Prezista Information
Prezista (Darunavir) Indications And Usage
Prezista (Darunavir) , co-administered with ritonavir (Prezista (Darunavir) /ritonavir), and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV-1) infection.
This indication is based on analyses of plasma HIV-1 RNA levels and CD4+ cell counts from 2 controlled Phase 3 trials of 48 weeks duration in antiretroviral treatment-naïve and treatment-experienced patients and 2 controlled Phase 2 trials of 96 weeks duration in clinically advanced, treatment-experienced adult patients.
Prezista (Darunavir) , co-administered with ritonavir (Prezista (Darunavir) /ritonavir), and with other antiretroviral agents, is indicated for the treatment of HIV-1 infection in pediatric patients 3 years of age and older [].
This indication is based on 24-week analyses of plasma HIV-1 RNA levels and CD4+ cell counts from 2 open-label Phase 2 trials in antiretroviral treatment-experienced pediatric patients (one trial in patients 6 to less than 18 years of age and one trial in patients 3 to less than 6 years of age).
In treatment-experienced adult and pediatric patients, the following points should be considered when initiating therapy with Prezista (Darunavir) /ritonavir:
Prezista (Darunavir) Dosage And Administration
Prezista (Darunavir) must be co-administered with ritonavir to exert its therapeutic effect. Failure to correctly co-administer Prezista (Darunavir) with ritonavir will result in plasma levels of darunavir that will be insufficient to achieve the desired antiviral effect and will alter some drug interactions.
Patients who have difficulty swallowing Prezista (Darunavir) tablets can use the 100 mg/mL Prezista (Darunavir) oral suspension.
Do not use once daily dosing in pediatric patients.
Healthcare professionals should pay special attention to accurate dose selection of Prezista (Darunavir) , transcription of the medication order, dispensing information and dosing instruction to minimize risk for medication errors, overdose, and underdose.
Prescribers should select the appropriate dose of Prezista (Darunavir) /ritonavir for each individual child based on body weight (kg) and should not exceed the recommended dose for treatment-experienced adults.
Before prescribing Prezista (Darunavir) , children weighing greater than or equal to 15 kg should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow a tablet, the use of Prezista (Darunavir) oral suspension should be considered.
The recommended dose of Prezista (Darunavir) /ritonavir for pediatric patients (3 to less than 18 years of age and weighing at least 10 kg is based on body weight (see,and) and should not exceed the recommended treatment-experienced adult dose (Prezista (Darunavir) /ritonavir 600/100 mg twice daily). Prezista (Darunavir) should be taken with ritonavir twice daily and with food.
Prezista (Darunavir) Contraindications
Co-administration of Prezista (Darunavir) /ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). These drugs and other contraindicated drugs (which may lead to reduced efficacy of darunavir) are listed in Table 4 [,].
Due to the need for co-administration of Prezista (Darunavir) with ritonavir, please refer to ritonavir prescribing information for a description of ritonavir contraindications.
Prezista (Darunavir) Warnings And Precautions
Prezista (Darunavir) must be co-administered with ritonavir and food to achieve the desired antiviral effect. Failure to administer Prezista (Darunavir) with ritonavir and food may result in a loss of efficacy of darunavir.
Please refer to ritonavir prescribing information for additional information on precautionary measures.
Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) has been reported with Prezista (Darunavir) /ritonavir. During the clinical development program (N=3063), hepatitis was reported in 0.5% of patients receiving combination therapy with Prezista (Darunavir) /ritonavir. Patients with pre-existing liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities including severe hepatic adverse events.
Post-marketing cases of liver injury, including some fatalities, have been reported. These have generally occurred in patients with advanced HIV-1 disease taking multiple concomitant medications, having co-morbidities including hepatitis B or C co-infection, and/or developing immune reconstitution syndrome. A causal relationship with Prezista (Darunavir) /ritonavir therapy has not been established.
Appropriate laboratory testing should be conducted prior to initiating therapy with Prezista (Darunavir) /ritonavir and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases, especially during the first several months of Prezista (Darunavir) /ritonavir treatment.
Evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) in patients on Prezista (Darunavir) /ritonavir should prompt consideration of interruption or discontinuation of treatment.
During the clinical development program (n=3063), severe skin reactions, accompanied by fever and/or elevations of transaminases in some cases, have been reported in 0.4% of subjects. Stevens-Johnson Syndrome was rarely (less than 0.1%) reported during the clinical development program. During post-marketing experience toxic epidermal necrolysis has been reported. Discontinue Prezista (Darunavir) /ritonavir immediately if signs or symptoms of severe skin reactions develop. These can include but are not limited to severe rash or rash accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
Rash (all grades, regardless of causality) occurred in 10.3% of subjects treated with Prezista (Darunavir) /ritonavir []. Rash was mostly mild-to-moderate, often occurring within the first four weeks of treatment and resolving with continued dosing. The discontinuation rate due to rash in subjects using Prezista (Darunavir) /ritonavir was 0.5%.
Rash occurred more commonly in treatment-experienced subjects receiving regimens containing Prezista (Darunavir) /ritonavir + raltegravir compared to subjects receiving Prezista (Darunavir) /ritonavir without raltegravir or raltegravir without Prezista (Darunavir) /ritonavir. However, rash that was considered drug related occurred at similar rates for all three groups. These rashes were mild to moderate in severity and did not limit therapy; there were no discontinuations due to rash.
Prezista (Darunavir) Adverse Reactions
The overall safety profile of Prezista (Darunavir) /ritonavir 800/100 mg once daily and Prezista (Darunavir) /ritonavir 600/100 mg twice daily is based on clinical trials and post-marketing data, and is consistent with the data presented below.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Due to the need for co-administration of Prezista (Darunavir) with ritonavir, please refer to ritonavir prescribing information for ritonavir-associated adverse reactions.
Prezista (Darunavir) Drug Interactions
See also and .
Table 9 provides dosing recommendations as a result of drug interactions with Prezista (Darunavir) /ritonavir. These recommendations are based on either drug interaction studies or predicted interactions due to the expected magnitude of interaction and potential for serious adverse events or loss of efficacy.
In addition to the drugs included in Table 9, the interaction between Prezista (Darunavir) /ritonavir and the following drugs were evaluated in clinical studies and no dose adjustments are needed for either drug [see ]: atazanavir, efavirenz, etravirine, nevirapine, omeprazole, ranitidine, rilpivirine, and tenofovir disoproxil fumarate.
Prezista (Darunavir) Use In Specific Populations
The Centers for Disease Control and Prevention recommend that HIV-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV.
mothers should be instructed not to breastfeed if they are receiving Prezista (Darunavir)
Do not administer Prezista (Darunavir) /ritonavir in pediatric patients below 3 years of age because of toxicity and mortality observed in juvenile rats dosed with darunavir (from 20 mg/kg to 1000 mg/kg) up to days 23 to 26 of age [ ].
Do not administer Prezista (Darunavir) /ritonavir once daily in pediatric patients.
The safety, pharmacokinetic profile, and virologic and immunologic responses of Prezista (Darunavir) /ritonavir were evaluated in treatment-experienced HIV-1-infected pediatric subjects 3 to less than 18 years of age and weighing at least 10 kg [,]. Frequency, type, and severity of adverse drug reactions in pediatric subjects were comparable to those observed in adults []. Please see for dosing recommendations for pediatric subjects 3 to less than 18 years of age and weighing at least 10 kg.
Prezista (Darunavir) Overdosage
Human experience of acute overdose with Prezista (Darunavir) /ritonavir is limited. Single doses up to 3200 mg of the oral solution of darunavir alone and up to 1600 mg of the tablet formulation of darunavir in combination with ritonavir have been administered to healthy volunteers without untoward symptomatic effects.
No specific antidote is available for overdose with Prezista (Darunavir) . Treatment of overdose with Prezista (Darunavir) consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. If indicated, elimination of unabsorbed active substance is to be achieved by emesis or gastric lavage. Administration of activated charcoal may also be used to aid in removal of unabsorbed active substance. Since Prezista (Darunavir) is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substance.
Prezista (Darunavir) Description
Prezista (Darunavir) is an inhibitor of the human immunodeficiency virus (HIV-1) protease.
Prezista (Darunavir) (darunavir), in the form of darunavir ethanolate, has the following chemical name: [(1,2)-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamic acid (3,3a,6a)-hexahydrofuro[2,3-]furan-3-yl ester monoethanolate. Its molecular formula is CHNOS • CHOH and its molecular weight is 593.73. Darunavir ethanolate has the following structural formula:
Darunavir ethanolate is a white to off-white powder with a solubility of approximately 0.15 mg/mL in water at 20°C.
Prezista (Darunavir) 100 mg/mL oral suspension is available as a white to off-white opaque suspension for oral administration.
Prezista (Darunavir) 75 mg tablets are available as white, caplet-shaped, film-coated tablets for oral administration. Prezista (Darunavir) 150 mg tablets are available as white, oval-shaped, film-coated tablets for oral administration. Prezista (Darunavir) 600 mg tablets are available as orange, oval-shaped, film-coated tablets for oral administration. Prezista (Darunavir) 400 mg tablets are available as light orange, oval-shaped, film-coated tablets for oral administration.
Each mL of the oral suspension contains darunavir ethanolate equivalent to 100 mg darunavir. In addition, each mL contains the inactive ingredients hydroxypropyl cellulose, microcrystalline cellulose, sodium carboxymethylcellulose, methylparaben sodium, citric acid monohydrate, sucralose, masking flavor, strawberry cream flavor, hydrochloric acid (for pH adjustment) and purified water.
Each 75 mg tablet contains darunavir ethanolate equivalent to 75 mg of darunavir. Each 150 mg tablet contains darunavir ethanolate equivalent to 150 mg of darunavir. Each 400 mg tablet contains darunavir ethanolate equivalent to 400 mg of darunavir. Each 600 mg tablet contains darunavir ethanolate equivalent to 600 mg of darunavir. During storage, partial conversion from ethanolate to hydrate may occur; however, this does not affect product quality or performance. Each tablet also contains the inactive ingredients colloidal silicon dioxide, crospovidone, magnesium stearate, and microcrystalline cellulose. The tablet film coating, OPADRY White, contains polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, and titanium dioxide. The tablet film coating, OPADRY Orange, contains FD&C Yellow No. 6, polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, and titanium dioxide.
All dosages for Prezista (Darunavir) are expressed in terms of the free form of darunavir.
Prezista (Darunavir) Clinical Pharmacology
In an open-label, randomized, placebo- and active-controlled, four-way crossover trial, 40 healthy subjects were administered supratheraputic doses of darunavir/ritonavir 1600/100 mg once daily and 800/100 mg twice daily for seven days.
At the mean maximum darunavir concentration of 6599 ng/mL observed in this study, the mean increase in QTcF was 2.2 ms with a 90% two-sided confidence interval (CI) of -2.0 to 6.3 ms. When evaluating the 2-sided 90% CI on the time-matched mean changes in QTcF versus placebo control, the upper bounds of both darunavir/ritonavir groups never exceeded the 10 ms boundary. In the setting of this trial, darunavir/ritonavir did not appear to prolong the QTc interval.
Prezista (Darunavir) How Supplied/storage And Handling
Prezista (Darunavir) 100 mg/mL oral suspension is a white to off-white opaque liquid supplied in amber-colored multiple-dose bottles containing darunavir ethanolate equivalent to 100 mg of darunavir per mL packaged with a 6 mL oral dosing syringe with 0.2 mL gradations.
Prezista (Darunavir) 75 mg tablets are supplied as white, caplet-shaped, film-coated tablets containing darunavir ethanolate equivalent to 75 mg of darunavir per tablet. Each tablet is debossed with "75" on one side and "TMC" on the other side.
Prezista (Darunavir) 150 mg tablets are supplied as white, oval-shaped, film-coated tablets containing darunavir ethanolate equivalent to 150 mg of darunavir per tablet. Each tablet is debossed with "150" on one side and "TMC" on the other side.
Prezista (Darunavir) 400 mg tablets are supplied as light orange, oval-shaped, film-coated tablets containing darunavir ethanolate equivalent to 400 mg of darunavir per tablet. Each tablet is debossed with "400MG" on one side and "TMC" on the other side.
Prezista (Darunavir) 600 mg tablets are supplied as orange, oval-shaped, film-coated tablets containing darunavir ethanolate equivalent to 600 mg of darunavir per tablet. Each tablet is debossed with "600MG" on one side and "TMC" on the other side.
Prezista (Darunavir) is packaged in bottles in the following configuration:
100 mg/mL oral suspension – 200 mL bottles (NDC 59676-565-01)
75 mg tablets—bottles of 480 (NDC 59676-563-01)
150 mg tablets—bottles of 240 (NDC 59676-564-01)
400 mg tablets—bottles of 60 (NDC 59676-561-01)
600 mg tablets—bottles of 60 (NDC 59676-562-01)
Prezista (Darunavir) Patient Counseling Information
A statement to patients and healthcare providers is included on the product's bottle label: A Patient Package Insert for Prezista (Darunavir) is available for patient information.
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