da-RU-na-veer

• HIV infection (must be used with ritonavir and with other antiretrovirals).

• Inhibits HIV-1 protease, selectively inhibiting the cleavage of HIV-encoded specific polyproteins in infected cells. This prevents the formation of mature virus particles.

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

Absorption: Without ritonavir — 37% absorbed following oral administration; with ritonavir — 82%. Food ↑ absorption by 30%.

Distribution: Unknown.

Protein Binding: 95% bound to plasma proteins.

Metabolism/Excretion: Extensively metabolized by CYP3A enzyme system. 41% eliminated unchanged in feces, 8% in urine.

Half-life: 15 hr.

Contraindicated in:

• Concurrent use of alfuzosin, dronedarone, colchicine (in renal/hepatic impairment), elbasvir/grazoprevir, ergot derivatives, ivabradine, lomitapide, lovastatin, lurasidone, midazolam (PO), naloxegol, pimozide, ranolazine, rifampin, sildenafil (Revatio), simvastatin, triazolam, or St. John's wort
• Lactation: Avoid breastfeeding in mothers infected with HIV.

Use Cautiously in:

• Hepatic impairment
• Sulfa allergy
• OB: Considered a preferred protease inhibitor (when combined with ritonavir) for pregnant females living with HIV who are antiretroviral-nave (as initial therapy), who have had antiretroviral therapy in the past but are restarting, or who require a new antiretroviral regimen (due to poor tolerance or poor virologic response of current regimen)
• Pedi: Children <3 yr (safety and efficacy not established)
• Geri: Consider age-related impairment in hepatic function, concurrent chronic disease states and drug therapy in older adults.

Based on concurrent use with ritonavir

Derm: DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, rash, acute generalized exanthematous pustulosis.

Endo: Graves' disease, hyperglycemia.

GI: HEPATOTOXICITY, autoimmune hepatitis, constipation, diarrhea, nausea, vomiting.

Metab: body fat redistribution.

MS: polymyositis.

Neuro: Guillan-Barré syndrome.

Misc: immune reconstitution syndrome.

Drug-Drug:

• May ↑ 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.
• May ↑ colchicine levels and cause serious/life-threatening reactions; ↓ dose of colchicine; concurrent use contraindicated in patients with renal or hepatic impairment.
• Rifampin↑ metabolism and may ↓ antiretroviral effectiveness, concurrent use is contraindicated.
• Concurrent use with indinavir may ↑ darunavir and indinavir levels.
• ↑levels and risk of myopathy from atorvastatin, rosuvastatin, or pravastatin; use lowest dose of these agents; do not exceed atorvastatin dose of 20 mg/day.
• Concurrent use with efavirenz results in ↓ darunavir levels and ↑ efavirenz levels; use combination cautiously.
• Lopinavir/ritonavir may ↓ levels; concurrent use not recommended.
• Saquinavir may ↓ levels; concurrent use not recommended.
• May ↑ maraviroc levels; ↓ maraviroc dose to 150 mg twice daily.
• May ↑ levels of lidocaine, quinidine, disopyramide, mexiletine, propafenone, flecainide, and amiodarone; use cautiously and with available blood level monitoring.
• ↑digoxin levels; blood level monitoring recommended.
• May ↑ carbamazepine levels; blood level monitoring recommended.
• May ↓ phenytoin or phenobarbital levels; blood level monitoring recommended.
• May ↑ clonazepam levels.
• May ↓ levels of warfarin; monitor INR.
• May ↑ levels of trazodone, amitriptyline, desipramine, imipramine, and nortriptyline; use cautiously and ↓ dose if necessary.
• May ↑ levels of clarithromycin; ↓ dose of clarithromycin if CCr 60 mL/min.
• May ↑ levels of ketoconazole, isavuconazole, and itraconazole; do not exceed itraconazole or ketoconazole dose >200 mg/day.
• Ketoconazole, isavuconazole, itraconazole, and posaconazole may ↑ levels.
• May ↓ levels of voriconazole; concurrent use not recommended.
• Concurrent use with rifabutin↑ rifabutin levels and ↑ darunavir levels (may be due to ritonavir); ↓ rifabutin dose to 150 mg every other day.
• Rifapentin may ↓ levels; concurrent use not recommended.
• May ↑ levels of beta-blockers; may need to ↓ dose.
• May ↑ levels of amlodipine, diltiazem, felodipine, nifedipine, nicardipine, or verapamil; monitor clinical response carefully.
• Dexamethasone may ↓ levels/effects; consider use of alternative corticosteroid, such as beclomethasone or prednisolone.
• May ↑ levels of systemic, inhaled, nasal, or ophthalmic corticosteroids (betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, or triamcinolone; consider alternative corticosteroid such as beclomethasone, prednisone, or prednisolone.
• May ↑ levels of cyclosporine, tacrolimus, or sirolimus; blood level monitoring recommended.
• May ↑ levels of everolimus; concurrent use not recommended.
• May ↑ levels of irinotecan; discontinue darunavir/ritonavir 1 wk before starting irinotecan therapy.
• May ↓ levels of methadone; may need to ↑ dose.
• May ↑ risperidone and thioridazine levels; may need to ↓ dose.
• May ↑ levels of sildenafil, vardenafil, tadalafil, or avanafil; single dose should not exceed the following (sildenafil 25 mg in 48 hr; vardenafil 2.5 mg in 72 hr; tadalafil 10 mg in 72 hr); concurrent use with avanafil not recommended.
• May ↓ levels of sertraline and paroxetine; adjust dose by clinical response.
• May ↓ levels and contraceptive efficacy of some combined hormonal contraceptives and progestin-only contraceptives (alternative methods of nonhormonal contraception recommended).
• May ↑ risk of hyperkalemia when used with drospirenone.
• May ↑ levels of salmeterol; concurrent use not recommended.
• May ↑ bosentan levels; initiate bosentan at 62.5 mg once daily or every other day once patient receiving darunavir for 10 days; if patient already receiving bosentan, discontinue bosentan 36 hr before initiation of darunavir and then restart bosentan 10 days later at 62.5 mg once daily or every other day.
• May ↑ tadalafil (Adcirca) levels; initiate tadalafil (Adcirca) at 20 mg once daily once patient receiving darunavir for 1 wk; if patient already receiving tadalafil (Adcirca), discontinue tadalafil (Adcirca) 24 hr before initiation of darunavir and then restart tadalafil (Adcirca) 7 days later at 20 mg once daily.
• May ↑ lumefantrine levels and risk of QT interval prolongation.
• May ↑ quetiapine levels; consider alternative antipsychotic therapy; if not possible, ↓ quetiapine dose to 1/6 of current dose.
• May ↑ levels of and risk of bleeding with apixaban, dabigatran, and rivaroxaban; concurrent use not recommended.
• May ↑ dasatinib and nilotinib levels; may need to ↓ dose or ↑ dosing interval of dasatinib and nilotinib.
• May ↑ vinblastine and vincristine levels; may need to temporarily hold darunavir-ritonavir or initiate another antiretroviral regimen.
• May ↑ levels of buspirone, diazepam, estazolam, midazolam (IV), and zolpidem; ↓ dose of sedative.
• May ↓ omeprazole levels; consider ↑ omeprazole dose (not to exceed 40 mg/day).
• May ↑ levels of glecaprevir/pibrentasvir; concurrent use not recommended.
• May ↑ ticagrelor levels and risk of bleeding; concurrent use not recommended.
• May ↓ antiplatelet effects of clopidogrel; concurrent use not recommended.
• May ↑ fesoterodine and solifenacin levels; should not exceed fesoterodine dose of 4 mg once daily or solifenacin dose of 5 mg once daily.
• May ↑ levels/risk of respiratory depression with opioids including buprenorphine, buprenorphine/naloxone, fentanyl, and tramadol; carefully monitor opioid effects when cobicistat with darunavir is initiated, dose adjustment of opioid may be necessary.

Drug-Natural Products:

• St. John's wort↑ metabolism and may ↓ antiretroviral effectiveness; concurrent use contraindicated.

• PO (Adults): Therapy-naive — 800 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution) — 800 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with 1 darunavir resistance associated substitution or if genotypic testing not performed) — 600 mg twice daily with ritonavir 100 mg twice daily; Pregnancy — 600 mg twice daily with ritonavir 100 mg twice daily; if patient taking 800 mg once daily with ritonavir 100 mg once daily before pregnancy, may continue with this regimen if they are virologically suppressed (HIV-1 RNA <50 copies/mL), and if switch to twice daily regimen may compromise tolerability or compliance.
• PO, (Oral suspension or tablets) (Children 3–17 yr and 40 kg): Therapy-naive — 800 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution) — 800 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with 1 darunavir resistance associated substitution or if genotypic testing not performed) — 600 mg twice daily with ritonavir 100 mg twice daily.
• PO, (Oral suspension or tablets) (Children 3–17 yr and 30–39.9 kg): Therapy-naive — 675 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution) — 675 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with 1 darunavir resistance associated substitution or if genotypic testing not performed) — 450 mg twice daily with ritonavir 60 mg twice daily.
• PO, (Oral suspension or tablets) (Children 3–17 yr and 15–29.9 kg): Therapy-naive — 600 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution) — 600 mg once daily with ritonavir 100 mg once daily; Therapy-experienced (with 1 darunavir resistance associated substitution or if genotypic testing not performed) — 375 mg twice daily with ritonavir 48 mg twice daily.
• PO, (Oral suspension only) (Children 3–17 yr and 14–14.9 kg): Therapy-naive — 490 mg once daily with ritonavir 96 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution) — 490 mg once daily with ritonavir 96 mg once daily; Therapy-experienced (with 1 darunavir resistance associated substitution or if genotypic testing not performed) — 280 mg twice daily with ritonavir 48 mg twice daily.
• PO, (Oral suspension only) (Children 3–17 yr and 13–13.9 kg): Therapy-naive — 455 mg once daily with ritonavir 80 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution) — 455 mg once daily with ritonavir 80 mg once daily; Therapy-experienced (with 1 darunavir resistance associated substitution or if genotypic testing not performed) — 260 mg twice daily with ritonavir 40 mg twice daily.
• PO, (Oral suspension only) (Children 3–17 yr and 12–12.9 kg): Therapy-naive — 420 mg once daily with ritonavir 80 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution) — 420 mg once daily with ritonavir 80 mg once daily; Therapy-experienced (with 1 darunavir resistance associated substitution or if genotypic testing not performed) — 240 mg twice daily with ritonavir 40 mg twice daily.
• PO, (Oral suspension only) (Children 3–17 yr and 11–11.9 kg): Therapy-naive — 385 mg once daily with ritonavir 64 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution) — 385 mg once daily with ritonavir 64 mg once daily; Therapy-experienced (with 1 darunavir resistance associated substitution or if genotypic testing not performed) — 220 mg twice daily with ritonavir 32 mg twice daily.
• PO, (Oral suspension only) (Children 3–17 yr and 10–10.9 kg): Therapy-naive — 350 mg once daily with ritonavir 64 mg once daily; Therapy-experienced (with no darunavir resistance associated substitution) — 350 mg once daily with ritonavir 64 mg once daily; Therapy-experienced (with 1 darunavir resistance associated substitution or if genotypic testing not performed) — 200 mg twice daily with ritonavir 32 mg twice daily.

• PO: Must be administered with a meal or light snack along with ritonavir 100 mg to be effective. The type of food is not important. Tablets should be swallowed whole with water or milk; do not chew.
  • Administer oral suspension 8 mL dose as two 4-mL doses using syringe provided along with ritonavir and food.

Prezista

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: protease inhibitors

(Generic available)

• Oral suspension: 100 mg/mL;
• Tablets: 75 mg; 150 mg; 600 mg; 800 mg;
• In combination with: cobicistat (Prezcobix); cobicistat, emtricitabine, tenofovir alafenamide (Symtuza). See Appendix [not included in this PDA edition].