Prezista


darunavir ethanolate

Prezista

Action

Inhibits human immunodeficiency virus-1 (HIV-1) protease, preventing formation of mature virus particles

Availability

Oral suspension: 100 mg/ml

Tablets: 75 mg, 150 mg, 400 mg, 600 mg

Indications and dosages

➣ HIV infection in treatment-naïve and treatment-experienced patients with no darunavir resistanceassociated substitutions

Adults: 800 mg (two 400-mg tablets) or 8 ml (two 4-ml doses) oral suspension P.O. with ritonavir 100 mg P.O. daily

➣ HIV infection in treatment-experienced patients with at least one darunavir resistance-associated substitution

Adults: 600 mg (one 600-mg tablet) or 6 ml oral suspension P.O. b.i.d. with ritonavir 100 mg P.O. b.i.d.

➣ HIV infection (with ritonavir and other retrovirals)

Children age 3 to younger than 18 weighing 40 kg (88 lb) or more: 600 mg (tablets) or 6 ml (oral suspension) P.O. b.i.d. with ritonavir 100 mg (capsules or tablets) or 1.25 ml (oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 30 kg (66 lb) to less than 40 kg: 450 mg (tablets) or 4.6 ml (oral suspension) P.O. b.i.d. with ritonavir 60 mg (0.75 ml oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 15 kg (33 lb) to less than 30 kg: 375 mg (tablets) or 3.8 ml (oral suspension) P.O. b.i.d. with ritonavir 50 mg (0.6 ml oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 14 kg (31 lb) to less than 15 kg: 280 mg (2.8 ml oral suspension) P.O. b.i.d. with ritonavir 48 mg (0.6 ml oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 13 kg (29 lb) to less than 14 kg: 260 mg (2.6 ml oral suspension) P.O. b.i.d. with ritonavir 40 mg (0.5 ml oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 12 kg (26 lb) to less than 13 kg: 240 mg (2.4 ml oral suspension) P.O. b.i.d. with ritonavir 40 mg (0.5 ml oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 11 kg (24 lb) to less than 12 kg: 220 mg (2.2 ml oral suspension) P.O. b.i.d. with ritonavir 32 mg (0.4 ml oral solution) P.O. b.i.d.

Children age 3 to younger than 18 weighing 10 kg (22 lb) to less than 11 kg: 200 mg (2 ml oral suspension) P.O. b.i.d. with ritonavir 32 mg (0.4 ml oral solution) P.O. b.i.d.

Children's dosage shouldn't exceed treatment-experienced adult dosage.

Contraindications

• Concurrent administration with drugs (including alfuzosin, cisapride, dihydroergotamine, ergonovine, ergotamine, lovastatin, methylergonovine, midazolam, pimozide, rifampin, sildenafil, simvastatin, terfenadine, triazolam, and St. John's wort)

Precautions

Use cautiously in:

• hypersensitivity to drug or its components (including sulfa)

• severe hepatic impairment (use not recommended)

• diabetes mellitus, hemophilia, hepatic dysfunction or disease

• concurrent use of carbamazepine, phenobarbital, phenytoin (use not recommended)

• elderly patients

• pregnant or breastfeeding patients

• children younger than age 3 (safety and efficacy not established; don't use).

Administration

• Give with ritonavir and food.

• Before administering, assess children weighing 15 kg (33 lb) or more for the ability to swallow tablets. If a child is unable to reliably swallow a tablet, consider using oral suspension. Give 8ml dose as two 4-ml administrations using the oral dosing syringe included.

Don't give concurrently with alfuzosin, cisapride, dihydroergotamine, ergonovine, ergotamine, methylergonovine, midazolam, pimozide, rifampin, sildenafil, simvastatin, terfenadine, terfenadine, or St. John's wort.

• Don't use once-daily dosing in children.

Adverse reactions

CNS: asthenia, fatigue, headache, transient ischemic attack, confusion, disorientation, anxiety, irritability, altered mood, memory impairment, vertigo, rigors, peripheral neuropathy, paresthesia, hypoesthesia, somnolence, nightmares

CV: tachycardia, hypertension, myocardial infarction

EENT: nasopharyngitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, abdominal distention, flatulence, dry mouth, anorexia

GU: renal insufficiency, nephrolithiasis, polyuria, gynecomastia, acute renal failure

Metabolic: diabetes mellitus, polydipsia, obesity

Musculoskeletal: arthralgia, myalgia, extremity pain, osteopenia, osteoporosis

Respiratory: dyspnea, cough

Skin: allergic dermatitis, eczema, inflammation, toxic skin eruption, dermatitis medicamentosa, hyperhidrosis, folliculitis, maculopapular rash, alopecia, erythema multiforme, Stevens-Johnson syndrome

Other: body fat redistribution, lipoatrophy, decreased appetite, hiccups, pyrexia, night sweats, hyperthermia, peripheral edema, immune reconstitution syndrome (inflammatory response to indolent or residual opportunistic infections)

Interactions

Drug-drug. Amiodarone, atorvastatin, bepridil, clarithromycin, cyclosporine, felodipine, fluticasone propionate (inhalation), lidocaine (systemic), nicardipine, nifedipine, pravastatin, quinidine, sildenafil, sirolimus, tacrolimus, tadalafil, trazodone, vardenafil: increased blood levels of these drugs

Astemizole, cisapride, terfenadine: increased risk of serious or lifethreatening reactions (such as arrhythmias)

Carbamazepine, dexamethasone (systemic), phenobarbital, phenytoin, rifampin: decreased darunavir blood level

Efavirenz: decreased blood levels of both drugs

Ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine): increased risk of acute ergot toxicity

Hormonal contraceptives: decreased ethinyl estradiol blood level; may decrease contraceptive efficacy

Itraconazole, ketoconazole: increased blood levels of these drugs and darunavir

Lopinavir/ritonavir, saquinavir: decreased effects of these drugs

Lovastatin, pimozide, simvastatin: increased risk of myopathy

Methadone, voriconazole, warfarin: decreased blood levels of these drugs

Midazolam, triazolam: increased risk of respiratory depression or increased sedation

Paroxetine, sertraline: decreased effects of these drugs

Rifabutin: increased rifabutin blood level, decreased darunavir blood level (when given with ritonavir)

Voriconazole: decreased voriconazole and increased darunavir blood levels

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, gamma-glutamyltransferase, lipase, lipids, partial thromboplastin time, plasma prothrombin time, total cholesterol, triglycerides, uric acid: increased levels

Bicarbonate, calcium, lymphocytes, platelets, total absolute neutrophils, white blood cells: decreased levels

Bilirubin, serum glucose, sodium: increased or decreased levels

Drug-food. Any food: increased drug absorption

Drug-herbs. St. John's wort: decreased darunavir blood level

Patient monitoring

• During initial treatment phase, stay alert for immune reconstitution syndrome.

• Monitor liver function studies frequently in patients with preexisting hepatic dysfunction or disease.

• Monitor blood glucose levels frequently in patients with diabetes mellitus.

• Carefully monitor patient receiving antiarrhythmics and HMG-CoA reductase inhibitors while taking this drug.

• Monitor International Normalized Ratio when giving drug with warfarin.

Patient teaching

• Instruct patient to take drug with ritonavir and food, as prescribed.

• Advise patient to inform prescriber of other drugs and supplements he's taking (including vitamins and herbs) before starting drug or taking new medication.

Urge patient to immediately report side effects (especially rash).

• Emphasize that drug doesn't cure HIV infection.

• Advise patient using hormonal contraceptives to use alternative contraceptive method while taking this drug.

• Advise patients who are pregnant or recently gave birth not to breastfeed because of risk of passing HIV infection to infant and potentially serious adverse drug reactions.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.

darunavir

(da-ru-na-veer) darunavir,

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 dailyOral (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 dailyOral (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 dailyOral (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 dailyOral (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 dailyOral (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 dailyOral (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 dailyOral (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.