REZOLSTA Film-coated tablet Ref.[51238] Active ingredients: Cobicistat Darunavir Darunavir and Cobicistat

Therapy should be initiated by a healthcare provider experienced in the management of HIV infection.

Posology

The recommended dose regimen in adults and adolescents aged 12 years and older, weighing at least 40 kg, is one tablet taken once daily with food.

ART-naïve patients

The recommended dose regimen is one film-coated tablet of REZOLSTA once daily taken with food.

ART-experienced patients

One film-coated tablet of REZOLSTA once daily 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 (see section 4.1).

^* DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V, L89V.

In all other ART-experienced patients or if HIV-1 genotype testing is not available, the use of REZOLSTA is not appropriate and another antiretroviral regimen should be used. Refer to the Summary of Product Characteristics of other antiretroviral medicinal products for dosing information.

Advice on missed doses

If REZOLSTA is missed within 12 hours of the time it is usually taken, patients should be instructed to take the prescribed dose of REZOLSTA with food as soon as possible. If this is noticed later than 12 hours of 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 medicine, another dose of REZOLSTA should be taken with food as soon as possible. If a patient vomits more than 4 hours after taking the medicine, the patient does not need to take another dose of REZOLSTA until the next regularly scheduled time.

Special populations

Elderly

Limited information is available in this population, and therefore, REZOLSTA should be used with caution in patients above 65 years of age (see sections 4.4 and 5.2).

Hepatic impairment

There are no pharmacokinetic data regarding the use of REZOLSTA in patients with hepatic impairment.

Darunavir and cobicistat are metabolised by the hepatic system. Separate trials of darunavir/ritonavir and cobicistat suggest no dose adjustment is recommended in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment, however, REZOLSTA should be used with caution in these patients.

There are no data regarding the use of darunavir or cobicistat in patients with severe hepatic impairment. Severe hepatic impairment could result in an increase of darunavir and/or cobicistat exposure and a worsening of its safety profile. Therefore, REZOLSTA 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

Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine. REZOLSTA should not be initiated in patients with creatinine clearance less than 70 mL/min, if any co-administered medicinal product (e.g. emtricitabine, lamivudine, tenofovir disoproxil (as fumarate, phosphate or succinate), or adefovir dipivoxil) requires dose adjustment based on creatinine clearance (see sections 4.4, 4.8 and 5.2).

Based on the very limited renal elimination of cobicistat and darunavir, no special precautions or dose adjustments of REZOLSTA are required for patients with renal impairment. Darunavir, cobicistat, or the combination of both have not been studied in patients receiving dialysis, and therefore no recommendation can be made for these patients (see section 5.2).

For more information consult the cobicistat Summary of Product Characteristics.

Paediatric population

The safety and efficacy of REZOLSTA in paediatric patients aged 3 to 11 years, or weighing <40 kg, have not been established (see sections 4.4 and 5.3). No data are available. REZOLSTA should not be used in paediatric patients below 3 years of age because of safety concerns (see sections 4.4 and 5.3).

Pregnancy and postpartum

Treatment with REZOLSTA during pregnancy results in low darunavir exposure (see sections 4.4 and 5.2). Therefore, therapy with REZOLSTA should not be initiated during pregnancy, and women who become pregnant during therapy with REZOLSTA 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

Oral use.

To ensure administration of the entire dose of both darunavir and cobicistat, the tablet should be swallowed whole. For patients unable to swallow the whole tablet, REZOLSTA may be split into two pieces using a tablet-cutter, and the entire dose should be consumed immediately after splitting.

Patients should be instructed to take REZOLSTA within 30 minutes after completion of a meal (see sections 4.4, 4.5 and 5.2).

Human experience of acute overdose with REZOLSTA or darunavir in combination with cobicistat 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 REZOLSTA. Treatment of overdose with REZOLSTA consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. Since darunavir and cobicistat are highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substances.

2 years.

6 weeks after opening the bottle.

This medicinal product does not require any special storage conditions.

White, high density polyethylene (HDPE) bottle containing 30 tablets, fitted with polypropylene (PP) child resistant closure with induction seal.

Pack size of one bottle.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.