Darunavir (Monograph)
Brand name: Prezista
Drug class: HIV Protease Inhibitors
Introduction
Antiretroviral; HIV protease inhibitor (PI).
Uses for Darunavir
Treatment of HIV Infection
Treatment of HIV infection with low-dose ritonavir (ritonavir-boosted darunavir) in adult and pediatric patients ≥3 years of age weighing ≥10 kg; used in conjunction with other antiretrovirals.
Treatment of HIV infection with cobicistat (cobicistat-boosted darunavir) in treatment-naïve or treatment-experienced adult and pediatric patients weighing ≥40 kg; used in conjunction with other antiretrovirals.
Boosted darunavir is commonly used as part of a fully suppressive antiretroviral regimen in conjunction with 2 nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs); consult guidelines for the most current information on recommended regimens. Selection of an initial antiretroviral regimen should be individualized based on factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, access, and cost.
Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)
Ritonavir-boosted darunavir used in conjunction with 2 NRTIs forpostexposure prophylaxis of HIV infection following occupational exposure [off-label]† [off-label] (PEP) in healthcare personnel and other individuals.
The US Public Health Service (USPHS) recommends 3-drug regimen of raltegravir and emtricitabine and tenofovir disoproxil fumarate (tenofovir DF) as preferred regimen for PEP following occupational exposures to HIV. Ritonavir-boosted darunavir and 2 NRTIs is one of several alternative regimens. 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.
Management of occupational exposures to HIV is complex and evolving; consult infectious diseases specialists, clinicians with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at888-448-4911) whenever possible. Do not delay initiation of PEP while waiting for expert consultation.
Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)
Ritonavir-boosted darunavir used in conjunction with 2 NRTIs for postexposure prophylaxis of HIV infection following nonoccupational exposure [off-label]† [off-label] (nPEP) after sexual, injection drug use, or other nonoccupational exposures.
When nPEP indicated in adults and adolescents ≥13 years of age with normal renal function, US Centers for Disease Control and Prevention (CDC) state preferred regimen is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (given as emtricitabine/tenofovir DF; Truvada); recommended alternative regimen in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF.
Consult infectious diseases specialists, clinicians with expertise in administration of antiretroviral agents, and/or the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) if nPEP indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if considering a regimen not included in CDC guidelines, source virus is known or likely to be resistant to antiretrovirals, or healthcare provider is inexperienced in prescribing antiretrovirals. Do not delay initiation of nPEP while waiting for expert consultation.
Darunavir Dosage and Administration
General
Pretreatment Screening
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In antiretroviral-experienced patients, the treatment history and genotype and/or phenotype testing is recommended prior to therapy initiation of ritonavir-boosted or cobicistat-boosted darunavir to test for drug susceptibility of the HIV-1 virus
-
Prior to initiation of cobicistat-boosted darunavir (administered as fixed-combination darunavir/cobicistat or, alternatively, as single-entity darunavir and single-entity cobicistat), assess estimated creatinine clearance (Clcr). If initiating cobicistat-boosted darunavir with concomitant tenofovir disoproxil fumarate (tenofovir DF), also assess urine glucose and urine protein; additional monitoring of serum phosphorus is recommended in patients with or at risk of renal impairment.
Patient Monitoring
-
In patients with underlying cirrhosis, chronic hepatitis, or baseline serum aminotransferase elevations, monitor liver serum biochemistries, particularly during the first few months of treatment with ritonavir-boosted or cobicistat-boosted darunavir.
-
Perform routine monitoring of estimated Clcr, urine glucose, urine protein, and additional phosphorus monitoring in patients with or at risk for renal impairment when cobicistat-boosted darunavir is used concomitantly with tenofovir DF.
-
Monitor patients closely for renal safety when there is a confirmed serum creatinine increase of >0.4 mg/dL from baseline while on cobicistat-boosted darunavir.
-
Monitor patients with a known sulfonamide allergy after initiation of darunavir.
Dispensing and Administration Precautions
-
Darunavir is commercially available as a single entity and in various fixed-combination preparations containing additional antiretroviral agents. Refer to full prescribing information for specific, distinct uses of the combination products. Since antiretroviral agents contained in the fixed combination preparations also may be available in single-entity or other fixed-combination preparations, exercise care to ensure that therapy is not duplicated if a fixed combination is used in conjunction with other antiretrovirals.
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The Institute for Safe Medication Practices (ISMP) list of error-prone abbreviations, symbols, and dose designations states that the use of abbreviations for antiretroviral medications (e.g., DOR, TAF, TDF) during the medication use process should be avoided as their use has been associated with serious medication errors.
Administration
Oral Administration
Administer orally in conjunction with low-dose ritonavir (ritonavir-boosted darunavir) once or twice daily with food. Alternatively, administer orally in conjunction with cobicistat (cobicistat-boosted darunavir) once daily with food. Do not administer without low-dose ritonavir or cobicistat.
Darunavir is also commercially available in the following fixed-combination tablets for oral use: darunavir/cobicistat (Prezcobix) and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (Symtuza). See the full prescribing information for administration of each of these combination products.
Ritonavir-boosted Darunavir
Administer single-entity darunavir as tablets or oral suspension at same time as single-entity ritonavir capsules, tablets, or oral solution.
Oral suspension:Use in those who have difficulty swallowing tablets. Administer suspension using oral dosing syringe supplied by the manufacturer. If a 675- or 800-mg dose is indicated, give dose as two 3.4- or 4-mL administrations, respectively, using the oral dosing syringe. Supplied as a white to off-white opaque suspension; shake prior to each dose.
Tablets: Swallow tablets whole with a drink (e.g., water, milk). Assess ability to swallow tablets in children weighing ≥15 kg; consider darunavir oral suspension in those unable to reliably swallow tablets.
Cobicistat-boosted Darunavir
Administer fixed-combination tablets containing both drugs (darunavir/cobicistat). Alternatively, administer single-entity darunavir as tablets or oral suspension at same time as single-entity cobicistat tablets.
Dosage
Single-entity darunavir available as oral suspension or tablets containing darunavir ethanolate; dosage expressed in terms of darunavir.
Darunavir/cobicistat available as fixed-combination tablets containing darunavir ethanolate (800 mg of darunavir) and cobicistat (150 mg).
Pediatric Patients
Treatment of HIV Infection in Antiretroviral-naïve Pediatric Patients
Oral
Ritonavir-boosted darunavir (pediatric patients 3 years 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). (See Table 1 and Table 2.)
Dosage (in mL) rounded up for convenient measuring using oral dosing syringe provided by manufacturer.
|
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.
|
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 mLa) once daily |
100 mg (1.25 mL) once daily |
|
≥40 kg |
800 mg (8 mL) once daily |
100 mg (1.25 mL) once daily |
Treatment of HIV Infection in Antiretroviral-experienced Pediatric Patients
Oral
Genotypic testing recommended to identify substitutions associated with darunavir resistance (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).
Ritonavir-boosted darunavir (pediatric patients 3 years to <18 years of age weighing ≥10 kg with no substitutions 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). (See Table 3 and Table 4.)
Dosage (in mL) rounded up for convenient measuring using oral dosing syringe provided by manufacturer.
|
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.
|
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 |
Ritonavir-boosted darunavir (pediatric patients 3 years 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). (See Table 5 and Table 6.)
|
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.
|
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 |
Cobicistat-boosted darunavir in pediatric patients weighing ≥ 40 kg without any mutations associated with darunavir resistance: 1 tablet of darunavir/cobicistat (800 mg of darunavir and 150 mg of cobicistat) once daily. Alternatively, single-entity darunavir 800 mg (one 800-mg darunavir tablet or 8 mL of darunavir oral suspension containing 100 mg/mL) once daily can be administered in conjunction with single-entity cobicistat (150 mg once daily). Both drugs must be administered in conjunction with other antiretroviral agents active against HIV-1.
Adults
Treatment of HIV Infection in Antiretroviral-naïve Patients
Oral
Ritonavir-boosted darunavir: Single-entity darunavir 800 mg (one 800-mg tablet or 8 mL of oral suspension containing 100 mg/mL) once daily in conjunction with low-dose ritonavir (100 mg once daily).
Cobicistat-boosted darunavir: 1 tablet of darunavir/cobicistat (800 mg of darunavir and 150 mg of cobicistat) once daily. Alternatively, single-entity darunavir 800 mg (one 800-mg darunavir tablet or 8 mL of darunavir oral suspension containing 100 mg/mL) once daily in conjunction with single-entity cobicistat (150 mg once daily).
Treatment of HIV Infection in Antiretroviral-experienced Adults
Genotypic testing recommended to identify substitutions associated with darunavir resistance (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).
Ritonavir-boosted darunavir in patients with no substitutions associated with darunavir resistance: Single-entity darunavir 800 mg (one 800-mg tablet or 8 mL of oral suspension containing 100 mg/mL) once daily in conjunction with low-dose ritonavir (100 mg once daily).
Ritonavir-boosted darunavir in patients with ≥1 substitution associated with darunavir resistance: Single-entity darunavir 600 mg (one 600-mg tablet or 6 mL of oral suspension containing 100 mg/mL) twice daily in conjunction with low-dose ritonavir (100 mg twice daily).
Ritonavir-boosted darunavir when genotypic testing not feasible: Single-entity darunavir 600 mg (one 600-mg tablet or 6 mL of oral suspension containing 100 mg/mL) twice daily in conjunction with low-dose ritonavir (100 mg twice daily).
Cobicistat-boosted darunavir: 1 tablet of darunavir/cobicistat (800 mg of darunavir and 150 mg of cobicistat) once daily. Alternatively, single-entity darunavir 800 mg (one 800-mg darunavir tablet or 8 mL of darunavir oral suspension containing 100 mg/mL) once daily in conjunction with single-entity cobicistat (150 mg once daily).
Darunavir dosage of 600 mg twice daily in conjunction with cobicistat not recommended.
Postexposure Prophylaxis following Occupational Exposure to HIV [PEP, off-label]† [off-label]
Oral
Ritonavir-boosted darunavir: Single-entity darunavir 800 mg once daily in conjunction with low-dose ritonavir (100 mg once daily). Alternatively, single-entity darunavir 600 mg twice daily in conjunction with low-dose ritonavir (100 mg twice daily). Use in conjunction with 2 NRTIs.
Initiate PEP as soon as possible following exposure to HIV (preferably within hours); continue for 28 days, if tolerated.
Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)† [off-label]
Oral
Ritonavir-boosted darunavir: single-entity darunavir 800 mg daily with low-dose ritonavir (100 mg once daily). Use in conjunction with 2 NRTIs. Initiate nPEP as soon as possible (within 72 hours) following nonoccupational exposure that represents a substantial risk for HIV transmission and continue for 28 days. nPEP may not be recommended if exposed individual seeks care >72 hours after exposure.
Special Populations
Hepatic Impairment
Ritonavir-boosted darunavir: Dosage adjustments not necessary in patients with mild to moderate hepatic impairment (Child-Pugh class A or B). Not recommended for use in those with severe hepatic impairment (Child-Pugh class C).
Cobicistat-boosted darunavir: Dosage adjustments not necessary in patients with mild to moderate hepatic impairment (Child-Pugh class A or B). Do not use in those with severe hepatic impairment (Child- Pugh class C).
Renal Impairment
Ritonavir-boosted darunavir: No pharmacokinetic data in renal impairment; however, manufacturer states that renal clearance of darunavir is limited.
Cobicistat-boosted darunavir: Assess estimated Clcr prior to initiation of fixed-combination darunavir/cobicistat or, alternatively, single-entity darunavir with single-entity cobicistat. Do not usecobicistat-boosted darunavir in conjunction with tenofovir DF in patients with estimated Clcr <70 mL/minute.
Geriatric Use
Ritonavir-boosted or cobicistat-boosted darunavir: Select dosage with caution because of age-related decreases in hepatic function, concomitant disease, or other drug therapy.
Pregnant Females
Use ritonavir-boosted darunavir. Cobicistat-boosteddarunavir should not be used in pregnancy.
Ritonavir-boosted darunavir (twice-daily regimen): 600 mg of single-entity darunavir (one 600-mg tablet or 6 mL of the oral suspension containing 100 mg/mL) twice daily with single-entity ritonavir 100 mg twice daily.
Ritonavir-boosted darunavir (once-daily regimen): 800 mg of single-entity darunavir once daily (one 800-mg tablet or 8 mL of the oral suspension containing 100 mg/mL once daily) with single-entity ritonavir 100 mg once daily be used only in females already stabilized on this regimen prior to pregnancy who are virologically suppressed (i.e., plasma HIV-1 RNA levels <50 copies/mL) and in whom a change to a twice-daily regimen may compromise tolerability or compliance.
Cautions for Darunavir
Contraindications
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Concomitant use of ritonavir-boosted darunavir or cobicistat-boosted darunavir with drugs highly dependent on cytochrome P-450 (CYP) isoenzyme CYP3A for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events.
-
Concomitant use of cobicistat-boosteddarunavir with drugs that are CYP3A inducers which may lead to lower darunavir and cobicistat exposures and potential loss of efficacy and the development of resistance.
-
Examples of drugs contraindicated for administration with ritonavir-boosted darunavir or cobicistat-boosted darunavir include: alfuzosin, carbamazepine, phenobarbital, phenytoin, colchicine in patients with renal or hepatic impairment, rifampin, lurasidone, pimozide, dronedarone, ivabradine, ranolazine, dihydroergotamine (DHE), ergotamine, methylergonovine, St. John's wort (Hypericum perforatum), the fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir), lomitapide, lovastatin, simvastatin, naloxegol, orally administered midazolam and triazolam, and sildenafil (Revatio) for treatment of pulmonary arterial hypertension.
Warnings/Precautions
Warnings
Coadministration of Single-entity Darunavir with Ritonavir
Single-entity darunavir must be coadministered with ritonavir and food to achieve the desired antiviral effect. Failure to administer single-entity darunavir with ritonavir and food may result in a loss of efficacy of darunavir.
Dermatologic Reactions
Severe skin reactions, sometimes accompanied by fever and/or increased serum aminotransferase concentrations, reported with ritonavir-boosted darunavir. Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, and acute, generalized exanthematous pustulosis reported.
Immediately discontinue ritonavir-boosted or cobicistat-boosted 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).
Sulfonamide Sensitivity
Darunavir contains a sulfonamide moiety; may cause allergic-type reaction in certain susceptible individuals.
Use ritonavir-boosted or cobicistat-boosted darunavir with caution and close monitoring in patients with known hypersensitivity to sulfonamide-containing drugs.
Hepatotoxicity
Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) reported in clinical studies. Patients with preexisting liver dysfunction, including HIV-infected patients coinfected with HBV or HCV, have increased risk for liver function abnormalities. Postmarketing reports of liver injury (in some cases fatal) in patients receiving ritonavir-boosted darunavir; 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.
Conduct appropriate laboratory tests to evaluate hepatic function prior to and periodically during ritonavir-boosted or cobicistat-boosted darunavir therapy. Consider increased AST/ALT monitoring in patients with hepatitis, cirrhosis, or elevated aminotransferase concentrations prior to therapy, especially during first several months of therapy.
Consider interrupting or discontinuing ritonavir-boosted or cobicistat-boosted 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).
Renal Effects
Cobicistat decreases estimated Clcr by inhibiting tubular secretion of creatinine without affecting actual renal glomerular function; consider this effect when interpreting changes in estimated Clcr in patients receiving cobicistat-boosted darunavir, particularly those needing Clcr monitoring due to a medical condition or other concomitant drugs.
Assess estimated Clcr prior to initiating cobicistat-boosted darunavir. Although cobicistat may cause only modest increases in Scr and modest declines in estimated Clcr without affecting renal glomerular function, closely monitor patient for renal safety if Scr increases >0.4 mg/dL from baseline during cobicistat-boosted darunavir therapy.
Manufacturer states dosage recommendations not available for drugs requiring dosage adjustments in patients with renal impairment who are receiving cobicistat-boosted darunavir; consider alternative concomitant drugs that do not require dosage adjustments based on renal impairment.
New-onset or worsening renal impairment, including acute renal failure and Fanconi syndrome, reported in patients receiving cobicistat in an antiretroviral regimen that also includes tenofovir DF. Concomitant use of cobicistat-boosted darunavir and tenofovir DF not recommended in patients with estimated Clcr <70 mL/minute or in patients who are receiving (or recently received) a nephrotoxic agent. Whenever cobicistat-boosted darunavir and tenofovir DF are used concomitantly, document urine glucose and urine protein at baseline and monitor estimated Clcr, urine glucose, and urine protein throughout concomitant therapy. In addition, monitor serum phosphorus in those with or at risk for renal impairment.
Interactions
Darunavir must be used in conjunction with a pharmacokinetic enhancer (i.e., low-dose ritonavir or cobicistat). Failure to administer darunavir with recommended dosage of ritonavir or cobicistat may result in subtherapeutic darunavir concentrations and inadequate antiviral response. When ritonavir-boosted or cobicistat-boosted darunavir used, consider cautions, precautions, contraindications, and drug interactions associated with both darunavir and the pharmacokinetic enhancer.
Concomitant use of ritonavir-boosted or cobicistat-boosted darunavir with certain drugs is contraindicated or requires particular caution. Concomitant use with some drugs may result in clinically important adverse effects, including severe, life-threatening, or fatal events due to higher exposures of the concomitant drug or higher exposures of darunavir and/or the pharmacokinetic enhancer (i.e., low-dose ritonavir or cobicistat). Concomitant use with other drugs may result in drug interactions leading to loss of therapeutic effect of ritonavir-boosted or cobicistat-boosted darunavir and possible development of resistance. Because ritonavir and cobicistat are inhibitors of CYP3A, interactions with drugs affecting or metabolized by CYP3A are of particular concern.
Consider that concomitant use of cobicistat-boosted darunavir with other drugs may result in different drug interactions than those observed or expected with ritonavir-boosted darunavir due to complex or unknown mechanisms of drug interactions.
Concomitant use of ritonavir-boosted or cobicistat-boosted darunavir with other drugs that are administered in conjunction with a pharmacokinetic enhancer (e.g., ritonavir-boosted HIV PIs, ritonavir-boosted paritaprevir, elvitegravir) is not recommended. Dosage recommendations for such regimens not established; concomitant use of more than one pharmacokinetic enhancer may result in complex drug interactions, including decreased plasma concentrations of the antiretroviral leading to loss of therapeutic effect and development of resistance.
Consider potential drug interactions prior to and during use of ritonavir-boosted or cobicistat-boosted darunavir. Monitor for adverse effects associated with drugs used concomitantly with ritonavir-boosted or cobicistat-boosted darunavir.
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.
Initiate or adjust antidiabetic therapy (e.g., insulin, oral hypoglycemic agents) as needed.
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 jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.
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.
Fat Redistribution
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 reported. Mechanisms and long-term consequences unknown; causal relationship not established.
Hemophilia A and B
Increased bleeding, including spontaneous skin hematomas and hemarthrosis, reported with HIV PIs; causal relationship not established.
Increased hemostatic therapy (e.g., antihemophilic factor) may be needed.
HIV Resistance
Possibility of cross-resistance to other HIV PIs not evaluated. Effect of ritonavir-boosted darunavir therapy on subsequent therapy with other PIs unknown.
Use in Pediatric Patients Below 3 Years of Age
Use of single-agent darunavir in combination with ritonavir not recommended in pediatric patients <3 years of age because of toxicity and mortality observed in animal studies.
Specific Populations
Pregnancy
Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].
Available human and animal data suggest that darunavir does not increase the risk of major birth defects overall compared to background rate.
Cobicistat-boosted darunavir: Manufacturer states to not use cobicistat-boosted darunavir in pregnancy due to reduced exposures in the second and third trimesters. An alternative regimen is recommended.
Lactation
Not known whether darunavir, ritonavir, or cobicistat distributed into human milk; darunavir and cobicistat distributed into milk in rats.
The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
Female and Males of Reproductive Potential
Darunavir may reduce efficacy of combined hormonal contraceptives and progestin-only pill. Advise patients to use an effective alternative (non-hormonal) contraceptive method or add a barrier method of contraception. For co-administration with drospirenone, clinical monitoring is recommended due to the potential for hyperkalemia. No data are available to make recommendations regarding coadministration with other hormonal contraceptives.
Pediatric Use
Ritonavir-boosted darunavir: Not recommended in children <3 years of age; toxicity and mortality reported in juvenile rats.
Ritonavir-boosted darunavir: Adverse effects in children 3 years to <18 years of age similar to those reported in adults.
Cobicistat-boosted darunavir: Safety and efficacy established in patients weighing ≥ 40 kg.
Geriatric Use
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.
Ritonavir-boosted or cobicistat-boosted darunavir: Use with caution and monitor because of age-related decreases in hepatic function and concomitant disease and drug therapy.
Hepatic Impairment
Ritonavir-boosted darunavir: Pharmacokinetics not altered in individuals with mild or moderate hepatic impairment (Child-Pugh class A or B). Pharmacokinetics not evaluated in patients with severe hepatic impairment (Child-Pugh class C); not recommended in such patients.
Cobicistat-boosted darunavir: Pharmacokinetics not established in individuals with mild or moderate hepatic impairment (Child-Pugh class A or B); no clinically important pharmacokinetic changes when cobicistat used alone in individuals with mild or moderate hepatic impairment. Pharmacokinetics of cobicistat-boosted darunavir or cobicistat alone not evaluated in patients with severe hepatic impairment (Child-Pugh class C); cobicistat-boosted darunavir not recommended in such patients.
Risk for liver function abnormalities, including severe adverse hepatic effects, increased in patients with preexisting hepatic impairment, including those with HBV or HCV infection.
Monitor liver function during first several months of treatment with ritonavir-boosted darunavir when the drug used in patients with underlying chronic hepatitis or cirrhosis or in patients with pretreatment elevated liver enzymes.
Consider interruption or discontinuance of ritonavir-boosted or cobicistat-boosted darunavir if there is evidence of new or worsening liver disease.
Darunavir exposure not altered in HIV-infected patients coinfected with HBV or HCV.
Renal Impairment
Ritonavir-boosted darunavir: No pharmacokinetic data in renal impairment; however, manufacturer states that renal clearance of darunavir is limited.
Cobicistat-boosted darunavir: Assess estimated Clcr prior to initiation of fixed-combination darunavir/cobicistat or, alternatively, single-entity darunavir with single-entity cobicistat. Manufacturer states do not use cobicistat-boosted darunavir in conjunction with tenofovir DF in patients with estimated Clcr <70 mL/minute.,
Common Adverse Effects
Adverse effects of at least moderate intensity (greater than or equal to Grade 2) reported in more than 5% of patients receiving ritonavir-boosted or cobicistat-boosted darunavir in conjunction with other antiretrovirals are diarrhea, nausea, vomiting, abdominal pain, headache, and rash.
Drug Interactions
Darunavir, ritonavir, and cobicistat metabolized principally by CYP3A. Darunavir, ritonavir, and cobicistat inhibit CYP3A and CYP2D6.
Darunavir must be used with a pharmacokinetic enhancer (i.e., low-dose ritonavir or cobicistat); consider drug interactions associated with both darunavir and the pharmacokinetic enhancer. Interactions reported or expected with ritonavir-boosted darunavir may differ from those reported or expected with cobicistat-boosted darunavir.
The following drug interactions are based on studies using ritonavir-boosted darunavir, or studies using cobicistat alone. Drug interaction studies not available to date using cobicistat-boosted darunavir administered either as fixed-combination darunavir/cobicistat or as single-entity darunavir given with single-entity cobicistat.
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
CYP3A inducers: Potential pharmacokinetic interactions with ritonavir-boosted or cobicistat-boosted darunavir (increased clearance of darunavir, ritonavir, or cobicistat; possible loss of antiretroviral efficacy and development of resistance).
CYP3A inhibitors: Potential pharmacokinetic interactions with ritonavir-boosted or cobicistat-boosted darunavir (increased plasma concentrations of darunavir, ritonavir, or cobicistat).
CYP3A substrates: Potential pharmacokinetic interactions with ritonavir-boosted or cobicistat-boosted darunavir (altered metabolism of CYP3A substrates).
CYP2D6 substrates: Potential pharmacokinetic interactions with ritonavir-boosted or cobicistat-boosted darunavir (increased plasma concentrations of CYP2D6 substrates; possible increased or prolonged therapeutic effects and increased risk of associated adverse effects).
Drugs Affected by P-glycoprotein Transport
P-gp substrates: Potential pharmacokinetic interactions with ritonavir-boosted or cobicistat-boosted darunavir (increased plasma concentrations of P-gp substrates; possible increased or prolonged therapeutic effects and increased risk of associated adverse effects).
P-gp inhibitors: Potential pharmacokinetic interactions with ritonavir-boosted or cobicistat-boosted darunavir (decreased clearance of darunavir and ritonavir leading to increased plasma concentrations).
Drugs Affecting or Affected by Other Membrane Transporters
BCRP, OATP1B1, or OATP1B3 substrates: Potential pharmacokinetic interactions with cobicistat-boosted darunavir (increased plasma concentrations of such substrates; possible increased or prolonged therapeutic effects and increased risk of associated adverse effects).
Specific Drugs
|
Drug |
Interaction |
Comments |
|---|---|---|
|
Abacavir |
Ritonavir-boosted or cobicistat-boosted darunavir: Pharmacokinetic interactions not expected No in vitro evidence of antagonistic antiretroviral effects with darunavir |
Ritonavir-boosted darunavir: Dosage adjustments not needed |
|
Alfuzosin |
Ritonavir-boosted or cobicistat-boosted darunavir: Potential for serious and/or life-threatening reactions (e.g., hypotension) |
Concomitant use contraindicated |
|
Antacids |
Acid-modifying drugs not expected to alter darunavir exposure |
|
|
Antiarrhythmic agents (amiodarone, disopyramide, dronedarone, flecainide, systemic lidocaine, mexiletine, propafenone, quinidine) |
Ritonavir-boosted or cobicistat- boosted darunavir: Possible increased antiarrhythmic agent concentrations |
Dronedarone: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated Amiodarone, disopyramide, flecainide, systemic lidocaine, mexiletine, propafenone, quinidine: Monitor antiarrhythmic concentrations |
|
Anticoagulants, oral (apixaban, dabigatran, edoxaban, rivaroxaban, warfarin) |
Apixaban, edoxaban, dabigatran, rivaroxaban: Possible increased anticoagulant concentrations if used with ritonavir-boosted orcobicistat-boosted darunavir Warfarin: Decreased warfarin concentrations and no change in darunavir concentrations if used with ritonavir-boosted darunavir; effect of concomitant use with cobicistat-boosted darunavir unknown |
Apixaban: Refer to apixaban prescribing information for dosing instructions if used concomitantly with ritonavir-boostedor cobicistat-boosted darunavir Rivaroxaban: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir not recommended Dabigatran: Concomitant use with ritonavir-boostedor cobicistat-boosted darunavir based upon indication, concomitant P-gp inhibitors, and renal impairment. Refer to dabigatran prescribing information for specific recommendations regarding concomitant use; clinical monitoring recommended Edoxaban: Refer to the prescribing information for edoxaban for dosing when used concomitantly with ritonavir-boosted or cobicistat-boosted darunavir; clinical monitoring recommended during concomitant use Warfarin: Monitor INR if used with ritonavir- or cobicistat-boosted darunavir |
|
Anticonvulsants (carbamazepine, eslicarbazepine, ethosuximide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin) |
Carbamazepine: If used with ritonavir-boosted darunavir, increased carbamazepine concentrations and no change in darunavir concentrations; if used with cobicistat-boosted darunavir, increased carbamazepine concentrations, decreased cobicistat concentrations, and possibility of substantially decreased darunavir concentrations, loss of therapeutic effect and development of resistance Eslicarbazepine: Possible decreased cobicistat concentrations if used with cobicistat-boosted darunavir; effect on darunavir concentrations unknown Oxcarbazepine: If used with cobicistat-boosted darunavir, decreased cobicistat concentrations, but effect on darunavir concentrations unknown Phenobarbital, phenytoin: If used with ritonavir-boosted darunavir, possible decreased phenobarbital concentrations, but no change in darunavir concentrations; if used with cobicistat-boosted darunavir, decreased cobicistat and darunavir concentrations expected and may result in loss of therapeutic effect and development of resistance, but effect on phenobarbital concentrations unknown |
Carbamazepine: If used with ritonavir-boosted darunavir, dosage adjustments not needed, but monitor carbamazepine concentrations and adjust anticonvulsant dosage to achieve appropriate clinical effect; concomitant use with cobicistat-boosted darunavir contraindicated Eslicarbazepine: Consider alternative anticonvulsant or alternative antiretroviral; if used concomitantly with cobicistat-boosted darunavir, monitor for lack or loss of antiretroviral response Oxcarbazepine: In patients receiving cobicistat-boosted darunavir, consider alternative anticonvulsant or alternative antiretroviral or, if concomitant use necessary, monitor for lack or loss of virologic response Phenobarbital, phenytoin: If used with ritonavir-boosteddarunavir, monitor anticonvulsant concentrations or consider alternative anticonvulsant; concomitant use with cobicistat-boosted darunavir contraindicated |
|
Antifungals, azoles (isavuconazole, itraconazole, ketoconazole, posaconazole, voriconazole) |
Isavuconazole: Possible increased isavuconazole, cobicistat, and darunavir concentrations if used with cobicistat-boosted darunavir Possible increased isavuconazole and darunavir concentrations if used with ritonavir-boosted darunavir Itraconazole: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased itraconazole, darunavir, and cobicistat concentrations Ketoconazole: If used with ritonavir-boosted or cobicistat- boosted darunavir, increased ketoconazole, darunavir, and cobicistat concentrations Posaconazole: If used with ritonavir-boosted or cobicistat- boosted darunavir, possible increased posaconazole, darunavir,and cobicistat concentrations Voriconazole: If used with ritonavir-boosted darunavir, possible decreased voriconazole concentrations; data not available regarding use with cobicistat-boosted darunavir |
Isavuconazole: Monitor for darunavir and cobicistat-associated adverse effects and virologic efficacy if used with ritonavir-boosted or cobicistat-boosted darunavir; monitor for isavuconazole adverse reactions Itraconazole: If used with ritonavir-boostedor cobicistat- boosted darunavir, monitor for itraconazole-, darunavir-, and ritonavir- or cobicistat- associated adverse effects and consider monitoring itraconazole concentrations; itraconazole dosage >200 mg daily not recommended Ketoconazole: If used with ritonavir-boostedor cobicistat-boosteddarunavir, monitor for ketoconazole-, darunavir-, and ritonavir- or cobicistat-associated adverse effects; ketoconazole dosage >200 mg daily not recommended in those receiving ritonavir-boosted darunavir Posaconazole: If used with ritonavir-boosted or cobicistat- boosted darunavir, monitor for posaconazole-, darunavir-, and ritonavir- or cobicistat-associated adverse effects Voriconazole: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir not recommended unless benefits outweigh risks |
|
Antimalarial agents |
Fixed combination of artemether and lumefantrine (artemether/lumefantrine): If used with ritonavir-boosted darunavir, decreased concentrations and AUC of artemether and active metabolite of artemether, increased concentrations and AUC of lumefantrine and increased risk of QT interval prolongation, but no effect on darunavir or ritonavir concentrations or AUC; if used with cobicistat-boosted darunavir, effects on lumefantrine and artemether concentrations unknown |
Artemether/lumefantrine: If used with ritonavir-boosted or cobicistat-boosteddarunavir, monitor for antimalarial efficacy and lumefantrine toxicity (e.g., QT interval prolongation); dosage adjustments not needed if used with ritonavir-boosted darunavir, but use caution |
|
Antimycobacterials (rifabutin, rifampin, rifapentine) |
Rifabutin: If used with ritonavir-boosted darunavir, increased rifabutin and darunavir concentrations; if used with cobicistat-boosted darunavir, possible increased rifabutin concentrations, but effect on darunavir and cobicistat concentrations unknown Rifampin: If used with ritonavir-boosted or cobicistat-boosted darunavir, substantially decreased darunavir concentrations and possible loss of antiretroviral effects Rifapentine: If used with ritonavir-boosted or cobicistat-boosted darunavir, decreased darunavir concentrations expected |
Rifabutin: If used concomitantly with ritonavir-boosted or cobicistat-boosted darunavir, reduce rifabutin dosage to 150 mg once every other day (further reduction may be needed) and monitor for adverse effects (e.g., neutropenia, uveitis) Rifampin: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated Rifapentine: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir not recommended |
|
Antineoplastic agents (dasatinib, irinotecan, nilotinib, vinblastine, vincristine) |
Dasatinib, irinotecan, nilotinib, vinblastine, vincristine: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased antineoplastic concentrations |
Dasatinib, nilotinib: If used with ritonavir-boosted or cobicistat-boosted darunavir, reduced dosage of the antineoplastic may be needed Irinotecan: If used with ritonavir-boostedor cobicistat-boosted darunavir, discontinue ritonavir-boostedor cobicistat-boosted darunavir therapy at least 7 days prior to initiation of irinotecan. Do not use irinotecan concomitantly unless no therapeutic alternatives are available Vincristine, vinblastine: If used with ritonavir-boosted or cobicistat-boosted darunavir, consider temporarily withholding antiretroviral regimen in patients with clinically important hematologic or GI adverse effects; if antiretroviral regimen must be withheld for a prolonged period, consider changing to different antiretroviral regimen that does not include a CYP3A or P-gp inhibitor |
|
Antipsychotics (lurasidone, perphenazine, pimozide, quetiapine, risperidone, thioridazine) |
Lurasidone: If used with ritonavir-boosted or cobicistat-boosted darunavir, potential for serious and/or life-threatening adverse effects Perphenazine, risperidone, thioridazine: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased antipsychotic concentrations Pimozide: If used with ritonavir-boosted or cobicistat-boosted darunavir, potential for serious and/or life-threatening adverse effects (e.g., cardiac arrhythmias) Quetiapine: If used with ritonavir-boosted or cobicistat-boosted darunavir, increased quetiapine concentrations expected |
Lurasidone: Concomitant use with ritonavir-boosted or cobicistat-boosteddarunavir contraindicated Perphenazine, risperidone, thioridazine: Decreased antipsychotic dosage may be needed if used with ritonavir-boosted or cobicistat-boosted darunavir Pimozide: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated Quetiapine: Consider alternative antiretroviral; if ritonavir-boosted or cobicistat-boosted darunavir necessary in patient receiving stable quetiapine dosage, reduce quetiapine dosage to one-sixth of original dosage and monitor for quetiapine efficacy and adverse effects. If initiating quetiapine in patients taking ritonavir-boosted or cobicistat-boosteddarunavir, refer to quetiapine prescribing information for initial dosing and titration information. |
|
Atazanavir |
Unboosted atazanavir: Depending on regimen used, no clinically important change in atazanavir or darunavir concentrations or AUC No in vitro evidence of antagonistic antiretroviral effects with darunavir |
Ritonavir-boosted atazanavir: Concomitant use with ritonavir- boosted darunavir not recommended |
|
Avanafil |
Ritonavir-boosted or cobicistat-boosted darunavir: Increased avanafil concentrations and increased risk of avanafil- associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope) |
Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use not recommended |
|
Benzodiazepines (clonazepam, diazepam, estazolam, midazolam, triazolam) |
Clonazepam: If used with ritonavir-boosted or cobicistat-boosted darunavir, increased clonazepam concentrations Diazepam: If used with ritonavir-boostedor cobicistat-boosted darunavir, possible increased diazepam concentrations Estazolam: If used with ritonavir-boosted or cobicistat-boosteddarunavir, possible increased estazolam concentrations Midazolam or triazolam: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased midazolam or triazolam concentrations and potential for serious and/or life-threatening effects (e.g., prolonged or increased sedation or respiratory depression) |
Clonazepam: If used with ritonavir-boostedor cobicistat-boosted darunavir, monitor patient clinically Diazepam: If used with ritonavir-boosted or cobicistat-boosted darunavir, titrate diazepam dosage, consider lower diazepam dosage, and monitor for adverse effects Estazolam: If used with ritonavir-boosted or cobicistat-boosted darunavir, titrate estazolam dosage, consider lower estazolam dosage, and monitor for adverse effects Oral midazolam or triazolam: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated Parenteral midazolam: Use concomitantly with ritonavir-boostedor cobicistat-boosted darunavir with caution and in monitored setting where respiratory depression and/or prolonged sedation can be managed; consider reduced midazolam dosage, especially if multiple midazolam doses are given |
|
β-Adrenergic blocking agents (carvedilol, metoprolol, timolol) |
Carvedilol, metoprolol, timolol: If used with ritonavir-boosted or cobicistat-boosted darunavir, possible increased concentrations of the β-blocker |
Carvedilol, metoprolol, timolol: If used with ritonavir-boostedor cobicistat-boosted darunavir, clinical monitoring recommended and reduced dosage of β-blocker may be needed |
|
Bosentan |
Ritonavir-boosted darunavir: Possible increased bosentan concentrations Cobicistat-boosted darunavir: Possible increased bosentan concentrations and decreased darunavir and cobicistat concentrations |
In patients already receiving ritonavir-boosted or cobicistat-boosted darunavir for ≥10 days, initiate bosentan using dosage of 62.5 mg once daily or every other day based on individual tolerability In patients already receiving bosentan, discontinue bosentan for at least 36 hours prior to initiating ritonavir-boosted or cobicistat-boosteddarunavir; after ≥10 days of ritonavir-boostedor cobicistat-boosted darunavir, resume bosentan using dosage of 62.5 mg once daily or every other day based on individual tolerability If ritonavir-boosted darunavir is switched to cobicistat-boosted darunavir, maintain current bosentan dosage |
|
Buprenorphine, buprenorphine/naloxone |
Ritonavir-boosted darunavir: Increased norbuprenorphine concentrations and AUC Cobicistat-boosted darunavir: Effect on buprenorphine or buprenorphine/naloxone unknown |
Ritonavir-boosted darunavir: Dosage adjustments not needed, but monitor patient Cobicistat-boosted darunavir: If initiating buprenorphine or buprenorphine/naloxone in patient already receiving cobicistat-boosted darunavir, use lowest possible dosage and carefully titrate to desired therapeutic effect; if initiating cobicistat-boosted darunavir in patient already receiving buprenorphine or buprenorphine/naloxone, monitor patient and consider that dosage adjustments may be needed |
|
Buspirone |
Ritonavir-boosted or cobicistat- boosted darunavir: Possible increased buspirone concentrations |
Ritonavir-boosted or cobicistat- boosted darunavir: Titration of buspirone recommended, consider lower buspirone dosage, and monitor for adverse effects |
|
Calcium-channel blocking agents (amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil) |
Ritonavir-boosted or cobicistat-boosted darunavir: Increased calcium-channel blocking agent concentrations |
Ritonavir-boosted or cobicistat- boosted darunavir: Use concomitantly with caution; clinical monitoring recommended |
|
Cisapride |
Ritonavir-boosted or cobicistat-boosted darunavir: Potential for serious and/or life-threatening effects such as cardiac arrhythmias |
Ritonavir-boosted or cobicistat- boosted darunavir: Concomitant use contraindicated |
|
Clopidogrel |
Ritonavir-boosted or cobicistat-boosteddarunavir: Decreased concentration of clopidogrel active metabolite |
Ritonavir-boostedor cobicistat-boosted darunavir: Concomitant use not recommended |
|
Cobicistat |
Increased darunavir concentrations and AUC; used as a pharmacokinetic enhancer (pharmacokinetic booster) for therapeutic advantage (cobicistat-boosted darunavir) |
|
|
Colchicine |
Ritonavir-boosted or cobicistat- boosted darunavir: Increased colchicine concentrations |
Patients with renal or hepatic impairment: Concomitant use of colchicine and ritonavir-boosted or cobicistat-boosted darunavir contraindicated Colchicine for treatment of gout flares: In those receiving ritonavir-boosted or cobicistat- 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 later Colchicine for prophylaxis of gout flares: In those receiving ritonavir-boosted or cobicistat-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 daily Colchicine for treatment of familial Mediterranean fever (FMF): In those receiving ritonavir-boosted or cobicistat-boosted darunavir, use maximum colchicine dosage of 0.6 mg daily (may be given as 0.3 mg twice daily) |
|
Corticosteroids |
Steroids that undergo CYP3A inhibition: Increased corticosteroid concentrations if used with ritonavir-boosted or cobicistat-boosteddarunavir; may result in adrenal insufficiency or Cushing's syndrome. These corticosteroids include: betamethasone, budesonide, ciclosenide, fluticasone, methylprednisolone, mometasone, triamcinolone Dexamethasone (systemic): Decreased darunavir or ritonavir concentrations if used with ritonavir-boosted darunavir; decreased darunavir or cobicistat concentrations if used with cobicistat-boosted darunavir; possible decreased antiretroviral efficacy |
Consider alternative corticosteroids that are less affected by CYP3A inhibition (e.g., beclomethasone, prednisone, prednisolone), particularly for long-term use Dexamethasone with ritonavir-boosted darunavir or cobicistat-boosted darunavir: Consider alternative corticosteroid |
|
Delavirdine |
No in vitro evidence of antagonistic antiretroviral effects with darunavir |
|
|
Dextromethorphan |
Ritonavir-boosted darunavir:Increased dextromethorphan concentrations |
|
|
Didanosine |
Didanosine delayed-release capsules: No change in didanosine or darunavir concentrations if used with ritonavir-boosted or cobicistat-boosted darunavir No in vitro evidence of antagonistic antiretroviral effects with darunavir |
Administer didanosine (without food) 1 hour before or 2 hours after ritonavir-boosted darunavir (with food) or cobicistat-boosted darunavir (with food) |
|
Digoxin |
Ritonavir-boosted or cobicistat- boosted darunavir: Increased digoxin concentrations |
Ritonavir-boosted or cobicistat-boosted darunavir: Titrate the dosage of digoxin and monitor serum digoxin concentrations to the desired clinical effect |
|
Dolutegravir |
Ritonavir-boosted darunavir: No clinically important effect on pharmacokinetics of either drug Cobicistat-boosted darunavir: Clinically important interactions not expected |
|
|
Efavirenz |
Ritonavir-boosted darunavir: Decreased darunavir AUC; increased efavirenz AUC Cobicistat-boosted darunavir: Possible decreased darunavir and cobicistat concentrations; possible loss of therapeutic effect and development of darunavir resistance No in vitro evidence of antagonistic antiretroviral effects with darunavir |
Ritonavir-boosted darunavir: Usual dosages can be used Cobicistat-boosteddarunavir: Concomitant use not recommended |
|
Elbasvir and grazoprevir |
Ritonavir-boosted or cobicistat-boosted darunavir: Increased elbasvir and grazoprevir concentrations; may increase risk of elevated ALT concentrations |
Ritonavir-boosted or cobicistat- boosted darunavir: Concomitant use with fixed combination of elbasvir and grazoprevir contraindicated |
|
Emtricitabine |
Ritonavir-boosted or cobicistat-boosted darunavir: Pharmacokinetic interactions not expected No in vitro evidence of antagonistic antiretroviral effects with darunavir |
|
|
Enfuvirtide |
No in vitro evidence of antagonistic antiretroviral effects with darunavir |
|
|
Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine) |
Ritonavir-boosted or cobicistat-boosteddarunavir: Potential for serious or life-threatening adverse effects (e.g., peripheral vasospasm, ischemia of extremities) |
Concomitant use with ritonavir-boosted or cobicistat-boosteddarunavir contraindicated |
|
Estrogens/progestins |
Oral hormonal contraceptives containing ethinyl estradiol and norethindrone: Decreased ethinyl estradiol and norethindrone concentrations if used with ritonavir-boosted darunavir; data not available regarding use with cobicistat-boosted darunavir Oral hormonal contraceptives containing ethinyl estradiol and drospirenone: Decreased concentrations of ethinyl estradiol, effects on drospirenone unknown if used with ritonavir-boosted darunavir; decreased concentrations of ethinyl estradiol, increased drosperinone concentrations if used with cobicistat-boosted darunavir Progestin-only contraceptives: Possible reduced efficacy of contraceptive |
Ritonavir-boosted or cobicistat-boosteddarunavir: Use additional or alternative nonhormonal contraception methods Clinical monitoring for hyperkalemia recommended if ritonavir-boosted or cobicistat-boosted darunavir used with drospirenone containing oral contraceptives |
|
Etravirine |
Ritonavir-boosteddarunavir: Decreased etravirine AUC, but no change in darunavir concentrations; safety and efficacy of ritonavir-boosted darunavir and etravirine established in clinical studies Cobicistat-boosted darunavir: Possible decreased cobicistat concentrations; effect on darunavir pharmacokinetics unknown; possible loss of therapeutic effect and development of darunavir resistance |
Ritonavir-boosteddarunavir: Dosage adjustments not needed Cobicistat-boosteddarunavir: Concomitant use not recommended |
|
Fentanyl |
Ritonavir-boosted or cobicistat- boosteddarunavir: Possible increased fentanyl concentrations |
Ritonavir-boosted or cobicistat-boosted darunavir: Carefully monitor patient for fentanyl therapeutic and adverse effects, including potentially fatal respiratory depression |
|
Fesoterodine |
Ritonavir-boosted or cobicistat-boosted darunavir: Increased fesoterodine concentrations expected |
Ritonavir-boosted or cobicistat- boosted darunavir: When used concomitantly, do not exceed 4 mg of fesoterodine daily |
|
Glecaprevir and pibrentasvir |
Ritonavir-boosted or cobicistat-boosted darunavir: Increased glecaprevir and pibrentasvir concentrations; concomitant use not recommended |
|
|
Histamine H2-receptor antagonists (e.g., famotidine) |
Ritonavir-boosted or cobicistat-boosted darunavir: No clinically important effects expected if used with histamine H2-receptor antagonists |
Histamine H2-receptor antagonists: Dosage adjustments not needed if used with ritonavir-boosted or cobicistat-boosted darunavir |
|
HMG-CoA reductase inhibitors (statins) |
Atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin: Increased antilipemic agent concentrations and AUC if used with ritonavir-boosted or cobicistat-boosted darunavir; increased risk of statin-associated adverse effects, including myopathy and rhabdomyolysis Pitavastatin: Data not available regarding use with cobicistat-boosted darunavir |
Atorvastatin: If used with ritonavir-boosted or cobicistat-boosteddarunavir, do not exceed atorvastatin dosage of 20 mg daily; carefully titrate atorvastatin dosage; use lowest necessary dosage with close monitoring for adverse effects Lovastatin: Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated Pitavastatin: if used with cobicistat-boosted darunavir, initiate pitavastatin at lowest necessary dosage, titrate dosage, and monitor patient for safety Pravastatin: If used with ritonavir-boosted or cobicistat-boosted darunavir, carefully titrate pravastatin dosage; use lowest necessary dosage with close monitoring for adverse effects Rosuvastatin: If used with ritonavir-boosted or cobicistat- boosted darunavir, carefully titrate rosuvastatin dosage; use lowest necessary dosage with close monitoring for adverse effects; if used with cobicistat-boosted darunavir, do not exceed rosuvastatin dosage of 20 mg daily Simvastatin: Concomitant use with ritonavir-boostedor cobicistat-boosted darunavir contraindicated |
|
Immunosuppressive agents (cyclosporine, everolimus, sirolimus, tacrolimus) |
Cyclosporine, everolimus, sirolimus, tacrolimus: Increased immunosuppressive agent concentrations expected if used with ritonavir-boosted or cobicistat-boosteddarunavir |
Cyclosporine, sirolimus, tacrolimus: Monitor plasma concentrations of immunosuppressive agent if used concomitantly with ritonavir-boostedor cobicistat-boosted darunavir Everolimus: Concomitant use with ritonavir-boostedor cobicistat-boosted darunavir not recommended |
|
Indinavir |
Ritonavir-boosted darunavir: Increased concentrations and AUC of darunavir and indinavir No in vitro evidence of antagonistic antiretroviral effects with darunavir |
Appropriate dosages for concomitant use not established |
|
Ivabradine |
Ritonavir-boosted or cobicistat-boosted darunavir: Increased ivabradine concentrations expected |
Ritonavir-boosted or cobicistat- boosted darunavir: Concomitant use contraindicated |
|
Lamivudine |
Ritonavir-boosted or cobicistat-boosted darunavir: Pharmacokinetic interactions unlikely No in vitro evidence of antagonistic antiretroviral effects with darunavir |
|
|
Lomitapide |
Ritonavir-boosted or cobicistat-boosted darunavir: Increased lomitapide concentrations |
Concomitant use of lomitapide contraindicated |
|
Lopinavir/ritonavir |
Ritonavir-boosted darunavir: Decreased darunavir concentrations; no change in lopinavir concentrations No in vitro evidence of antagonistic antiretroviral effects with darunavir |
Concomitant use not recommended; appropriate dosages with respect to safety and efficacy not established |
|
Macrolides (clarithromycin, erythromycin) |
Clarithromycin: Increased clarithromycin concentrations if used with ritonavir-boosteddarunavir; increased darunavir, cobicistat, and clarithromycin concentrations if used with cobicistat-boosted darunavir Erythromycin: Increased darunavir, cobicistat, and macrolide concentrations if used with cobicistat-boosted darunavir |
Clarithromycin: If used concomitantly with ritonavir- boosted darunavir, modification of usual clarithromycin dosage not needed in patients with normal renal function, but reduce clarithromycin dosage by 50% if Clcr30–60 mL/minute and reduce by 75% if Clcr<30 mL/minute; consider alternative (e.g., azithromycin) in patients receiving ritonavir-boosted or cobicistat-boosteddarunavir Erythromycin: Consider alternative anti-infective in patients receiving cobicistat-boosted darunavir |
|
Maraviroc |
Increased maraviroc concentrations and AUD if used with ritonavir-boosted or cobicistat-boosted darunavir |
Ritonavir-boosted or cobicistat-boosted darunavir: Recommended maraviroc dosage is 150 mg twice daily |
|
Methadone |
Ritonavir-boosted darunavir: Decreased methadone concentrations Cobicistat-boosted darunavir: Effect on methadone pharmacokinetics unknown |
Ritonavir-boosted darunavir: Adjustment of methadone dosage not needed when initiating ritonavir-boosted darunavir; but closely monitor for opiate withdrawal since some patients may need adjustment of methadone maintenance dosage Cobicistat-boosted darunavir: Initiate methadone using lowest possible dosage and titrate carefully to desired therapeutic effect; if initiating cobicistat-boosted darunavir in patient already receiving methadone, monitor patient and consider that adjustment of methadone dosage may be needed |
|
Naloxegol |
Ritonavir-boosted or cobicistat-boosted darunavir: Increased naloxegol concentrations expected |
Ritonavir-boostedor cobicistat- boosteddarunavir: Concomitant use contraindicated |
|
Nelfinavir |
No in vitro evidence of antagonistic antiretroviral effects with darunavir |
|
|
Nevirapine |
Ritonavir-boosted darunavir: Increased nevirapine and darunavir concentrations Cobicistat-boosted darunavir: Possible decreased cobicistat concentrations; effect on darunavir pharmacokinetics unknown; possible loss of therapeutic effect and development of antiretroviral resistance No in vitro evidence of antagonistic antiretroviral effects with darunavir |
Ritonavir-boosteddarunavir: Dosage adjustments not needed Cobicistat-boosted darunavir: Concomitant use not recommended |
|
Oxycodone |
Cobicistat-boosted darunavir: Possible increased oxycodone concentrations |
Ritonavir-boosted or cobicistat-boosted darunavir: Carefully monitor patient for oxycodone therapeutic and adverse effects, including potentially fatal respiratory depression |
|
Prasugrel |
Ritonavir-boosted or cobicistat-boosted darunavir: Active metabolite concentrations of prasugrel not affected |
Ritonavir-boosted or cobicistat-boosted darunavir: Dosage adjustments not needed |
|
Proton pump inhibitors (PPIs) |
Ritonavir-boosted darunavir: Decreased omeprazole concentrations, but no change in darunavir concentrations Cobicistat-boosted darunavir: Clinically important interactions not expected |
Ritonavir-boosted darunavir: Monitor for decreased omeprazole efficacy; consider increasing dosage if symptoms not well controlled, but avoid omeprazole dosage >40 mg once daily |
|
Raltegravir |
Ritonavir-boosted or cobicistat-boosted darunavir: Clinically important interactions not expected |
Ritonavir-boosted or cobicistat- boosted darunavir: Dosage adjustments not needed |
|
Ranolazine |
Ritonavir-boosted or cobicistat-boosted darunavir: Possible serious and/or life-threatening adverse events |
Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use contraindicated |
|
Rilpivirine |
Ritonavir-boosted or cobicistat-boosteddarunavir: Clinically important interactions not expected |
Ritonavir-boosteddarunavir: Dosage adjustments not needed |
|
Ritonavir |
Increased darunavir concentrations and AUC; low-dose ritonavir (100 mg once daily) used as a pharmacokinetic enhancer for therapeutic advantage (ritonavir-boosted darunavir) No in vitro evidence of antagonistic antiretroviral effects with darunavir |
Ritonavir or ritonavir-containing preparations: Concomitant use with cobicistat-boosteddarunavir not recommended |
|
St. John's wort (Hypericum perforatum) |
Ritonavir-boostedor cobicistat-boosted darunavir: Potential decreased darunavir concentrations; possible decreased antiretroviral efficacy |
Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use contraindicated |
|
Salmeterol |
Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased salmeterol concentrations and increased risk of QT interval prolongation, palpitations, and sinus tachycardia |
Ritonavir-boosted or cobicistat-boosted darunavir: Concomitant use not recommended |
|
Saquinavir |
Ritonavir-boosted darunavir: Decreased darunavir concentrations, but saquinavir concentrations unchanged No in vitro evidence of antagonistic antiretroviral effects with darunavir |
Ritonavir-boosted darunavir: Concomitant use not recommended |
|
Selective serotonin-reuptake inhibitors (SSRIs) |
Paroxetine, sertraline: Decreased SSRI concentrations and AUCs and no change in darunavir concentrations if used with ritonavir-boosted darunavir; possible pharmacokinetic interactions if used with cobicistat- boosted darunavir, but effect on SSRI concentrations unknown |
Paroxetine, sertraline: Titrate SSRI dosage based on clinical response in patients receiving ritonavir-boostedor cobicistat- boosteddarunavir; if ritonavir-boosted darunavir initiated in those on stable SSRI dosage, monitor for clinical response |
|
Sildenafil |
Ritonavir-boosted or cobicistat- boosted darunavir: Increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope) |
Sildenafil (Revatio) for treatment of pulmonary arterial hypertension (PAH): Concomitant use with ritonavir-boosted or cobicistat-boosted darunavir contraindicated Sildenafil for treatment of erectile dysfunction: In patients receiving ritonavir-boosted or cobicistat-boosted darunavir, do not exceed sildenafil dosage of 25 mg once every 48 hours; closely monitor for sildenafil-associated adverse effects |
|
Solifenacin |
Ritonavir-boosted or cobicistat- boosted darunavir: Increased solifenacin concentrations expected |
Ritonavir-boosted or cobicistat-boosted darunavir: When used concomitantly, do not exceed 5 mg of solifenacin daily |
|
Tadalafil |
Ritonavir-boostedor cobicistat- boosted darunavir: Possible increased tadalafil concentrations and increased risk of tadalafil- associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope) |
Tadalafil for treatment of PAH in patients who have been receiving ritonavir-boosted or cobicistat-boosted darunavir for ≥1 week: Use initial tadalafil dosage of 20 mg once daily; if tolerated, may increase dosage to 40 mg once daily Ritonavir-boosted or cobicistat- boosted darunavir in patients receiving tadalafil for PAH: Discontinue tadalafil for at least 24 hours prior to initiating ritonavir-boosted or cobicistat- boosted darunavir; after ≥1 week of the antiretroviral, may resume tadalafil at dosage of 20 mg once daily and, if tolerated, may increase dosage to 40 mg once daily Tadalafil for treatment of erectile dysfunction: In patients receiving ritonavir-boosted or cobicistat-boosteddarunavir, do not exceed tadalafil dosage of 10 mg once every 72 hours; closely monitor for tadalafil-related adverse effects |
|
Tenofovir DF |
Ritonavir-boosted darunavir: Increased tenofovir concentrations and AUC; increased darunavir concentrations and AUC Cobicistat-boosted darunavir: No in vitro evidence of antagonistic antiretroviral effects with darunavir |
Ritonavir-boosted darunavir: Manufacturer of darunavir states usual dosage of ritonavir-boosted darunavir and tenofovir DF can be used Cobicistat-boosted darunavir: Assess baseline estimated Clcr, urine glucose, and urine protein; not recommended in patients with estimated Clcr <70 mL/minute |
|
Ticagrelor |
Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased ticagrelor concentrations |
Ritonavir-boosted or cobicistat-boosted darunavir: Avoid concomitant use |
|
Tipranavir |
No in vitro evidence of antagonistic antiretroviral effects with darunavir |
|
|
Tramadol |
Cobicistat-boosted darunavir: Increased tramadol concentrations |
Cobicistat-boosted darunavir: Decreased tramadol dosage may be needed |
|
Trazodone |
Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased trazodone concentrations and increased risk of nausea, dizziness, hypotension, syncope |
Ritonavir-boosted or cobicistat-boosted darunavir: Use lowest possible trazodone dosage and monitor for adverse CNS and cardiovascular effects |
|
Tricyclic antidepressants (amitriptyline, desipramine, doxepin, imipramine, nortriptyline) |
Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased concentrations of the TCA and increased risk of nausea, dizziness, hypotension, syncope |
Ritonavir-boosted or cobicistat-boosted darunavir: Use lowest possible antidepressant dosage based on clinical assessment and/or antidepressant concentrations |
|
Vardenafil |
Ritonavir-boosted or cobicistat-boosted darunavir: Possible increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, visual disturbances, prolonged erection, syncope) |
Ritonavir-boosted or cobicistat-boosted darunavir: Vardenafil for treatment of erectile dysfunction: Do not exceed dosage of 2.5 mg once every 72 hours; closely monitor for vardenafil-related adverse effects |
|
Zidovudine |
Ritonavir-boosted or cobicistat-boosteddarunavir: Pharmacokinetic interactions unlikely No in vitro evidence of antagonistic antiretroviral effects with darunavir |
|
|
Zolpidem |
Ritonavir-boosted or cobicistat-boosteddarunavir: Increased zolpidem concentrations |
Ritonavir-boosted or cobicistat-boosted darunavir: Titrate and use lower initial zolpidem dosage; monitor patients for prolonged or adverse zolpidem effects |
Darunavir Pharmacokinetics
Absorption
Bioavailability
Darunavir must be administered with low-dose ritonavir (ritonavir-boosted darunavir) or cobicistat (cobicistat- boosted darunavir). Ritonavir and cobicistat are pharmacokinetic enhancers (pharmacokinetic boosters) that decrease metabolism of darunavir, resulting in increased darunavir plasma concentrations and AUC.
Pharmacokinetic parameters reported with once-daily regimen of ritonavir-boosted darunavir (darunavir 800 mg and ritonavir 100 mg) are similar to those reported with once-daily regimen of cobicistat-boosted darunavir (darunavir 800 mg and cobicistat 150 mg).
Ritonavir-boosted darunavir: Peak plasma concentrations of darunavir attained approximately 2.5–4 hours after a dose.
Cobicistat-boosted darunavir: Peak plasma concentrations of darunavir attained approximately 4–4.5 hours after a dose.
Food
Food increases darunavir bioavailability.
Ritonavir-boosted darunavir: Administration with food increases darunavir peak plasma concentrations and AUC by approximately 40%.
Cobicistat-boosted darunavir: Administration with high-fat meal increases darunavir peak plasma concentrations and AUC by approximately 127 and 70%, respectively.
Distribution
Extent
Not known whether darunavir distributed into human milk; distributed into milk in rats.
Plasma Protein Binding
Darunavir: 95%.
Binds principally to α1-acid-glycoprotein.
Elimination
Metabolism
Darunavir extensively metabolized by CYP3A.
Elimination Route
Following administration of ritonavir-boosted darunavir, darunavir eliminated principally in feces unchanged; approximately 80% of darunavir dose excreted in feces and 14% excreted in urine.
Hemodialysis or peritoneal dialysis unlikely to remove darunavir, ritonavir, or cobicistat.
Half-life
15 hours after dose of ritonavir-boosted darunavir.
7 hours after dose of cobicistat-boosted darunavir.
Special Populations
Ritonavir-boosted darunavir in pediatric patients 3 years to <18 years of age weighing ≥10 kg: Darunavir concentrations and AUC comparable to those reported in adults.
Ritonavir-boosted darunavir in renal impairment: Darunavir pharmacokinetics not affected in those with moderate renal impairment (Clcr 30–60 mL/minute). Not studied in those with severe renal impairment or end- stage renal disease.
Cobicistat-boosted darunavir in renal impairment: Pharmacokinetics not studied.
Ritonavir-boosted darunavir in hepatic impairment: Pharmacokinetics in those with mild or moderate hepatic impairment (Child-Pugh class A or B) similar to those with normal hepatic function. Not studied in those with severe hepatic impairment.
HBV or HCV coinfection: No effect on darunavir exposure in those receiving ritonavir-boosted darunavir; effect on pharmacokinetics of cobicistat-boosted darunavir not evaluated.
Stability
Storage
Oral
Suspension
Darunavir: 25°C (excursions permitted between 15–30°C). Do not refrigerate or freeze; avoid excessive heat.
Tablets
Darunavir: 25°C (excursions permitted between 15–30°C).
Darunavir/cobicistat: 20–25°C (may be exposed to 15–30°C).
Actions
-
Darunavir is extensively metabolized by CYP3A and must be administered in conjunction with a pharmacokinetic enhancer (pharmacokinetic booster) to improve the pharmacokinetic profile of the drug.
-
Concomitant use with low-dose ritonavir (ritonavir-boosted darunavir) or with cobicistat (cobicistat-boosted darunavir) results in decreased metabolism and increased plasma concentrations and AUC of darunavir.
-
Antiretroviral activity is due to darunavir.
-
Active against HIV-1.
-
Darunavir inhibits replication of HIV-1 by interfering with HIV proteases.
-
Darunavir-resistant HIV-1, including strains with decreased susceptibility to other HIV PIs, has been reported.
-
Varying degrees of cross-resistance occur among HIV PIs.
-
Some clinical isolates of HIV-1 with reduced susceptibility to darunavir have been resistant to atazanavir, fosamprenavir, indinavir, lopinavir, and nelfinavir.
Advice to Patients
-
Advise patients of the critical nature of adherence with HIV therapy and importance of remaining under the care of a clinician. Advise patients of the importance of taking medications as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.
-
Advise patients on the importance of using darunavir with low-dose ritonavir ritonavir-boosted darunavir) or with cobicistat (cobicistat-boosted darunavir). Advise patients on the importance of using ritonavir-boosted or cobicistat-boosted darunavir in conjunction with other antiretrovirals to make a complete regimen.
-
When using ritonavir-boosted darunavir, advise patients on the importance of taking single-entity darunavir with food and at the same time as single-entity ritonavir. Advise patients on the importance of swallowing darunavir tablets whole with a drink (e.g., water, milk).
-
When using cobicistat-boosted darunavir, advise patients on the importance of taking the fixed-combination tablet containing both drugs (darunavir/cobicistat) with food; alternatively, advise patients on the importance of taking single-entity darunavir with food and at the same time as single-entity cobicistat.
-
Advise patients that drug-induced hepatitis has occurred. Advise patients on the importance of notifying their 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).
-
Advise patients that mild to severe skin reactions have occurred. Advise patients on the importance of immediately discontinuing ritonavir-boosted or cobicistat-boosted darunavir and contacting their 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).
-
Advise patients that redistribution/accumulation of body fat may occur with antiretroviral therapy, with as yet unknown long-term health effects.
-
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
-
Advise females to inform clinicians if they are or plan to become pregnant or plan to breast-feed. Advise HIV-infected females not to breast-feed. Advise females to use a reliable nonhormonal (e.g., barrier) method of contraception due to potential interactions with hormonal contraceptives.
-
Advise patients of other important precautionary information.
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
|
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
|---|---|---|---|---|
|
Oral |
Suspension |
100 mg (of darunavir) per mL |
Prezista |
Janssen Products LP |
|
Tablets, film-coated |
75 mg |
Prezista |
Janssen Products LP |
|
|
150 mg |
Prezista |
Janssen Products LP |
||
|
600 mg |
Prezista |
Janssen Products LP |
||
|
800 mg |
Prezista |
Janssen Products LP |
|
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
|---|---|---|---|---|
|
Oral |
Tablets, film-coated |
800 mg (of darunavir) with Cobicistat 150 mg |
Prezcobix |
Janssen Products LP |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions December 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.
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