Rifampicin: while the application in healthy volunteers and rifampicin, which is an inducer of isoenzymes and, bosentan plasma concentrations decreased by 58%, and in some patients – 90%. Because of this, perhaps a significant reduction in the effect when used together with rifampicin. Data on the joint application with other inducers of the isoenzyme , such as carbamazepine, phenobarbital, phenytoin, and drugs, which include St. John’s wort is not enough, however, with high probability in their joint application can not be excluded a significant reduction in the effectiveness of drug treatment anabolic halo side effects .
Epoprostenol: limited findings, in which 10 children received in combination with epoprostenol indicate that after single and multiple administration of these drugs in the blood plasma concentration Cmax and bosentan were similar in patients receiving and not receiving infusions of epoprostenol.
Sildenafil: while the use at a dose of 125 mg 2 times / day. (equilibrium state) and sildenafil at a dose of 80 mg three times / day. for 6 days in healthy volunteers, a decrease of sildenafil and a 63% increase in bosentan – 50%. Changes in plasma concentrations are not clinically relevant drug dose adjustment is required.
Digoxin, nimodipine, losartan: the simultaneous use at a dose of 500 mg 2 times / day. for 7 days, followed by reduction of digoxin concentrations in plasma , respectively. The mechanism of this interaction is probably due to the influence on glycoprotein F. The clinical significance of this interaction is negligible. Concomitant use of nimodipine or losartan has no effect on the exposure of bosentan.
Lopinavir / ritonavir (and other protease inhibitors, increased activity) , while the use anabolic halo side effects at a dose of 125 mg 2 times / day. and lopinavir + ritonavir 400 + 100 mg 2 times / day. for 9.5 days in healthy volunteers bosentan minimum initial concentration in blood plasma was about 48-fold higher concentration compared with when only one of bosentan. The equilibrium concentration in the blood plasma of bosentan on day 9 was 5 times higher than when only bosentan. Inhibition of by ritonavir and transport protein responsible for the transport of bosentan in hepatocytes, thereby reducing the clearance of bosentan, and probably so can explain the mechanism of this interaction. Patients simultaneously receiving and preparations containing lopinavir + ritonavir or other protease inhibitors, increased activity is necessary to monitor drug tolerability anabolic halo side effects .
When used together with for 9.5 days, the concentration of lopinavir and ritonavir is reduced to clinically insignificant level (approximately 14% and 17%, respectively). Necessary to monitor the efficacy of the HIV therapy.
It is assumed that other protease inhibitors increased activity in combination with ritonavir can provide the same effect.
Other protease inhibitors increased activity: in the absence of data, can not be given specific recommendations on the use of bosentan with other drugs in this group. Due to the severe toxic effects on the liver nevirapine, which can also enhance the adverse effect on the liver bosentan not recommended the use of the combination joint.
Increasing the activity associated with taking anabolic halo side effects , is dose-dependent. Changes in activity of “liver” transaminases usually occur within the first 26 weeks of therapy, but may occur at a later date. Liver dysfunction risk may also increase while the use drugs suppressing the BSEP, such as rifampicin, glibenclamide and cyclosporine, although evidence on this is limited.
Treatment with anabolic halo side effects is associated with a dose-dependent decrease in hemoglobin. In placebo-controlled studies involving the use of bosentan decrease in hemoglobin is not progressive, the hemoglobin is stabilized after the first 4-12 weeks of therapy. It is recommended to check this indicator before starting therapy with , at 1 and 3 months of treatment, and subsequently – 1 time in 3 months. If there is a clinically significant decrease in hemoglobin should be further examination of the patients in order to establish the reasons and the need for appropriate therapy.