Prezista 600 mg film-coated tablets

Update to Local representative contact details

Approval of variation type II - WS2342- crystal nephropathy + CHMP-requested text on HIV transmission and breastfeeding - day 27 - 7Dec2022

Approval of variation type II - WS2342- crystal nephropathy + CHMP-requested text on HIV transmission and breastfeeding - day 27 - 7Dec2022

EU Approval EMEA/H/C/707/WS/2250

EU Approval EMEA/H/C/707/WS/2250

Section 4.5          Interaction with other medicinal products and other forms of interaction

Interaction table

Table 1:                Interactions between the individual components of Prezista and other medicinal   products

Corticosteroids - updated to address co-administration of cutaneous administered corticosteroids sensitive to CYP3A inhibition in section 4.5 (interaction table)

Updates are in red

Deleted: “for intranasal or inhalation use”

               “e.g. fluticasone propionate or other inhaled or nasal corticosteroids ”

Section 2.            What you need to know before you take PREZISTA

The effects of other medicines might be influenced if you take PREZISTA. Tell your doctor if you take:

• Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory conditions of the skin, eyes, joints and muscles and other inflammatory conditions. These medicines are generally taken orally, inhaled, injected or applied to the skin. If alternatives cannot be used, its use should only take place after medical evaluation and under close monitoring by your doctor for corticosteroid side effects.
   
  Updates are in red
  Last revision date : 09/2021

4.2     Posology and method of administration

A once daily dose regimen of PREZISTA 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/lL.

If a patient vomits within 4 hours of taking the medicine, another dose of PREZISTA with ritonavir 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 PREZISTA with ritonavir until the next regularly scheduled time.

4.4     Special warnings and precautions for use

ART‑experienced patients – once daily dosing

PREZISTA used in combination with cobicistat or low dose ritonavir once daily in ART‑experienced patients should not be used in patients with one or more darunavir resistance associated mutations (DRV‑RAMs) or HIV‑1 RNA ≥ 100,000 copies/ml or CD4+ cell count < 100 cells x 10⁶/l L (see section 4.2). Combinations with optimised background regimen (OBRs) other than ≥ 2 NRTIs have not been studied in this population. Limited data are available in patients with HIV‑1 clades other than B (see section 5.1).

4.5     Interaction with other medicinal products and other forms of interaction

5.1     Pharmacodynamic properties

PREZISTA/ritonavir 800/100 mg once daily in ART‑experienced patients should not be used in patients with one or more darunavir resistance associated mutations (DRV‑RAMs) or HIV‑1 RNA ≥ 100,000 copies/ml or CD4+ cell count < 100 cells x 10⁶/lL (see section 4.2 and 4.4). Limited data is available in patients with HIV‑1 clades other than B.

5.2     Pharmacokinetic properties

The pharmacokinetics of darunavir in combination with ritonavir taken once daily in 12 ART‑naïve paediatric patients, aged 12 to < 18 years and weighing at least 40 kg, showed that PREZISTA/ritonavir 800/100 mg once daily results in darunavir exposure that was comparable to that achieved in adults receiving PREZISTA/ritonavir 800/100 mg once daily. Therefore the same once daily dosage may be used in treatment‑experienced adolescents aged 12 to < 18 years and weighing at least 40 kg 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 L (see section 4.2).

*    DRV‑RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V

The pharmacokinetics of darunavir in combination with ritonavir taken once daily in 10 treatment‑experienced paediatric patients, aged 3 to < 6 years and weighing at least 14 kg to < 20 kg, showed that weight‑based dosages resulted in darunavir exposure that was comparable to that achieved in adults receiving PREZISTA/ritonavir 800/100 mg once daily (see section 4.2). In addition, pharmacokinetic modeling and simulation of darunavir exposures in paediatric patients across the ages of 3 to < 18 years confirmed the darunavir exposures as observed in the clinical studies and allowed the identification of weight‑based PREZISTA/ritonavir once daily dosing regimens for paediatric patients weighing at least 15 kg that are either ART‑naïve or treatment‑experienced paediatric patients without DRV‑RAMs* and who have plasma HIV‑1 RNA < 100,000 copies/ml and CD4+ cell count ≥ 100 cells x 10⁶/l L (see section 4.2).

*    DRV‑RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V

6.6     Special precautions for disposal

No special requirements.

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

4.2     Posology and method of administration

A once daily dose regimen of PREZISTA 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/lL.

If a patient vomits within 4 hours of taking the medicine, another dose of PREZISTA with ritonavir 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 PREZISTA with ritonavir until the next regularly scheduled time.

4.4     Special warnings and precautions for use

ART‑experienced patients – once daily dosing

PREZISTA used in combination with cobicistat or low dose ritonavir once daily in ART‑experienced patients should not be used in patients with one or more darunavir resistance associated mutations (DRV‑RAMs) or HIV‑1 RNA ≥ 100,000 copies/ml or CD4+ cell count < 100 cells x 10⁶/l L (see section 4.2). Combinations with optimised background regimen (OBRs) other than ≥ 2 NRTIs have not been studied in this population. Limited data are available in patients with HIV‑1 clades other than B (see section 5.1).

4.5     Interaction with other medicinal products and other forms of interaction

5.1     Pharmacodynamic properties

PREZISTA/ritonavir 800/100 mg once daily in ART‑experienced patients should not be used in patients with one or more darunavir resistance associated mutations (DRV‑RAMs) or HIV‑1 RNA ≥ 100,000 copies/ml or CD4+ cell count < 100 cells x 10⁶/lL (see section 4.2 and 4.4). Limited data is available in patients with HIV‑1 clades other than B.

5.2     Pharmacokinetic properties

The pharmacokinetics of darunavir in combination with ritonavir taken once daily in 12 ART‑naïve paediatric patients, aged 12 to < 18 years and weighing at least 40 kg, showed that PREZISTA/ritonavir 800/100 mg once daily results in darunavir exposure that was comparable to that achieved in adults receiving PREZISTA/ritonavir 800/100 mg once daily. Therefore the same once daily dosage may be used in treatment‑experienced adolescents aged 12 to < 18 years and weighing at least 40 kg 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 L (see section 4.2).

*    DRV‑RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V

The pharmacokinetics of darunavir in combination with ritonavir taken once daily in 10 treatment‑experienced paediatric patients, aged 3 to < 6 years and weighing at least 14 kg to < 20 kg, showed that weight‑based dosages resulted in darunavir exposure that was comparable to that achieved in adults receiving PREZISTA/ritonavir 800/100 mg once daily (see section 4.2). In addition, pharmacokinetic modeling and simulation of darunavir exposures in paediatric patients across the ages of 3 to < 18 years confirmed the darunavir exposures as observed in the clinical studies and allowed the identification of weight‑based PREZISTA/ritonavir once daily dosing regimens for paediatric patients weighing at least 15 kg that are either ART‑naïve or treatment‑experienced paediatric patients without DRV‑RAMs* and who have plasma HIV‑1 RNA < 100,000 copies/ml and CD4+ cell count ≥ 100 cells x 10⁶/l L (see section 4.2).

*    DRV‑RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V

6.6     Special precautions for disposal

No special requirements.

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

3.       How to take PREZISTA

Always use this medicine exactly as described in this leaflet or as your doctor, pharmacist or nurse has told you. Check with your doctor, pharmacist or nurse if you are not sure.

Even if you feel better, do not stop taking PREZISTA and ritonavir without talking to your doctor.

After therapy has been initiated, the dose or dosage form must not be changed or therapy must not be stopped without instruction of the doctor.

Dose for adults who have not taken antiretroviral medicines before (your doctor will determine this)

You will require a different dose of PREZISTA which cannot be administered with these 600 milligram tablets. Other strengths of PREZISTA are available.

Dose for adults who have taken antiretroviral medicines before (your doctor will determine this)

The dose is either:

• 600 milligram PREZISTA (2 tablets containing 300 milligram of PREZISTA or 1 tablet containing 600 milligram of PREZISTA) together with 100 milligram ritonavir twice daily.
  OR
• 800 milligram PREZISTA (2 tablets containing 400 milligram of PREZISTA or 1 tablet containing 800 milligram of PREZISTA) together with 100 milligram ritonavir once daily. PREZISTA 400 milligram and 800 milligram tablets are only to be used to construct the once daily 800 milligram regimen.
   
  Please discuss with your doctor which dose is right for you.

What PREZISTA looks like and contents of the pack

Film‑coated, orange, oval shaped tablet, mentioning TMC on one side, 600MG on the other side. 60 tablets in a plastic bottle.

PREZISTA is also available as 75 milligram, 150 milligram, 300 milligram, 400 milligram and 800 milligram film‑coated tablets and 100 milligram per milliliter oral suspension.

3.       How to take PREZISTA

Always use this medicine exactly as described in this leaflet or as your doctor, pharmacist or nurse has told you. Check with your doctor, pharmacist or nurse if you are not sure.

Even if you feel better, do not stop taking PREZISTA and ritonavir without talking to your doctor.

After therapy has been initiated, the dose or dosage form must not be changed or therapy must not be stopped without instruction of the doctor.

Dose for adults who have not taken antiretroviral medicines before (your doctor will determine this)

You will require a different dose of PREZISTA which cannot be administered with these 600 milligram tablets. Other strengths of PREZISTA are available.

Dose for adults who have taken antiretroviral medicines before (your doctor will determine this)

The dose is either:

• 600 milligram PREZISTA (2 tablets containing 300 milligram of PREZISTA or 1 tablet containing 600 milligram of PREZISTA) together with 100 milligram ritonavir twice daily.
  OR
• 800 milligram PREZISTA (2 tablets containing 400 milligram of PREZISTA or 1 tablet containing 800 milligram of PREZISTA) together with 100 milligram ritonavir once daily. PREZISTA 400 milligram and 800 milligram tablets are only to be used to construct the once daily 800 milligram regimen.
   
  Please discuss with your doctor which dose is right for you.

1.       NAME OF THE MEDICINAL PRODUCT

PREZISTA 75 mg film‑coated tablets

PREZISTA 150 mg film‑coated tablets

PREZISTA 300 mg film‑coated tablets

PREZISTA 600 mg film‑coated tablets

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

PREZISTA 75 mg film‑coated tablets

Each film‑coated tablet contains 75 mg of darunavir (as ethanolate).

PREZISTA 150 mg film‑coated tablets

Each film‑coated tablet contains 150 mg of darunavir (as ethanolate).

PREZISTA 300 mg film‑coated tablets

Each film‑coated tablet contains 300 mg of darunavir (as ethanolate).

Excipient with known effect: Each tablet contains 1.375 mg sunset yellow FCF (E110).

3.       PHARMACEUTICAL FORM

PREZISTA 75 mg film‑coated tablets

Film‑coated tablet.

White caplet shaped tablet of 9.2 mm, debossed with “75” on one side and “TMC” on the other side.

PREZISTA 150 mg film‑coated tablets

Film‑coated tablet.

White oval shaped tablet of 13.7 mm, debossed with “150” on one side and “TMC” on the other side.

PREZISTA 300 mg film‑coated tablets

Film‑coated tablet.

Orange oval shaped tablet of 17.3 mm, debossed with “300MG” on one side and “TMC114” on the other side.

4.1     Therapeutic indications

PREZISTA, 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).

PREZISTA 75 mg, 150 mg, 300 mg, and 600 mg tablets may be used to provide suitable dose regimens (see section 4.2):

4.2     Posology and method of administration

ART‑experienced adult patients

The recommended dose regimen is 600 mg twice daily taken with ritonavir 100 mg twice daily taken with food. PREZISTA 75 mg, 150 mg, 300 mg, and 600 mg tablets can be used to construct the twice daily 600 mg regimen.

The use of 75 mg and 150 mg tablets to achieve the recommended dose is appropriate when there is a possibility of hypersensitivity to specific colouring agents, or difficulty in swallowing the 300 mg or 600 mg tablets.

4.4     Special warnings and precautions for use

PREZISTA 300 mg tablets and 600 mg tablets contain sunset yellow FCF (E110) which may cause an allergic reaction.

6.1     List of excipients

PREZISTA 300 mg film‑coated tablets

Tablet core

Microcrystalline cellulose

Colloidal anhydrous silica

Crospovidone

Magnesium stearate

Tablet film‑coat

Poly(vinyl alcohol) – partially hydrolysed

Macrogol 3350

Titanium dioxide (E171)

Talc

Sunset yellow FCF (E110)

6.3     Shelf life

PREZISTA 75 mg, 150 mg and 600 mg film‑coated tablets

3 years

PREZISTA 300 mg film‑coated tablets

2 years

6.5     Nature and contents of container

PREZISTA 300 mg film‑coated tablets

Opaque, white, high density polyethylene (HDPE) plastic, 160 ml bottle containing 120 tablets, fitted with polypropylene (PP) child resistant closure.

Pack size of one bottle.

8.       MARKETING AUTHORISATION NUMBER(S)

PREZISTA 300 mg film‑coated tablets

EU/1/06/380/001

zolpidem zoldipem

4.3     Contraindications

• Added    dabigatran,
   
  4.5     Interaction with other medicinal products and other forms of interaction

4.4     Special warnings and precautions for use

Immune reactivation syndrome 

Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment (see section 4.8).

4.8     Undesirable effects 

Immune reconstitution inflammatory syndrome

In HIV infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment (see section 4.4).

4.4     Special warnings and precautions for use

Immune reactivation syndrome

Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment (see section 4.8).

NEW Combined SmPC

4.3          Contraindications

-                 alfuzosin (alpha 1‑adrenoreceptor antagonist)

-                 amiodarone, bepridil, dronedarone, quinidine, ranolazine, systemic lidocaine (antiarrhythmics/antianginals)

-                 astemizole, terfenadine (antihistamines)

-                 colchicine when used in patients with renal and/or hepatic impairment (antigout) (see section 4.5)

-                 ergot derivatives (e.g. dihydroergotamine, ergometrine, ergotamine, methylergonovine)

-                 elbasvir/grazoprevir (hepatitis C virus direct-acting antiviral)

-                 cisapride (gastrointestinal motility agent)

-                 lurasidone, pimozide, quetiapine, sertindole (antipsychotics/neuroleptics) (see section 4.5)

-                 triazolam, midazolam administered orally (sedatives/hypnotics) (for caution on parenterally administered midazolam, see section 4.5)

-                 sildenafil ‑ when used for the treatment of pulmonary arterial hypertension, avanafil (PDE‑5 inhibitors)

-                 simvastatin,  and lovastatin and lomitapide (HMG‑CoA reductase inhibitors) (see section 4.5)

-                 ticagrelor (antiplatelets) (see section 4.5).

4.4          Special warnings and precautions for use

PREZISTA must always be given orally should only be used in combination with low dose ritonavir as a pharmacokinetic enhancer and in combination with other antiretroviral medicinal products (see section 5.2). The Summary of Product Characteristics of ritonavir as appropriate, must therefore be consulted prior to initiation of therapy with PREZISTA.

Efavirenz in combination with boosted PREZISTA/ritonavir 800/100 mg once daily may result in sub‑optimal darunavir C_min. If efavirenz is to be used in combination with PREZISTA/ritonavir, the PREZISTA/ritonavir 600/100 mg twice daily regimen should be used. See the Summary of Product Characteristics for PREZISTA 150 mg, 300 mg or 600 mg tablets  (see section 4.5).

Life‑threatening and fatal drug interactions have been reported in patients treated with colchicine and strong inhibitors of CYP3A and P‑glycoprotein (P‑gp; see sections 4.3 and 4.5).

PREZISTA 300 mg tablets and 600 mg tablets contain sunset yellow FCF (E110) which may cause an allergic reaction.

Medicinal products that affect darunavir/ritonavir exposure

….Co‑administration of darunavir and ritonavir and other medicinal products that inhibit CYP3A may decrease the clearance of darunavir and ritonavir and may result in increased plasma concentrations of darunavir and ritonavir (e.g. indinavir, systemic azole antifungalss like ketoconazole and clotrimazole). These interactions are described in the interaction table below.

4.9     Overdose

There is no specific antidote for overdose with PREZISTA. Treatment of overdose with PREZISTA consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.  If indicated, elimination of unabsorbed active substance is to be achieved by emesis.

10.     DATE OF REVISION OF THE TEXT

22 June 2017 15 February 2018

.3       Contraindications

-                 elbasvir/grazoprevir (hepatitis C virus direct-acting antiviral)

-                 lurasidone, pimozide, quetiapine, sertindole (antipsychotics/neuroleptics) (see section 4.5)

4.5     Interaction with other medicinal products and other forms of interaction

Ritonavir inhibits the transporters P‑glycoprotein, OATP1B1 and OATP1B3, and co‑administration with substrates of these transporters can result in increased plasma concentrations of these compounds (e.g. dabigatran etexilate, digoxin, statins and bosentan; see the Interaction table below).

addition in red text 

4.2     Posology and method of administration

Pregnancy and postpartum

No dose adjustment is required for darunavir/ritonavir during pregnancy and postpartum. Prezista should be used during pregnancy only if the potential benefit justifies the potential risk (see sections 4.4, 4.6 and 5.2).

4.4     Special warnings and precautions for use

Pregnancy

Prezista should be used during pregnancy only if the potential benefit justifies the potential risk. Caution should be used in pregnant women with concomitant medications which may further decrease darunavir exposure (see sections 4.5 and 5.2).

4.6     Fertility, pregnancy and lactation

Pregnancy

As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, the animal data as well as the clinical experience in pregnant women should be taken into account.

There are no adequate and well controlled studies on pregnancy outcome with darunavir in pregnant women. Studies in animals do not indicate direct harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).

PREZISTA co‑administered with cobicistat or low dose ritonavir should be used during pregnancy only if the potential benefit justifies the potential risk.

4.8     Undesirable effects

5.1     Pharmacodynamic properties

Pregnancy and postpartum

Darunavir/ritonavir (600/100 mg twice daily or 800/100 mg once daily) in combination with a background regimen was evaluated in a clinical trial of 34 pregnant women (17 in each arm) during the second and third trimesters, and postpartum. Virologic response was preserved throughout the study period in both arms. No mother to child transmission occurred in the infants born to the 29 subjects who stayed on the antiretroviral treatment through delivery. There were no new clinically relevant safety findings compared with the known safety profile of darunavir/ritonavir in HIV 1 infected adults (see sections 4.2, 4.4 and 5.2).

5.2     Pharmacokinetic properties

Pregnancy and postpartum

The exposure to total darunavir and ritonavir after intake of darunavir/ritonavir 600/100 mg twice daily and darunavir/ritonavir 800/100 mg once daily as part of an antiretroviral regimen was generally lower during pregnancy compared with postpartum. However, for unbound (i.e. active) darunavir, the pharmacokinetic parameters were less reduced during pregnancy compared to postpartum, due to an increase in the unbound fraction of darunavir during pregnancy compared to postpartum.

In women receiving darunavir/ritonavir 600/100 mg twice daily during the second trimester of pregnancy, mean intra‑individual values for total darunavir C_max, AUC_12h and C_min were 28%, 24% and 17% lower, respectively, as compared with postpartum; during the third trimester of pregnancy, total darunavir C_max, AUC_12h and C_min values were 19%, 17% lower and 2% higher, respectively, as compared with postpartum.

In women receiving darunavir/ritonavir 800/100 mg once daily during the second trimester of pregnancy, mean intra‑individual values for total darunavir C_max, AUC_12h and C_min were 34%, 34% and 32% lower, respectively, as compared with postpartum; during the third trimester of pregnancy, total darunavir C_max, AUC_12h and C_min values were 31%, 35% and 50% lower, respectively, as compared with postpartum.

4.4          Special warnings and precautions for use

While effective viral suppression with antiretroviral therapy has been proven to substantially reduce the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission should be taken in accordance with national guidelines.

Patients should be advised that current antiretroviral therapy does not cure HIV and has not been proven to prevent the transmission of HIV to others through blood or sexual contact. Appropriate precautions should continue to be employed.

4.2 posology -addition

For dosage recommendations in paediatric patients 12 to 17 years of age and weighing at least 40 kg with prior exposure to antiretroviral medicinal products but without DRV‑RAMs* and who have plasma HIV‑1 RNA < 100,000 copies/ml and CD4+ cell count ≥ 100 cells x 10⁶/l a dose regimen of 800 mg once daily may be used (see Summary of Product Characteristics of the PREZISTA 100 mg/ml oral suspension, and PREZISTA 400 mg and 800 mg tablets).

*    DRV‑RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V

4.4          Special warnings and precautions for use

Severe skin reactions

During the clinical development program (N=3,063), severe skin reactions, which may be accompanied with fever and/or elevations of transaminases, have been reported in 0.4% of patients. DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) and Stevens‑Johnson Syndrome has been rarely (< 0.1%) reported, and during post‑marketing experience toxic epidermal necrolysis and acute generalised exanthematous pustulosis have been reported.

 4.8 undesirable effects – change to frequency category for some ADRs

Addition of DRESS and reporting ADR statements

In the 96 week analysis, the safety profile of PREZISTA/rtv 800/100 mg once daily in treatment‑naïve subjects was similar to that seen with PREZISTA/rtv 600/100 mg twice daily in treatment‑experienced subjects except for nausea which was observed more frequently in treatment‑naïve subjects. This was driven by mild intensity nausea. No new safety findings were identified in the 192 week analysis of the treatment‑naive subjects in which the mean treatment duration of PREZISTA/rtv 800/100 mg once daily was 162.5 weeks.

Efficacy of PREZISTA 800 mg once daily co‑administered with 100 mg ritonavir once daily in ART‑naïve patients

The evidence of efficacy of PREZISTA/ritonavir 800/100 mg once daily is based on the analyses of 96192 week data from the randomised, controlled, open‑label Phase III trial ARTEMIS in antiretroviral treatment‑naïve HIV‑1 infected patients comparing PREZISTA/ritonavir 800/100 mg once daily with lopinavir/ritonavir 800/200 mg per day (given as a twice‑daily or as a once‑daily regimen). Both arms used a fixed background regimen consisting of tenofovir disoproxil fumarate 300 mg once daily and emtricitabine 200 mg once daily.

Non‑inferiority in virologic response to the PREZISTA/ritonavir treatment, defined as the percentage of patients with plasma HIV‑1 RNA level < 50 copies/ml, was demonstrated (at the pre‑defined 12% non‑inferiority margin) for both Intent‑To‑Treat (ITT) and On Protocol (OP) populations in the 48 week analysis. These results were confirmed in the analyses of data at 96 weeks of treatment in the ARTEMIS trial. These results were sustained up to 192 weeks of treatment in the ARTEMIS trial.

Section 4.3 Contra-indications

Addition of sildenafil when used for treatment of pulmonary hypertension.

Section 4.4 Special warnings

Warning added for life threatening/fatal drug interactions in patients treated with colchicine and strong inhibitors of CYP3A and Pgp.

Section 4.5 Interactions

Addition of information for sildenafil (when used for pulmonary hypertension), colchicine, bosentan, salmeterol.