Drug Detail:Prezista (Darunavir [ da-roon-a-veer ])
Generic Name: darunavir ethanolate 75mg
Drug Class: Protease inhibitors
Testing Prior to Initiation of PREZISTA/ritonavir
In treatment-experienced patients, treatment history, genotypic and/or phenotypic testing is recommended to assess drug susceptibility of the HIV-1 virus [see Microbiology (12.4)]. Refer to Dosage and Administration (2.3), (2.4) and (2.5) for dosing recommendations.
Appropriate laboratory testing such as serum liver biochemistries should be conducted prior to initiating therapy with PREZISTA/ritonavir [see Warnings and Precautions (5.2)].
Monitoring During Treatment with PREZISTA/ritonavir
Patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases should be monitored for elevation in serum liver biochemistries, especially during the first several months of PREZISTA/ritonavir treatment [see Warnings and Precautions (5.2)].
Recommended Dosage in Adult Patients
PREZISTA must be co-administered with ritonavir to exert its therapeutic effect. Failure to correctly co-administer PREZISTA 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 tablets can use the 100 mg per mL PREZISTA oral suspension.
Treatment-Naïve Adult Patients
The recommended oral dose of PREZISTA is 800 mg (one 800 mg tablet or 8 mL of the oral suspension) taken with ritonavir 100 mg (one 100 mg tablet or capsule or 1.25 mL of a 80 mg per mL ritonavir oral solution) once daily and with food. An 8 mL PREZISTA dose should be taken as two 4 mL administrations with the included oral dosing syringe.
Treatment-Experienced Adult Patients
The recommended oral dosage for treatment-experienced adult patients is summarized in Table 1.
Baseline genotypic testing is recommended for dose selection. However, when genotypic testing is not feasible, PREZISTA 600 mg taken with ritonavir 100 mg twice daily is recommended.
| Formulation and Recommended Dosing | ||
|---|---|---|
| Baseline Resistance | PREZISTA tablets with ritonavir tablets or capsule | PREZISTA oral suspension (100 mg/mL) with ritonavir oral solution (80 mg/mL) |
|
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| With no darunavir resistance associated substitutions* | One 800 mg PREZISTA tablet with one 100 mg ritonavir tablet/capsule, taken once daily with food | 8 mL† PREZISTA oral suspension with 1.25 mL ritonavir oral solution, taken once daily with food |
| With at least one darunavir resistance associated substitutions*, or with no baseline resistance information | One 600 mg PREZISTA tablet with one 100 mg ritonavir tablet/capsule, taken twice daily with food | 6 mL PREZISTA oral suspension with 1.25 mL ritonavir oral solution, taken twice daily with food |
Recommended Dosage During Pregnancy
The recommended dosage in pregnant patients is PREZISTA 600 mg taken with ritonavir 100 mg twice daily with food.
PREZISTA 800 mg taken with ritonavir 100 mg once daily should only be considered in certain pregnant patients who are already on a stable PREZISTA 800 mg with ritonavir 100 mg once daily regimen prior to pregnancy, are virologically suppressed (HIV-1 RNA less than 50 copies per mL), and in whom a change to twice daily PREZISTA 600 mg with ritonavir 100 mg may compromise tolerability or compliance.
Recommended Dosage in Pediatric Patients (age 3 to less than 18 years)
Healthcare professionals should pay special attention to accurate dose selection of PREZISTA, 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/ritonavir for each individual child based on body weight (kg) and should not exceed the recommended dose for adults.
Before prescribing PREZISTA, 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 oral suspension should be considered.
The recommended dose of PREZISTA/ritonavir for pediatric patients (3 to less than 18 years of age and weighing at least 10 kg is based on body weight (see Tables 2, 3, 4, and 5) and should not exceed the recommended adult dose. PREZISTA should be taken with ritonavir and with food.
The recommendations for the PREZISTA/ritonavir dosage regimens were based on pediatric clinical trial data and population pharmacokinetic modeling and simulation [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)].
Dosing Recommendations for Treatment-Naïve Pediatric Patients or Antiretroviral Treatment-Experienced Pediatric Patients with No Darunavir Resistance Associated Substitutions
Pediatric Patients Weighing At Least 10 kg but Less than 15 kg
The weight-based dose in antiretroviral treatment-naïve pediatric patients or antiretroviral treatment-experienced pediatric patients with no darunavir resistance associated substitutions is PREZISTA 35 mg/kg once daily with ritonavir 7 mg/kg once daily using the following table:
| Body weight (kg) | Formulation: PREZISTA oral suspension (100 mg/mL) and ritonavir oral solution (80 mg/mL) |
|---|---|
| Dose: once daily with food | |
|
|
| Greater than or equal to 10 kg to less than 11 kg |
PREZISTA 3.6 mL† (350 mg) with ritonavir 0.8 mL (64 mg) |
| Greater than or equal to 11 kg to less than 12 kg |
PREZISTA 4 mL† (385 mg) with ritonavir 0.8 mL (64 mg) |
| Greater than or equal to 12 kg to less than 13 kg |
PREZISTA 4.2 mL (420 mg) with ritonavir 1 mL (80 mg) |
| Greater than or equal to 13 kg to less than 14 kg |
PREZISTA 4.6 mL† (455 mg) with ritonavir 1 mL (80 mg) |
| Greater than or equal to 14 kg to less than 15 kg |
PREZISTA 5 mL† (490 mg) with ritonavir 1.2 mL (96 mg) |
Pediatric Patients Weighing At Least 15 kg
Pediatric patients weighing at least 15 kg can be dosed with PREZISTA oral tablet(s) or suspension using the following table:
| Body weight (kg) | Formulation: PREZISTA tablet(s) and ritonavir capsules or tablets (100 mg) | Formulation: PREZISTA oral suspension (100 mg/mL) and ritonavir oral solution (80 mg/mL) |
|---|---|---|
| Dose: once daily with food | Dose: once daily with food | |
|
||
| Greater than or equal to 15 kg to less than 30 kg | PREZISTA 600 mg with ritonavir 100 mg | PREZISTA 6 mL (600 mg) with ritonavir 1.25 mL (100 mg) |
| Greater than or equal to 30 kg to less than 40 kg | PREZISTA 675 mg with ritonavir 100 mg | PREZISTA 6.8 mL†‡ (675 mg) with ritonavir 1.25 mL (100 mg) |
| Greater than or equal to 40 kg | PREZISTA 800 mg with ritonavir 100 mg | PREZISTA 8 mL‡ (800 mg) with ritonavir 1.25 mL (100 mg) |
Dosing Recommendations for Treatment-Experienced Pediatric Patients with At Least One Darunavir Resistance Associated Substitutions
Pediatric Patients Weighing At Least 10 kg but Less than 15 kg
The weight-based dose in antiretroviral treatment-experienced pediatric patients with at least one darunavir resistance associated substitution is PREZISTA 20 mg/kg twice daily with ritonavir 3 mg/kg twice daily using the following table:
| Body weight (kg) | Formulation: PREZISTA oral suspension (100 mg/mL) and ritonavir oral solution (80 mg/mL) |
|---|---|
| Dose: twice daily with food | |
|
|
| Greater than or equal to 10 kg to less than 11 kg | PREZISTA 2 mL (200 mg) with ritonavir 0.4 mL (32 mg) |
| Greater than or equal to 11 kg to less than 12 kg | PREZISTA 2.2 mL (220 mg) with ritonavir 0.4 mL (32 mg) |
| Greater than or equal to 12 kg to less than 13 kg | PREZISTA 2.4 mL (240 mg) with ritonavir 0.5 mL (40 mg) |
| Greater than or equal to 13 kg to less than 14 kg | PREZISTA 2.6 mL (260 mg) with ritonavir 0.5 mL (40 mg) |
| Greater than or equal to 14 kg to less than 15 kg | PREZISTA 2.8 mL (280 mg) with ritonavir 0.6 mL (48 mg) |
Pediatric Patients Weighing At Least 15 kg
Pediatric patients weighing at least 15 kg can be dosed with PREZISTA oral tablet(s) or suspension using the following table:
| Body weight (kg) | Formulation: PREZISTA tablet(s) and ritonavir tablets, capsules (100 mg) or oral solution (80 mg/mL) | Formulation: PREZISTA oral suspension (100 mg/mL) and ritonavir oral solution (80 mg/mL) |
|---|---|---|
| Dose: twice daily with food | Dose: twice daily with food | |
|
||
| Greater than or equal to 15 kg to less than 30 kg | PREZISTA 375 mg with ritonavir 0.6 mL (48 mg) | PREZISTA 3.8 mL (375 mg)† with ritonavir 0.6 mL (48 mg) |
| Greater than or equal to 30 kg to less than 40 kg | PREZISTA 450 mg with ritonavir 0.75 mL (60 mg) | PREZISTA 4.6 mL (450 mg)† with ritonavir 0.75 mL (60 mg) |
| Greater than or equal to 40 kg | PREZISTA 600 mg with ritonavir 100 mg | PREZISTA 6 mL (600 mg) with ritonavir 1.25 mL (100 mg) |
The use of PREZISTA/ritonavir in pediatric patients below 3 years of age is not recommended [see Warnings and Precautions (5.10) and Use in Specific Populations (8.4)].
Not Recommended in Patients with Severe Hepatic Impairment
No dosage adjustment is required in patients with mild or moderate hepatic impairment. No data are available regarding the use of PREZISTA/ritonavir when co-administered to subjects with severe hepatic impairment; therefore, PREZISTA/ritonavir is not recommended for use in patients with severe hepatic impairment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
