darunavir/cobicistat/emtricitabine/tenofovir alafenamide

Drug-drug:

↑levels and risk of toxicity from alfuzosin, dronedarone, elbasvir/grazoprevir, ergot derivatives (dihydroergotamine, ergotamine, methylergonovine), ivabradine, lomitapide, lovastatin, lurasidone, midazolam (oral), pimozide, ranolazine, sildenafil (Revatio), simvastatin, and triazolam; concurrent use contraindicated.
May ↑ naloxegol levels, which can precipitate opioid withdrawal symptoms; concurrent use contraindicated.
Strong CYP3A4 inducers, including carbamazepine, phenobarbital, phenytoin, and rifampin, may ↓ levels and effectiveness of cobicistat, darunavir, and tenofovir; concurrent use contraindicated.
May ↑ levels and risk of toxicity of colchicine; concurrent use in patients with renal/hepatic impairment contraindicated; for others ↓ dose (for gout flare: 0.6 mg followed by 0.3 mg 1 hr later; may repeat no sooner than 3 days; for prophylaxis of gout flare: if dose was originally 0.6 mg twice daily, ↓ to 0.3 mg once daily; if original regimen was 0.6 mg once daily, ↓ to 0.3 mg every other day; for treatment of familial Mediterranean fever: not to exceed 0.6 mg once daily or 0.3 mg twice daily).
Clarithromycin and erythromycin may ↑ levels and risk of toxicity of darunavir and cobicistat; consider alternative anti-infectives.
May ↑ levels and risk of toxicity of dasatinib, nilotinib, vinblastine, and vincristine; careful monitoring for toxicity and dose adjustments recommended.
May ↑ bleeding risk with apixaban and rivaroxaban; may need to adjust apixaban dose; avoid concurrent use with rivaroxaban.
Effect on warfarin is not known; monitor INR.
Oxcarbazepine and eslicarbazepine may ↓ levels and effectiveness of cobicistat and tenofovir; consider alternative anticonvulsant or antiretroviral therapy.
May ↑ levels and risk of toxicity of clonazepam; careful anticonvulsant monitoring recommended.
May ↑ levels and risk of toxicity of tricyclic antidepressants and trazodone; careful dosing of antidepressants recommended (effect on SSRIs is unknown).
May ↑ levels and risk of toxicity of ketoconazole, isavuconazonium, and itraconazole; effect on voriconazole unknown; concurrent use with voriconazole not recommended.
Effects are unknown with artemether/lumefantrine; monitor for ↓ antimalarial activity or QT interval prolongation.
May ↑ levels and risk of toxicity of rifabutin; ↓ rifabutin dose to 150 mg every other day.
Rifapentine may ↓ levels and effectiveness of darunavir and tenofovir; concurrent use not recommended.
May ↑ levels and risk of toxicity of neuroleptics metabolized by CYP3A or CYP2D6, including perphenazine, risperidone, and thioridazine; ↓ dose of neuroleptic may be necessary.
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 and monitor for adverse effects.
May ↑ levels and risk of toxicity of beta blockers metabolized by CYP2D6, including metoprolol, carvedilol, and timolol; clinical monitoring recommended.
May ↑ levels and risk of toxicity of calcium channel blockers metabolized by CYP3A, including amlodipine, diltiazem, felodipine, nifedipine, or verapamil; careful monitoring recommended.
May ↑ levels and risk of toxicity of antiarrhythmics, including amiodarone, disopyramide, flecainide, mexiletine, propafenone, and quinidine; careful monitoring and titration is recommended.
May ↑ levels and risk of toxicity of digoxin; closely monitor digoxin levels and adjust dose as needed.
Dexamethasone may ↓ levels and effectiveness of cobicistat and darunavir; consider use of alternative corticosteroid, such as prednisone or prednisolone.
May ↑ levels of corticosteroids (all routes of administration) primarily metabolized by the CYP3A isoenzyme (e.g., betamethasone, budesonide, ciclesonide, fluticasone, methylprednisolone, mometasone, or triamcinolone), which may ↑ the risk of Cushing disease and adrenal suppression; consider alternative corticosteroid, such as beclomethasone, prednisone, or prednisolone.
Bosentan may ↑ levels and risk of toxicity of bosentan and ↓ levels and effectiveness of darunavir and cobicistat; dose alteration is required (initiating bosentan in patients already receiving darunavir/cobicistat/emtricitabine/tenofovir alafenamide for ≥10 days: bosentan 62.5 mg daily or every other day, depending on tolerance; initiating darunavir/cobicistat/emtricitabine/tenofovir alafenamide in patient already receiving bosentan: discontinue bosentan for 10 days; resume bosentan at 62.5 mg daily or every other day, depending on tolerance).
May ↑ levels and risk of toxicity of glecaprevir/pibrentasvir; concurrent use not recommended.
Nephrotoxic agents, including NSAIDs, ↑ risk of nephrotoxicity; avoid concurrent use.
May ↓ levels and contraceptive efficacy of some combined hormonal contraceptives; additional or alternative methods of nonhormonal contraception recommended.
May ↑ risk of hyperkalemia when used with drospirenone.
May ↑ levels and risk of toxicity of immunosuppressants metabolized by CYP3A, including cyclosporine, everolimus, sirolimus, and tacrolimus; therapeutic monitoring recommended.
May ↑ levels and risk of toxicity of irinotecan; discontinue darunavir/cobicistat/emtricitabine/tenofovir alafenamide ≥1 wk before starting irinotecan therapy.
May ↑ levels and risk of toxicity of salmeterol ; concurrent use not recommended.
May ↑ levels and risk of myopathy from atorvastatin, fluvastatin, pitavastatin, pravastatin, or rosuvastatin; use lowest dose of these agents; do not exceed atorvastatin or rosuvastatin dose of 20 mg/day.
May ↑ levels and risk of respiratory depression with opioids, including buprenorphine, buprenorphine/naloxone, fentanyl, oxycodone, and tramadol; carefully monitor for opioid effects; dose adjustment of opioid may be necessary.
May ↑ levels and risk of toxicity of PDE-5 inhibitors, including avanafil, sildenafil, tadalafil, and vardenafil; avanafil use is not recommended; sildenafil: use for pulmonary hypertension is contraindicated; when used for erectile dysfunction, single dose should not exceed 25 mg/48 hr; tadalafil: for pulmonary hypertension, initiating tadalafil in patients receiving darunavir/cobicistat/emtricitabine/tenofovir alafenamide for ≥7 days—20 mg once daily initially; may be titrated to 40 mg once daily; initiating darunavir/cobicistat/emtricitabine/tenofovir alafenamide in patients receiving tadalafil—discontinue tadalafil 24 hr prior to initiating therapy; after 7 days reinstitute tadalafil at 20 mg once daily; may be ↑ to 40 mg once daily; for erectile dysfunction, single dose should not exceed 10 mg/72 hr; vardenafil: for erectile dysfunction, single dose should not exceed 2.5 mg/72 hr.
May ↑ levels and risk of bleeding with ticagrelor; concurrent use not recommended.
May ↓ antiplatelet effects of clopidogrel; concurrent use not recommended.
May ↑ levels and risk of excess sedation/respiratory depression from some sedative/hypnotics metabolized by CYP3A, including buspirone, diazepam, and parenteral midazolam; concurrent with other sedative/hypnotics metabolized by CYP3A should be undertaken with caution; dose ↓ may be necessary.
May ↑ levels and risk of toxicity of fesoterodine and solifenacin; should not exceed fesoterodine dose of 4 mg once daily or solifenacin dose of 5 mg once daily.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness of cobicistat, darunavir, and tenofovir levels; concurrent use contraindicated.

Availability ⬆ ⬇

Tablets: darunavir 800 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥40 kg): One tablet (darunavir 800 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg) once daily.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Darunavir: Inhibits HIV-1 protease, selectively inhibiting the cleavage of HIV-encoded specific polyproteins in infected cells. This prevents the formation of mature virus particles. Cobicistat: Strongly inhibits CYP3A enzymes, enhancing systemic exposure to darunavir. Emtricitabine: Phosphorylated intracellularly, where it inhibits HIV reverse transcriptase, resulting in viral DNA chain termination. Tenofovir alafenamide: Phosphorylated intracellularly, where it inhibits HIV reverse transcriptase, resulting in disruption of DNA synthesis.

Therapeutic effects:

Increased CD4 cell counts and decreased viral load with subsequent slowed progression of HIV infection and its sequelae.

Classifications ⬆ ⬇

Therapeutic Classification: antiretrovirals, pharmacoenhancers

Pharmacologic Classification: protease inhibitors, enzyme inhibitors, nucleoside reverse transcriptase inhibitors

Pharmacokinetics ⬆ ⬇

Darunavir

Absorption: Food enhances oral absorption.

Distribution: Unknown.

Protein Binding: 95%.

Metabolism/Excretion: Extensively metabolized by the liver via the CYP3A isoenzyme; 41% excreted unchanged in feces, 8% in urine.

Half-Life: 9.4 hr.

Cobicistat

Absorption: Absorption follows oral administration.

Distribution: Unknown.

Protein Binding: 97–98%.

Metabolism/Excretion: Metabolized by the liver primarily by the CYP3A isoenzyme and to a lesser extent by the CYP2D6 isoenzyme; 86.2% excreted in feces, 8.2% in urine.

Half-Life: 3.2 hr.

Emtricitabine

Absorption: 93% absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Not significantly metabolized; 86% excreted in urine, 14% in feces.

Half-Life: 7.5 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: 0.5 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
Darunavir (PO)	unknown	3 hr	24 hr
Cobicistat (PO)	unknown	3 hr	24 hr
Emtricitabine (PO)	rapid	1.5 hr	24 hr
Tenofovir (PO)	unknown	0.5 hr	24 hr

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise to read Patient Information before starting therapy and with each Rx refill in case of changes. Instruct patient to take as directed, even if feeling better.
Do not take more than prescribed amount, and do not stop taking without consulting health care provider. Discontinuing therapy may lead to severe exacerbations.
Take missed doses as soon as remembered unless almost time for next dose; do not double doses. Caution patient not to share or trade tablets with others.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications, especially St. John's wort.
Inform patient of importance of HBV testing before starting antiretroviral therapy.
Inform patient that Symtuza does not cure HIV and may ↓ 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.
Advise patient to notify health care provider 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; 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) occur.
Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
Emphasize the importance of regular follow-up exams and blood counts to determine progress.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected. Encourage pregnant women to enroll in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263 to monitor pregnancy outcomes. Advise patient that pregnancy is not recommended during treatment and to avoid breastfeeding during therapy.

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Indications ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Classifications ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Pronunciation ⬆