Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
Darunavir Krka, co-administered with low dose ritonavir is indicated in combination with other antiretroviral medicinal products for the treatment of patients with human immunodeficiency virus (HIV-1) infection (see section 4.2).
Darunavir Krka 600 mg tablets may be used to provide suitable dose regimens (see section 4.2):
In deciding to initiate treatment with darunavir co-administered with low dose ritonavir, careful consideration should be given to the treatment history of the individual patient and the patterns of mutations associated with different agents. Genotypic or phenotypic testing (when available) and treatment history should guide the use of darunavir (see sections 4.2, 4.4 and 5.1).
Therapy should be initiated by a healthcare provider experienced in the management of HIV infection. After therapy with darunavir has been initiated, patients should be advised not to alter the dose, dose form or discontinue therapy without discussing with their healthcare provider.
Darunavir must always be given orally with low dose ritonavir as a pharmacokinetic enhancer and in combination with other antiretroviral medicinal products. The Summary of Product Characteristics of ritonavir must, therefore, be consulted prior to initiation of therapy with darunavir.
Darunavir Krka 600 mg film coated tablets must not be chewed or crushed. This strength is not suitable for doses below 600 mg. It is not possible to administer all paediatric doses with this product. Other tablet strengths and formulations of darunavir are available.
The recommended dose regimen is 600 mg twice daily taken with ritonavir 100 mg twice daily taken with food. Darunavir Krka 600 mg tablets can be used to construct the twice daily 600 mg regimen.
For dose recommendations in ART-naïve patients see the Summary of Product Characteristics for Darunavir Krka 400 mg and 800 mg tablets.
The weight-based dose of darunavir and ritonavir in paediatric patients is provided in the table below.
Table 1. Recommended dose for treatment-naïve paediatric patients (3 to 17 years) with darunavir and ritonavira:
| Body weight (kg) | Dose (once daily with food) |
|---|---|
| ≥15 kg to <30 kg | 600 mg darunavir/100 mg ritonavir once daily |
| ≥30 kg to <40 kg | 675 mg darunavir/100 mg ritonavir once daily |
| ≥40 kg 800 mg | darunavir/100 mg ritonavir once daily |
a ritonavir oral solution: 80 mg/ml
Darunavir twice daily taken with ritonavir taken with food is usually recommended. A once daily dose regimen of darunavir taken with ritonavir taken with food may be used in patients with prior exposure to antiretroviral medicinal products but 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.
* DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V
The recommended dose of darunavir with low dose ritonavir for paediatric patients is based on body weight and should not exceed the recommended adult dose (600/100 mg twice daily or 800/100 mg once daily).
Table 2. Recommended dose for treatment-experienced paediatric patients (3 to 17 years) with darunavir and ritonavira:
| Body weight (kg) | Dose (once daily with food) | Dose(twice daily with food) |
|---|---|---|
| ≥15 kg – <30 kg | 600 mg darunavir/100 mg ritonavir once daily | 375 mg darunavir/50 mg ritonavir twice daily |
| ≥30 kg – <40 kg | 675 mg darunavir/100 mg ritonavir once daily | 450 mg darunavir/60 mg ritonavir twice daily |
| ≥40 kg | 800 mg darunavir/100 mg ritonavir once daily | 600 mg darunavir/100 mg ritonavir twice daily |
a with ritonavir oral solution: 80 mg/ml
For ART-experienced paediatric patients HIV genotypic testing is recommended. However, when HIV genotypic testing is not feasible, the darunavir/ritonavir once daily dosing regimen is recommended in HIV protease inhibitor-naïve paediatric patients and the twice daily dosing regimen is recommended in HIV protease inhibitor-experienced patients.
In case a dose of darunavir and/or ritonavir is missed within 6 hours of the time it is usually taken, patients should be instructed to take the prescribed dose of darunavir and ritonavir with food as soon as possible. If this is noticed later than 6 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 15 hour half-life of darunavir in the presence of ritonavir and the recommended dosing interval of approximately 12 hours.
If a patient vomits within 4 hours of taking the medicinal product, another dose of darunavir with ritonavir should be taken with food as soon as possible. If a patient vomits more than 4 hours after taking the medicinal product, the patient does not need to take another dose of darunavir with ritonavir until the next regularly scheduled time.
Limited information is available in this population, and therefore, darunavir should be used with caution in this age group (see sections 4.4 and 5.2).
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 must not be used in patients with severe hepatic impairment (Child-Pugh Class C) (see sections 4.3, 4.4 and 5.2).
No dose adjustment is required in patients with renal impairment (see sections 4.4 and 5.2).
Darunavir/ritonavir should not be used in children with a body weight of less than 15 kg as the dose for this population has not been established in a sufficient number of patients (see section 5.1).
Darunavir/ritonavir should not be used in children below 3 years of age because of safety concerns (see sections 4.4 and 5.3).
The weight-based dose regimen for darunavir and ritonavir is provided in the tables above.
No dose adjustment is required for darunavir/ritonavir during pregnancy and postpartum. Darunavir/ritonavir should be used during pregnancy only if the potential benefit justifies the potential risk (see sections 4.4, 4.6 and 5.2).
Patients should be instructed to take darunavir with low dose ritonavir within 30 minutes after completion of a meal. The type of food does not affect the exposure to darunavir (see sections 4.4, 4.5 and 5.2).
Human experience of acute overdose with darunavir co-administered with low dose ritonavir is limited. Single doses up to 3 200 mg of darunavir as oral solution alone and up to 1 600 mg of the tablet formulation of darunavir in combination with ritonavir have been administered to healthy volunteers without untoward symptomatic effects.
There is no specific antidote for overdose with darunavir. Treatment of overdose with darunavir consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.
Since darunavir is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substance.
3 years.
Shelf life after first opening: 3 months.
Keep the bottle tightly closed in order to protect from moisture.
For storage conditions after first opening of the medicinal product, see section 6.3.
Bottle (HDPE), child resistant tamper evident PP closure with a desiccant:
Not all pack sizes may be marketed.
No special requirements for disposal.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
