DARUNAVIR KRKA 400 mg / 800 mg Film-coated tablet Ref.[8767] Active ingredients: Darunavir

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.

The interaction profile of darunavir depends on whether ritonavir is used as pharmacokinetic enhancer. Darunavir may therefore have different contraindications and recommendations for concomitant medicinal products depending on whether the compound is boosted with ritonavir (see sections 4.3, 4.4 and 4.5).

Posology

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 as appropriate, must therefore be consulted prior to initiation of therapy with darunavir.

This product is only available as film coated tablets and is thus not suitable for patients who are unable to swallow intact tablets, for example young children. For use in these patients, more suitable formulations containing darunavir should be checked for their availability.

ART-naïve adult patients

The recommended dose regimen is 800 mg once daily taken with ritonavir 100 mg once daily taken with food. Darunavir Krka 400 mg and 800 mg tablets can be used to construct the once daily 800 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 section 4.1) a regimen of 800 mg once daily with ritonavir 100 mg once daily taken with food may be used. Darunavir Krka 400 mg and 800 mg tablets can be used to construct the once daily 800 mg regimen.
• In all other ART-experienced patients or if HIV-1 genotype testing is not available, the recommended dose regimen is 600 mg twice daily taken with ritonavir 100 mg twice daily taken with food. See the Summary of Product Characteristics for Darunavir Krka 600 mg tablets.

^* 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 800 mg once daily with ritonavir 100 mg once daily taken with 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 section 4.1) a regimen of 800 mg once daily with ritonavir 100 mg once daily taken with food may be used. Darunavir Krka 400 mg and 800 mg tablets can be used to construct the once daily 800 mg regimen. The dose of other pharmacokinetic enhancer to be used with darunavir in children less than 18 years of age has not been established.
• In all other ART-experienced patients or if HIV-1 genotype testing is not available, the recommended dose regimen is described in the Summary of Product Characteristics for Darunavir Krka 600 mg tablets.

^* 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 and/or ritonavir is missed within 12 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 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.

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.

Special populations

Elderly

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).

Hepatic impairment

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).

Renal impairment

No dose adjustment is required for darunavir/ritonavir in patients with renal impairment (see sections 4.4 and 5.2).

Paediatric population

Darunavir Krka should not be used in children:

• below 3 years of age, because of safety concerns (see sections 4.4 and 5.3), or,
• less than 15 kg body weight, as the dose for this population has not been established in a sufficient number of patients (see section 5.1).

For dose recommendations in children see the Summary of Product Characteristics for Darunavir Krka 600 mg tablets.

Pregnancy and postpartum

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).

Treatment with darunavir/cobicistat 800/150 mg during pregnancy results in low darunavir exposure (see sections 4.4 and 5.2). Therefore, therapy with darunavir/cobicistat should not be initiated during pregnancy, and women who become pregnant during therapy with darunavir/cobicistat should be switched to an alternative regimen (see sections 4.4 and 4.6). Darunavir/ritonavir may be considered as an alternative.

Method of administration

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 cobicistat or 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.

400 mg film-coated tablets:

Bottle (HDPE), child resistant tamper evident PP closure with a desiccant:

• 30 tablets: 1 bottle of 30 film-coated tablets,
• 60 tablets: 2 bottles of 30 film-coated tablets,
• 90 tablets: 3 bottles of 30 film-coated tablets,
• 180 tablets: 6 bottles of 30 film-coated tablets.

800 mg film-coated tablets:

Bottle (HDPE), child resistant tamper evident PP closure with a desiccant:

• 30 tablets: 1 bottle of 30 film-coated tablets,
• 90 tablets. 3 bottles of 30 film-coated tablets.

No special requirements for disposal.