darunavir


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Related to darunavir: Raltegravir

darunavir

(da-ru-na-veer) ,

Prezista

(trade name)

Classification

Therapeutic: antiretrovirals
Pharmacologic: protease inhibitors
Pregnancy Category: C

Indications

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

Action

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.

Pharmacokinetics

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 and Excretion: Extensively metabolized by CYP3A enzyme system. 41% eliminated unchanged in feces, 8% in urine.
Half-life: 15 hr.

Time/action profile

ROUTEONSETPEAKDURATION
POunknown2.5–4 hr12 hr

Contraindications/Precautions

Contraindicated in: Concurrent alfuzosin, sildenafil (Revatio), ergot derivatives, midazolam (PO), pimozide, triazolam, lovastatin, simvastatin, rifampin, or St. John's wort; Lactation: HIV may be transmitted in human milk; Pediatric: Children <3 yr.
Use Cautiously in: Hepatic impairment;Sulfa allergy; Geriatric: Consider age-related impairment in hepatic function, concurrent chronic disease states and drug therapy; Obstetric: Use only if maternal benefit outweighs fetal risk.

Adverse Reactions/Side Effects

Based on concurrent use with ritonavir

Gastrointestinal

  • hepatotoxicity (life-threatening)
  • constipation
  • diarrhea
  • nausea
  • vomiting

Endocrinologic

  • hyperglycemia

Metabolic

  • body fat redistribution

Dermatologic

  • stevens-johnson syndrome (life-threatening)
  • toxic epidermal necrolysis (life-threatening)
  • rash (most frequent)

Miscellaneous

  • immune reconstitution syndrome

Interactions

Drug-Drug interaction

Darunavir and ritonavir are both inhibitors of CYP3A and are metabolized by CYP3A. Multiple drug-drug interactions can be expected with drugs that share, inhibit, or induce these pathways. Consult product information for more specific details.↑ blood levels and risk of toxicity from ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine ), sildenafil (Revatio), alfuzosin, pimozide, lovastatin, simvastatin, midazolam (oral), and triazolam ; concurrent use is contraindicated.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.Lopivavir/ritonavir may ↓ levels; although concurrent use is not recommended, additional ritonavir may be required.Saquinavir may ↓ levels; concurrent use is not recommended.↑ levels of lidocaine, quinidine, 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.↓ levels of warfarin ; monitor INR.↑ levels of trazodone and desipramine ; use cautiously and ↓ dose if necessary.↑ levels of clarithromycin ; ↓ dose of clarithromycin if CCr ≤60 mL/min.↑ levels of ketoconazole and itraconazole ; daily dose of itraconazole or ketoconazole should not be >200 mg.↓ 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.↑ levels of beta-blockers ; may need to ↓ dose.↑ levels of felodipine, nifedipine, or nicardipine ; monitor clinical response carefully.Dexamethasone ↓ levels.May ↑ levels of inhaled fluticasone ; choose alternative inhaled corticosteroid.↑ levels of cyclosporine, tacrolimus, or sirolimus ; blood level monitoring recommended.↓ levels of methadone.↑ risperidone and thioridazine levels; may need to ↓ dose.May ↑ levels of sildenafil, vardenafil, or tadalafil ; may result in hypotension, syncope, visual changes, and prolonged erection (↓ dose of sildenafil to 25 mg q 48 hr, vardenafil to 2.5 mg q 72 hr, and tadalafil to 10 mg q 72 hr recommended).↓ levels of sertraline and paroxetine ; adjust dose by clinical response.May ↓ levels and contraceptive efficacy of some estrogen-based hormonal contraceptives including ethinyl estradiol (alternative or additional methods of contraception recommended).May ↑ risk of adverse effects with salmeterol ; concurrent use not recommended.May ↑ bosentan levels; initiate bosentan at 62.5 mg once daily or every other day; if patient already receiving bosentan, discontinue bosentan at least 36 hr before initiation of darunavir and then restart bosentan at least 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; if patient already receiving tadalfil (Adcirca), discontinue tadalafil (Adcirca) at least 24 hr before initiation of darunavir and then restart tadalafil (Adcirca) at least 7 days later at 20 mg once daily.May ↑ colchicine levels; ↓ dose of colchicine; do not administer colchicine if patients have renal or hepatic impairment.Concurrent use with raltegravir may ↑ risk of rash.Concurrent use with telaprevir or boceprevir results in ↓ darunavir, telaprevir, and boceprevir levels; concurrent use not recommended.May ↑ lumefantrine levels and risk of QT interval prolongationSt. John's wort ↑ metabolism and may ↓ antiretroviral effectiveness; concurrent use is contraindicated.

Route/Dosage

genetic implication 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.
Oral (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; genetic implication Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed)—600 mg twice daily with ritonavir 100 mg twice daily.
Oral (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; genetic implication Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed)—600 mg twice daily with ritonavir 100 mg twice daily
Oral (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; genetic implication Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed)—450 mg twice daily with ritonavir 60 mg twice daily
Oral (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; genetic implication Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed)—375 mg twice daily with ritonavir 48 mg twice daily
Oral (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; genetic implication Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed)—280 mg twice daily with ritonavir 48 mg twice daily
Oral (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; genetic implication Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed)—260 mg twice daily with ritonavir 40 mg twice daily
Oral (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; genetic implication Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed)—240 mg twice daily with ritonavir 40 mg twice daily
Oral (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; genetic implication Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed)—220 mg twice daily with ritonavir 32 mg twice daily
Oral (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; genetic implication Therapy-experienced (with ≥1 darunavir resistance associated substitution or if genotypic testing not performed)—200 mg twice daily with ritonavir 32 mg twice daily

Availability

Tablets: 75 mg, 150 mg, 400 mg, 600 mg, 800 mg
Oral suspension: 100 mg/mL

Nursing implications

Nursing assessment

  • Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
  • Assess for allergy to sulfonamides.
  • Monitor patient for development of rash; usually maculopapular and self-limited. May cause Stevens-Johnson syndrome or toxic epidermal necrolysis. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
  • Lab Test Considerations: Monitor viral load and CD4 counts regularly during therapy.
    • May cause ↑ serum AST, ALT, GGT, total bilirubin, alkaline phosphatase, pancreatic amylase, pancreatic lipase, triglycerides, total cholesterol, and uric acid concentrations. Monitor hepatic function prior to and periodically during therapy. Hepatotoxicity may require interruption or discontinuation of therapy.

Potential Nursing Diagnoses

Risk for infection (Indications)
Noncompliance (Patient/Family Teaching)

Implementation

  • Oral: 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 and two 4-mL doses using syringe provided along with ritonavir and food.

Patient/Family Teaching

  • 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.
  • Inform patient that darunavir does not cure AIDS or prevent associated or opportunistic infections. Darunavir does not 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), or rash occur.
  • Advise patients taking oral contraceptives to use a nonhormonal method of birth control during darunavir therapy. Advise female patients to avoid breast feeding during therapy with darunavir.
  • 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 and monitor for side effects.

Evaluation/Desired Outcomes

  • Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
  • Decrease in viral load and improvement in CD4 cell counts.

darunavir

an antiretroviral.
indication This drug is used to inhibit HIV-1 protease by preventing maturation of the virus.
contraindication Known hypersensitivity to this drug prohibits its use.
adverse effects Adverse effects of this drug include dizziness, somnolence, anorexia, dry mouth, nephrolithiasis, rash, pain, asthenia, hyperlipidemia, and lipodystrophy. Life-threatening side effects include insulin-resistant hyperglycemia and ketoacidosis. Common side effects include headache, insomnia, diarrhea, abdominal pain, nausea, and vomiting.

darunavir

A protease inhibitor antiretroviral drug said to outperform other protease inhibitor drugs both virologically and immunologically. It is claimed to be safe and well-tolerated and to be designed to resist drug resistance. Used in combination with ritonavir other antiretroviral drugs it produces an impressive drop in HIV RNA and a marked increase in CD4 cells.
References in periodicals archive ?
Does darunavir penetrate critical compartments like the central nervous system (CNS) and genital fluids?
Pharmacokinetic (PK) interaction between darunavir in combination with low-dose ritonavir (DRV/r) and rifabutin (RFB).
Initial efficacy and toxicity data with boosted darunavir (approved by the FDA in 2006), when compared with Kaletra, are very encouraging, and Tibotec is positioning the drug as a serious competitor to lopinavir/ritonavir after demonstrating good results in heavily treated patients and in those with moderate resistance, as well as in PI-naive patients.
Impressively, in those patients receiving darunavir and enfuvirtide for the first time along with raltegravir, 89% of patients achieved a viral load <50 copies/ml at 48 weeks.
The approval of the protease inhibitor darunavir and the fusion inhibitor enfuviritide .
darunavir 800 mg/cobicistat 150 mg) tablets are a prescription medicine indicated for the treatment of human immunodeficiency virus (HIV-1) in combination with other antiretroviral agents for treatment-naive and treatment-experienced adult patients with no darunavir resistance-associated substitutions (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).
Darunavir (TMC114, DRV) and tipranavir (TPV) are important new ritonavir-boosted protease inhibitors, with efficacy in patients who have had prior treatment failure with this class and whose viruses exhibit extensive resistance-conferring mutations in the protease gene.
In June 2011, Gilead entered into an agreement with Janssen R&D Ireland for the development of a fixed-dose combination of cobicistat and the protease inhibitor darunavir.
para]]Expanded Policy will Increase Access for Darunavir Pediatric Formulations in 128 Resource-Limited Countries[[/para]]
superior to two other commonly prescribed HIV medicines: boosted darunavir and Atripla.
These drugs included all fixed-dose combinations, especially those that will be on the State's first-line regimen, generic versions of some of the ARVs, darunavir, raltegravir, etravirine, and generic abacavir.