CELSENTRI dose should be decreased to 150 mg twice daily when co-administered with a PI; except in combination with tipranavir/ritonavir orfosamprenavir/ritonavir where the dose should be 300 mg BID.Maraviroc does not significantlyaffect PI drug levels.01000007310009 \ 1.0 \ Approved \ 21-Feb-2008 11:00IndinavirFosamprenavir/ritonavirTipranavir/ritonavir 500 mg/200 mg BID (maraviroc 150 mg BID) NNRTI + PI Efavirenz 600 mg QD + lopinavir/ritonavir 400mg/100 mg BID (maraviroc 300 mg BID) Efavirenz 600 mg QD + saquinavir/ritonavir 1000 mg/100 mg BID (maraviroc 100 mg BID) Efavirenz and atazanavir/ritonavir or darunavir/ritonavir AntibioticsSulphamethoxazole/Trimethoprim 800 mg/160 mg BID (maraviroc 300 mg BID) Rifampicin 600 mg QD (maraviroc 100 mg BID)Rifampicin + efavirenzRifabutin + PIClarithromycin, TelithromycinAntifungals Ketoconazole 400 mg QD (maraviroc 100 mg BID)Limited data are available for co-administration with indinavir.Indinavir is a potent CYP3A4 inhibitor.Population PK analysis in phase 3 studies suggests dose reduction of maraviroc when coadministered with indinavir gives appropriate maraviroc exposure.

Begränsad data tillgänglig för samtidig behandling med nelfinavir.Nelfinavir är en potent CYP3A4-hämmare och kan förväntas höja koncentrationen av maravirok.Begränsad data tillgänglig för samtidig behandling med indinavir.Indinavir är en potent CYP3A4-hämmare.Farmakokinetiska populationsanalyser i fas 3-studier visar att dossänkning av maravirok ger lämplig exponering då maraviok administreras tillsammans med indinavir.

Tipranavir/ritonavir 500 mg/200 mg BID (maraviroc 150 mg BID) NNRTI + PI Efavirenz 600 mg QD + lopinavir/ritonavir 400mg/100 mg BID (maraviroc 300 mg BID) Efavirenz 600 mg QD + saquinavir/ritonavir 1000 mg/100 mg BID (maraviroc 100 mg BID) Efavirenz and atazanavir/ritonavir or darunavir/ritonavir AntibioticsSulphamethoxazole/Trimethoprim 800 mg/160 mg BID (maraviroc 300 mg BID) Rifampicin 600 mg QD (maraviroc 100 mg BID)Rifampicin + efavirenzRifabutin + PIClarithromycin, TelithromycinAntifungals Ketoconazole 400 mg QD (maraviroc 100 mg BID)Limited data are available for co-administration with indinavir.Indinavir is a potent CYP3A4 inhibitor.Population PK analysis in phase 3 studies suggests dose reduction of maraviroc when coadministered with indinavir gives appropriate maraviroc exposure.Fosamprenavir is considered to be a moderate CYP3A4 inhibitor.Population PK studies suggest that a dose adjustment of maraviroc is not required.Maraviroc AUC12 1.02 (0.65, 1.87) Maraviroc Cmax:0.86 (0.37, 3.20) Tipranavir/ritonavir concentrations were consistent with historical data.Maraviroc AUC12:2.53 (1.71, 3.15) Maraviroc Cmax:1.25 (0.87, 2.82) Efavirenz, lopinavir/ritonavir concentrations not measured, no effect expected.Maraviroc AUC12:5.00 (3.04, 6.31) Maraviroc Cmax:2.26 (0.68, 4.09) Efavirenz, saquinavir/ritonavir concentrations not measured, no effect expected.Not studied.Based on the extent of inhibition by atazanavir/ritonavir or darunavir/ritonavir in the absence of efavirenz, an increased exposure is expected.Maraviroc AUC12:1.11 (0.84, 1.53) Maraviroc Cmax:1.19 (0.69, 1.73) Sulphamethoxazole/trimethoprim concentrations not measured, no effect expected.Maraviroc AUC:0.37 (90% CI:0.33, 0.41) Maraviroc Cmax:0.34 (90% CI:0.26, 0.43) Rifampicin concentrations not measured, no effect expected.Combination with two inducers has not been studied.There may be a risk of suboptimal levels with risk of loss of virologic response and resistance development.Not studied.Rifabutin is considered to be a weaker inducer than rifampicin.When combining rifabutin with protease inhibitors that are potent inhibitors of CYP3A4 a net inhibitory effect on maraviroc is expected.Not studied, but both are potent CYP3A4 inhibitors and would be expected to increase maraviroc concentrations.Maraviroc AUCtau:5.00 (2.40, 9.62) Maraviroc Cmax:3.38 (1.11, 7.68) Ketoconazole concentrations not measured, no effect is expected.24CELSENTRI 300 mg twice daily and tipranavir/ritonavir or fosamprenavir/ritonavir can be co-administered without dose adjustment.CELSENTRI dose should be decreased to 150 mg twice daily when co-administered with efavirenz in the presence of a PI (except fosamprenavir/ritonavirwhere the dose should be 300 mgtwice daily) .CELSENTRI 300 mg twice daily and sulphamethoxazole/trimethoprim can be co-administered without dose adjustment.CELSENTRI dose should be increased to 600 mg twice daily when co-administered with rifampicin in the absence of a potent CYP3A4 inhibitor.This dose adjustment has not been studied in HIV patients.See also section 4.4.

Dosen CELSENTRI bör minskas till 150 mg två gånger dagligen vidsamtidig administreringmed en PI, förutom ikombination medtipranavir/ritonavir ellerfosamprenavir/ritonavir dådosen bör vara 300 mgBID.Maravirok ger ingensignifikant påverkan påläkemedelsnivåerna av PI.CELSENTRI 300 mg två gånger dagligen och tipranavir/ritonavir eller fosamprenavir/ritonavirkan administrerassamtidigt utandosjustering.Dosen CELSENTRI bör minskas till 150 mg tvågånger dagligen vidsamtidig administreringmed efavirenz i närvaro aven PI (förutomfosamprenavir/ritonavir dådosen bör vara 300 mg tvågånger dagligen) .CELSENTRI 300 mg tvågånger dagligen ochsulfametoxazol/trimetoprim kan administreras samtidigt utan dosjustering.Dosen CELSENTRI bör ökas till 600 mg två gånger dagligen vid samtidig administrering av rifampicin i frånvaro av en potent CYP3A4-hämmare.Denna dosjustering har intestuderats hos HIV-patienter.Se även avsnitt 4. 4.