elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate

Elvitegravir

Absorption: Absorption follows oral administration.

Distribution: Unknown.

Protein Binding: 98–99%.

Metabolism/Excretion: Metabolized by the CYP3A isoenzyme; 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/Excretion: Metabolized by the CYP3A isoenzyme and to a small extent by the CYP2D6 isoenzyme; 86.2 eliminated in feces; 8.2% in urine.

Half-Life: 3.5 hr.

Emtricitabine

Absorption: 93% absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Some metabolism, 86% renally excreted, 14% fecal excretion.

Half-Life: 10 hr.

Tenofovir Disoproxil Fumarate

Absorption: Tenofovir disoproxil fumarate is a prodrug, which is split into tenofovir, the active component.

Distribution: Absorption is enhanced by food.

Metabolism/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

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Severe hepatic impairment;
Concurrent use of alfuzosin, carbamazepine, ergot derivatives, lomitapide, lovastatin, lurasidone, phenobarbital, phenytoin, pimozide, rifampin, sildenafil (Revatio), simvastatin, triazolam, or St. John's wort;
Renal impairment (do not initiate if CCr <70 mL/min, discontinue if CCr <50 mL/min);
OB: Not recommended in pregnancy (significantly lower concentrations of elvitegravir and cobicistat);
Lactation: Breastfeeding not recommended in mothers with HIV.

Use Cautiously in:

Chronic hepatitis B virus (HBV) infection (may exacerbate following discontinuation);
Female or obese patients (may be at ↑ risk for lactic acidosis/hepatic steatosis);
Pedi: Children <12 yr (safety and effectiveness not established);
Geri: Older adults may be more sensitive to drug effects; consider age-related ↓ in renal, hepatic, and cardiovascular function as well as concurrent disease states and medications.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash, hyperpigmentation

Endo: Graves disease

F and E: hypophosphatemia

GU: ↑serum creatinine, proteinuria, ACUTE RENAL FAILURE/FANCONI SYNDROME

GI: diarrhea, nausea, autoimmune hepatitis, LACTIC ACIDOSIS/HEPATOMEGALY WITH STEATOSIS

Metab: hyperlipidemia

MS: bone pain, ↓bone mineral density, muscle pain, osteomalacia, polymyositis

Neuro: abnormal dreams, dizziness, Guillain-Barré syndrome, headache, insomnia, drowsiness

Misc: immune reconstitution syndrome.

Interactions ⬆ ⬇

Drug-drug:

May significantly ↑ levels and risk of toxicity of alfuzosin, dihydroergotamine, ergotamine, lomitapide, lovastatin, lurasidone, methylergonovine, pimozide, sildenafil (when used for pulmonary hypertension), simvastatin, and triazolam; concurrent use contraindicated.
Carbamazepine, phenobarbital, phenytoin, or rifampin may significantly ↓ levels and effectiveness of cobicistat and elvitegravir and ↑ risk of resistance; concurrent use contraindicated.
Nephrotoxic agents, including NSAIDs, ↑ risk of nephrotoxicity; avoid concurrent use.
Acyclovir, cidofovir, ganciclovir, valacyclovir, and valganciclovir may ↑ levels and risk of toxicity of emtricitabine and tenofovir.
Antacids or laxatives containing aluminum or magnesium, as well as calcium supplements, iron supplements, zinc supplements, multivitamins, and sucralfate, may ↓ levels and effectiveness of elvitegravir; separate administration by ≥2 hr.
May ↑ levels and risk of toxicity of 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; ↓ dose of clarithromycin by 50% in patients with CCr 50–60 mL/min.
Oxcarbazepine may ↓ levels and effectiveness of cobicistat and elvitegravir; consider using alternative anticonvulsant.
May ↑ levels and risk of toxicity of clonazepam and ethosuximide; clinical monitoring recommended.
May ↑ levels and risk of toxicity of SSRIs (except for sertraline), tricyclic antidepressants, and trazodone; careful titration and monitoring recommended.
May ↑ levels and risk of toxicity of itraconazole, ketoconazole, and voriconazole; maximum daily dose of ketoconazole or itraconazole should not exceed 300 mg; use voriconazole with extreme caution. These azole antifungals may also ↑ levels of cobicistat and elvitegravir.
May ↑ levels and risk of toxicity of 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 3 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.
Rifabutin or rifapentine may ↓ levels and effectiveness of cobicistat and elvitegravir and may foster resistance; concurrent use not recommended.
May ↑ levels and risk of toxicity of beta blockers; careful monitoring recommended; ↓ dose of beta blocker if necessary.
May ↑ levels and risk of toxicity of calcium channel blockers; careful monitoring recommended.
Concurrent use of corticosteroids that induce CYP3A, including betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, prednisone, and triamcinolone, may ↓ levels and effectiveness and ↑ risk of resistance to elvitegravir; consider use of other corticosteroids, such as beclomethasone or prednisolone.
Concurrent use of corticosteroids that are CYP3A substrates, including betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, prednisone, and triamcinolone, may ↑ risk of Cushing disease and adrenal suppression; consider use of other corticosteroids, such as beclomethasone or prednisolone.
May ↑ levels and risk of toxicity 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.
May ↑ levels and risk of toxicity of atorvastatin; initiate atorvastatin at lowest dose titrate cautiously; do not exceed dose of 20 mg/day.
May ↑ levels and risk of toxicity of norgestimate and levonorgestrel and ↓ levels and effectiveness of ethinyl estradiol; consider using nonhormonal contraception.
↑risk of hyperkalemia with contraceptives containing drospirenone; closely monitor serum potassium concentrations.
May ↑ levels and risk of toxicity of immunosuppressants, including cyclosporine, sirolimus, and tacrolimus; careful monitoring recommended.
May ↑ levels and risk of toxicity of salmeterol; concurrent use not recommended.
May ↑ levels and risk of toxicity of neuroleptics, including perphenazine, risperidone, and thioridazine; neuroleptic dose may need to ↓.
May ↑ levels and risk of toxicity of quetiapine; if taking quetiapine when initiating therapy, consider alternative antiretroviral therapy or ↓ quetiapine dose to ⅙ of the original dose.
May ↑ levels and risk of toxicity of 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).
May ↑ levels and risk of sedation of sedative/hypnotics, including midazolam, clorazepate, diazepam, estazolam, buspirone, and zolpidem; concurrent use with oral midazolam is contraindicated; dose ↓ of parenteral midazolam should be considered; clinical monitoring and dose reduction if necessary is recommended for others.
Ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir may ↑ levels and risk of toxicity of tenofovir.
May ↑ bleeding risk with rivaroxaban; avoid concurrent use.
May ↑ bleeding risk with apixaban; if taking apixaban 5–10 mg twice daily, ↓ apixaban dose by 50%; if taking apixaban 2.5 mg twice daily, avoid concurrent use.
May ↑ bleeding risk with dabigatran; may need to avoid concurrent use if patient has moderate or severe renal impairment (depends on dabigatran indication).
May ↑ bleeding risk with edoxaban; ↓ edoxaban dose by 50% when used for venous thromboembolism treatment in patients with moderate or severe renal impairment.
May ↑ levels and risk of toxicity of buprenorphine and ↓ levels and effectiveness of naloxone; carefully monitor for sedation and altered cognitive effects.
May ↑ levels and risk of toxicity of fentanyl and tramadol; monitor for respiratory depression; consider ↓ tramadol dose.
May ↑ bleeding risk with ticagrelor; concurrent use not recommended.
May ↓ antiplatelet effects of clopidogrel, which may ↑ risk of thrombosis; concurrent use not recommended.

Drug-Natural Products:

St. John's wort may significantly ↓ levels and effectiveness of cobicistat and elvitegravir and ↑ risk 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

Assessment ⬆ ⬇

Assess for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
Monitor bone mineral density in patients who have a history of pathologic bone fracture or are at risk for osteoporosis or bone loss. Consider calcium and vitamin D supplementation.

Lab Test Considerations:

Monitor viral load and CD4 cell count regularly during therapy.
- Assess for HBV. Stribild is not approved for administration in patients with HIV and HBV. If therapy is discontinued, may cause severe exacerbation of HBV. Monitor liver function in coinfected patients for several months after stopping therapy.
- Monitor liver function tests prior to, during, and following therapy.
- Determine serum phosphorous before initiating and periodically during therapy.
- May ↑ serum creatinine, AST, ALT, total bilirubin, total cholesterol, LDL, amylase, and triglycerides. Lactic acidosis may occur with hepatic toxicity causing hepatic steatosis; may be fatal, especially in women.
- Monitor serum creatinine, CCr, urine glucose, and urine protein prior to and periodically during therapy. CCr should be >70 mL/min before starting therapy. In patients with chronic kidney disease, assess CCr, serum phosphorus, urine glucose, and urine protein prior to and periodically during therapy. May cause hypophosphatemia in patients with renal impairment. Assess patients with persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness for proximal renal tubulopathy; evaluate renal function promptly.

Implementation ⬆ ⬇

Do not confuse elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate with elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide.
PO: Administer once daily with food.

Patient/Family Teaching ⬆ ⬇

Emphasize the importance of taking Stribild as directed, at the same time each day. Do not take more than prescribed amount. Take missed doses with a meal if remembered unless almost time for next dose; do not double doses. Advise patient to read Patient Information prior to starting therapy and with each Rx refill in case of changes.
Do not stop taking without consulting health care provider. Discontinuing therapy may lead to severe exacerbations. Inform patient of importance of HBV testing before starting antiretroviral therapy.
Advise patient to take antacids 2 hr before or 4 hr after and H₂ antagonists 12 hr before or 4 hr after Stribild.
Instruct patient that Stribild should not be shared with others.
Inform patient that Stribild does not cure HIV or prevent associated or opportunistic infections. Stribild may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading HIV to others. Advise patient that the long-term effects of Stribild are unknown at this time.
Advise patient to notify health care provider immediately if symptoms of lactic acidosis (nausea, vomiting, unusual or unexpected stomach discomfort, and weakness) occur.
Immune reconstitution syndrome may trigger opportunistic infections or autoimmune disorders. Notify health care provider if symptoms (signs and symptoms of an infection or inflammation) occur.
May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications, especially St. John's wort.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Encourage women who become pregnant during Stribild therapy to join the Antiviral Pregnancy Registry that monitors pregnancy outcomes in women exposed to Stribild during pregnancy. Enroll patient by calling 1-800-258-4263.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆