Prezista

Pronunciation

Generic Name: Darunavir
Class: HIV Protease Inhibitors
VA Class: AM800
Chemical Name: [(1S,2R) - 3 - [[(4 - Aminophenyl)sulfonyl](2 - methylpropyl)amino] - 2 - hydroxy - 1 - (phenylmethyl)propyl] - carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester
Molecular Formula: C27H37N3O7SC27H37N3O7S•C2H5OH
CAS Number: 206361-99-1

Introduction

Antiretroviral; HIV protease inhibitor (PI).1 2 3

Uses for Prezista

Treatment of HIV Infection

Treatment of HIV-1 infection.1 Must be used in conjunction with low-dose ritonavir (ritonavir-boosted darunavir) and other antiretroviral agents.1

For initial treatment in antiretroviral-naive adults and adolescents, experts state that ritonavir-boosted darunavir (once daily) in conjunction with tenofovir disoproxil fumarate (tenofovir DF) and emtricitabine (or lamivudine) is a recommended PI-based regimen that can be used regardless of baseline viral load or CD4+ T-cell count;200 ritonavir-boosted darunavir in conjunction with abacavir and lamivudine (or emtricitabine) is an alternative PI-based regimen for initial treatment, but use only in those who are human leukocyte antigen (HLA)-B*5701 negative.200

Slideshow: Flashback: FDA Drug Approvals 2013

For initial treatment in antiretroviral-naive pediatric patients, experts state that ritonavir-boosted darunavir (twice daily) and 2 nucleoside reverse transcriptase inhibitors (NRTIs) is an alternative (not preferred) regimen in children 3 to <12 years of age and ritonavir-boosted darunavir (once daily) in conjunction with 2 NRTIs is an alternative (not preferred) PI-based regimen in children ≥12 years of age.201

Use of ritonavir-boosted darunavir in antiretroviral-experienced adults, adolescents, or pediatric patients should be guided by genotypic and phenotypic viral resistance testing and the individual’s prior antiretroviral treatment.1

Postexposure Prophylaxis following Occupational Exposure to HIV

Postexposure prophylaxis of HIV infection following occupational exposure (PEP) in health-care personnel and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.199

USPHS recommends 3-drug regimen of raltegravir and emtricitabine and tenofovir DF as preferred regimen for PEP following occupational exposures to HIV.199 Ritonavir-boosted darunavir and 2 NRTIs is one of several alternative regimens.199 Preferred dual NRTI option for use with ritonavir-boosted darunavir is emtricitabine and tenofovir DF; alternatives are tenofovir DF and lamivudine, zidovudine and lamivudine, or zidovudine and emtricitabine.199

Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible.199 Do not delay initiation of PEP while waiting for expert consultation.199

Prezista Dosage and Administration

Administration

Oral Administration

Administer orally in conjunction with low-dose ritonavir (ritonavir-boosted darunavir).1 Do not use without low-dose ritonavir.1 200 201

Take darunavir and low-dose ritonavir at same time and with food.1

Oral Suspension

Use oral suspension in those who have difficulty swallowing tablets.1

Administer suspension using oral dosing syringe supplied by the manufacturer.1 If 800-mg dose is indicated, give dose as two 4-mL administrations using the oral dosing syringe.1

Supplied as a white to off-white opaque suspension;1 shake prior to each dose.1

Tablets

Swallow tablets whole with a drink (e.g., water, milk).1

Assess children weighing ≥15 kg for ability to swallow tablets; consider oral suspension in those unable to reliably swallow tablets.1

Dosage

Available as oral suspension or tablets containing darunavir ethanolate; dosage expressed in terms of darunavir.1

Pediatric Patients

Treatment of HIV Infection

To avoid medication errors, use extra care in calculating dose, transcribing medication order, dispensing prescription, and providing dosing instructions.1

Dosage of ritonavir-boosted darunavir in children and adolescents 3 to <18 years of age weighing ≥10 kg is based on weight.1

Antiretroviral-naive Pediatric Patients
Oral

Pediatric patients 3 to <18 years of age weighing ≥10 kg: Dosage based on weight (approximately 35 mg/kg once daily with ritonavir 7 mg/kg once daily in those weighing <15 kg).1 (See Table 1 and Table 2.)

Dosage (in mL) rounded up for convenient measuring using oral dosing syringe provided by manufacturer.1

Table 1: Dosage of Ritonavir-boosted Darunavir in Antiretroviral-naive Pediatric Patients 3 to <18 Years of Age Weighing 10 to <15 kg 1

Body Weight

Darunavir Dosage (Oral Suspension Containing 100 mg/mL)

Ritonavir Dosage (Oral Solution Containing 80 mg/mL)

≥10 to <11 kg

350 mg (3.6 mL) once daily

64 mg (0.8 mL) once daily

≥11 to <12 kg

385 mg (4 mL) once daily

64 mg (0.8 mL) once daily

≥12 to <13 kg

420 mg (4.2 mL) once daily

80 mg (1 mL) once daily

≥13 to <14 kg

455 mg (4.6 mL) once daily

80 mg (1 mL) once daily

≥14 to <15 kg

490 mg (5 mL) once daily

96 mg (1.2 mL) once daily

Dosage (in mL) rounded up for convenient measuring using oral dosing syringe provided by manufacturer.1

Table 2: Dosage of Ritonavir-boosted Darunavir in Antiretroviral-naive Pediatric Patients 3 to <18 Years of Age Weighing ≥15 kg1

Body Weight

Darunavir Dosage (Oral Suspension Containing 100 mg/mL or Tablets)

Ritonavir Dosage (Oral Solution Containing 80 mg/mL or 100-mg Capsules or Tablets)

≥15 to <30 kg

600 mg (6 mL) once daily

100 mg (1.25 mL) once daily

≥30 to <40 kg

675 mg (6.8 mL) once daily

100 mg (1.25 mL) once daily

≥40 kg

800 mg (8 mL) once daily

100 mg (1.25 mL) once daily

Antiretroviral-experienced Pediatric Patients
Oral

Genotypic testing recommended to identify mutations associated with darunavir resistance (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).1

Pediatric patients 3 to <18 years of age weighing ≥10 kg with no mutations associated with darunavir resistance: Dosage based on weight (approximately 35 mg/kg once daily with ritonavir 7 mg/kg once daily in those weighing <15 kg).1 (See Table 3 and Table 4.)

Dosage (in mL) rounded up for convenient measuring using oral dosing syringe provided by manufacturer.1

Table 3: Dosage of Ritonavir-boosted Darunavir in Antiretroviral-experienced Pediatric Patients 3 to <18 Years of Age Weighing 10 to <15 kg without Any Mutations Associated with Darunavir Resistance1

Body Weight

Darunavir Dosage (Oral Suspension Containing 100 mg/mL)

Ritonavir Dosage (Oral Solution Containing 80 mg/mL)

≥10 to <11 kg

350 mg (3.6 mL) once daily

64 mg (0.8 mL) once daily

≥11 to <12 kg

385 mg (4 mL) once daily

64 mg (0.8 mL) once daily

≥12 to <13 kg

420 mg (4.2 mL) once daily

80 mg (1 mL) once daily

≥13 to <14 kg

455 mg (4.6 mL) once daily

80 mg (1 mL) once daily

≥14 to <15 kg

490 mg (5 mL) once daily

96 mg (1.2 mL) once daily

Dosage (in mL) rounded up for convenient measuring using oral dosing syringe provided by manufacturer.1

Table 4: Dosage of Ritonavir-boosted Darunavir in Antiretroviral-experienced Pediatric Patients 3 to <18 Years of Age Weighing ≥15 kg without Any Mutations Associated with Darunavir Resistance1

Body Weight

Darunavir Dosage (Oral Suspension Containing 100 mg/mL or Tablets)

Ritonavir Dosage (Oral Solution Containing 80 mg/mL or 100-mg Capsules or Tablets)

≥15 to <30 kg

600 mg (6 mL) once daily

100 mg (1.25 mL) once daily

≥30 to <40 kg

675 mg (6.8 mL) once daily

100 mg (1.25 mL) once daily

≥40 kg

800 mg (8 mL) once daily

100 mg (1.25 mL) once daily

Pediatric patients 3 to <18 years of age weighing ≥10 kg with at least 1 mutation associated with darunavir resistance: Dosage based on weight (approximately 20 mg/kg twice daily with ritonavir 3 mg/kg twice daily in those weighing <15 kg).1 (See Table 5 and Table 6.)

Table 5: Dosage of Ritonavir-boosted Darunavir in Antiretroviral-experienced Pediatric Patients 3 to <18 Years of Age Weighing 10 to <15 kg with ≥1 Mutation Associated with Darunavir Resistance1

Body Weight

Darunavir Dosage (Oral Suspension Containing 100 mg/mL)

Ritonavir Dosage (Oral Solution Containing 80 mg/mL)

≥10 to <11 kg

200 mg (2 mL) twice daily

32 mg (0.4 mL) twice daily

≥11 to <12 kg

220 mg (2.2 mL) twice daily

32 mg (0.4 mL) twice daily

≥12 to <13 kg

240 mg (2.4 mL) twice daily

40 mg (0.5 mL) twice daily

≥13 to <14 kg

260 mg (2.6 mL) twice daily

40 mg (0.5 mL) twice daily

≥14 to <15 kg

280 mg (2.8 mL) twice daily

48 mg (0.6 mL) twice daily

Dosage (in mL) rounded up for convenient measuring using oral dosing syringe provided by manufacturer.1

Table 6: Dosage of Ritonavir-boosted Darunavir in Antiretroviral-experienced Pediatric Patients 3 to <18 Years of Age Weighing ≥15 kg with ≥1 Mutation Associated with Darunavir Resistance1

Body Weight

Darunavir Dosage (Oral Suspension Containing 100 mg/mL or Tablets)

Ritonavir Dosage (Oral Solution Containing 80 mg/mL or 100-mg Capsules or Tablets)

≥15 to <30 kg

375 mg (3.8 mL) twice daily

48 mg (0.6 mL) twice daily

≥30 to <40 kg

450 mg (4.6 mL) twice daily

60 mg (0.75 mL) twice daily

≥40 kg

600 mg (6 mL) twice daily

100 mg (1.25 mL) twice daily

Adults

Treatment of HIV Infection
Antiretroviral-naive Adults
Oral

800 mg (one 800-mg tablet or 8 mL of oral suspension containing 100 mg/mL) once daily with low-dose ritonavir (100 mg once daily).1

Antiretroviral-experienced Adults
Oral

Genotypic testing recommended to identify mutations associated with darunavir resistance (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).1

No mutations associated with darunavir resistance: 800 mg (one 800-mg tablet or 8 mL of oral suspension containing 100 mg/mL) once daily with low-dose ritonavir (100 mg once daily).1

At least 1 mutation associated with darunavir resistance: 600 mg (one 600-mg tablet or 6 mL of oral suspension containing 100 mg/mL) twice daily with low-dose ritonavir (100 mg twice daily).1

Genotypic testing not feasible: 600 mg (one 600-mg tablet or 6 mL of oral suspension containing 100 mg/mL) twice daily with low-dose ritonavir (100 mg twice daily).1

Postexposure Prophylaxis following Occupational Exposure to HIV
Oral

800 mg once daily with low-dose ritonavir (100 mg once daily).199 Alternatively, 600 mg twice daily with low-dose ritonavir (100 mg twice daily).199 Used in conjunction with 2 NRTIs (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).199

Initiate PEP as soon as possible following exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.199

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection
Oral

Do not exceed dosage recommended for antiretroviral-experienced adults.1

Special Populations

Hepatic Impairment

Dosage adjustments not necessary in patients with mild to moderate hepatic impairment (Child-Pugh class A or B).1 200 Do not use in those with severe hepatic impairment (Child-Pugh class C).1 200

Renal Impairment

Experts state dosage adjustments not necessary.200

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Cautions for Prezista

Contraindications

  • Concomitant use with drugs highly dependent on CYP3A for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., alfuzosin, cisapride, ergot alkaloids, lovastatin, simvastatin, oral midazolam, triazolam, pimozide, sildenafil [Revatio] for treatment of pulmonary arterial hypertension).1 (See Specific Drugs under Interactions.)

  • Concomitant use with drugs that may decrease darunavir concentrations resulting in possible loss of virologic response (e.g., rifampin, St. John’s wort [Hypericum perforatum]).1 (See Specific Drugs under Interactions.)

Warnings/Precautions

Sensitivity Reactions

Dermatologic Reactions

Severe skin reactions, sometimes accompanied by fever and/or increased serum transaminase concentrations, may occur.1 Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, and acute, generalized exanthematous pustulosis reported.1

Immediately discontinue darunavir if manifestations of severe skin reactions occur (e.g., severe rash, rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia).1

Sulfonamide Sensitivity

Darunavir contains a sulfonamide moiety; use with caution in patients with known sulfonamide allergy.1

Hepatic Effects

Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) reported in clinical studies.1 Postmarketing reports of liver injury (in some cases fatal); liver injury generally occurred in patients with advanced HIV infection who were receiving multiple concomitant drugs, were coinfected with HBV or HCV, and/or were developing immune reconstitution syndrome.1

Conduct appropriate laboratory tests before starting darunavir; monitor periodically thereafter.1 Consider increased AST/ALT monitoring in patients with hepatitis, cirrhosis, or elevated transaminase concentrations prior to therapy, especially during first several months of therapy.1

Consider interrupting or discontinuing darunavir in patients who develop manifestations suggestive of new or worsening hepatic impairment (e.g., fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly, clinically important increases in hepatic enzyme concentrations).1

Interactions

Darunavir is administered concomitantly with low-dose ritonavir (ritonavir-boosted darunavir).1 Failure to administer with recommended low-dose ritonavir will result in subtherapeutic darunavir concentrations and inadequate antiviral response.1 Consider the usual cautions, precautions, and contraindications associated with ritonavir.1

Concomitant use with certain drugs is not recommended or requires particular caution.1 200 (See Specific Drugs under Interactions.)

Hyperglycemic and Diabetogenic Effects

Hyperglycemia (potentially persistent), new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of PIs; diabetic ketoacidosis has occurred.1

Initiate or adjust antidiabetic therapy (e.g., insulin, oral hypoglycemic agents) as needed.1

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]); this may necessitate further evaluation and treatment.1

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.1

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and general cushingoid appearance.1 Mechanisms and long-term consequences unknown; causal relationship not established.1

Hemophilia A and B

Increased bleeding, including spontaneous skin hematomas and hemarthrosis, reported with HIV PIs;1 causal relationship not established.1

Increased hemostatic therapy (e.g., antihemophilic factor) may be needed.1

HIV Resistance

Possibility of cross-resistance to other HIV PIs not evaluated.1 Effect of ritonavir-boosted darunavir therapy on subsequent therapy with other PIs unknown.1

Specific Populations

Pregnancy

Category C.1

Antiretroviral Pregnancy Registry at 800-258-4263.1

Although data are limited regarding use in pregnant women, experts state that ritonavir-boosted darunavir and 2 NRTIs can be considered an alternative PI-based regimen for initial treatment in pregnant women.202

Lactation

Distributed into milk in rats;1 not known whether distributed into human milk.1

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.1

Pediatric Use

Do not use in children <3 years of age; toxicity and mortality reported in juvenile rats.1

Adverse effects in children 3 to <18 years of age similar to those reported in adults.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1

Use with caution and monitor because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Hepatic Impairment

Risk for liver function abnormalities, including severe adverse hepatic effects, in patients with preexisting hepatic impairment, including those with HBV or HCV infection.1

Pharmacokinetics not altered in individuals with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.1

Not recommended in patients with severe hepatic impairment.1

Renal Impairment

Pharmacokinetics not altered in patients with Clcr≥30 mL/minute.1 Not studied in patients with severe renal impairment or end-stage renal disease.1

Common Adverse Effects

Diarrhea,1 9 nausea,1 9 vomiting,1 abdominal pain,1 headache,1 9 rash.1

Interactions for Prezista

Darunavir metabolized principally by CYP3A.1

Darunavir and ritonavir inhibit CYP3A4 and CYP2D6.1

In vivo data suggest ritonavir-boosted darunavir inhibits P-glycoprotein transport system.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors or inducers of CYP3A4 with possible alteration in metabolism of darunavir or ritonavir.1

Potential pharmacokinetic interaction with drugs metabolized by CYP3A or CYP2D6 with possible altered metabolism of drug metabolized by CYP3A or CYP2D6.1

Specific Drugs

Drug

Interaction

Comments

Abacavir

Pharmacokinetic interaction not expected1

No in vitro evidence of antagonistic antiretroviral effects 1

Alfuzosin

Potential for serious and/or life-threatening reactions (e.g., hypotension)1

Concomitant use contraindicated1

Antiarrhythmic agents (amiodarone, dronedarone, flecainide, systemic lidocaine, propafenone, quinidine)

Possible increased antiarrhythmic agent concentrations1

Use concomitantly with caution; monitor antiarrhythmic concentrations1

Amiodarone, dronedarone: Some experts state do not use concomitantly200

Anticoagulants, oral (rivaroxaban, warfarin)

Rivaroxaban: Possible increased rivaroxaban concentrations; may increase bleeding risk200

Warfarin: Decreased warfarin concentrations; no change in darunavir concentrations1

Rivaroxaban: Avoid concomitant use200

Warfarin: Monitor INR,1 200 especially when initiating or discontinuing darunavir;200 adjust warfarin dosage as needed200

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Carbamazepine: Increased carbamazepine concentrations; no change in darunavir concentrations1

Phenobarbital, phenytoin: Decreased concentrations of the anticonvulsant; no change in darunavir concentrations1

Carbamazepine: Dosage adjustments not needed; monitor carbamazepine concentrations and adjust anticonvulsant dosage to achieve appropriate clinical effect1

Phenobarbital, phenytoin: Monitor anticonvulsant concentrations;1 some clinicians suggest considering alternatives to phenobarbital and phenytoin200

Antifungals, azoles (itraconazole, ketoconazole, voriconazole)

Itraconazole: Possible increased darunavir and itraconazole concentrations1

Ketoconazole: Possible increased darunavir and ketoconazole concentrations1

Voriconazole: Possible decreased voriconazole concentrations1

Itraconazole: Consider monitoring itraconazole concentrations; itraconazole dosage >200 mg daily not recommended1 200 unless itraconazole concentrations used to guide dosage200

Ketoconazole: Dosage >200 mg daily not recommended 1

Voriconazole: Do not use concomitantly unless benefits outweigh risks;1 200 if used, consider monitoring voriconazole concentrations and adjusting voriconazole dosage accordingly200

Antimalarial Agents

Fixed combination of artemether and lumefantrine (artemether/lumefantrine): Decreased concentrations and AUC of artemether and active metabolite of artemether; increased concentrations and AUC of lumefantrine; no effect on darunavir or ritonavir concentrations or AUC; possible increased risk of QT interval prolongation1

Artemether/lumefantrine: Use concomitantly with caution; dosage adjustments not needed1

Antimycobacterials, rifamycins (rifabutin, rifampin, rifapentine)

Rifabutin: Increased rifabutin and darunavir concentrations1

Rifampin: Decreased darunavir concentrations; possible decreased antiretroviral effects1

Rifapentine: Possible decreased darunavir concentrations200

Rifabutin: Reduce rifabutin dosage to 150 mg once every other day (further reduction may be needed); monitor for adverse effects;1 200 monitor for antimycobacterial response and consider therapeutic drug monitoring200

Rifampin: Concomitant use contraindicated 1

Rifapentine: Concomitant use not recommended200

Antipsychotics (pimozide, quetiapine, risperidone, thioridazine)

Pimozide: Potential for serious and/or life-threatening adverse effects (e.g., cardiac arrhythmias)1

Quetiapine, risperidone, thioridazine: Potential for increased concentrations of the antipsychotic1

Pimozide: Concomitant use contraindicated1

Quetiapine: Initiate at lowest dosage and titrate as needed; if initiating ritonavir-boosted darunavir in patient receiving quetiapine, reduce quetiapine to one-sixth of original dosage; monitor for efficacy and adverse effects of quetiapine200

Risperidone, thioridazine: Reduced dosage of the antipsychotic may be needed1

Atazanavir

Depending on regimen used, no clinically important change in atazanavir or darunavir concentrations or AUC1

No in vitro evidence of antagonistic antiretroviral effects1

Ritonavir-boosted atazanavir: Concomitant use not recommended1

If used concomitantly, some experts recommend darunavir 600 mg twice daily, ritonavir 100 mg twice daily, and atazanavir 300 mg once daily200

Avanafil

Possible increased avanafil concentrations200

Concomitant use not recommended200

Bedaquiline

Possible increased bedaquiline concentrations200

Clinical importance unknown; use with caution and monitor for QTc interval prolongation and liver dysfunction200

Benzodiazepines (e.g., midazolam, triazolam)

Midazolam or triazolam: Possible increased concentrations of midazolam or triazolam; potential for serious and/or life-threatening effects (e.g., prolonged or increased sedation or respiratory depression)1

Alprazolam, diazepam: Possible increased concentrations of alprazolam or diazepam200

Midazolam or triazolam: Concomitant use contraindicated;1 some experts state a single parenteral dose of midazolam can be used with caution in a monitored situation for procedural sedation200

Alprazolam, diazepam: Consider alternative (e.g., lorazepam, oxazepam, temazepam)200

β-Adrenergic blocking agents (metoprolol, timolol)

Metoprolol, timolol: Possible increased concentrations of the β-adrenergic blocking agent1

Metoprolol, timolol: Caution; dose reduction of the β-adrenergic blocking agent may be needed1

Boceprevir

Decreased concentrations and AUC of boceprevir, darunavir, and ritonavir;1 19 185 17 200 possible reduced efficacy of HCV and HIV treatment regimens17 18 19

Concomitant use not recommended1 185 200

If boceprevir was initiated for treatment of chronic HCV in a patient coinfected with HIV receiving a suppressive antiretroviral regimen containing ritonavir-boosted darunavir, inform patient of possible drug interaction and closely monitor for HCV treatment response and potential HCV and HIV virologic rebound17 18 200

Bosentan

Possible increased bosentan concentrations1

In patients already receiving ritonavir-boosted darunavir for ≥10 days, initiate bosentan using dosage of 62.5 mg once daily or every other day based on individual tolerability1

In patients already receiving bosentan, discontinue bosentan for at least 36 hours prior to initiating ritonavir-boosted darunavir; after ≥10 days of ritonavir-boosted darunavir, resume bosentan using dosage of 62.5 mg once daily or every other day based on individual tolerability1

Buprenorphine, buprenorphine/naloxone

Increased norbuprenorphine concentrations and AUC1 200

Dosage adjustments not needed;1 200 monitor patient200

Calcium-channel blocking agents (e.g., diltiazem, felodipine, nicardipine, nifedipine)

Diltiazem: Possible increased diltiazem concentrations200

Felodipine, nicardipine, nifedipine: Increased calcium-channel blocking agent concentrations1

Diltiazem: Use concomitantly with caution;200 adjust diltiazem dosage based on clinical response and toxicities200

Felodipine, nicardipine, nifedipine: Use concomitantly with caution; clinical monitoring recommended1

Cisapride

Potential for serious and/or life-threatening effects such as cardiac arrhythmias 1

Concomitant use contraindicated1

Clarithromycin

Increased clarithromycin concentrations1

Modification of usual clarithromycin dosage not needed in patients with normal renal function; reduce clarithromycin dosage by 50% if Clcr 30–60 mL/minute and reduce by 75% if Clcr <30 mL/minute;1 some experts state monitor patients for clarithromycin-related toxicities or consider alternative macrolide (e.g., azithromycin)200

Colchicine

Increased colchicine concentrations1

Patients with renal or hepatic impairment: Concomitant use of colchicine and ritonavir-boosted darunavir not recommended1

Colchicine for treatment of gout flares: In those receiving ritonavir-boosted darunavir, use initial colchicine dose of 0.6 mg followed by 0.3 mg 1 hour later and repeat dose no earlier than 3 days later1

Colchicine for prophylaxis of gout flares: In those receiving ritonavir-boosted darunavir, decrease colchicine dosage to 0.3 mg once daily in those originally receiving 0.6 mg twice daily or decrease dosage to 0.3 mg once every other day in those originally receiving 0.6 mg once daily1

Colchicine for treatment of familial Mediterranean fever (FMF): In those receiving ritonavir-boosted darunavir, use maximum colchicine dosage of 0.6 mg daily (may be given as 0.3 mg twice daily)1

Corticosteroids (beclomethasone, budesonide, dexamethasone, fluticasone, methylprednisolone, prednisolone, prednisone, triamcinolone)

Budesonide or fluticasone (orally inhaled, intranasal): Increased corticosteroid concentrations;1 200 may result in adrenal insufficiency, including Cushing's syndrome200

Beclomethasone (orally inhaled): Clinically important pharmacokinetic interaction not expected200

Methylprednisolone, prednisolone, or triamcinolone (intra-articular or other local injections): Increased corticosteroid concentrations;200 may result in adrenal insufficiency, including Cushing's syndrome200

Budesonide or prednisone (systemic): Increased corticosteroid concentrations;200 may result in adrenal insufficiency, including Cushing's syndrome200

Dexamethasone (systemic): Decreased darunavir concentrations; possible decreased antiretroviral efficacy1

Budesonide or fluticasone (orally inhaled, intranasal): Do not use concomitantly unless potential benefits of the corticosteroid outweigh risks of systemic corticosteroid adverse effects;200 consider alternative (e.g., beclomethasone), especially when long-term corticosteroid use anticipated1 200

Beclomethasone (orally inhaled): Dosage adjustments not needed200

Methylprednisolone, prednisolone, or triamcinolone (intra-articular or other local injections): Do not use concomitantly; consider alternative nonsteroidal therapies; if intra-articular corticosteroid required, use alternative antiretroviral that does not alter CYP3A4 activity (e.g., dolutegravir, raltegravir)200

Budesonide or prednisone (systemic): Do not use concomitantly unless potential benefits outweigh risks of systemic corticosteroid adverse effects200

Dexamethasone (systemic): Use concomitantly with caution; consider alternative corticosteroid for long-term use200

Delavirdine

No in vitro evidence of antagonistic antiretroviral effects 1

Didanosine

Didanosine delayed-release capsules: No change in didanosine or darunavir concentrations1

Conflicting administration instructions with didanosine and food1

No in vitro evidence of antagonistic antiretroviral effects 1

Administer darunavir with low-dose ritonavir (with food) 1 hour after or 2 hours before didanosine (without food)1

Digoxin

Increased digoxin concentrations1

Use lowest possible initial dose of digoxin; monitor digoxin concentrations and adjust dose as clinically indicated1

Dextromethorphan

Increased dextromethorphan concentrations1

Dolutegravir

No clinically important effect on pharmacokinetics of either drug1

Efavirenz

Decreased darunavir AUC; increased efavirenz AUC1 200

No in vitro evidence of antagonistic antiretroviral effects 1

Clinical importance unknown200

Usual dosages can be used;1 200 some experts recommend close clinical monitoring; consider monitoring plasma concentrations of darunavir and efavirenz200

Elvitegravir and cobicistat

Fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir (EVG/COBI/TDF/FTC): Altered concentrations of elvitegravir, cobicistat, and/or darunavir200

EVG/COBI/TDF/FTC: Concomitant use not recommended200

Emtricitabine

Pharmacokinetic interaction not expected1

No in vitro evidence of antagonistic antiretroviral effects1

Etravirine

Decreased etravirine AUC; no change in darunavir concentrations; safety and efficacy of ritonavir-boosted darunavir and etravirine established in clinical studies1 200

No in vitro evidence of antagonistic antiretroviral effects214

Dosage adjustments not needed1 200

Enfuvirtide

No in vitro evidence of antagonistic antiretroviral effects1

Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine)

Potential for serious or life-threatening adverse effects (e.g., peripheral vasospasm, ischemia of extremities)1

Concomitant use contraindicated1

If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving darunavir, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible202

Estrogens/progestins

Oral hormonal contraceptives containing ethinyl estradiol and norgestimate or norethindrone: Decreased ethinyl estradiol and norethindrone concentrations1

Use alternative nonhormonal contraception methods1

Fosamprenavir

Data not available regarding concomitant use200

Histamine H2- receptor antagonists (e.g., ranitidine)

Ranitidine: No clinically important effect on darunavir concentrations or AUC1

Ranitidine: Dosage adjustments not needed1

HMG-CoA reductase inhibitors (statins)

Atorvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin: Increased plasma concentrations and AUC of the antilipemic agents; increased risk of statin-associated adverse effects, including myopathy and rhabdomyolysis1 186 200

Pitavastatin: Decreased pitavastatin AUC; no clinically important effect on darunavir concentrations12 200

Atorvastatin: Do not exceed atorvastatin dosage of 20 mg daily;1 186 200 carefully titrate atorvastatin dosage; use lowest necessary dosage with close monitoring for adverse effects1 200

Lovastatin: Concomitant use contraindicated1 186 200

Pitavastatin: Dosage adjustments not necessary200

Pravastatin: Carefully titrate pravastatin dosage; use lowest necessary dosage with close monitoring for adverse effects1 200

Rosuvastatin: Carefully titrate rosuvastatin dosage; use lowest necessary dosage with close monitoring for adverse effects1 200

Simvastatin: Concomitant use contraindicated1 186 200

Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)

Potential for increased immunosuppressive agent concentrations1

Monitor plasma concentrations of immunosuppressive agent if used concomitantly1

Indinavir

Increased concentrations and AUC of darunavir and indinavir1

No in vitro evidence of antagonistic antiretroviral effects1

Appropriate dosages for concomitant use not established1

Lamivudine

Pharmacokinetic interactions unlikely1

No in vitro evidence of antagonistic antiretroviral effects1

Lopinavir/ritonavir

Decreased darunavir concentrations; no change in lopinavir concentrations1

No in vitro evidence of antagonistic antiretroviral effects1

Concomitant use not recommended; appropriate dosages with respect to safety and efficacy not established1 200

Maraviroc

Increased maraviroc concentrations and AUC1 200 224

No in vitro evidence of antagonistic antiretroviral effects224

Ritonavir-boosted darunavir: Recommended maraviroc dosage is 150 mg twice daily 1 200 224

Methadone

Decreased methadone concentrations1

Methadone dosage adjustments not needed when ritonavir-boosted darunavir is initiated;1 200 closely monitor for opioid withdrawal since maintenance methadone dosage may need to be adjusted in some patients1 200

Nelfinavir

No in vitro evidence of antagonistic antiretroviral effects1

Nevirapine

Increased nevirapine and darunavir concentrations1 200

No in vitro evidence of antagonistic antiretroviral effects1

Dosage adjustments not needed1 200

Proton pump inhibitors

Omeprazole: Decreased omeprazole concentrations1

Dosage adjustments not needed1

Raltegravir

Decreased raltegravir AUC;200 no clinically important effect on pharmacokinetics of ritonavir-boosted darunavir1 225

Dosage adjustments not needed1 200

Rilpivirine

Increased rilpivirine concentrations and AUC; no clinically important effect on darunavir concentrations or AUC226

No in vitro evidence of antagonistic antiretroviral effects226

Dosage adjustments not needed1 226

Ritonavir

Increased darunavir concentrations and AUC;1 2 200 concomitant low-dose ritonavir used to therapeutic advantage (ritonavir-boosted darunavir)1 2 200

No in vitro evidence of antagonistic antiretroviral effects1

Selective serotonin-reuptake inhibitors (SSRIs)

Paroxetine, sertraline: Decreased SSRI concentrations; no change in darunavir concentrations1

Paroxetine, sertraline: Titrate SSRI dosage based on clinical response; if ritonavir-boosted darunavir initiated in those on stable SSRI dosage, monitor for clinical response1

St. John’s wort (Hypericum perforatum)

Potential decreased darunavir concentrations; possible decreased antiretroviral efficacy1

Concomitant use contraindicated1

Salmeterol

Possible increased salmeterol concentrations and increased risk of QT interval prolongation, palpitations, and sinus tachycardia1

Concomitant use not recommended1 200

Saquinavir

Decreased darunavir concentrations; unchanged saquinavir concentrations1

No in vitro evidence of antagonistic antiretroviral effects1

Concomitant use not recommended1

Sildenafil

Increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope)1

Sildenafil (Revatio) for treatment of pulmonary arterial hypertension (PAH): Concomitant use with ritonavir-boosted darunavir contraindicated;1 safe and effective dosage for concomitant use not established1

Sildenafil for treatment of erectile dysfunction: Do not exceed sildenafil dosage of 25 mg once every 48 hours; closely monitor for sildenafil-associated adverse effects1 200

Simeprevir

Increased concentrations and AUC of simeprevir and darunavir187 200

Concomitant use not recommended187 200

Sofosbuvir

Slightly increased sofosbuvir concentrations and AUC; no clinically important effect on darunavir pharmacokinetics188

Dosage adjustments not needed188

Stavudine

Pharmacokinetic interaction unlikely1

No in vitro evidence of antagonistic antiretroviral effects1

Tadalafil

Possible increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope)1

Tadalafil (Adcirca) for treatment of PAH in patients who have been receiving ritonavir-boosted darunavir for ≥1 week: Use initial tadalafil dosage of 20 mg once daily; if tolerated, may increase dosage to 40 mg once daily1

Ritonavir-boosted darunavir in patients receiving tadalafil (Adcirca) for PAH: Discontinue tadalafil for at least 24 hours prior to initiating ritonavir-boosted darunavir; after ≥1 week of the antiretroviral agent, may resume tadalafil at dosage of 20 mg once daily and, if tolerated, may increase dosage to 40 mg once daily1

Tadalafil for treatment of erectile dysfunction: Do not exceed tadalafil dosage of 10 mg once every 72 hours; closely monitor for tadalafil-related adverse effects1 200

Tadalafil for treatment of benign prostatic hyperplasia: Do not exceed tadalafil dosage of 2.5 mg once daily200

Telaprevir

Decreased darunavir and telaprevir concentrations and AUCs1 200

Concomitant use not recommended1 200

Tenofovir

Increased tenofovir concentrations and AUC;1 200 increased darunavir concentrations and AUC1

No in vitro evidence of antagonistic antiretroviral effects1

Clinical importance unknown; monitor for tenofovir toxicity200

Manufacturer of darunavir states usual dosage of ritonavir-boosted darunavir and tenofovir can be used 1

Tipranavir

Data not available regarding concomitant use200

No in vitro evidence of antagonistic antiretroviral effects 1

Trazodone

Possible increased antidepressant concentrations and increased risk of nausea, dizziness, hypotension, syncope1

Use concomitantly with caution;1 consider reduced trazodone dosage;1 use lowest possible trazodone dosage and monitor for adverse CNS and cardiovascular effects200

Tricyclic antidepressants (amitriptyline, desipramine, imipramine, nortriptyline)

Desipramine: Possible increased desipramine concentrations and increased risk of nausea, dizziness, hypotension, syncope1

Amitriptyline, imipramine, nortriptyline: Possible increased concentrations of the tricyclic antidepressant200

Desipramine: Use concomitantly with caution;1 consider reduced antidepressant dosage1

Amitriptyline, imipramine, nortriptyline: Use lowest possible antidepressant dosage; titrate antidepressant dosage based on clinical assessment and/or antidepressant concentrations200

Vardenafil

Possible increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope)1

Vardenafil for treatment of erectile dysfunction: Do not exceed vardenafil dosage of 2.5 mg once every 72 hours; closely monitor for vardenafil-related adverse effects1 200

Zidovudine

Pharmacokinetic interaction unlikely1

No in vitro evidence of antagonistic antiretroviral effects1

Prezista Pharmacokinetics

Absorption

Bioavailability

Darunavir administered concomitantly with low-dose ritonavir (ritonavir-boosted darunavir).1 Ritonavir decreases metabolism of darunavir, resulting in increased plasma darunavir concentrations.1

Peak plasma darunavir concentrations attained approximately 2.5–4 hours after a dose.1

Food

Food increases darunavir bioavailability.1

Compared with administration in fasting state, administration of ritonavir-boosted darunavir tablets with food increases peak darunavir concentrations and AUC approximately 40%.1

Distribution

Extent

Distributed into CSF; clinical importance unknown.21

Not known whether distributed into human milk;1 distributed into milk in rats.1

Plasma Protein Binding

95%.1

Binds principally to α1-acid-glycoprotein.1

Elimination

Metabolism

Darunavir extensively metabolized by CYP3A.1

Elimination Route

Following administration of ritonavir-boosted darunavir, eliminated principally in feces as unchanged darunavir.1 Approximately 80% of darunavir dose excreted in feces and 14% excreted in urine.1

Half-life

15 hours.1

Special Populations

Pediatric patients 3 to <18 years of age weighing ≥10 kg: Darunavir concentrations and AUC comparable to those reported in adults.1

Moderate renal impairment (Clcr 30–60 mL/minute): Pharmacokinetics not affected.1

Severe renal impairment or end-stage renal disease: No pharmacokinetic data.1

Unlikely to be removed by hemodialysis or peritoneal dialysis.1

Hepatic impairment: Pharmacokinetics in individuals with mild hepatic impairment (Child-Pugh class A) or moderate hepatic impairment (Child-Pugh class B) similar to values in individuals with normal hepatic function.1 Pharmacokinetics not evaluated in those with severe hepatic impairment.1

HBV or HCV coinfection: No effect on darunavir exposure.1

Higher darunavir concentrations reported in females compared with males; dosage adjustments not required.1

Stability

Storage

Oral

Suspension

25°C (may be exposed to 15–30°C).1 Do not refrigerate or freeze;1 avoid excessive heat.1

Tablets

25°C (may be exposed to 15–30°C).1

Actions and Spectrum

  • Darunavir is administered in conjunction with low-dose ritonavir (ritonavir-boosted darunavir).1

  • Darunavir is extensively metabolized by CYP3A; ritonavir is a potent inhibitor of CYP3A.1 Concomitant use of these drugs results in decreased metabolism and increased plasma concentrations of darunavir.1

  • Antiretroviral activity is due to darunavir.1

  • Active against HIV-1.1 Also has some activity against HIV type 2 (HIV-2).13 200

  • Darunavir inhibits replication of HIV-1 by interfering with HIV proteases.1

  • Darunavir-resistant HIV-1, including strains with decreased susceptibility to other HIV PIs, has been reported.1 3

  • Varying degrees of cross-resistance occur among HIV PIs.1

  • Some clinical isolates of HIV-1 with reduced susceptibility to darunavir have been resistant to atazanavir, fosamprenavir, indinavir, lopinavir, and nelfinavir.1

Advice to Patients

  • Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.1 200 Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.1

  • Importance of using darunavir with low-dose ritonavir; importance of using these 2 drugs in conjunction with other antiretrovirals.1

  • Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.1

  • Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others.200 Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.1 200

  • Importance of reading patient information provided by the manufacturer.1

  • Importance of taking darunavir with food and at the same time as ritonavir.1 Importance of swallowing darunavir tablets whole with a drink (e.g., water, milk).1

  • Once-daily regimen: If a dose of darunavir or ritonavir is missed by <12 hours, take the dose as soon as it is remembered and take the next dose at the regularly scheduled time.1 If a dose of darunavir or ritonavir is missed by >12 hours, omit the dose and take the next dose at the regularly scheduled time.1 Do not take a double dose to make up for a missed dose.1

  • Twice-daily regimen: If a dose of darunavir or ritonavir is missed by <6 hours, take the dose as soon as it is remembered and take the next dose at the regularly scheduled time.1 If a dose of darunavir or ritonavir is missed by >6 hours, omit the dose and take the next dose at the regularly scheduled time.1 Do not take a double dose to make up for a missed dose.1

  • Advise patients that drug-induced hepatitis has occurred.1 Importance of notifying clinician if manifestations of liver disease occur (e.g., jaundice of skin or eyes; dark tea-colored urine; pale stools; nausea; vomiting; loss of appetite; pain, aching, or sensitivity in right upper quadrant of abdomen).1

  • Advise patients that mild to severe skin reactions have occurred.1 Importance of immediately discontinuing ritonavir-boosted darunavir and contacting clinician if manifestations of severe skin reactions occur (e.g., severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia).1

  • Redistribution/accumulation of body fat may occur with antiretroviral therapy, with as yet unknown long-term health effects.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products (e.g., St. John’s wort), and any concomitant illnesses.1

  • Advise patients receiving selective phosphodiesterase type 5 (PDE5) inhibitors (e.g., avanafil, sildenafil, tadalafil, vardenafil) that they may be at increased risk of PDE5 inhibitor-associated adverse effects (e.g., hypotension, visual changes, priapism) and that any symptoms should be promptly reported to clinician.1 Should not be used concomitantly with sildenafil used for treatment of PAH.1

  • Importance of women using a reliable nonhormonal (e.g., barrier) method of contraception because of the potential interaction with hormonal contraceptives.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Darunavir Ethanolate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Suspension

100 mg (of darunavir) per mL

Prezista

Janssen

Tablets, film-coated

75 mg (of darunavir)

Prezista

Janssen

150 mg (of darunavir)

Prezista

Janssen

600 mg (of darunavir)

Prezista

Janssen

800 mg (of darunavir)

Prezista

Janssen

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 07/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Prezista 400MG Tablets (JANSSEN PRODUCTS): 60/$1,086.03 or 120/$2,172.06

Prezista 600MG Tablets (JANSSEN PRODUCTS): 60/$1,129.04 or 180/$3,196.00

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 30, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Janssen. Prezista (darunavir) prescribing information. Titusville, NJ; 2014 Apr.

2. Koh Y, Nakata H, Maeda K et al. Novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro. Antimicrob Agents Chemother. 2003; 47:3123-9. [PubMed 14506019]

3. De Meyer S, Azijn H, Surleraux D et al. TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother. 2005; 49:2314-21. [PubMed 15917527]

6. Banhegyi D, Esser S, Opravil M, Lefebvre E. TMC114/r outperforms investigator-selected PI(s) in treatment-experienced patients: 24-week primary efficacy and safety analysis of POWER 1. 1st European and Central Asian AIDS conference , Moscow, Russia, 2006 May 15–17. Poster. From Tibotec website ().

9. Madruga JV, Berger D, McMurchie M et al. Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial. Lancet. 2007; 370:49-58. [PubMed 17617272]

10. Ortiz R, DeJesus E, Khanlou H et al. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1 infected patients at week 48. AIDS. 2008; 22:1389-97. [PubMed 18614861]

12. Kowa Pharmaceuticals America. Livalo (pitavastatin) tablets prescribing information. Montgomery, AL; 2012 Feb.

13. Desbois D, Roquebert B, Peytavin G et al. In vitro phenotypic susceptibility of human immunodeficiency virus type 2 clinical isolates to protease inhibitors. Antimicrob Agents Chemother. 2008; 52:1545-8. [PubMed 18227188]

17. Food and Drug Administration. FDA drug safety communication: Important drug interactions between Victrelis (boceprevir) and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitor drugs. 2012 Feb 8. From FDA website. Accessed 2012 Apr 23.

18. Food and Drug Administration. FDA drug safety communication: Updated information on drug interactions between Victrelis (boceprevir) and certain boosted HIV protease inhibitor drugs. 2012 Apr 26. From FDA website. Accessed 2012 Jul 9.

19. Hulskotte EG, Feng HP, Xuan F et al. Pharmacokinetic interactions between the hepatitis C virus protease inhibitor boceprevir and ritonavir-boosted HIV-1 protease inhibitors atazanavir, darunavir, and lopinavir. Clin Infect Dis. 2013; 56:718-26. [PubMed 23155151]

20. Orkin C, DeJesus E, Khanlou H et al. Final 192-week efficacy and safety of once-daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV-1-infected treatment-naïve patients in the ARTEMIS trial. HIV Med. 2013; 14:49-59. [PubMed 23088336]

21. Croteau D, Rossi SS, Best BM et al. Darunavir is predominantly unbound to protein in cerebrospinal fluid and concentrations exceed the wild-type HIV-1 median 90% inhibitory concentration. J Antimicrob Chemother. 2013; 68:684-9. [PubMed 23143899]

185. Merck & Co. Victrelis (boceprevir) capsules prescribing information. Whitehouse Station, NJ; 2012 Apr.

186. Food and Drug Administration. FDA drug safety communication: Interactions between certain HIV or hepatitis C drugs and cholesterol-lowering statin drugs can increase the risk of muscle injury. 2012 Mar 1. From FDA website. Accessed 2012 Apr 23.

187. Janssen Products LP. Olysio (simeprevir) capsules prescribing information. Titusville, NJ; 2013 Nov.

188. Gilean Sciences Inc. Sovaldi (sofosbuvir) tablet prescribing information. Foster City, CA; 2013 Dec.

199. Kuhar DT, Henderson DK, Struble KA et al. Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis. Infect Control Hosp Epidemiol. 2013; 34:875-92. [PubMed 23917901]

200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (May 1, 2014). Updates may be available at HHS AIDS Information (AIDSinfo) website.

201. Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in pediatric HIV infection (February 12, 2014). Updates may be available at HHS AIDS Information (AIDSinfo) website.

202. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, US Department of Health and Human Services (HHS). Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States (March 28, 2014). Updates may be available at HHS AIDS Information (AIDSinfo) website.

214. Janssen. Intelence (etravirine) tablets prescribing information. Raritan, NJ; 2012 Mar.

224. ViiV Healthcare. Selzentry (maraviroc) tablets prescribing information. Research Triangle Park, NC; 2011 Nov.

225. Merck Sharp & Dohme. Isentress (raltegravir) film-coated tablets, chewable tablets, and for oral suspension prescribing information. Whitehouse Station, NJ; 2013 Dec.

226. Tibotec Therapeutics. Edurant (rilpivirine) tablets prescribing information. Raritan, NJ; 2011 May.

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