REZOLSTA 800 mg/150 mg film coated tablets

  • Name:

    REZOLSTA 800 mg/150 mg film coated tablets

  • Company:
    info
  • Active Ingredients:

    Cobicistat, darunavir ethanolate

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 18/12/19

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Summary of Product Characteristics last updated on medicines.ie: 18/12/2019

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Janssen Sciences Ireland

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When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 18 December 2019 PIL

Reasons for updating

  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 18 December 2019 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 9 August 2019 PIL

Reasons for updating

  • Change to Section 1 - what the product is
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision
  • Removal of Black Inverted Triangle

Updated on 8 August 2019 SmPC

Reasons for updating

  • Change to section 3 - Pharmaceutical form
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text
  • Removal of Black Inverted Triangle

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 9 May 2019 SmPC

Reasons for updating

  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 9 May 2019 PIL

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 6 - what the product contains
  • Change to section 6 - date of revision

Updated on 8 May 2019 SmPC

Reasons for updating

  • Change to section 4.3 - Contraindications
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 27 November 2018 PIL

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 6 - date of revision

Updated on 27 November 2018 SmPC

Reasons for updating

  • Change to section 4.3 - Contraindications
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.3     Contraindications 

  • Added    dabigatran,
     
    4.5     Interaction with other medicinal products and other forms of interaction
  • ANTICOAGULANT/PLATELET AGGREGATION INHIBITOR

    Apixaban

    Edoxaban

    Dabigatran etexilate

    Rivaroxaban

    Based on theoretical considerations co‑administration of REZOLSTA with these anticoagulants may increase concentrations of the anticoagulant, which may lead to an increased bleeding risk.

    (CYP3A and/or P‑glycoprotein inhibition)

    Co‑administration of REZOLSTA and these anticoagulants is not recommended.

    Dabigatran

    Ticagrelor

    Based on theoretical considerations co‑administration of REZOLSTA with dabigatran or ticagrelor may increase concentrations of the anticoagulant.

    (CYP3A and/or P‑glycoprotein inhibition).

    Concomitant administration of REZOLSTA with dabigatran or ticagrelor is contraindicated.

     

    Use of other antiplatelets not affected by CYP inhibition or induction (e.g. prasugrel) is recommended (see section 4.3).

     

    HEPATITIS C VIRUS (HCV) DIRECT‑ACTING ANTIVIRALS

    NS3‑4A inhibitors

     

    Glecaprevir/pibrentasvir

    Based on theoretical considerations REZOLSTA may increase the exposure to glecaprevir and pibrentasvir.

    (Pgp, BCRP and/or OATP1B1/3 inhibition)

    It is not recommended to coadminister REZOLSTA with glecaprevir/pibrentasvir.

     

 

Updated on 30 October 2018 PIL

Reasons for updating

  • Change to section 6 - date of revision
  • Change in co-marketing arrangement

Updated on 29 October 2018 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

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).

Updated on 29 October 2018 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

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).

 

Updated on 4 July 2018 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.2 – Addition of pregnancy and postpartum section to inform about low darunavir exposure and consideration for alternative regimen.

Section 4.4 – Addition of pregnancy data (low darunavir exposure, cobicistat levels decrease and may not provide sufficient boosting); advice not to initiate during pregnancy or switch to alternative regimen.

Section 4.6 -  addition of pregnancy data: low darunavir exposure which may be associated with an increased risk of treatment failure and an increased risk of HIV transmission to the child; advice not to initiate during pregnancy or switch to alternative regimen.

Section 5.2 – addition of pregnancy and postpartum data

Section 10 – revision date of 29 June 2018

Updated on 4 July 2018 PIL

Reasons for updating

  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 6 - date of revision

Updated on 26 March 2018 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 26 March 2018 SmPC

Reasons for updating

  • Change to section 4.3 - Contraindications
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.9 - Overdose
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 

 

4.3     Contraindications

 

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

 

Patients with severe (Child‑Pugh Class C) hepatic impairment.

 

Co‑administration with the following medicinal products is contraindicated due to the potential for loss of therapeutic effect (see section 4.5):

-                 carbamazepine, phenobarbital, phenytoin (anticonvulsants)

-                 rifampicin (antimycobacterial)

-                 lopinavir/ritonavir

-                 St John’s wort, (Hypericum perforatum) (herbal product).

 

Co‑administration with the following medicinal products is contraindicated due to the potential for serious and/or life‑threatening adverse reactions (see section 4.5):

-                 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)

-                 rifampicin (antimycobacterial)

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

-                 cisapride (gastrointestinal motility agent)

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

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

-                 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 (platelet aggregation inhibitor).

 

 

4.4     Special warnings and precautions for use

 

REZOLSTA should not be initiated in patients with creatinine clearance less than 70 ml/min when co‑administered with one or more agent requiring dose adjustment based on creatinine clearance (e.g. emtricitabine, lamivudine, tenofovir disoproxil (as fumarate, phosphate or succinate)fumarate or adefovir dipivoxil) (see sections 4.2, 4.8 and 5.2).

 

  4.5   Interaction with other medicinal products and other forms of interaction

 

No drug interaction trials have been performed using REZOLSTA. As REZOLSTA contains darunavir and cobicistat, interactions that have been identified with darunavir (in combination with cobicistat or with low dose ritonavir) orand with cobicistat determine the interactions that may occur with REZOLSTA. Interaction trials with darunavir/cobicistat, darunavir/ritonavir and with cobicistat have only been performed in adults.

 

….

 

Co‑administration of REZOLSTA and other medicinal products that inhibit CYP3A may decrease the clearance of darunavir and cobicistat and may result in increased plasma concentrations of darunavir and cobicistat (e.g. systemic azoles antifungals such as  like ketoconazole and clotrimazole). These interactions are described in the interaction table below.

 

 

Tenofovir disoproxil fumarate*

 

*study was done with tenofovir disoproxil fumarate

Based on theoretical considerations REZOLSTA is expected to increase tenofovir plasma concentrations.

(P‑glycoprotein inhibition)

REZOLSTA and tenofovir disoproxil fumarate can be used without dose adjustments.

Monitoring of renal function may be indicated when REZOLSTA is given in combination with tenofovir disoproxil fumarate, particularly in patients with underlying systemic or renal disease, or in patients taking nephrotoxic agents.

Emtricitabine/tenofovir alafenamide

 

 

Tenofovir alafenamide

Tenofovir ↑

The recommended dose of emtricitabine/tenofovir alafenamide is 200/10 mg once daily when used with REZOLSTA.

 

ANTIANGINA/ANTIARRHYTHMIC

Disopyramide

Flecainide

Lidocaine (systemic)

Mexiletine

Propafenone

 

 

 

Amiodarone

Bepridil

Dronedarone

Lidocaine (systemic)

Quinidine

Ranolazine

Based on theoretical considerations REZOLSTA is expected to increase these antiarrhythmic plasma concentrations.

(CYP3A and/or CYP2D6 inhibition)

Caution is warranted and therapeutic concentration monitoring, if available, is recommended for these antiarrhythmics when co‑administered with REZOLSTA.

 

Co‑administration of amiodarone, bepridil, dronedarone, lidocaine (systemic), quinidine, or ranolazine and REZOLSTA is contraindicated (see section 4.3).

 

 

ANTICONVULSANTS

Clonazepam

Based on theoretical considerations REZOLSTA is expected to  increase concentrations of clonazepam

(inhibition of CYP3A)

Clinical monitoring is recommended when co‑administering REZOLSTA with clonazepam.

 

 

ANTIFUNGALS

Clotrimazole

Fluconazole

Itraconazole

Isavuconazole

Ketoconazole

Posaconazole

 

 

 

 

Voriconazole

Based on theoretical considerations REZOLSTA is expected to increase these antifungal plasma concentrations, and darunavir and/or cobicistat plasma concentrations may be increased by the antifungals.

(CYP3A inhibition and/or P‑gp inhibition)

 

Concentrations of voriconazole may increase or decrease when co‑administered with REZOLSTA.

Caution is warranted and clinical monitoring is recommended.

 

When co‑administration is required, the daily dose of itraconazole or ketoconazole should not exceed 200 mg.

 

 

Voriconazole should not be combined with REZOLSTA unless an assessment of the benefit/risk ratio justifies the use of voriconazole.

 

ANTIPSYCHOTICS/NEUROLEPTICS

Perphenazine

Risperidone

Thioridazine

 

 

 

 

 

 

 

Lurasidone

Pimozide

Sertindole

Quetiapine

Based on theoretical considerations REZOLSTA is expected to increase these neuroleptic plasma concentrations.

(CYP3A, CYP2D6  and/or P‑gp inhibition)(CYP2D6 inhibition)

Clinical monitoring is recommended when co‑administering REZOLSTA perphenazine, risperidone or thioridazine. For these neuroleptics, consider reducing the dose of the neuroleptic upon co‑administration with REZOLSTA.

 

The combination of lurasidone, pimozide, quetiapine or sertindole and REZOLSTA is contraindicated (see section 4.3).

 

 

 

HEPATITIS C VIRUS (HCV) DIRECT‑ACTING ANTIVIRALS

Boceprevir

Telaprevir

Based on theoretical considerations these antiviralsboceprevir may decrease darunavir and/or cobicistat plasma concentrations. REZOLSTA may decrease these antiviralboceprevir plasma concentrations.

It is not recommended to co‑administer REZOLSTA with boceprevir or telaprevir.

 

 

HMG CO‑A REDUCTASE INHIBITORS

Atorvastatin

Fluvastatin

Pitavastatin

Pravastatin

Rosuvastatin

 

 

 

 

 

 

 

 

 

 

 

 

 

Lovastatin

Simvastatin

Atorvastatin (10 mg once daily):

atorvastatin AUC ↑ 290%

atorvastatin Cmax ↑ 319%

atorvastatin Cmin ND

 

Rosuvastatin (10 mg once daily):

rosuvastatin AUC ↑ 93%

rosuvastatin Cmax 277%

rosuvastatin Cmin ND

 

Based on theoretical considerations REZOLSTA is expected to increase these HMG Co‑A reductase inhibitor plasma concentrations of fluvastatin, pitavastatin, pravastatin, lovastatin and simvastatin.

(CYP3A inhibition and/or transport)

Concomitant use of a HMG CoA reductase inhibitor and REZOLSTA may increase plasma concentrations of the lipid lowering agent, which may lead to adverse events such as myopathy.

 

When administration of HMG CoA reductase inhibitors and REZOLSTA is desired, it is recommended to start with the lowest dose and titrate up to the desired clinical effect while monitoring for safety.

 

 

 

Concomitant use of REZOLSTA with lovastatin and simvastatin is contraindicated (see section 4.3).

OTHER LIPID MODIFYING AGENTS

Lomitapide

Based on theoretical considerations, REZOLSTA is expected to increase the exposure of lomitapide when co-administered.

(CYP3A inhibition)

Co-administration is contraindicated (see section 4.3)

 

 

OESTROGEN‑BASED CONTRACEPTIVES

Drospirenone (3 mg once daily)

 

 

 

Ethinyl estradiol (0.02 mg once daily)

 

 

Norethindrone

drospirenone AUC ↑ 58%

drospirenone Cmax ↑ 15%

drospirenone Cmin ND

 

ethinylestradiol AUC ¯ 30%

ethinylestradiol Cmax ¯ 14%

ethinylestradiol Cmin ND

 

Based on theoretical considerations REZOLSTA may alter ethinyl estradiol and/or norethindrone plasma concentrations.

(CYP3A inhibition, UGT/SULT induction)

 

 

Plasma concentrations of drospirenone are increased when administered with darunavir/cobicistat. Alternative or additional contraceptive measures are recommended when oestrogen based contraceptives are co administered with REZOLSTA. Patients using oestrogens as

hormone replacement therapy

 should be clinically monitored for signs of oestrogen deficiency.

When REZOLSTA is coadministered with a drospirenone-containing product, clinical monitoring is recommended due to the potential for hyperkalaemia.

 

 

No dosing recommendations can be made on the use of

REZOLSTA with other oral contraceptives. Alternative forms of contraception should be considered.

 

 

 

 

4.9     Overdose

 

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. If indicated, elimination of unabsorbed active substance is to be achieved by emesis.

 

Administration of activated charcoal may also be used to aid in removal of unabsorbed active substance. Since darunavir and cobicistat are highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substances.

 

 

10.     DATE OF REVISION OF THE TEXT

 

2315 February 20187

Updated on 23 March 2018 PIL

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 6 - date of revision

Updated on 23 March 2018 PIL

Reasons for updating

  • New PIL for new product

Updated on 27 March 2017 SmPC

Reasons for updating

  • Change to section 4.3 - Contraindications
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.3     Contraindications

 

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

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

 

 

 

 

4.5     Interaction with other medicinal products and other forms of interaction

 

 

α1-ADRENORECEPTOR ANTAGONIST

Alfuzosin

Based on theoretical considerations REZOLSTA is expected to increase alfuzosin plasma concentrations.

(CYP3A inhibition)

Coadministration of REZOLSTA with alfuzosin is contraindicated (see section 4.3).

 

 

ANTIANGINA/ANTIARRHYTHMIC

Disopyramide

Flecainide

Mexiletine

Propafenone

 

 

 

Amiodarone

Bepridil

Dronedarone

Lidocaine (systemic)

Quinidine

Ranolazine

Based on theoretical considerations REZOLSTA is expected to increase these antiarrhythmic plasma concentrations.

(CYP3A and/or CYP2D6 inhibition)

Caution is warranted and therapeutic concentration monitoring, if available, is recommended for these antiarrhythmics when co‑administered with REZOLSTA.

 

Co‑administration of amiodarone, bepridil, dronedarone, lidocaine (systemic), quinidine, or ranolazine and REZOLSTA is contraindicated (see section 4.3).

 

 

ANTIPSYCHOTICS/NEUROLEPTICS

Perphenazine

Risperidone

Thioridazine

 

 

 

 

 

 

 

Lurasidone

Pimozide

Sertindole

Quetiapine

Based on theoretical considerations REZOLSTA is expected to increase these neuroleptic plasma concentrations.

(CYP2D6 inhibition)

Clinical monitoring is recommended when co‑administering REZOLSTA perphenazine, risperidone or thioridazine. For these neuroleptics, consider reducing the dose of the neuroleptic upon co‑administration with REZOLSTA.

 

The combination of lurasidone, pimozide, quetiapine or sertindole and REZOLSTA is contraindicated (see section 4.3).

 

 

HEPATITIS C VIRUS (HCV) DIRECT‑ACTING ANTIVIRALS

NS3‑4A inhibitors

Elbasvir/grazoprevir

Based on theoretical considerations REZOLSTA may increase the exposure to grazoprevir.

(OATP1B and CYP3A inhibition)

Concomitant use of REZOLSTA with elbasvir/grazoprevir is contraindicated (see section 4.3).

 

 

4.8     Undesirable effects

 

 

Musculoskeletal and connective tissue disorders

common

myalgia, osteonecrosis*

 

uncommon

osteonecrosis*

Updated on 23 March 2017 PIL

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 15 November 2016 SmPC

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.5     Interaction with other medicinal products and other forms of interaction

CORTICOSTEROIDS

Corticosteroids primarily metabolised by CYP3A (including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone).Budesonide

Fluticasone

 

 

 

 

 

 

Prednisone

Interaction not studied with any of the components of REZOLSTA.

 

Plasma concentrations of these medicinal products may be increased when co-administered with REZOLSTA, resulting in reduced serum cortisol concentrations. Based on theoretical considerations REZOLSTA is expected to increase these corticosteroid plasma concentrations.

(CYP3A inhibition)

Concomitant use of REZOLSTA and corticosteroids that are metabolised by CYP3A (e.g. fluticasone propionate or other inhaled or nasal corticosteroids) may increase the risk of development of systemic corticosteroid effects, including Cushing’s syndrome and adrenal suppression.

 

Co-administration with CYP3A-metabolised corticosteroids is not recommended unless the potential benefit to the patient outweighs the risk, in which case patients should be monitored for systemic corticosteroid effects.

Alternative corticosteroids which are less dependent on CYP3A metabolism e.g. beclomethasone for intranasal or inhalational use should be considered, particularly for long term use.Co‑administration of REZOLSTA and budesonide or fluticasone is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid side effects.

 

Concomitant use of REZOLSTA may increase the risk for development of systemic corticosteroid effects, including Cushing’s syndrome and adrenal suppression. Clinical monitoring is recommended when co‑administering REZOLSTA with corticosteroids.

Updated on 11 November 2016 PIL

Reasons for updating

  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 6 - date of revision

Updated on 2 February 2016 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

$04.4     Special warnings and precautions for use$0$0 $0$0 $0$0Diabetesmellitus/hyperglycaemia$0$0New onset diabetes mellitus, hyperglycaemia, orexacerbation of existing diabetes mellitus has been reported in patientsreceiving antiretroviral therapy, including HIV PIs. In some of these patientsthe hyperglycaemia was severe and in some cases also associated withketoacidosis. Many patients had confounding medical conditions some of whichrequired therapy with agents that have been associated with the development ofdiabetes mellitus or hyperglycaemia.$0$0 $0$0Fatredistribution and metabolic disorders$0$0Combination antiretroviral therapy has beenassociated with redistribution of body fat (lipodystrophy) in HIV infectedpatients. The long‑term consequences of these events are currently unknown.Knowledge about the mechanism is incomplete. A connection between viscerallipomatosis and HIV PIs and lipoatrophy and NRTIs has been hypothesised. Ahigher risk of lipodystrophy has been associated with individual factors suchas older age and with drug related factors such as longer duration ofantiretroviral treatment and associated metabolic disturbances. Clinicalexamination should include evaluation for physical signs of fat redistribution.Consideration should be given to measurement of fasting serum lipids and bloodglucose. Lipid disorders should be managed as clinically appropriate (seesection 4.8).$0$0 $0$0 $0$0Weight and metabolic parameters$0$0An increase in weight and in levels of blood lipidsand glucose may occur during antiretroviral therapy. Such changes may in partbe linked to disease control and life style. For lipids, there is in some casesevidence for a treatment effect, while for weight gain there is no strongevidence relating this to any particular treatment. For monitoring of bloodlipids and glucose reference is made to established HIV treatment guidelines.Lipid disorders should be managed as clinically appropriate.$0$0 $0$0 $0$0 $0$04.8     Undesirable effects$0$0 $0$0 $0$0$0$0$0$0$0Metabolism and nutritiondisorders$0$0$0$0$0$0common$0$0$0$0lipodystrophy(including lipohypertrophy, lipodystrophy, lipoatrophy)*, anorexia,diabetes mellitus, hypercholesterolaemia, hypertriglyceridaemia,hyperlipidaemia$0$0$0$0$0$0$0 $0$0 $0$0 $0$0 $0$0 $0$0 $0$0Description of selectedadverse reactions$0$0 $0$0Lipodystrophy$0$0Combination antiretroviral therapy has beenassociated with redistribution of body fat (lipodystrophy) in HIV patients,including loss of peripheral and facial subcutaneous fat, increased intra‑abdominaland visceral fat, breast hypertrophy and dorsocervical fat accumulation (buffalohump) (see section 4.4).$0$0 $0$0Metabolicabnormalities$0$0Combination antiretroviral therapy has also beenassociated with metabolic abnormalities such as hypertriglyceridaemia,hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia(see section 4.4).$0$0 $0$0 $0$0Metabolic parameters$0$0Weight and levels of blood lipids and glucose mayincrease during antiretroviral therapy (see section 4.4).$0$0 $0

Updated on 1 February 2016 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects

Updated on 2 March 2015 SmPC

Reasons for updating

  • New SPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

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Updated on 2 March 2015 PIL

Reasons for updating

  • New PIL for new product