Last Updated on eMC 12-07-2018 View medicine  | Janssen-Cilag Ltd Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or 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 - Fertility, pregnancy and lactation
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:06-07-2018

Legal Category:POM

Black Triangle (CHM): YES

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.

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • 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 4.7 - 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 5.2 - Pharmacokinetic properties

Date of revision of text on the SPC:12-04-2018

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



· Administrative changes to sections 4.1, 4.2, 4.4, 4.5, 4.7, 4.8, 5.1.

 · Section 4.7 deletion of “no or negligible influence on the ability to drive and use machines” statement.

 · Section 4.8 Changes to frequency of adverse reactions; addition of increased low density lipoprotein (common); dyslipidaemia and hyperglycemia (both uncommon)

 · Section 5.1 addition of ATC code; addition of AMBER and EMERALD trial data

Reasons for adding or 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

Date of revision of text on the SPC:15-02-2018

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



4.3     Contraindications

 

-                 , simvastatin, and lovastatin and lomitapide  (see section 4.5)

 

 

4.5     Interaction with other medicinal products and other forms of interaction

 

 

Co‑administration of Symtuza 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 azole antifungals like ketoconazole and clotrimazole). These interactions are described in the interaction table below.

 

 

Clonazepam

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

(inhibition of CYP3A)

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

 

 

ANTIPSYCHOTICS/NEUROLEPTICS

Perphenazine

Risperidone

Thioridazine

 

 

 

 

 

 

 

Lurasidone

Pimozide

Quetiapine

Sertindole

Based on theoretical considerations DRV/COBI is expected to increase these neuroleptic plasma concentrations.

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

 

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

 

The combination of lurasidone, pimozide, quetiapine or sertindole and Symtuza is contraindicated (see section4.3).

 

 

HMGCO‑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 DRV/COBI is expected to increase these HMGCo‑A reductase inhibitor plasma concentrations of fluvastatin, pitavastatin, pravastatin, lovastatin and simvastatin.

(CYP3A inhibition and/or transport)

Concomitant use of a HMGCoA reductase inhibitor and Symtuza may increase plasma concentrations of the lipid lowering agent, which may lead to adverse reactions such as myopathy.

When administration of HMGCoA reductase inhibitors and Symtuza 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 Symtuza with lovastatin and simvastatin is contraindicated (see section4.3).

OTHER LIPID MODIFYING AGENTS

Lomitapide

Based on theoretical considerations, Symtuza 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 Ethinylestradiol (3mg/0.02mg once daily)

Ethinyl estradiol

Norethindrone

drospirenone AUC ↑ 58%

drospirenone Cmax ↑ 15%

drospirenone Cmin ND

ethinylestradiol AUC ¯ 30%

ethinylestradiol Cmax ¯ 14%

ethinylestradiol Cmin ND

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

 

Alternative or additional contraceptive measures are recommended when oestrogen based contraceptives are co administered with Symtuza. Patients using oestrogens as

hormone replacement therapy

should be clinically monitored for signs of oestrogen deficiency.

When Symtuza 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 Symtuza with oral contraceptives. Alternative forms of contraception should be considered.

 

4.9     Overdose

Treatment of overdose with Symtuza consists of general supportive measures, including monitoring of vital signs as well as observation of the clinical status of the patient. If indicated, elimination of unabsorbed active substance is to be achieved by emesis.

Reasons for adding or updating:

  • Change to section 6.5 - Nature and contents of container
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:30-10-2017

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



6.5     Nature and contents of container

 

White, high density polyethylene (HDPE) bottle with a silica gel desiccant (contained in a separate sachet or canister) fitted with polypropylene (PP) child resistant closure with induction seal.

 

Pack size of oneEach bottle containsing 30 tablets.

Pack size of one bottle or three bottles per carton.

 

8.       MARKETING AUTHORISATION NUMBER(S)

 

EU/1/17/1225/001- 30 film-coated tablets

EU/1/17/1225/002- 90 film-coated tablets (3 x 30)

 

 

Reasons for adding or updating:

  • New SPC for new product