Daru-Rito Dosage/Direction for Use

Therapy should be initiated by a health care provider experienced in the management of HIV infection. After therapy with Darunavir/Ritonavir Tablets 400 mg/50 mg has been initiated, patients should be advised not to alter the dosage, dose form or discontinue therapy without discussing with their health care provider.
Posology: ART-naïve adult patients: The recommended dose regimen is Darunavir 800 mg once daily with ritonavir 100 mg once daily taken with food. Darunavir/Ritonavir Tablets 400 mg/50 mg can be used to construct the once daily Darunavir/Ritonavir 800/100 mg regimen.
ART-experienced adult patients: The recommended dose regimens are as follows: In ART-experienced patients with no darunavir resistance associated mutations (DRV-RAMs)* and who have plasma HIV-1 RNA <100,000 copies/ml and CD4+ cell count ≥100 cells x 10⁶/l (see Indications/Uses) a regimen of 800 mg once daily with ritonavir 100 mg once daily taken with food may be used. Darunavir/Ritonavir Tablets 400/50 mg tablets can be used to construct the once daily Darunavir/Ritonavir 800/100 mg regimen.
In all other ART-experienced patients or if HIV-1 genotype testing is not available, the recommended dose regimen is Darunavir 600 mg twice daily taken with ritonavir 100 mg twice daily taken with food.
* DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V.
ART-naïve paediatric patients (3 to 17 years of age and weighing at least 40 kg): The recommended dose regimen is Darunavir 800 mg once daily with ritonavir 100 mg once daily taken food.
ART-experienced paediatric patients (3 to 17 years of age and weighing at least 40 kg): The recommended dose regimens are as follows: In ART-experienced patients without DRV-RAMs* and who have plasma HIV-1 RNA <100,000 copies/ml and CD4+ cell count ≥100 cells x 10⁶/l (see Indications/Uses) a regimen of Darunavir 800 mg once daily with ritonavir 100 mg once daily taken with food may be used. Darunavir/Ritonavir Tablets 400/50 mg tablets can be used to construct the once daily Darunavir/Ritonavir 800/100 mg regimen.
* DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V.
Advice on missed doses: If a once daily dose of Darunavir/Ritonavir is missed within 12 hours of the time it is usually taken, patients should be instructed to take the prescribed dose of Darunavir/Ritonavir with food as soon as possible. If this is noticed later than 12 hours after the time it is usually taken, the missed dose should not be taken and the patient should resume the usual dosing schedule.
This guidance is based on the half-life of darunavir in the presence of ritonavir and the recommended dosing interval of approximately 24 hours.
Special populations: Elderly: Limited information is available in this population, and therefore, Darunavir/Ritonavir should be used with caution in this age group (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: Darunavir: Darunavir is metabolised by the hepatic system. No dose adjustment is recommended in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment, however, Darunavir should be used with caution in these patients. No pharmacokinetic data are available in patients with severe hepatic impairment. Severe hepatic impairment could result in an increase of darunavir exposure and a worsening of its safety profile. Therefore, Darunavir/Ritonavir Tablets 400/50 mg must not be used in patients with severe hepatic impairment (Child-Pugh Class C) (see Contraindications, Precautions and Pharmacology: Pharmacokinetics under Actions).
Ritonavir: Ritonavir should not be given as a pharmacokinetic enhancer to patients with decompensated liver disease (see Contraindications). In the absence of pharmacokinetic studies in patients with stable severe hepatic impairment (Child Pugh Grade C) without decompensation, caution should be exercised when Ritonavir is used as a pharmacokinetic enhancer as increased levels of the co-administered PI may occur.
Renal impairment: No dose adjustment is required for darunavir/ritonavir in patients with renal impairment (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Paediatric population: Darunavir/Ritonavir should not be used in paediatric patients below 3 years of age or less than 15 kg body weight (see Precautions and Pharmacology: Toxicology: Preclinical safety data under Actions).
ART-naïve paediatric patients (less than 3 years of age or less than 15 kg body weight): No recommendations on posology can be made in this population.
ART-experienced paediatric patients (3 to 17 years of age and weighing at least 40 kg): Darunavir exposures in treatment-naïve adolescents 12 to 17 years weighing at least 40 kg receiving Darunavir/ritonavir 800/100 mg once daily have been determined and were found to be within the therapeutic range as has been established in adults receiving Darunavir/ritonavir 800/100 mg once daily. As a consequence, since Darunavir/ritonavir 800/100 mg once daily has also been registered for use in treatment-experienced adults without darunavir resistance associated mutations (DRV-RAMs)* and who have plasma HIV-1 RNA <100,000 copies/ml and CD4+ cell count ≥100 cells x 10⁶/l, the same indication of Darunavir 800 mg once daily applies to treatment-experienced children 3 to 17 years weighing at least 40 kg.
* DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V.
Darunavir should not be used in children less than 15 kg body weight as the dose for this population has not been established in a sufficient number of patients. Darunavir should not be used in children below 3 years of age because of safety concerns.
Pregnancy and postpartum: No dose adjustment is required for darunavir/ritonavir during pregnancy and postpartum. Darunavir/Ritonavir Tablets 400/50 mg should be used during pregnancy only if the potential benefit justifies the potential risk (see Precautions, Use in Pregnancy & Lactation and Pharmacology: Pharmacokinetics under Actions).
Method of administration: Patients should be instructed to take Darunavir/Ritonavir Tablets 400/50 mg within 30 minutes after completion of a meal. The type of food does not affect the exposure to darunavir (see Precautions, Interactions and Pharmacology: Pharmacokinetics under Actions).