drugs metabolized by the cytochrome P450 system,particularly CYP1A2, may be inhibited by interferon.Theophylline and ribavirin toxicities are of particularconcern, as concentrations are increased.3

PIA2a carries 3 boxed warnings. The first, for psychi-atric effects, cautions use in patients with a history of sui-cide or suicidal ideation, homicidal ideation, depression,relapse of drug addiction, or drug overdose. The secondwarns of a risk of infections, which should be ruled out inthe presence of fever. Lastly, autoimmune disorders suchas systemic lupus erythematosus and thyroiditis and is-chemic disorders such as ischemic colitis and myocardialinfarction may occur.3 Treatment should be discontinued ifliver dysfunction is observed. HBV flares during treatmentare possible. Stopping treatment is warranted with an in-crease in liver enzymes more than 10 times the upper limitof normal or if increased bilirubin is noted.3

Transmission risks and the HBV/hepatitis A virus vac-cination status of sexual partners and household mem-bers may be assessed. A missed dose of interferon maybe administered within 2 days without interruption in apatient’s dosing schedule; beyond 2 days, a health-careprovider should be contacted.

RIBAVIRIN

Ribavirin, a nucleoside analogue, is used in the treat-ment of HCV and in an aerosolized form to treat respira-tory syncytial virus in infants. Ribavirin, in combinationwith PIA2A, is also indicated for the treatment of chronicHCV.20 Although its mechanism of action has not beendetermined, ribavirin should not be used alone.22

Ribavirin dosing for the treatment of HCV dependson the patient’s weight and the viral genotype. It has notbeen studied in patients with creatinine clearance lessthan 50 mL/min; thus, it is not recommended in thispopulation or in patients with decompensated liver dis-ease.22

Because ribavirin has only been studied in combina-tion with PIA2A for safety and efficacy, reported adverseeffects are the result of both agents. Ribavirin’s primarytoxicity is hemolytic anemia (hemoglobin <10 g/dL).This anemia has been linked with risks of cardiac eventssuch as heart attacks. Patients should be assessed for car-diac risk factors prior to and after initiation of riba-virin.20,22


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Therapeutic choices varydepending on the hepatitis

subtype, tolerability of indicateddrugs, and treatment response.

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Hypersensitivity reactions manifesting as urticaria,bronchoconstriction, and angioedema are rare (<1%)with the combination therapy of ribavirin and PIA2A. Ifsuch a reaction is observed, treatment should be stoppedimmediately. Ribavirin is also associated with teratogenicand embryogenic effects.22 A negative pregnancy testshould be obtained before initiating treatment with riba-virin. Pregnancy should be avoided for at least 6 monthsafter stopping ribavirin therapy in both the male and fe-male partner.22

The use of both ribavirin and didanosine increases therisk of hepatic failure, peripheral neuropathy, pancreati-tis, and lactic acidosis. Ribavirin also exacerbates anemiaand neutropenia when coadministered with zidovudineand pancytopenia when used with azathioprine.22

Human Immunodeficiency Virus

The manifestations of HIV, an RNA virus, are associat-ed with the destruction of the body’s immune response,particularly CD4+ cells. As a patient’s cell count declines(indicating immune system damage), he or she is at in-creased risk for opportunistic infections, a frequent causeof death in patients not receiving antiretroviral therapy

(ART). ART may prevent additional damage to vital or-gans as a result of the inflammatory response to HIV it-self.23,24

HIV treatment utilizes ART combinations to preventthe development of viral resistance. Infected individualsshould be initiated on ART when their CD4 cell count isbetween 350 and 500 cells/mm3.23,24 Other factors forwhich treatment should be initiated can be found inTable 2.23,24

ART’s effectiveness is assessed by viral load. An effec-tive treatment regimen will result in an undetectable vi-ral load (<20 copies/mL), indicating reduced viral repli-cation. When viral replication is controlled, immunesystem recovery should occur. Immune recovery is as-sessed by measuring the CD4+ cell count every 3-6months.23,24

An adherence rate of at least 95% to all antiretroviralagents is the key to treatment success.25 This can be achallenging goal with a large number of pills, an in-creased dosing frequency, or intolerable adverse effects.To increase adherence, many manufacturers have devel-oped combination pills that incorporate at least 2 or 3medications or have investigated dosing regimens of re-duced frequency. There are 6 antiretroviral drug classes.



Table 3. First-Line Antiretroviral Treatmenta

DRUG CLASS DRUG/DOSE

Nucleoside/nucleotide reverse transcriptase inhibitorsb Tenofovir 300 mg and emtricitabine 200 mg by mouth daily

Nonnucleoside reverse transcriptase inhibitors Efavirenz 600 mg by mouth daily on empty stomach

Protease inhibitors Atazanavir 300 mg/ritonavir 100 mg by mouth daily with food

Darunavir 800 mg/ritonavir 100 mg by mouth daily with food

Integrase strain transfer inhibitors Raltegravir 400 mg by mouth twice daily

aDepartment of Health and Human Services 2009 and International AIDS Society 2010 guidelines.bIn combination with other first-line drugs from any of the above drug classes.

Table 2. Criteria for Starting Antiretroviral Therapy

DEPARTMENT OF HEALTH AND HUMAN SERVICES GUIDELINES INTERNATIONAL AIDS SOCIETY GUIDELINES

Should be initiated: Should be initiated:

AIDS-defining illness or opportunistic infections AIDS-defining illness or opportunistic infections

CD4 cell count <350 cells/mm3 CD4 cell count <350-500 cells/mm3

pregnancy pregnancy

HIV-associated nephropathy CD4 cell count decline >100 per year

treatment for hepatitis B is warranted HIV-1 RNA >100,000 copies/mL

Recommend initiation: Recommend initiation:

CD4 cell count >350-500 cells/mm3 and active HBV or HCV

possibly >500 cells/mm3 active or high risk for cardiovascular disease

Factors to consider: >60 years of age

CD4 cell count decline >100 cells/mm3 per year HIV-associated nephropathy

high viral load >100,000 copies/mL symptomatic primary HIV infection

HIV-serodiscordant couples

Consider initiation:

CD4 count >500 cells/mm3

HBV = hepatitis B virus; HCV = hepatitis C virus.



First-line treatment agents are shown in Table 3.23,24 Also,a full list of antiretroviral agents, with doses and adverseeffects, can be found in Table 4.23,24

NUCLEOSIDE/NUCLEOTIDE REVERSE TRANSCRIPTASEINHIBITORS

Nucleoside/nucleotide reverse transcriptase inhibitors(NRTIs), the backbone of current antiretroviral regimens,inhibit the production of HIV DNA from RNA. They com-pete for the use of the reverse transcriptase enzyme thatprevents chain elongation and terminates viral replication.

All NRTIs may be administered without regard tomeals except didanosine, which must be taken on anempty stomach.23,26 All except stavudine and zidovudinecan be administered once daily.23 Lastly, all NRTIs, withthe exception of abacavir, should be renally adjusted.27

Abacavir has recommendations for dosing in hepatic im-pairment.23

This class carries a black-box warning for lactic acido-sis, with risk of hepatic impairment, severe liver enlarge-ment, and death. Female sex, obesity, and pregnancy in-crease this risk.23,28 Other adverse effects include fatredistribution and lipodystrophy, which are primarily as-sociated with stavudine, didanosine, and zidovudine asa result of their affinity for mitochondrial DNA poly-merase.23,29 Although the onset of these physical changesis gradual, patients eventually exhibit central obesity,limb atrophy, and, potentially, dorsocervical fat enlarge-ment.29

Most antiretroviral regimens incorporate eitherlamivudine or emtricitabine in combination with teno-fovir or abacavir.23 Patients coinfected with HBV andHIV require treatment for both infections. Tenofovir witheither lamivudine or emtricitabine can be used, as theyare active against HBV and HIV.30-33 However, it is impor-tant to note that patients coinfected with HIV/HBV areat risk of hepatitis B exacerbation at medication initiationor upon withdrawal. Monitoring for such manifestationsis warranted.34

Although lamivudine is indicated for treatment ofboth HIV and HBV, dosing is different for each disease

state.30,32 HIV dosing is higher, making Epivir-HBV an in-appropriate choice for coinfected patients. All doses oflamivudine are generally well tolerated.30

Emtricitabine, in combination with tenofovir, is rec-ommended as the preferred backbone for HIV-treat-ment–naïve patients.23 Since emtricitabine and lamivu-dine are structurally related, patients who developresistance to lamivudine also have resistance to emtricit-abine. For this reason, this combination of NRTIs is notrecommended. Although emtricitabine is active in vivoand in vitro against HBV, it does not carry FDA approval.Instead, it is a therapeutic option, in combination withtenofovir, for the treatment of HBV in HIV patients.23,31,32

Abacavir is available as a coformulation with lamivu-dine (Epzicom) or with zidovudine and lamivudine(Trizivir). It possesses a black-box warning for a poten-tially deadly hypersensitivity reaction. This hypersensi-tivity reaction manifests as a diffuse skin rash, fever,chills, malaise, nausea, muscle pain, and shortness ofbreath. All patients should be screened for the HLA-B*5701 allele before an abacavir-containing regimen isinitiated.27 HLA-B*5701 positive individuals should notreceive abacavir due to an increased risk of this reac-tion.23 If a hypersensitivity reaction is suspected, the pa-tient should never be rechallenged, as death may occur.Use of abacavir has also been controversially linked tothe development of myocardial infarctions.34 Thus clini-cians should weigh the risk versus benefit of use of aba-cavir in patients who are already at high risk or whohave had a cardiovascular event or those with a viralload >100,000 copies/mL.35,36

Zidovudine, in combination with lamivudine andlopinavir/ritonavir twice daily, is indicated for pregnantpatients, as there is significant data on prevention of ma-ternal to fetal HIV-1 transmission.23,37-40 Common adverseeffects include bone marrow suppression, anemia, and lessoften, neutropenia. A complete blood cell count should bemonitored 2-8 weeks postinitiation of zidovudine, then ev-ery 3-6 months.23 Myopathy, lactic acidosis, and hepatotox-icity have also been reported. In such cases, treatmentshould be discontinued under medical supervision. Pa-tients should contact their provider to report any seizure,weight loss, loss of appetite, or weight gain.39

Didanosine in combination with efavirenz and emtricit-abine or lamivudine is considered an acceptable regimenin treatment-naïve patients only.23 Didanosine andemtricitabine should not be used with atazanavir due toinferior response.41 Didanosine carries a black-box warn-ing for pancreatitis, which occurs more frequently athigher doses.26 Other adverse effects include optic neuri-tis and retinal changes; a routine eye exam while on di-danosine therapy is recommended. Peripheral neuropa-thy that manifests as numbness, leg pains or tingling,and portal hypertension has also been reported. Thismay warrant the discontinuation of didanosine.26

Adverse effects associated with stavudine are exten-sive and include pancreatitis and peripheral neuropathy.Fatal and nonfatal pancreatitis has been reported when


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The manifestations of HIV, anRNA virus, are associated withthe destruction of the body’s

immune response, particularlyCD4+ cells.

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stavudine is used with didanosine, resulting in a black-box warning against the use of this combination.42 Zi-dovudine inhibits stavudine metabolism, leading to drugaccumulation and increasing toxicity; this combination iscontraindicated.40 The use of stavudine in any first-linecombination is not encouraged.23,24

Tenofovir is a preferred treatment for HIV and HBVcoinfection.23,24,31 Tenofovir in combination with emtri-citabine is the preferred NRTI for treatment-naïve pa-tients.23,24 This combination is also coformulated withefavirenz, providing potent virologic suppression.43,44

Although generally well tolerated, tenofovir possessesa black-box warning for HBV exacerbation with treat-ment discontinuation.31 Another adverse event is boneloss45; however, the long-term effect of tenofovir use onbone health and the risk of fractures is unknown.45 Fan-coni syndrome—acute renal failure and kidney injury,with reduction in phosphate level— has also been associ-ated with tenofovir use.46 Its use with other nephrotoxicagents or in patients with preexisting renal diseaseshould be avoided, if possible.23,46

Tenofovir use with other antiretroviral agents shouldbe assessed.23,24 When used in combination with didano-sine, tenofovir increases didanosine toxicity. Didanosinedose reduction or discontinuation is recommended to re-duce the incidence of pancreatitis and neuropathy.Atazanavir increases tenofovir concentrations, whiletenofovir reduces atazanavir concentrations. Patients ontenofovir should be monitored for nephrotoxicity, and ri-tonavir should be added to enhance the effect ofatazanavir. Lopinavir/ritonavir also increases tenofovirconcentration.44 Monitoring of renal function is alwaysrecommended.31,44

NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

Nonnucleoside reverse transcriptase inhibitors(NNRTIs) bind to the nonactive site of the reverse tran-scriptase enzyme, interrupting viral protein synthesis atthe HIV binding site. All NNRTIs are metabolized by theliver and inhibit or induce cytochrome P450 system en-zymes. Their long half-lives allow once- or twice-dailydosing. Potential adverse effects of this class of drugs arehepatotoxicity and rash. Unfortunately, poor adherenceto these agents can result in cross-resistance betweenefavirenz and nevirapine.18 Etravirine may still havesome activity in such cases and is therefore recommend-ed as a second-line agent, in combination with a proteaseinhibitor (PI)–containing regimen.23,24

Efavirenz, a preferred agent, is recommended for usein conjunction with 2 NRTIs, preferably tenofovir andemtricitabine.23,24 This triple-drug combination pill(Atripla) can be taken once daily, improving patient ad-herence. CNS effects include vivid dreams, confusion,dizziness, and sedation. These effects are worse in the first2-4 weeks of therapy. To reduce these effects, efavirenz-containing regimens should be taken on an empty stom-ach, just prior to bedtime.47 Moreover, in a clinical trial,

26% of patients developed a rash compared with 17% inthe placebo arm. Most rashes resolved within the first 2weeks of use. Less than 0.1% of rashes progressed to a se-vere form, Stevens-Johnson syndrome, in which blister-ing and shedding of the outer layers of skin occur.44

Efavirenz is contraindicated in women of childbearingage who are not using 2 forms of birth control or thoseconsidering pregnancy within 12 weeks.47 Case reportson efavirenz exposure during the first trimester of preg-nancy have described neural tube defects; however, ameta-analysis and a systematic review of outcomes of anobservational cohort concluded that a larger sample sizeis needed to prove the relationship between neural tubedefects in the first trimester of pregnancy and efavirenzexposure.48 Meanwhile, efavirenz remains classified aspregnancy category D.18,47 Lastly, multiple interactionswith this drug class should prompt a review for potentialinteractions between any NNRTI and other hepaticallymetabolized medications.

Nevirapine is contraindicated for use in men whoseCD4 count is more than 400 cells/mm3 and in womenwith a CD4 cell count more than 250 cells/mm3. Use inindividuals with CD4 cell counts above these cut offs orin persons with underlying hepatic disease (ie, hepatitis)increases the risk of rash, hepatotoxicity, and death.49

Etravirine has a greater barrier to resistance. It too pos-sesses the risk for erythema multiforme (Stevens-Johnsonsyndrome). Twice-daily administration with food is rec-ommended to achieve appropriate concentrations.50

PROTEASE INHIBITORS

PIs prevent the protease enzyme cleavage of provirusparticles into active viral components. Although thisclass is extremely potent, tolerability, adverse effects, pillburden, and drug interactions remain a challenge. Admin-istration requirements vary, but most should be taken withfood to improve tolerability. All PIs are hepatically metabo-lized by and inhibit or induce the cytochrome P450 en-zymes, making drug interactions a common concern. Inter-actions may decrease ART effectiveness or increasepotential toxicities of other medications. Class adverse ef-fects include gastrointestinal upset, hyperglycemia, hyper-lipidemia, hepatotoxicity, cardiovascular events, and in-creased bleeding in hemophiliacs. The extent of theseeffects varies among agents.23,24

Ritonavir was one of the first PIs introduced. However,due to poor tolerability (ie, diarrhea and vomiting) and anextensive adverse effect profile, this drug is no longer a pri-mary treatment agent.23,24 Instead, ritonavir 100 mg or 200mg is currently recommended for use in combinationwith most PIs and fewer other antiretroviral agents toboost concentrations. Ritonavir inhibits drug metabo-lism, reducing dosing frequency and pill burden of otheragents.23

In 2010, a new tablet formulation was FDA approved.This formulation does not require refrigeration, which isa requirement of the capsule formulation.51,52 The newer






TAB

LE 4

. HIV

Med

icat

ions

DR

UG

DO

SAG

E FO

RM

STA

ND

AR

D A

DU

LT D

OSI

NG

AD

VER

SE E

FFEC

TS/C

OM

MEN

TS

Lam

ivud

inea

Epiv

ir 1

0 m

g/m

L (2

40 m

L) s

traw

berr

y-ba

nana

HIV

: 150

mg

by m

outh

twic

e da

ily o

r 30

0 m

g by

H

epat

itis

trea

tmen

t age

nt, l

actic

aci

dosi

s(E

pivi

r, Ep

ivir-

HB

V)

flavo

r fo

r tr

eatm

ent o

f HIV

m

outh

dai

ly in

com

bina

tion

with

2 o

ther

Pr

egna

ncy

cate

gory

CEp

ivir-

HB

V 5

mg/

mL

(240

mL)

str

awbe

rry-

antir

etro

vira

l age

nts

bana

na fl

avor

Hep

atiti

s B

: 100

mg

by m

outh

dai

ly fo

r at

leas

t 1 y

Epiv

ir 1

50 m

g, 3

00-m

g ta

blet

sEp

ivir-

HB

V 1

00-m

g ta

blet

s

Emtr

icita

bine

a 20

0-m

g ca

psul

e an

d 10

-mg/

mL

solu

tion

in20

0 m

g by

mou

th (c

apsu

le) o

nce

daily

or

240

mg

by

Skin

hyp

erpi

gmen

tatio

n (m

ore

frequ

ent a

mon

g no

n-w

hite

pts

.)(E

mtr

iva)

cotto

n ca

ndy

flavo

rm

outh

(sol

utio

n) d

aily

; cap

sule

and

ora

l sol

utio

nPr

egna

ncy

cate

gory

Bno

t int

erch

ange

able

on

mg-

to-m

g ba

sis

Aba

cavi

rb(Z

iage

n)30

0-m

g ta

blet

, Zia

gen

20 m

g/m

L (2

40 m

L)30

0 m

g by

mou

th tw

ice

daily

or

600

mg

by m

outh

Seve

re h

yper

sens

itivi

ty r

eact

ion

(mos

t com

mon

with

in fi

rst 4

-6 w

k of

in a

str

awbe

rry-

bana

na fl

avor

daily

in c

ombi

natio

n w

ith o

ther

ART

ther

apy

and

linke

d to

pre

senc

e of

the

HLA

-B*5

701

alle

le);

pts.

sho

uld

not b

e re

chal

leng

ed d

ue to

incr

ease

d ris

k of

ana

phyl

axis

, hyp

oten

sion

, an

d de

ath;

myo

card

ial i

nfar

ctio

n w

hen

used

with

did

anos

ine

inob

serv

atio

nal c

ohor

t stu

dies

Pr

egna

ncy

cate

gory

C

Zid

ovud

inea

300-

mg

tabl

et, 1

00-m

g ca

psul

e,50

-mg/

5-m

L60

0 m

g/da

y in

2 d

ivid

ed d

oses

with

oth

er A

RT

Bon

e m

arro

w s

uppr

essi

on, a

nem

ia, n

eutr

open

ia, G

I int

oler

ance

, myo

path

y,(R

etro

vir)

stra

wbe

rry

flavo

r sy

rup;

inje

ctio

nLa

bor

and

deliv

ery:

2 m

g/kg

load

ing

dose

follo

wed

hepa

toto

xici

ty, n

ail p

igm

enta

tion,

hea

dach

e, la

ctic

aci

dosi

sso

lutio

n of

20

mg/

mL

by a

1-m

g/kg

/h c

ontin

uous

infu

sion

unt

il um

bilic

al

Preg

nanc

y ca

tego

ry C

cord

is c

lam

ped

HIV

pos

texp

osur

e pr

even

tion:

300

mg

twic

e da

ilyw

ith la

miv

udin

e 15

0 m

g by

mou

th tw

ice

daily

Did

anos

inea

Vid

ex E

C 1

25-,

200-

, 250

-, 40

0-m

g ca

psul

es;

Dos

e ba

sed

on b

ody

wei

ght:

≥60

kg, 4

00 m

g on

ce

GI i

ntol

eran

ce, p

ancr

eatit

is, p

erip

hera

lneu

ropa

thy,

lact

ic a

cido

sis

with

(Vid

ex E

C)

buffe

red

tabl

ets

(non

-EC

) no

long

erda

ily, w

ith te

nofo

vir,

250

mg

once

dai

ly; <

60 k

g,

hepa

tic s

teat

osis

, non

-cir

rhot

ic p

orta

l hyp

erte

nsio

nav

aila

ble

250

mg

once

dai

ly, w

ith te

nofo

vir,

200

mg

once

Preg

nanc

y ca

tego

ry B

Ora

l sol

utio

n V

idex

10

mg/

mL

daily

(with

out t

enof

ovir,

take

n on

em

pty

stom

ach)

Stav

udin

ea(Z

erit)

15-,

20-,

30-,

and

40-m

g ca

psul

es o

r 1-m

g/m

LB

ody

wei

ght ≥

60 k

g, 4

0 m

g tw

ice

daily

; <60

kg,

Peri

pher

al n

euro

path

y, li

poat

roph

y, p

ancr

eatit

is, l

actic

aci

dosi

s w

ith

oral

sol

utio

n30

mg

twic

e da

ilyhe

patic

ste

atos

is, h

yper

lipid

emia

, rap

idly

pro

gres

sive

asc

endi

ngne

urom

uscu

lar

wea

knes

sPr

egna

ncy

cate

gory

C

Teno

fovi

ra(V

irea

d)30

0-m

g ta

blet

HIV

and

hep

atiti

s B

infe

ctio

n: 3

00 m

g by

mou

th d

aily

Ren

al in

suffi

cien

cy, F

anco

ni’s

synd

rom

e, o

steo

mal

acia

/ dec

reas

e in

bon

em

iner

al d

ensi

ty, a

sthe

nia,

hea

dach

e, d

iarr

hea,

nau

sea,

vom

iting

,fla

tule

nce

Trea

tmen

t of c

hoic

e fo

r H

BV,

pos

sibl

e ex

acer

batio

nsPr

egna

ncy

cate

gory

B

Efav

iren

z (S

ustiv

a)50

- an

d 20

0-m

g ca

psul

es, 6

00 m

g ta

blet

600

mg

once

dai

ly o

n an

em

pty

stom

ach

Ras

h, S

teve

ns-J

ohns

on s

yndr

ome,

diz

zine

ss, n

ause

a, h

eada

che,

viv

iddr

eam

s, h

allu

cina

tions

, sui

cida

l ide

atio

n an

d de

pres

sion

, hep

atot

oxic

ityri

skPr

egna

ncy

cate

gory

D

Fals

e po

sitiv

e ca

nnab

inoi

d an

d be

nzod

iaze

pine

scr

eeni

ng a

ssay

s

Nev

irap

ine

20

0-m

g ta

blet

s, 5

0-m

g/5-

mL

susp

ensi

on20

0 m

g on

ce d

aily

for 1

4 da

ys (l

ead-

in p

erio

d), t

hen

Ras

h, in

clud

ing

Stev

ens-

John

son

synd

rom

e;(V

iram

une)

200

mg

twic

e da

ilyhe

patit

is, i

nclu

ding

fata

l hep

atic

nec

rosi

sR

epea

t lea

d-in

per

iod

if of

f med

icat

ion

>7

days

Mild

-to-

mod

erat

e ra

sh w

ithou

t con

stitu

tiona

l sy

mpt

oms,

con

tinue

lead

-in p

erio

d un

til ra

sh re

solv

es

<28

day

s





Etra

viri

ne (I

ntel

ence

)10

0-m

g ta

blet

200

mg

bid

with

food

Ras

h, h

yper

sens

itivi

ty r

eact

ions

with

pos

sibl

e or

gan

dysf

unct

ion,

incl

udin

g he

patic

failu

re

Ata

zana

virb

100-

, 150

-, 3

00-,

and

400

-mg

caps

ules

300

mg

with

rito

navi

r, 10

0 m

g, o

r 40

0 m

g w

ith fo

odIn

dire

ct h

yper

bilir

ubin

emia

, neu

tral

lipi

d pr

ofile

, nep

hrol

ithia

sis

(flan

k(R

eyat

az)

pain

, abd

omin

al p

ain,

dys

uria

, inc

reas

e in

uri

nary

freq

uenc

y), p

ossi

ble

PR p

rolo

ngat

ion,

hyp

ergl

ycem

ia, s

kin

rash

, Ste

vens

-Joh

nson

syn

drom

e,G

I int

oler

ance

Preg

nanc

y ca

tego

ry B

Dar

unav

ir (P

rezi

sta)

75-,

150

-, 4

00-,

600

-, a

nd 8

00-m

g ta

blet

s80

0 m

g w

ith r

itona

vir,

100

mg

(trea

tmen

t-na

ïve

pts.

) Sk

in ra

sh (1

0%),

hype

rlip

idem

ia, h

yper

glyc

emia

, fat

mal

dist

ribu

tion,

or 6

00 m

g w

ith r

itona

vir

100

mg

(trea

tmen

t-di

arrh

ea a

nd n

ause

a, v

omiti

ngex

peri

ence

d pt

s.) t

wic

e da

ily w

ith fo

odPr

egna

ncy

cate

gory

C

Fosa

mpr

enav

irb

700-

mg

tabl

et, 5

0-m

g/m

L or

al s

uspe

nsio

n14

00 m

g tw

ice

daily

with

out r

itona

vir,

1400

mg

Skin

rash

(19%

) (us

e ca

utio

n in

pts

. with

kno

wn

sulfa

alle

rgy)

, dia

rrhe

a, ra

sh,

(Lex

iva)

once

dai

ly w

ith r

itona

vir

100

or 2

00 m

g, o

r 70

0 m

ghe

adac

he, h

yper

lipid

emia

, tra

nsam

inas

e el

evat

ions

, rar

e ne

phro

lithi

asis

,w

ith r

itona

vir

100

mg

twic

e da

ilyvo

miti

ng

Preg

nanc

y ca

tego

ry C

Indi

navi

rb(C

rixi

van)

10

0-, 2

00-,

and

400

-mg

caps

ules

800

mg

ever

y 8

h on

an

empt

y st

omac

h, o

r 80

0 m

gK

idne

y st

ones

(ade

quat

e hy

drat

ion

need

ed),

abdo

min

al p

ain,

fatig

ue, b

ack

with

rito

navi

r 10

0-20

0 m

g tw

ice

daily

with

out

pain

, GI i

ntol

eran

ce, n

ause

a, fa

t mal

dist

ribu

tion,

hyp

erlip

idem

ia, i

ndir

ect

rega

rd to

mea

lshy

perb

iliru

bine

mia

Preg

nanc

y ca

tego

ry C

Nel

finav

ir (V

irac

ept)

625-

and

250

-mg

tabl

ets;

50

mg/

g po

wde

r12

50 m

g tw

ice

daily

or

750

mg

3 tim

es d

aily

with

Dia

rrhe

a, n

ause

a, in

crea

sed

liver

enz

ymes

, inc

reas

ed tr

igly

ceri

des

and

for

reco

nstit

utio

nfo

odch

oles

tero

l, hy

perg

lyce

mia

Pr

egna

ncy

cate

gory

B

Use

with

cau

tion

in h

epat

ic im

pair

men

t

Tipr

anav

ir (A

ptiv

us)

250-

mg

caps

ule,

100

-mg/

mL

oral

sol

utio

n50

0 m

g w

ith r

itona

vir,

200

mg

twic

e da

ilyR

ash,

hyp

ertr

igly

ceri

dem

ia, h

yper

chol

este

role

mia

, hep

atot

oxic

ity;

intr

acra

nial

hem

orrh

age

whe

n us

ed in

com

bina

tion

with

rito

navi

rPr

egna

ncy

cate

gory

CC

ontr

aind

icat

ed in

Chi

ld-P

ugh

clas

ses

B a

nd C

Saqu

inav

ir (I

nvir

ase)

200-

mg

caps

ule-

tabl

ets;

500

-mg

tabl

et10

00 m

g co

adm

inis

tere

d w

ith r

itona

vir

100

mg

Nau

sea,

vom

iting

, hyp

erlip

idem

ia,h

epat

otox

icity

twic

e da

ilyPr

egna

ncy

cate

gory

BU

se w

ith c

autio

n in

hep

atic

insu

ffici

ency

Lopi

navi

r/ri

tona

vir

200-

mg/

50-m

g ta

blet

s; 1

00 m

g/25

mg

oral

40

0 m

g/10

0 m

g tw

ice

daily

(tre

atm

ent-

expe

rien

ced

GI i

ntol

eran

ce, h

yper

lipid

emia

, inc

reas

ed L

FT re

sults

, inc

ludi

ng tr

ansa

min

ases

; (K

alet

ra)

solu

tion

or p

regn

ant)

or 8

00 m

g/20

0 m

g da

ily (t

reat

men

t-hy

perg

lyce

mia

, car

diov

ascu

lar

PR a

nd Q

T in

terv

alpr

olon

gatio

n (r

are)

naïv

e)

Rito

navi

r (N

orvi

r)10

0-m

g ca

psul

e; 1

00-m

g ta

blet

only

for

boos

ting

GI i

ntol

eran

ce, i

ncre

ases

in tr

igly

ceri

des

and

lipid

s

Ral

tegr

avir

(Ise

ntre

ss)

400-

mg

tabl

et40

0 m

g tw

ice

daily

Few

dru

g in

tera

ctio

ns, r

are

crea

tinin

e ki

nase

ele

vatio

ns

Enfu

virt

ide

(Fuz

eon)

108-

mg

lyop

hiliz

ed p

owde

r90

mg

subc

utan

eous

ly tw

ice

daily

Loca

l inj

ectio

n si

te r

eact

ions

, rar

e (<

1%) h

yper

sens

itivi

ty r

eact

ion

Mar

avir

oc (S

elze

ntry

) 15

0- a

nd 3

00-m

g ta

blet

s15

0 m

g tw

ice

daily

with

str

ong

inhi

bito

rs (a

llA

bdom

inal

pai

n, m

uscu

losk

elet

al s

ympt

oms,

pyr

exia

, ras

h, o

rtho

stat

icpr

otea

se in

hibi

tors

exc

ept t

ipra

navi

r); 3

00 m

g tw

ice

hypo

tens

ion

daily

with

enf

uver

tide,

nev

irap

ine,

NRT

Is, a

nd

tipra

navi

r/ri

tona

vir;

600

mg

twic

e da

ily w

ithef

avir

enz,

etr

avir

ine

ART

= a

ntir

etro

vira

l the

rapy

; GI =

gas

troi

ntes

tinal

; HB

V =

hep

atiti

s B

vir

us; L

FT =

live

r fu

nctio

n te

sts;

NRT

Is =

nuc

leos

ide

reve

rse

tran

scri

ptas

e in

hibi

tors

.a D

ose

adju

stm

ent r

equi

red

in r

enal

impa

irm

ent.

b Dos

e ad

just

men

t req

uire

d in

hep

atic

impa

irm

ent.



tablet does require administration with food to achieveappropriate concentrations.51,52

Kaletra, a combination PI, incorporates ritonavir withlopinavir to provide effective drug concentrations. Dos-ing for treatment-naïve patients is once daily, as opposedto twice daily for treatment-experienced patients withdrug resistance.52 Despite gastrointestinal upset and in-creases in cholesterol, particularly triglycerides, it re-mained a preferred agent for years. In 2009, Kaletra wasnoted to increase the risk of PR and QT interval prolon-gation.53 It has been reclassified as an alternative treat-ment agent in treatment-naïve patients.23 It remains apreferred agent in pregnancy, in which case it is adminis-tered twice daily.52

Atazanavir offers improved tolerability with a goodlipid profile.23,54 Its once-daily dosing, with or without ri-tonavir, increases adherence. Boosting with ritonavir ispreferred and required with tenofovir use.23 Administra-tion with food is required to increase absorption and lim-it variability in drug concentrations.55 Use of antacids, H2

antagonists, or proton pump inhibitors can decrease theeffectiveness of atazanavir. Assessment of administrationtimes and doses is important as they may result in treat-ment failure because of insufficient atazanavir levels.55

Adverse effects of hyperbilirubinemia, occasionally re-sulting in mild symptoms of jaundice or scleral icterus,are possible although not pathogenic. Less common ad-verse events include a mild-to-moderate rash, prolonga-tion of PR intervals, and rare cases of nephrolithiasis atincreased concentrations.55

Darunavir in combination with ritonavir offers goodtolerability, once-daily dosing, and potency.56-58 Treatment-experienced patients currently receive twice-daily dos-ing.23 Administration with food is required.56-58 Darunaviris generally well tolerated except that a skin rash may oc-cur in about 10% of patients as a result of its sulfa moiety.Occasionally this rash is severe, with erythema multiformeand Stevens-Johnson syndrome occurring. Caution shouldbe used in patients with HBV or HBC, as darunavir usecan result in liver enzyme increases.56-58

Dosing and potential adverse effects of nonpreferredPIs, fosamprenavir, indinavir, nelfinavir, tipranavir, andsaquinavir may be found in Table 4.59-63

INTEGRASE STRAND TRANSFER INHIBITOR

Raltegravir blocks the integrase enzyme’s ability to in-corporate newly manufactured HIV DNA into the host’scell DNA. Although a preferred treatment agent withtenofovir and emtricitabine, it can also be used in combi-nation with other effective antiretroviral agents for treat-ment-experienced patients.23,24 Dosing is twice dailywithout food restrictions. Potential drug interactions arelimited, as raltegravir is not metabolized nor is it an in-ducer or inhibitor of the cytochrome P450 system, but in-stead is metabolized by glucuronidation.64,65

It was well tolerated in clinical trials, with limited gas-trointestinal upset compared with placebo, and did not

increase cholesterol levels.64,65 Rare creatinine kinase ele-vations associated with myopathy and rhabdomyolysishave been reported with raltegravir, particularly whenused in combination with other drugs that have the samerisk factors.66

Dosing and common adverse effects of less commonlyused agents, namely enfuvirtide, a fusion inhibitor, andmaraviroc, a CCR5 antagonist, can be found in Table 4.67,68

Summary

Viral infections (ie, HIV, HSV, HCV, and HBV) are of-ten sexually transmitted. The Centers for Disease Controland Prevention and the Department of Health and Hu-man Services offer easily accessible detailed guidelinesthat help with the management of hepatitis, sexuallytransmitted diseases, and HIV. Although expert clini-cians are often the primary health-care professionals in-volved in the management of viral infections, pharmacytechnicians are on the front line with pharmacists duringthe dispensing of these antiviral agents. Being knowl-edgeable about commonly prescribed antiviral medica-tions and related diseases improves the pharmacist’sidentification of drug interactions, management of ad-verse effects, appropriate dosing, and key counselingpoints.

References

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