Darunavirdosage

Testing: In treatment-experienced patients, treatment history genotypic and/or phenotypic testing is recommended prior to initiation of therapy with darunavir/ritonavir to assess drug susceptibility of the HIV-1 virus Monitor serum liver chemistry tests before and during therapy with darunavir/ritonavir. Treatment-naïve adult patients and treatment-experienced adult patients with no darunavir resistance associated substitutions: 800 mg (one 800 mg tablet) taken with ritonavir 100 mg once daily and with food. Treatment-experienced adult patients with at least one darunavir resistance associated substitution: 600 mg (one 600 mg tablet) taken with ritonavir 100 mg twice daily and with food.

Pregnant patients: 600 mg (one 600 mg tablet) taken with ritonavir 100 mg twice daily and with food. Pediatric patients (3 to less than 18 years of age and weighing at least 10 kg): dosage of darunavir and ritonavir is based on body weight and should not exceed the adult dose. Darunavir should be taken with ritonavir and with food. Darunavir/ritonavir is not recommended for use in patients with severe hepatic impairment.

2.1 Testing

Prior to Initiation of Darunavir/ritonavir In treatment-experienced patients, treatment history, genotypic and/or phenotypic testing is recommended to assess drug susceptibility of the HIV-1 virus. Refer to Dosage and Administration, and for dosing recommendations. Appropriate laboratory testing such as serum liver biochemistries should be conducted prior to initiating therapy with darunavir/ritonavir.

2.2 Monitoring

During Treatment with Darunavir/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 darunavir/ritonavir treatment.

2.3 Recommended

Dosage in Adult Patients Darunavir must be co-administered with ritonavir to exert its therapeutic effect. Failure to correctly co-administer 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 darunavir tablets can use the 100 mg per mL darunavir oral suspension. Treatment-Naïve Adult Patients The recommended oral dose of darunavir 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 darunavir 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, darunavir 600 mg taken with ritonavir 100 mg twice daily is recommended. Table 1 Recommended Darunavir/ritonavir Dosage in Treatment-Experienced Adult Patients a V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V b An 8 mL darunavir dose should be taken as two 4 mL administrations with the included oral dosing syringe Baseline Resistance Formulation and Recommended Dosing Darunavir tablets with ritonavir tablets or capsule Darunavir oral suspension (100 mg/mL) with ritonavir oral solution (80 mg/mL) With no darunavir resistance associated substitutions a One 800 mg darunavir tablet with one 100 mg ritonavir tablet/capsule, taken once daily with food 8 mL b darunavir oral suspension with 1.25 mL ritonavir oral solution, taken once daily with food With at least one darunavir resistance associated substitutions a, or with no baseline resistance information One 600 mg darunavir tablet with one 100 mg ritonavir tablet/capsule, taken twice daily with food 6 mL darunavir oral suspension with 1.25 mL ritonavir oral solution, taken twice daily with food

2.4 Recommended

Dosage During Pregnancy The recommended dosage in pregnant patients is darunavir 600 mg taken with ritonavir 100 mg twice daily with food. Darunavir 800 mg taken with ritonavir 100 mg once daily should only be considered in certain pregnant patients who are already on a stable darunavir 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 darunavir 600 mg with ritonavir 100 mg may compromise tolerability or compliance.

2.5 Recommended

Dosage in Pediatric Patients (age 3 to less than 18 years) Healthcare professionals should pay special attention to accurate dose selection of 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 darunavir/ritonavir for each individual child based on body weight (kg) and should not exceed the recommended dose for adults. Before prescribing 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 darunavir oral suspension should be considered. The recommended dose of 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 Tables 2, 3, 4 and 5) and should not exceed the recommended adult dose. Darunavir should be taken with ritonavir and with food. The recommendations for the darunavir/ritonavir dosage regimens were based on pediatric clinical trial data and population pharmacokinetic modeling and simulation. 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 darunavir 35 mg/kg once daily with ritonavir 7 mg/kg once daily using the following table: Table 2 Recommended Dose for Pediatric Patients Weighing 10 kg to Less Than 15 kg Who are Treatment-Naïve or Treatment-Experienced with No Darunavir Resistance Associated Substitutions a a darunavir resistance associated substitutions: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V b The 350 mg, 385 mg, 455 mg and 490 mg darunavir dose for the specified weight groups were rounded up for suspension dosing convenience to 3.6 mL, 4 mL, 4.6 mL and 5 mL, respectively. Body weight (kg) Formulation: Darunavir 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 Darunavir 3.6 mL b (350 mg) with ritonavir 0.8 mL (64 mg) Greater than or equal to 11 kg to less than 12 kg Darunavir 4 mL b (385 mg) with ritonavir 0.8 mL (64 mg) Greater than or equal to 12 kg to less than 13 kg Darunavir 4.2 mL (420 mg) with ritonavir 1 mL (80 mg) Greater than or equal to 13 kg to less than 14 kg Darunavir 4.6 mL b (455 mg) with ritonavir 1 mL (80 mg) Greater than or equal to 14 kg to less than 15 kg Darunavir 5 mL b (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 darunavir oral tablet(s) using the following table: Table 3 Recommended Dose for Pediatric Patients Weighing At Least 15 kg Who are Treatment-Naïve or Treatment-Experienced with No Darunavir Resistance Associated Substitutions a a darunavir resistance associated substitutions: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V b The 675 mg dose using darunavir tablets for this weight group is rounded up to 6.8 mL for suspension dosing convenience. c The 6.8 mL and 8 mL darunavir dose should be taken as two (3.4 mL or 4 mL respectively) administrations with the included oral dosing syringe. Body weight (kg) Formulation: Darunavir tablet(s) and ritonavir capsules or tablets (100 mg) Formulation: Darunavir 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 Darunavir 600 mg with ritonavir 100 mg Darunavir 6 mL (600 mg) with ritonavir 1.25 mL (100 mg) Greater than or equal to 30 kg to less than 40 kg Darunavir 675 mg with ritonavir 100 mg Darunavir 6.8 mL bc (675 mg) with ritonavir 1.25 mL (100 mg) Greater than or equal to 40 kg Darunavir 800 mg with ritonavir 100 mg Darunavir 8 mL c (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 darunavir 20 mg/kg twice daily with ritonavir 3 mg/kg twice daily using the following table: Table 4 Recommended Dose for Pediatric Patients Weighing 10 kg to Less Than 15 kg Who are Treatment-Experienced with At Least One Darunavir Resistance Associated Substitution a a darunavir resistance associated substitutions: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V Body weight (kg) Formulation: Darunavir 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 Darunavir 2 mL (200 mg) with ritonavir 0.4 mL (32 mg) Greater than or equal to 11 kg to less than 12 kg Darunavir 2.2 mL (220 mg) with ritonavir 0.4 mL (32 mg) Greater than or equal to 12 kg to less than 13 kg Darunavir 2.4 mL (240 mg) with ritonavir 0.5 mL (40 mg) Greater than or equal to 13 kg to less than 14 kg Darunavir 2.6 mL (260 mg) with ritonavir 0.5 mL (40 mg) Greater than or equal to 14 kg to less than 15 kg Darunavir 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 darunavir oral tablet(s) or suspension using the following table: Table 5 Recommended Dose for Pediatric Patients Weighing At Least 15 kg Who are Treatment-Experienced with At Least One Darunavir Resistance Associated Substitution a a darunavir resistance associated substitutions: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V b The 375 mg and 450 mg dose using darunavir tablets for this weight group is rounded up to 3.8 mL and 4.6 mL for suspension dosing convenience. Body weight (kg) Formulation: Darunavir tablet(s) and ritonavir tablets, capsules (100 mg) or oral solution (80 mg/mL) Formulation: Darunavir 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 Darunavir 375 mg with ritonavir 0.6 mL (48 mg) Darunavir 3.8 mL (375 mg) b with ritonavir 0.6 mL (48 mg) Greater than or equal to 30 kg to less than 40 kg Darunavir 450 mg with ritonavir 0.75 mL (60 mg) Darunavir 4.6 mL (450 mg) b with ritonavir 0.75 mL (60 mg) Greater than or equal to 40 kg Darunavir 600 mg with ritonavir 100 mg Darunavir 6 mL (600 mg) with ritonavir 1.25 mL (100 mg) The use of darunavir/ritonavir in pediatric patients below 3 years of age is not recommended.

2.6 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 darunavir/ritonavir when co-administered to subjects with severe hepatic impairment; therefore, darunavir/ritonavir is not recommended for use in patients with severe hepatic impairment.