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:

Female patients 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.

Hepatitis B (may cause severe acute exacerbation).

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, POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B

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:

Concurrent administration of other drugs that depend mainly on CYP3A for metabolism and whose blood levels, when ↑, are associated with serious/life-threatening adverse reactions including 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/effectiveness of cobicistat and elvitegravir and ↑ risk of resistance; concurrent use contraindicated.
Nephrotoxic agents, including NSAIDs↑ risk of nephrotoxicity; avoid concurrent use
Drugs that induce CYP3A will ↓ levels/effectiveness of elvitegravir and cobicistat
Drugs that inhibit CYP3A will also ↑ levels/effectiveness of cobicistat
Acyclovir, cidofovir, ganciclovir, valacyclovir, and valganciclovir may ↓ renal elimination of emtricitabine and tenofovir, ↑ levels and effects.
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 at least 2 hr.
↑blood 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; ↓ dose of clarithromycin by 50% in patients with CCr 50–60 mL/min.
Oxcarbazepine may ↓ levels/effectiveness of cobicistat and elvitegravir; consider using alternative anticonvulsant
May ↑ levels of clonazepam and ethosuximide; clinical monitoring recommended.
↑levels and risk of adverse effects with SSRIs (except for sertraline), tricyclic antidepressants, and trazodone; careful titration and monitoring recommended.
↑levels 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.
↑levels 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 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.
Concurrent use with rifabutin or rifapentine may significantly ↓ levels/effectiveness of cobicistat and elvitegravir and may foster resistance, concurrent use is not recommended.
May ↑ levels and effects of beta blockers including metoprolol and timolol; careful monitoring is recommended, ↓ dose of beta blocker if necessary.
May ↑ levels 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 betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, prednisone, and triamcinolone, may ↓ levels/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's disease and adrenal suppression; consider use of other corticosteroids, such as beclomethasone or prednisolone.
↑levels 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.
↑levels and risk of adverse effect with atorvastatin; initiate atorvastatin at lowest dose titrate cautiously; do not exceed dose of 20 mg/day.
↑levels of norgestimate and levonorgestrel and ↓ levels of ethinyl estradiol; consider using nonhormonal contraception.
↑risk of hyperkalemia with contraceptives containing drospirenone; closely monitor serum potassium concentrations.
↑levels and effects of immunosuppressants including cyclosporine, sirolimus, and tacrolimus; careful monitoring recommended.
↑levels and risk of adverse cardiovascular reactions with salmeterol; concurrent use is not recommended.
↑blood levels and effects of neuroleptics including perphenazine, risperidone, and thioridazine; neuroleptic dose may need to ↓.
May ↑ levels of quetiapine; if taking quetiapine when initiating therapy, consider alternative antiretroviral therapy or ↓ quetiapine dose to ⅙ of the original dose and monitor for adverse effects
↑levels 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).
↑levels and risk of sedation with 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 ↑ tenofovir levels.
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/toxicity of buprenorphine and ↓ levels of naloxone; carefully monitor for sedation and altered cognitive effects.
May ↑ levels of fentanyl, and tramadol; monitor for respiratory depression; consider ↓ tramadol dose.
May ↑ levels of and risk of bleeding 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/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 hepatitis B virus (HBV). Stribild is not approved for administration in patients with HIV and HBV. May cause acute exacerbations of hepatitis B. Monitor liver function in coinfected patients for several mo after stopping therapy.
- Determine serum phosphorous before initiating and periodically during therapy.
- Monitor liver function tests before and periodically during therapy, especially in patients with underlying liver disease or marked ↑ transaminase. May cause ↑ 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 and do not stop taking without consulting health care professional. 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.
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 professional 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 professional 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 professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
Rep: Advise patients to notify health care professional if pregnancy is planned or suspected. Advise patient to avoid breastfeeding during Stribild 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.

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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 ⬆