With simultaneous use of a combination ritonavir and above anticoagulants anticoagulant concentration in the plasma can be increased as a result of inhibition of isoenzyme CYP3A or P-glycoprotein. The recommended dose of apixaban while the use of a combination ritonavir is 2.5 mg 2 times a day. The combination ritonavir and dabigatran should be used with caution and is not recommended in patients with severe renal insufficiency. Not recommended simultaneous use of a combination ritonavir and rivaroxaban.
Combination ritonavir can affect the plasma concentration of warfarin. With simultaneous use of warfarin, and this combination is recommended to monitor international normalized ratio.
Anticonvulsants (phenobarbital, phenytoin and carbamazepine)
Phenobarbital and phenytoin are inducers of CYP450 enzymes. Combination is not recommended in combination with these drugs, because it can cause a significant reduction in the plasma concentration of darunavir and thus decrease its therapeutic effect.
Investigation of the interaction between a combination ritonavir (600/100 mg 2 times a day), and carbamazepine (200 mg, 2 times a day) showed that the concentration of darunavir in this case does not change, while the concentration of ritonavir decreased by 49%. The concentration of carbamazepine is increased by 45%. Changes in dose for the combination ritonavir is required. If necessary, the simultaneous application of a combination of ritonavir and carbamazepine, patients should be observed in connection with the possibility of side effects of carbamazepine. We should be measured carbamazepine concentrations and its dose should be adjusted according to clinical manifestations. Thus, the dose of carbamazepine can be reduced by 25-50% when used together with a combination ritonavir.
With the simultaneous application of these antihistamines with a combination ritonavir, concentrations of antihistamines in the plasma can be increased. The simultaneous use of a combination ritonavir, with astemizole and terfenadine is contraindicated.
In the study of the interaction between a combination steroid masteronritonavir (600/100 mg 2 times a day) and the combination of artemether (80/480 mg, 6 doses taken at 0, 8, 24, 36, 48 and 60 hours) has been shown Lumefantrine concentration increase of 2.75 times, while the concentration of darunavir unchanged. The concentration of artemether and its active metabolite, dihydroartemisinin, was reduced by 16% and 18%, respectively. Combination and artemether / Lumefantrine can be used without dose adjustment. However, due to increasing concentrations Lumefantrine, this combination must be used with caution.
Paroxetine and sertraline
Investigation of the interaction between paroxetine (20 mg once daily) or sertraline (50 mg once a day) and a combinationsteroid masteron ritonavir (400mg / 100mg twice daily) showed that darunavir plasma concentration was independent of the presence of sertraline or paroxetine. On the other hand, in the presence of a combination Prezista ® / ritonavir plasma concentration of paroxetine and sertraline decreased by 49 and 39%, respectively. In cases where the selective serotonin reuptake inhibitors have to be used simultaneously with and ritonavir, you must carefully choose the dose of the inhibitors on the basis of the clinical assessment of antidepressant effect. In addition, patients receiving a stable dose of sertraline or paroxetine who start to treat the combination ritonavir, it is necessary to closely monitor the severity of the primary effect of the antidepressant.
Amitriptyline, imipramine, nortriptyline, trazodone, desipramine
The combined use ritonavir with the above mentioned antidepressants can cause an increase in antidepressant plasma concentrations due to the inhibition of isoenzymes CYP2D6 and / or CYP34. It can cause side effects such as nausea, dizziness, decreased blood pressure, fainting. If necessary, the joint use of these drugs and combinations ritonavir clinical monitoring of the patient is recommended, you may need a dose adjustment of antidepressant.
Sedative / hypnotic drugs
Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam, triazolam, zoldipem
The combined use steroid masteronritonavir with these sedative / hypnotic drugs may result in increased plasma concentrations due to the inhibition isoenzymes. In a joint application is recommended clinical monitoring, and to consider the possibility of reducing the dose of sedative / hypnotic drug.