Change to Section 3 – removal of Pfizer in debossing on tablets

 

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

Included the following two new sub-headings:

2.1 General description

2.2 Qualitative and quantitative composition

 

4.1     Therapeutic indications

4.2     Posology and method of administration

4.4     Special warnings and precautions for use

4.5     Interaction with other medicinal products and other forms of interaction

5.1     Pharmacodynamic properties

Minor editorial changes; addition of hyphenation of terms such as treatment-experienced, treatment-naïve, co-administration.

 

4.8     Undesirable effects

·         Minor editorial changes; addition of hyphenation of terms such as treatment-experienced, treatment-naïve, co-administration.

·         ‘NB’ replaced the asterix * as emphasis on the note at the end of Table 3, to read:

N.B. Adverse reactions captured in table 3 were assessed as possibly related to study drug by investigators

·         Added the full term for OBT at the end of Table 4, ro read:

OBT: Optimised Background Therapy 

 

Section 4.4 Special warnings and precautions for use

Updated the warning regarding Cardiovascular safety to add the following statements:

In the pivotal studies of treatment experienced patients (MOTIVATE) coronary heart disease events was more common in patients treated with CELSENTRI than with placebo (11 during 609 PY vs 0 during 111 PY of follow-up). In treatment naïve patients (MERIT) such events occurred at a similarly low rate with CELSENTRI and control (efavirenz).

When CELSENTRI was administered to healthy volunteers at doses higher than the recommended dose, cases of symptomatic postural hypotension were seen at a greater frequency than with placebo. However, when CELSENTRI was given at the recommended dose in HIV infected patients in Phase 3 studies, postural hypotension was seen at a similar rate compared to placebo/comparator. Caution should be used when administering CELSENTRI in patients with a history of postural hypotension or on concomitant medicinal products known to lower blood pressure.

Updated the warning regarding Hepatic safety with the following statement:

Hepatobiliary disorders reported in treatment naïve patients were uncommon and balanced between treatment groups (see section 4.8).

Section4.5 Interaction with other medicinal products and other forms of interaction

In Table 2 Interactions and dose recommendations with other medical products, regarding Etravirine and darunavir/ritonavir (maraviroc 150 mg BID), a minor editorial change to include the word ‘with’ in the recommendation, i.e.:

CELSENTRI dose should be decreased to 150 mg twice daily when co-administered with etravirine and PI (except fosamprenavir/ritonavir where the dose should be 300 mg twice daily)

Section 4.6 Fertility, pregnancy and lactation

Updated the heading to include Fertility.

Section 4.8 Undesirable effects

Updated following the review of data from Phase 2b/3 clinical trials (MOTIVATE 1 and MOTIVATE 2) and one study in treatment naïve adult patients (MERIT) infected with CCR5-tropic HIV-1.

Section 5.1 Pharmacodynamic properties

Updated link to EMA website to:

http://www.ema.europa.eu/htms/human/epar/eparintro

Section 7 MARKETING AUTHORISATION HOLDER

Changed from Pfizer to:

ViiV Healthcare UK Ltd, 980 Great West Road, Brentford, Middlesex, TW8 9GS, United Kingdom

 4.4 Special Warnings and Precautions

CELSENTRI is not recommended to be used in treatment naïve patients based on the results of a clinical study in this population (see section 5.1). 

Section 5.1 (i.e. end of clinical result-section)

Studies in CCR5-tropic Treatment Naïve Patients

An ongoing randomised, double-blinded study (MERIT), is exploring CELSENTRI versus efavirenz, both in combination with zidovudine/lamivudine (n=721, 1:1). After 48 weeks of treatment, CELSENTRI did not reach non-inferiority to efavirenz for the endpoint of HIV-1 RNA < 50 copies/mL (65.3 vs. 69.3 % respectively, lower confidence bound -10.9%).  More patients treated with CELSENTRI discontinued due to lack of efficacy (43 vs.15) and among patients with lack of efficacy, the proportion acquiring NRTI resistance (mainly lamivudine) was higher in the CELSENTRI arm. Fewer patients discontinued CELSENTRI due to adverse events (15 vs.49).

6.6 Special precautions for disposal

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

Update to SPC section 4.5: revise information on P-glycoprotein.

Section 9         Date of First Authorisation/Renewal of the Authorisation

                        18 September 2007