Names and pronunciation
(em-tri-sit′uh-bean/ril-pi-vir′een/ ten-oh-foh′veer) Complera
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Drug reference
(em-tri-sit′uh-bean/ril-pi-vir′een/ ten-oh-foh′veer) Complera
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Func. class.: Antiretroviral
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Chem. class.: Nucleoside reverse transcriptase inhibitor (NRTI)
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ACTION: • Emtricitabine: inhibits viral reverse transcriptase and is active both on HIV-1 and HBV • Tenofovir: inhibits viral reverse tran- scriptase and acts as a DNA chain terminator • Rilpivirine: inhibits HIV-1 reverse transcriptase; it does not compete for binding, nor does it require phosphory- lation to be active
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USES: HIV in treatment-naive patients with HIV RNA ≤100,000 copies/mL at initiation and certain virologically stable (HIV RNA <50 copies/mL) treatment- experienced patients
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CONTRAINDICATIONS: Hyper- sensitivity, hepatotoxicity, lactic acidosis
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Black Box Warning: Hepatitis B exacerbation Precautions: Alcoholism, autoimmune disease, bone fractures, breastfeeding, chil- dren, depression, females, Graves’ disease, Guillain-Barré syndrome, hepatic disease, hepatitis, hepatitis B and HIV coinfection, hepatitis C and HIV coinfection, hepato- megaly, HIV resistance, hypercholesterol- emia, hyperlipidemia, hypertriglyceridemia, hypophosphatemia, immune reconstitution syndrome, obesity, osteomalacia, osteopo- rosis, pregnancy, QT prolongation, renal failure, renal impairment, serious rash, suicidal ideation, torsades de pointes Black Box Warning: Hepatitis B exacer- bation: those with coexisting HBV and HIV infections who discontinue emtricitabine or tenofovir may experience severe acute hepatitis B exacerbation and hepatic de- compensation and hepatic failure. Those coinfected with HBV and HIV who discon- tinue this product, monitor LFTs q6wk E for the first 3 mo and q3-6mo thereafter. Resumption of anti–hepatitis B treatment may be required • Monitor serum bilirubin (total and direct), serum creatinine, urinalysis, LFTs, amylase, lipase, periodically
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SIDE EFFECTS CNS: Headache, abnormal dreams, depression, dizziness, insomnia, neu- ropathy, paresthesia, suicide, fatigue, drowsiness GI: Nausea, vomiting, anorexia, diar- rhea, abdominal pain, dyspepsia, hepa- tomegaly with stenosis (may be fatal), pancreatitis INTEG: Rash, skin discoloration MS: Arthralgia, myalgia, rhabdomyolysis GU: Glomerulonephritis membranous/ mesangioproliferative SYST: Change in body fat distribution, lactic acidosis
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INTERACTIONS • Do not use with efavirenz, lamiVUDine; treatment duplication Increase: rilpivirine level—CYP3A4 inhibitors (delavirdine, efavirenz, darunavir, tipranavir, atazanavir, fosam- prenavir, indinavir, nelfinavir, aldes- leukin IL-2, amiodarone, aprepitant, basiliximab, boceprevir, bromocriptine, chloramphenicol, clarithromycin, conivap- tan, danazol, dalfopristin, dasatinib, dil- tiazem, dronedarone, erythromycin, ethinyl estradiol, fluconazole, FLUox- etine, fluvoxamine, fosaprepitant, ima- tinib, isoniazid, itraconazole, ketocon- azole, lantreotide, lapatinib, miconazole, nefazodone, nicardipine, octreotide, posaconazole, quinine, ranolazine, rifAXIMin, tamoxifen, telaprevir, telithro- mycin, troleandomycin, verapamil, vori- conazole, zafirlukast) Decrease: emtricitabine level—interferons Increase: QT prolongation—class IA/III antidysrhythmics, some phenothi- azines, beta-agonists, local anesthetics, tricyclics, haloperidol, chloroquine, dro- peridol, pentamidine; CYP3A4 inhibitors (amiodarone, clarithromycin, erythro- mycin, telithromycin, troleandomycin), arsenic trioxide; CYP3A4 substrates (methadone, pimozide, QUEtiapine, quiNIDine, risperiDONE, ziprasidone) Increase: rilpivirine adverse reactions, fungal infections—fluconazole, voricon- azole Decrease: rilpivirine effect, treatment failure—CYP3A4 inducers (rifAMPin, rifapentine, rifabutin, primadone, phe- nytoin, PHENobarbital, nevirapine, naf- cillin, modafinil, griseofulvin, etravirine, efavirenz, barbiturates, bexarotene, bosentan, carBAMazepine, enzalu- tamide, dexamethasone), proton pump inhibitors Drug/Lab Test Increase: AST/ALT, glucose, amylase, bili- rubin, lipase, CK Decrease: neutrophils
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DOSAGE AND ROUTES • Adult/adolescent/child >12 yr and weighing ≥35 kg: PO 1 tablet (200 mg emtricitabine; 25 mg rilpivirine; 300 mg tenofovir) daily. Coadministra- tion with rifabutin, the rilpivirine dose needs to be increased to 50 mg/day; give an additional 25 mg/day of rilpiv- irine with a meal HIV prophylaxis after occupational exposure to HIV (unlabeled) • Adult: PO 1 tablet (200 mg emtri citabine; 25 mg rilpivirine; 300 mg tenofo- vir disoproxil fumarate) daily × 28 days Renal dose • Adult: PO CCr <50 mL/min: not recom- mended
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Available forms: Tablet 200-25-300 mg
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Administer: • Give with a meal • Antiretroviral drug resistance test- ing (preferably genotypic testing) be- fore use in treatment-naive patients and before changing therapy for treat- ment failure • For pregnant women, therapy should begin immediately after HIV diagnosis • Prior to initiating, identify virologic fail- ures; failures occurred more frequently in those with baseline HIV RNA concentra- tions >100,000 copies; CD4 counts <200 cells/mm3 • Avoid use of tenofovir-containing regi- mens in those with renal disease and os- teoporosis
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Assess: • HIV infection: assess symptoms of HIV, including opportunistic infec- tions, prior to and during treatment, some may be life-threatening; monitor plasma CD4+, CD8 cell counts, serum beta-2 microglobulin, serum ICD+24 antigen levels, treatment failures occur more often in those with baseline HIV-1 RNA concentrations >100,000 copies/mL than in those <100,000 copies/mL; monitor blood glucose, CBC with differential, serum choles- terol, lipid panel • Hepatotoxicity/lactic acidosis: mon- itor hepatitis B serology, LFTs, plasma hepatitis C RNA, lactic acidosis levels. If lab reports confirm these conditions, discontinue product. More common in females or those who are overweight. Avoid use in alcoholism • Pregnancy/breastfeeding: obtain preg- nancy testing before use
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Evaluate: • Improvement in CD4, HIV RNA counts, decreasing signs and symptoms of HIV Patient and caregiver information: • That hepatitis and HIV coinfected pa- tients should avoid consuming alcohol; offer vaccinations against hepatitis A and hepatitis B as appropriate • That GI complaints resolve after 2-3 wk of treatment • To take at the same time of day to main- tain blood level; not to crush, break, or chew • That product controls the symptoms of HIV but does not cure; patient is still able to infect others, that other products may be necessary to prevent other infec- tions • Lactic acidosis: to notify prescriber if fatigue, muscle aches/pains, abdomi- nal pain, difficulty breathing, nausea, vomiting, change in heart rhythm occur • Hepatotoxicity: to notify prescriber of dark urine, yellowing skin or eyes, clay-colored stools, anorexia, nausea, vomiting • Suicide: to report severe depression, suicidal ideation to prescriber immedi- ately • To report suspected or planned preg- nancy, not to breastfeed
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CLINICAL CONSIDERATIONS
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PHARMACOKINETICS • Emtricitabine: protein binding <4%, metabolized via oxidation half-life 10 hr, excreted renally (86%) and via feces (14%); peak 1-2 hr • Tenofovir: protein binding <0.7%, undergoes phosphorylation, eliminated by a combination of glomerular filtration and active renal tubular secretion, 70%- 80% excreted unchanged in urine half- life 17 hr, bioavailability is increased with a high-fat meal • Rilpivirine: protein binding 99.7% to albumin, metabolism via oxidation by CYP3A system, half-life 50 hr, excretion 85% feces, 6.1% urine, peak 4-5 hr
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• Adult/adolescent/child >12 yr and weighing ≥35 kg: PO 1 tablet (200 mg emtricitabine; 25 mg rilpivirine; 300 mg tenofovir) daily. Coadministra- tion with rifabutin, the rilpivirine dose needs to be increased to 50 mg/day; give an additional 25 mg/day of rilpiv- irine with a meal HIV prophylaxis after occupational exposure to HIV (unlabeled)
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• Adult: PO 1 tablet (200 mg emtri citabine; 25 mg rilpivirine; 300 mg tenofo- vir disoproxil fumarate) daily × 28 days Renal dose
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• Adult: PO CCr <50 mL/min: not recom- mended
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