PREZISTA® Oral Suspension Dosing Information for Pediatric Patients
The recommended oral dose of PREZISTA®/r for pediatric patients is dependent on body weight.
PREZISTA® 100-mg/mL oral suspension for treatment-naïve and treatment-experienced pediatric patients (3 to <18 years of age)
Once-daily dosing recommendations for PREZISTA® 100-mg/mL oral suspension for treatment-naïve and treatment-experienced pediatric patients with no DRV RAMs*1
*DRV RAMs=darunavir resistance-associated mutations: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V.
†Ritonavir oral solution: 80 mg/mL.
‡The 350-mg, 385-mg, 455-mg, 490-mg, and 675-mg darunavir doses for the specified weight groups were rounded up for suspension dosing convenience to 3.6 mL, 4 mL, 4.6 mL, 5 mL, and 6.8 mL, respectively.
Twice-daily dosing recommendations for PREZISTA® 100-mg/mL oral suspension for treatment-experienced pediatric patients with ≥1 DRV RAMs*1
*DRV RAMs=darunavir resistance-associated mutations: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V.
†Ritonavir oral solution: 80 mg/mL.
‡The 375-mg and 450-mg darunavir doses for the specified weight groups were rounded up for suspension dosing convenience to 3.8 mL and 4.6 mL, respectively.
- For ARV treatment-experienced patients, genotypic testing is recommended1
- When genotypic testing is not available, PREZISTA®/r twice-daily dosing is recommended1
Dosing Considerations1
- Do not use PREZISTA®/r in pediatric patients younger than 3 years of age
- PREZISTA® is always taken with ritonavir and with food
- Before prescribing, children weighing ≥15 kg should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow a tablet, PREZISTA® oral suspension should be considered
- The 6.8-mL and 8-mL darunavir doses should be taken as two (3.4 mL or 4 mL, respectively) administrations with the included oral dosing syringe
- The recommended dose of PREZISTA®/r for pediatric patients should not exceed the recommended adult dose
- Store PREZISTA® oral suspension at room temperature 77°F (25°C), with excursions permitted to 59°F-86°F (15°C-30°C)
- Do not refrigerate or freeze. Avoid exposure to excessive heat
- Shake oral suspension well before each usage; store in original container
- Strawberry cream flavor
- Refer to "Instructions for Use" in full Prescribing Information for further information
Recommendations for the PREZISTA®/r dosage regimens were based on the following1:
Once-daily dosing
- Results from one trial in treatment-naïve pediatric subjects 12 to <18 years of age demonstrating similar darunavir plasma exposures, virologic response rate, and safety profile compared with treatment-naïve adults
- Results from population pharmacokinetic modeling and simulation in children 3 to <12 years of age predicting similar darunavir plasma exposures compared with treatment-naïve adults. Although no clinical trial was conducted to collect exposure safety data, the predicted exposures from the once-daily dosing are supported by exposures observed in a pediatric clinical trial where twice-daily dosing was administered
Twice-daily dosing
- Results from two trials in treatment-experienced pediatric subjects 3 to <18 years of age demonstrating similar darunavir plasma exposures, virologic response rate, and safety profile compared with treatment-experienced adults
PREZISTA® Tablets Dosing Information for Pediatric Patients
The recommended oral dose of PREZISTA®/r for pediatric patients is dependent on body weight.
PREZISTA® 75-mg, 150-mg, 600-mg, and 800-mg tablets for treatment-naïve and treatment-experienced pediatric patients 3 to
<18 years of age
PREZISTA® 75 mg
(not shown actual size)
PREZISTA® 150 mg
(not shown actual size)
PREZISTA® 600 mg
(not shown actual size)
PREZISTA® 800 mg
(not shown actual size)
Pediatric patients who weigh at least 15 kg and are able to swallow tablets can be dosed using the following tables
Once-daily dosing recommendations for PREZISTA® tablets for treatment-naïve and treatment-experienced pediatric patients with no DRV RAMs*1
*DRV RAMs=darunavir resistance-associated mutations: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V.
The 75-mg and 600-mg tablets can be combined to achieve the recommended dose according to the patient's weight.
Twice-daily dosing recommendations for PREZISTA® tablets for treatment-experienced pediatric patients with ≥1 DRV RAMs*1
*DRV RAMs=darunavir resistance-associated mutations: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V.
The 75-mg and 150-mg tablets can be combined to achieve the recommended dose according to the patient's weight.
- For ARV treatment-experienced patients, genotypic testing is recommended1
- When genotypic testing is not available, PREZISTA®/r twice-daily dosing is recommended1
Dosing Considerations1
- Do not use PREZISTA®/r in pediatric patients younger than 3 years of age
- PREZISTA® is always taken with ritonavir and with food
- Before prescribing, children weighing ≥15 kg should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow a tablet, PREZISTA® oral suspension should be considered
- The recommended dose of PREZISTA®/r for pediatric patients should not exceed the recommended adult dose
- Store PREZISTA® tablets at room temperature 77°F (25°C), with excursions permitted to 59°F-86°F (15°C-30°C)
Recommendations for the PREZISTA®/r dosage regimens were based on the following:
Once-daily dosing
- Results from one trial in treatment-naïve pediatric subjects 12 to <18 years of age demonstrating similar darunavir plasma exposures, virologic response rate, and safety profile compared with treatment-naïve adults
- Results from population pharmacokinetic modeling and simulation in children 3 to <12 years of age predicting similar darunavir plasma exposures compared with treatment-naïve adults. Although no clinical trial was conducted to collect exposure safety data, the predicted exposures from the once-daily dosing are supported by exposures observed in a pediatric clinical trial where twice-daily dosing was administered
Twice-daily dosing
- Results from two trials in treatment-experienced pediatric subjects 3 to <18 years of age demonstrating similar darunavir plasma exposures, virologic response rate, and safety profile compared with treatment-experienced adults
Important Safety Information
Drug Interactions
- Coadministration of PREZISTA®/r 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 (eg, alfuzosin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, oral midazolam, triazolam, lovastatin, simvastatin, or sildenafil for the treatment of pulmonary arterial hypertension)
- Coadministration of PREZISTA®/r is also contraindicated with rifampin and products containing St. John’s wort (Hypericum perforatum) because this may cause significant decrease in plasma concentration of darunavir, resulting in loss of therapeutic effect and development of resistance
- Coadministration is not recommended with indinavir, lopinavir/ritonavir, saquinavir, salmeterol, boceprevir, telaprevir, and colchicine in patients with hepatic or renal impairment
- Caution should be used when prescribing agents such as sildenafil, vardenafil, tadalafil, or other substrates, inhibitors, or inducers of CYP3A in patients receiving PREZISTA®/r
Indication: Pediatric Patients
PREZISTA® (darunavir), coadministered with ritonavir (PREZISTA®/r), and with other antiretroviral agents (ARVs), is indicated for the treatment of human immunodeficiency virus (HIV-1) infection in pediatric patients 3 years of age and older.
The indication for ARV treatment-naïve pediatric patients or treatment-experienced pediatric patients with no darunavir resistance associated substitutions is based on a 48-week open-label Phase 2 trial in ARV treatment-naïve pediatric patients 12 to <18 years of age, and pharmacokinetic modeling and simulation for patients 3 to <12 years of age. The indication for treatment-experienced pediatric patients is based on 24-week analyses of plasma HIV-1 RNA levels and CD4+ cell counts from 2 open-label Phase 2 trials in ARV treatment-experienced pediatric patients (one trial in patients 6 to <18 years of age, and one trial in patients 3 to <6 years of age).
In treatment-experienced pediatric patients, the following points should be considered when initiating therapy with PREZISTA®/r:
- Treatment history and, when available, genotypic or phenotypic testing should guide the use of PREZISTA®/r
- The use of other active agents with PREZISTA®/r is associated with a greater likelihood of treatment response
This list of potential drug interactions is not complete.
Warnings & Precautions
- Pediatric Patients: Do not use PREZISTA®/r in pediatric patients below 3 years of age
- PREZISTA® must be coadministered with ritonavir and food to achieve the desired antiviral effect. Failure to administer PREZISTA® 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 (eg, acute hepatitis, cytolytic hepatitis) has been reported with PREZISTA®/r. During the clinical development program (N=3063), hepatitis has been reported in 0.5% of adults receiving combination therapy with PREZISTA®/r. Patients with preexisting liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities, including severe hepatic adverse events
- Severe Skin Reactions: Severe skin reactions (0.4%), accompanied by fever and/or elevations of transaminases in some cases, and Stevens-Johnson syndrome (<0.1%) have been reported in patients receiving PREZISTA®/r. During postmarketing experience, toxic epidermal necrolysis and acute generalized exanthematous pustulosis have been reported in patients receiving PREZISTA®/r. Discontinue PREZISTA®/r immediately if signs or symptoms of severe skin reactions develop (including, but 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)
- Sulfa Allergy: PREZISTA® should be used with caution in patients with known sulfonamide allergy
- Diabetes Mellitus/Hyperglycemia and Hemophilia: New-onset or exacerbations of preexisting diabetes mellitus, hyperglycemia, and increased bleeding in hemophiliacs have been reported in patients receiving protease inhibitors. Initiation or dose adjustments of insulin or oral hypoglycemic agents may be required. A causal relationship between protease inhibitors and these events has not been established
- Fat Redistribution: Redistribution and/or accumulation of body fat have been observed in patients receiving ARV therapy. The causal relationship, mechanism, and long-term consequences of these events have not been established
- Immune reconstitution syndrome has been reported in patients treated with combination ARV therapy, including PREZISTA®
- Resistance/Cross-Resistance: The potential for HIV cross-resistance among protease inhibitors has not been fully explored in PREZISTA®/r-treated patients
Postmarketing cases of liver injury, including some fatalities, have been reported. A causal relationship with PREZISTA®/r therapy has not been established
Appropriate laboratory testing should be conducted prior to initiating therapy with PREZISTA®/r 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 pretreatment elevations of transaminases, especially during the first several months of PREZISTA®/r 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, and hepatomegaly) in patients on PREZISTA®/r should prompt consideration of interruption or discontinuation of treatment
In clinical trials (N=3063), rash (all grades, generally mild to moderate, regardless of causality) occurred in 10.3% of adults receiving PREZISTA®/r. Discontinuation due to rash was 0.5%. Rash occurred more commonly in treatment-experienced adults receiving regimens containing PREZISTA®/r + raltegravir compared to subjects receiving either drug regimen alone. However, rash that was considered drug related occurred at similar rates. These rashes were mild to moderate in severity and did not limit therapy; there were no discontinuations due to rash
Autoimmune disorders (such as Graves disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time of onset is more variable and can occur many months after the initiation of treatment
Use in Specific Populations
- Hepatic impairment: PREZISTA®/r is not recommended for use in patients with severe hepatic impairment. There are no pharmacokinetic or safety data available in patients with severe hepatic impairment
- Pregnancy: PREZISTA® should be used during pregnancy only if the potential benefit justifies the potential risk. No adequate and well-controlled studies have been conducted in pregnant women
Adverse Reactions
- In treatment-experienced pediatric patients (3 to <6 years of age), the most common adverse drug reactions (≥3%) reported regardless of severity with PREZISTA®/r were diarrhea (19%), vomiting (14%), and rash (10%)
- In treatment-experienced pediatric patients (6 to <18 years of age), the most common adverse drug reactions (≥3%) reported regardless of severity with PREZISTA®/r were vomiting (13%), diarrhea (11%), abdominal pain (10%), headache (9%), rash (5%), nausea (4%), and fatigue (3%)
- In treatment-naïve pediatric patients (12 to <18 years of age), the most common adverse drug reactions (≥3%) reported regardless of severity with PREZISTA®/r were vomiting (33%), nausea (25%), diarrhea (16.7%), abdominal pain (8.3%), decreased appetite (8.3%), pruritus (8.3%), and rash (8.3%)
This is not a complete list of all adverse drug reactions reported with the use of PREZISTA®/r.
Please see accompanying full Prescribing Information for more details.
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