darunavir

REMS

HIV infection (in combination with ritonavir and other antiretrovirals).

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

Endo: Graves' disease, hyperglycemia.

GI: autoimmune hepatitis, constipation, diarrhea, HEPATOTOXICITY, 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.
↑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.
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 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's disease and adrenal suppression; 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, edoxaban, and rivaroxaban; concurrent use with rivaroxaban 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.

(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].

Genotypic testing of the baseline virus is recommended prior to initiating treatment in therapy-experienced patients. This testing is performed to screen for darunavir resistance associated substitutions, which may be helpful in determining whether the HIV virus will be susceptible to darunavir.

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.

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

Therapeutic Effects:

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

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: protease inhibitors

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.

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2.5–4 hr	12 hr

Emphasize the importance of taking darunavir with ritonavir exactly as directed, at evenly spaced times throughout day. Do not take more than prescribed amount and do not stop taking without consulting health care professional. If a dose of darunavir or ritonavir is missed by more than 6 hr, wait and take next dose at regularly scheduled time. If missed by less than 6 hr, take darunavir and ritonavir immediately and then take next dose at regularly scheduled time. If a dose is skipped, do not double doses. Advise patient to read the Patient Information sheet before starting therapy and with each Rx renewal in case changes have been made.
Instruct patient that darunavir should not be shared with others.
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.
Inform patient that darunavir does not cure AIDS or prevent associated or opportunistic infections. Darunavir may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom during sexual contact and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others. Advise patient that the long-term effects of darunavir are unknown at this time.
Inform patient that darunavir may cause hyperglycemia, hepatotoxicity, and severe skin reactions. Advise patient to notify health care professional promptly if signs of hyperglycemia (increased thirst or hunger; unexplained weight loss; increased urination; fatigue; or dry, itchy skin), hepatotoxicity (unexplained fatigue, anorexia, nausea, jaundice, abdominal pain, or dark urine), DRESS, or rash occur.
Advise patient to notify health care professional if signs and symptoms of immune reconstitution syndrome (signs and symptoms of an infection) 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.
Rep: Instruct females of reproductive potential using hormonal contraceptives to use an alternative nonhormonal method of contraception. Advise patient to notify health care professional if pregnancy is planned or suspected and to avoid breast feeding. If pregnant patient is exposed to darunavir, register patient in Antiretroviral Pregnancy Registry by calling 1-800-258-4263 to monitor pregnancy outcomes.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

NDC Code^*

50090- A-S Medication Solutions
50090-1491- PREZISTA 50090-1491-0- 60 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (50090-1491-0)

59676- Janssen Products LP
59676-562- PREZISTA 59676-562-01- 60 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (59676-562-01)

59676- Janssen Products LP
59676-563- PREZISTA 59676-563-01- 480 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (59676-563-01)

59676- Janssen Products LP
59676-564- PREZISTA 59676-564-01- 240 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (59676-564-01)

59676- Janssen Products LP
59676-565- PREZISTA 59676-565-01- 1 BOTTLE, GLASS in 1 CARTON (59676-565-01) > 200 mL in 1 BOTTLE, GLASS

59676- Janssen Products LP
59676-566- PREZISTA 59676-566-30- 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (59676-566-30)

70518- REMEDYREPACK INC.
70518-0689- PREZISTA 70518-0689-0- 30 TABLET, FILM COATED in 1 BLISTER PACK (70518-0689-0)

70518- REMEDYREPACK INC.
70518-1483- PREZISTA 70518-1483-0- 30 TABLET, FILM COATED in 1 BLISTER PACK (70518-1483-0)

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