Indications
Management of HIV infection, a complete regimen for
treatment-naı¨ve adults or in adults who are virologically
suppressed (HIV—1 RNA 50 copies/mL) on a stable
regimen for 6 mo with no history of treatment failure
and no known substitutions associated with resistance
to the individual components of this medication.
Action
Elvitegravir—An integrase strand transfer inhibitor
that inhibits an enzyme necessary for viral replication.
Cobicistat—A pharmacokinetic enhancer (inhibits
CYP3A and CYP2D6) enhancing systemic exposure to
elvitegravir. Emtricitabine—Phosphorylated intracellularly
where it inhibits HIV reverse transcriptase, resulting
in viral DNA chain termination. Tenofovir—
Phosphorylated intracellularly where it inhibits HIV reverse
transcriptase resulting in disruption of DNA synthesis.
Therapeutic Effects: Slowed progression of
HIV infection and decreased occurrence of sequelae.
Pharmacokinetics
elvitegravir
Absorption: Absorption follows oral administration.
Distribution: Unknown.
Protein Binding: 98–99%.
Metabolism and Excretion: Metabolized by
CYP3A, 94.5% eliminated in feces, 6.7% in urine.
Half-life: 12.9 hr.
cobicistat
Absorption: Absorption follows oral administration.
Distribution: Unknown.
Protein Binding: 97–98%.
Metabolism and Excretion: Metabolized by
CYP3A and to a small extent by CYP2D6, 86.2 eliminated
in feces, 8.2% in urine.
Half-life: 3.5 hr.
emtricitabine
Absorption: Rapidly and extensively absorbed; 93%
bioavailable.
Distribution: Unknown.
Metabolism and Excretion: Some metabolism,
86% renally excreted, 14% fecal excretion.
Half-life: 10 hr.
tenofovir
Absorption: Tenofovir disoproxil fumarate is a
prodrug, which is split into tenofovir, the active component.
Distribution: Absorption is enhanced by food.
Metabolism and Excretion: 70–80% excreted
unchanged in urine by glomerular filtration and active
tubular secretion.
Half-life: Unknown.
TIME/ACTION PROFILE
ROUTE ONSET PEAK DURATION
elvitegravir
PO
unknown 4 hr 24 hr
cobicistat PO unknown 3 hr 24 hr
emtricitabine
PO
rapid 1–2 hr 24 hr
tenofovir PO unknown 2 hr 24 hr
Contraindications/Precautions
Contraindicated in: Severe hepatic impairment;
Concurrent administration of other drugs that depend
mainly on CYP3A for metabolism and whose blood levels,
whenq, are associated with serious/life-threatening
adverse reactions; Concurrent administration of other
drugs that induce the CYP3A enzyme system which may
pblood levels/effectiveness and promote development
of viral resistance; Should not be used concurrently
with other antiretrovirals that contain cobicistat, elvitegravir,
emtricitabine, tenofovir, lamivudine, adefovir, or
ritonavir; Renal impairment (do not initiate if CCr 70
mL/min, discontinue if CCr 50 mL/min); Lactation:
HIV-infected women should not breast feed due to risk
of viral transmission.
Use Cautiously in: Female patients or obese patients
(may be atqrisk for lactic acidosis/hepatic steatosis);
Geri: Elderly may be more sensitive to drug effects;
consider age-relatedpin renal, hepatic, and
cardiovascular function; concurrent disease states and
medications; OB: Use during pregnancy only if potential
benefits justify fetal risks; Pedi: Children 12 yr (safety
and effectiveness not established).
Exercise Extreme Caution in: Hepatitis B (may
cause severe acute exacerbation).
Adverse Reactions/Side Effects
CNS: abnormal dreams, dizziness, headache, insomnia,
drowsiness. GU: ACUTE RENAL FAILURE/FANCONI SYNDROME,
qserum creatinine, proteinuria. GI: LACTIC ACIDOSIS/
HEPATOMEGALY WITH STEATOSIS, POST-TREATMENT
ACUTE EXACERBATION OF HEPATITIS B, diarrhea, nausea.
Derm: rash, hyperpigmentation. F and E: hypophosphatemia.
Metab:qlipids. MS: bone pain,pbone
mineral density, muscle pain, osteomalacia. Misc: immune
reconstitution syndrome.
Interactions
Drug-Drug: May alter blood levels and effects of
other drugs metabolized by the CYP3A or CYP2D6 enzyme
systems. Other drugs that induce the CYP3A system
can alter blood levels and effects. Concurrent administration
of other drugs that depend mainly on
CYP3A for metabolism and whose blood levels, whenq,
are associated with serious/life-threatening adverse reactions
including alfuzosin, dihydroergotamine,
ergotamine, lovastatin, oral midazolam, methylergonovine,
lurasidone, pimozide, sildenafil
(when used for pulmonary hypertension), simvastatin,
and triazolam; concurrent use contraindicated.
Carbamazepine, phenobarbital, phenytoin, or rifampin
may significantlyplevels/effectiveness of cobicistat
and elvitegravir andqrisk of resistance; concurrent
use contraindicated. Nephrotoxic agents, including
NSAIDsqrisk of nephrotoxicity; avoid concurrent use.
Drugs that induce CYP3A willplevels/effectiveness of
elvitegravir and cobicistat. Drugs that inhibit CYP3A will
alsoqlevels/effectiveness of cobicistat. Acyclovir, cidofovir,
ganciclovir, valacyclovir, and valganciclovir
mayprenal elimination of emtricitabine and tenofovir,
qlevels and effects. Antacids, including
aluminum and magnesium hydroxide, mayplevels
and effectiveness of elvitegravir (separate administration
by at least 2 hr).qblood levels and risk of toxicity
from amiodarone, digoxin, disopyramide, flecainide,
systemic lidocaine, mexiletine, propafenone
or quinidine; careful monitoring recommended. May
alter effects of warfarin. Concurrent use with clarithromycin
can result in altered levels of clarithromycin
and/or cobicistat (for patients with CCr 50–60 mL/min
pdose of clarithromycin by 50%), levels of cobicistat
may beq. Oxcarbamazepine mayplevels/effectiveness
of cobicistat and elvitegravir; consider using alternative
anticonvulsant. Mayqlevels of clonazepam and ethosuximide (clinical monitoring recommended).
qlevels and risk of adverse effects with SSRIs, tricyclic
antidepressants, and trazodone (careful titration
and monitoring recommended).qlevels of
itraconazole, ketoconazole, and voriconazole
(maximum daily dose of ketoconazole or itraconazole
should not exceed 300 mg, voriconazole with extreme
caution). These azole antifungals may alsoqlevels of
cobicistat and elvitegravir.qlevels and risk of toxicity
from colchicine (concurrent use is contraindicated in
patients with renal or hepatic impairment), gout
flares—0.6 mg followed by 0.3 mg 1 hr later, do not
repeat for at least three days; prophylaxis of gout
flares—0.3 mg once daily if original regimen was 0.6
mg twice daily, 0.3 mg every other day if original regimen
was 0.6 mg daily; treatment of familial Mediterranean
fever—not to exceed 0.6 mg daily, may be
given as 0.3 mg twice daily. Concurrent use with rifabutin
or rifapentine may significantlyplevels/effectiveness
of cobicistat and elvitegravir and may foster resistance,
concurrent use is not recommended. Mayq
levels and effects of beta blockers including metoprolol
and timolol; careful monitoring is recommended,
pdose of beta blocker if necessary. Mayqlevels
and effects of calcium channel blockers
including amlodipine, diltiazem, felodipine, nicardipine,
nifedipine, and verapamil; careful monitoring
is recommended. Concurrent use of corticosteroids
that induce CYP3A, including budesonide,
dexamethasone, methylprednisolone, prednisone,
or inhaled betamethasone, ciclesonide, fluticasone,
mometasone, and triamcinolone, mayp
levels/effectiveness andqrisk of resistance to elvitegravir
(consider use of other corticosteroids, such as beclomethasone
or prednisolone). Concurrent use of
corticosteroids that are metabolized by CYP3A including
budesonide, dexamethasone, methylprednisolone,
prednisone, or inhaled betamethasone,
ciclesonide, fluticasone, mometasone, and triamcinolone
mayqrisk of Cushing’s disease and adrenal
suppression (consider use of other corticosteroids,
such as beclomethasone or prednisolone).qlevels and
effects of bosentan (initiate bosentan at 62.5 mg daily
or every other day if already receiving elvitegravir/cobicistat/
emtricitabine/tenofovir for at least 10 days, if already
receiving bosentan discontinue at least 36 hr
prior to starting elvitegravir/cobicistat/emtricitabine/
tenofovir; after 10 days, bosentan may be restarted at
62.5 mg daily or every other day).qlevels and risk of
adverse effect with atorvastatin (initiate atorvastatin at
lowest dose and titrate cautiously).qlevels of norgestimate
andplevels of ethinyl estradiol (due to unpredictable
effects, non-hormonal contraception
should be considered).qlevels and effects of immunosuppressants
including cyclosporine, sirolimus,
and tacrolimus, careful monitoring recommended.q
levels and risk of adverse cardiovascular reactions with
salmeterol, concurrent use is not recommended.q
blood levels and effects of neuroleptics including
perphenazine, risperidone, and thioridazine,
neuroleptic dose may need top. Mayqlevels of quetiapine;
if taking quetiapine when initiating therapy,
consider alternative antiretroviral therapy orpquetiapine
dose to 1⁄6 of the original dose and monitor for
adverse effects.qlevels and risk of serious cardiovascular
adverse effects from PDE5 inhibitors including
sildenafil, tadalafil, and vardenafil(for pulmonary
hypertension—sildenafil is contraindicated; in patients
who have received elvitegravir/cobicistat/emtricitabine/
tenofovir for at least 7 days, tadalafil may be
started at 20 mg/day and carefully titrated if necessary
to 40 mg/day; in patients already receiving tadalafil, discontinue
for at least 24 hr before initiating elvitegravir/
cobicistat/emtricitabine/tenofovir; after 7 days, resume
at 20 mg/day and titrate as necessary to 40 mg/day; for
erectile dysfunction—sildenafil dose should not exceed
25 mg in 48 hr, vardenafil dose should not exceed
2.5 mg in 72 hr, and tadalafil dose should not exceed
10 mg in 72 hr).qlevels and risk of sedation with sedative/
hypnotics including midazolam, clorazepate,
diazepam, estazolam, flurazepam, buspirone,
and zolpidem; concurrent use with oral midazolam is
contraindicated, dose reduction of parenteral midazolam
should be considered, clinical monitoring and
dose reduction if necessary is recommended for others.
Ledipasvir/sofosbuvir mayqtenofovir levels.
Drug-Natural Products: St. John’s wort may significantlyplevels/
effectiveness of cobicistat and elvitegravir
andqrisk of resistance; concurrent use contraindicated.
Route/Dosage
PO (Adults and Children 12 yr and 35 kg): One
tablet once daily.
Availability
Tablets: elvitegravir 150 mg/cobicistat 150 mg/emtricitabine
200 mg/tenofovir 300 mg.
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