elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide

Elvitegravir

Absorption: Absorption follows oral administration.

Distribution: Unknown.

Protein Binding: 98–99%.

Metabolism/Excretion: Metabolized by the liver via 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 liver via the CYP3A isoenzyme and to a lesser extent by the CYP2D6 isoenzyme; 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/Excretion: Some metabolism; 86% eliminated in urine, 14% in feces.

Half-Life: 10 hr.

Tenofovir Alafenamide

Absorption: Tenofovir alafenamide is a prodrug, which is hydrolyzed into tenofovir, the active component; absorption enhanced by high-fat meals.

Distribution: Unknown.

Metabolism/Excretion: Tenofovir is phosphorylated to tenofovir diphosphate (active metabolite); 32% excreted in feces, <1% in urine.

Half-Life: 0.51 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

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 alafenamide PO	unknown	0.5 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;
Severe renal impairment or end-stage renal disease not receiving hemodialysis;
Severe hepatic impairment;
OB: Not recommended in pregnancy (significantly lower concentrations of elvitegravir and cobicistat);
Lactation: Breastfeeding not recommended in women with HIV.

Use Cautiously in:

Female patients or obese patients (may be at ↑ risk for lactic acidosis/hepatic steatosis);
Chronic hepatitis B virus (HBV) infection (may exacerbate following discontinuation);
Concurrent use of nephrotoxic drugs (↑ risk of renal impairment);
Pedi: Children 25 kg (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.

HBV (may cause severe acute exacerbation).

Adv. Reactions/Side Effects ⬆ ⬇

Endo: Graves' disease

F and E: hypophosphatemia

GI: nausea, autoimmune hepatitis, diarrhea, LACTIC ACIDOSIS/HEPATOMEGALY WITH STEATOSIS, POST-TREATMENT ACUTE EXACERBATION OF HBV

GU: proteinuria, ACUTE RENAL FAILURE/FANCONI SYNDROME

Metab: hyperlipidemia

MS: polymyositis

Neuro: Guillain-Barré syndrome, headache

Misc: fatigue, 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/effectiveness of cobicistat and elvitegravir and ↑ risk of resistance; concurrent use contraindicated.
Nephrotoxic agents, including NSAIDs and aminoglycosides, may ↑ risk of nephrotoxicity; avoid concurrent use.
Acyclovir, cidofovir, ganciclovir, valacyclovir, and valganciclovir may ↓ renal elimination and ↑ levels/toxicity of emtricitabine and tenofovir alafenamide.
May ↑ levels/toxicity of amiodarone, digoxin, disopyramide, flecainide, lidocaine, mexiletine, propafenone and quinidine; careful monitoring recommended.
May alter effects of warfarin; careful monitoring of INR recommended.
Concurrent use with clarithromycin may ↑ levels/toxicity of clarithromycin and/or cobicistat (for patients with CCr 50–60 mL/min, ↓ dose of clarithromycin by 50%).
May ↑ levels/toxicity of ethosuximide; clinical monitoring recommended.
Oxcarbazepine may ↓ levels/effectiveness of cobicistat, elvitegravir, and tenofovir alafenamide; consider using alternative anticonvulsant.
May ↑ levels/toxicity of SSRIs (except sertraline), tricyclic antidepressants, and trazodone; careful titration and monitoring recommended.
Concurrent use with itraconazole, ketoconazole, or voriconazole may ↑ levels/toxicity of itraconazole, ketoconazole, voriconazole, elvitegravir, and cobicistat (max dose of ketoconazole or itraconazole = 300 mg/day; assess risk vs. benefit before using voriconazole).
May ↑ levels/toxicity of colchicine; concurrent use contraindicated in renal or hepatic impairment; Dosing adjustment for gout flares: 0.6 mg, then 0.3 mg 1 hr later, do not repeat for ≥3 days; Dosing adjustment for gout flare prophylaxis: 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 once daily; Dosing adjustment for 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/effectiveness of cobicistat, elvitegravir, and tenofovir alafenamide and may foster resistance; concurrent use not recommended.
May ↑ levels/toxicity of beta blockers; careful monitoring recommended; ↓ dose of beta blocker if necessary.
May ↑ levels/toxicity of calcium channel blockers including amlodipine, diltiazem, felodipine, nicardipine, nifedipine, and verapamil; careful monitoring recommended.
Concurrent use of corticosteroids that are CYP3A inducers, 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.
May ↑ levels/toxicity of bosentan; initiate bosentan at 62.5 mg once daily or every other day if already receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for ≥10 days; if already receiving bosentan, discontinue bosentan ≥36 hr prior to starting elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide; after 10 days, bosentan may be restarted at 62.5 mg once daily or every other day.
May ↑ levels/toxicity of atorvastatin; initiate atorvastatin at lowest dose titrate cautiously; do not exceed dose of 20 mg/day.
May ↑ levels/toxicity of norgestimate and ↓ levels of ethinyl estradiol; due to unpredictable effects, nonhormonal contraceptive methods should be considered.
↑risk of hyperkalemia with contraceptives containing drospirenone; closely monitor serum potassium concentrations.
May ↑ levels/toxicity of immunosuppressants, including cyclosporine, sirolimus, and tacrolimus; careful monitoring recommended.
Cyclosporine may ↑ levels/toxicity of cobicistat and elvitegravir; careful monitoring recommended.
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 adverse cardiovascular effects with salmeterol, concurrent use not recommended.
↑levels/toxicity of neuroleptics, including perphenazine, risperidone, and thioridazine; may need to ↓ dose of neuroleptic.
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
May ↑ levels/toxicity of PDE5 inhibitors, including sildenafil, tadalafil, and vardenafil; Dosing adjustment for pulmonary hypertension: sildenafil is contraindicated; in patients who have received elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for ≥7 days, start tadalafil at 20 mg once daily and carefully titrate if tolerating to 40 mg once daily; in patients already receiving tadalafil, discontinue tadalafil for ≥24 hr before initiating elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide; after ≥1 wk, resume tadalafil at 20 mg once daily and titrate if tolerating to 40 mg once daily; Dosing adjustment 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/toxicity of sedative/hypnotics, including midazolam (parenteral), diazepam, buspirone, and zolpidem; consider dose ↓ of parenteral midazolam; clinical monitoring and dose ↓, if necessary, is recommended for other sedative/hypnotics.
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 treatment of venous thromboembolism in patients with moderate or severe renal impairment.
May ↑ bleeding risk with ticagrelor; concurrent use not recommended.
May ↓ antiplatelet effects of clopidogrel and ↑ risk of thromboembolic events; concurrent use not recommended.
Medications containing polyvalent cations, including calcium, magnesium, aluminum, iron, or zinc, may ↓ levels and effectiveness of elvitegravir; separate administration by ≥2 hr.

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 ≥25 kg): One tablet once daily.

Renal Impairment

PO (Adults ): CCr <15 mL/min AND receiving chronic hemodialysis: One tablet once daily (give after dialysis on dialysis days).

Availability ⬆ ⬇

Tablets: elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg

Assessment ⬆ ⬇

Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.

Lab Test Considerations:

Monitor viral load and CD4 count before and routinely during therapy to determine response.
- Assess for HBV. Genvoya is not approved for administration in patients with HIV and HBV. If therapy is discontinued, may cause severe exacerbation of hepatitis B. Monitor liver function in coinfected patients for several mo after stopping therapy.
- Monitor liver function tests prior to, during and following therapy. May cause ↑ LDL cholesterol, total cholesterol, and triglyceride concentrations. Lactic acidosis may occur with hepatic toxicity causing hepatic steatosis; may be fatal, especially in women. Discontinue therapy if symptoms occur.
- Calculate serum creatinine, CCr, urine glucose, and urine protein prior to and periodically during therapy and when clinically indicated. In patients with chronic kidney disease, assess serum creatinine, CCr, serum phosphorus, urine glucose, and urine protein prior to and periodically during therapy. May cause hypophosphatemia in patients with renal impairment.
- May cause hyperglycemia and glycosuria.

Implementation ⬆ ⬇

Do not confuse elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide with elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate.
PO: Administer once daily with food.
- Administer antacids at least 2 hr before or after medication.

Patient/Family Teaching ⬆ ⬇

Instruct patient on the importance of taking medication as directed, even if feeling better. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Discontinuing therapy may lead to severe exacerbations. Take missed doses as soon as 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. Caution patient not to share or trade Genvoya with others.
Inform patient of importance of HBV testing before starting antiretroviral therapy.
Advise patient if antacids containing aluminum, magnesium hydroxide, or calcium carbonate, take at least 2 hr before or after Genvoya.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
Advise patient to notify health care professional immediately if symptoms of lactic acidosis (nausea, vomiting, unusual or unexpected stomach discomfort; unusual muscle pain; difficulty breathing; feeling cold, especially in arms and legs; dizziness; fast or irregular heartbeat; and weakness or tiredness) liver problems (yellow skin or whites of eyes, dark urine, light-colored stools, loss of appetite, nausea, stomach pain) or signs of immune reconstitution syndrome (signs and symptoms of an infection or inflammation, can occur many months after start of therapy) occur.
Inform patient that Genvoya does not cure AIDS and may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and avoid sharing needles or donating blood to prevent spreading HIV to others.
Rep: Advise patient to notify health care professional if pregnancy is planned or suspected. Monitor viral load closely during pregnancy. Encourage patients who become pregnant during therapy to join the Antiretroviral Pregnancy Registry that monitors pregnancy outcomes in women exposed to Genvoya during pregnancy. Enroll patient by calling 1-800-258-4263. Advise female patient to avoid breastfeeding during therapy.
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 ⬆