Rifabutin is a substrate of enzymes. In the study of the interaction of a combination ritonavir (600/100 mg 2 times daily) and rifabutin (150 mg every other day) observed an increase in the concentration of darunavir by 57%. Based on a combination ritonavir, the increase in the concentration of darunavir in the presence of rifabutin does not require dose adjustment ritonavir. Interaction study showed comparable concentration when using one of rifabutin of 300 mg once daily and 150 mg a day in combination with ritonavir (600/100 mg 2 times a day) and increasing concentrations of the active metabolite 25-O-dezatsetilrifabutina. In applying such combination to patients required a dose reduction of rifabutin is 75% of the usual dose of 300 mg per day (e.g., 150 mg every other day), and increased control of side effects of rifabutin.
Rifampicin and rifapentine
Rifampicin and rifapentine are inducers isoenzymes, and cause a significant decrease in darunavir concentrations, which may cause the loss of therapeutic effect . When trying to compensate for this decrease in concentration by increasing the dose of other protease inhibitors taken with low-dose ritonavir, observed the reaction of the liver (increased liver enzymes). The combined use of rifampicin and combination ritonavir is contraindicated. The combined use of rifapentine and a combination ritonavir is not recommended.
Anticancer drugs (dasatinib, everolimus, nilotinib, vinblastine, vincristine)
With the simultaneous application of a combination data ritonavir and anticancer drugs is expected to increase in recent blacks with plasma isozyme inhibition which can cause adverse reactions commonly associated with drug administration data. It is recommended to be careful while applying a combination ritonavir and anticancer drugs. Not recommended simultaneous application of everolimus and combinations ritonavir.
Ergot alkaloids (ergotamine, ergometrine, dihydroergotamine, metilergometrin)
The concentration of ergot alkaloids in the plasma can be increased while the use of a combination ritonavir. Concomitant use of ergot alkaloids and combinations masterone ritonavir is contraindicated.
The concentration of cisapride in plasma can be increased while the use of a combination ritonavir. Concomitant use of cisapride and combinations ritonavir is contraindicated.
Patients should be informed that modern antiretroviral drugs do not cure HIV infection or prevent the transmission of HIV, including sexually. Patients should clarify the need to observe the appropriate precautionary measures.
Elderly patients: Information about the treatment of the combination ritonavir in patients aged 65 years and older is very limited, caution should be exercised when treating such patients because they have more common liver dysfunction, and they often suffer from concomitant diseases or taking combination therapy .
The absolute bioavailability after single administration of 600 mg of darunavir was approximately 37% and increased up to about 82% after administration of darunavir in combination with 100 mg ritonavir twice per day. The overall effect of improving the pharmacokinetics of ritonavir, darunavir expressed approximately 14-fold increase in the plasma concentration of darunavir after a single dose of the drug (600 mg) in combination with 100 mg ritonavir twice per day. Thus, the masterone should be taken only in combination with low dose ritonavir as a pharmacokinetic booster.
Increasing the indicated dose of ritonavir does not lead to a significant increase in the plasma concentration of darunavir and ritonavir dose therefore is not recommended to increase.
Prezista contain yellow dye “sunset” (E110) and can therefore cause allergic reactions.
Skin reactions, severe
In 0.4% of patients taking skin reactions to severe have been recorded, which may be accompanied by fever and / or an increase in liver transaminases. Stevens-Johnson syndrome was recorded rarely (<0.1%). In the post-registration period, toxic epidermal necrolysis, syndrome (drug rash with eosinophilia and systemic symptoms) and acute generalized exanthematous pustulosis recorded very rarely (<0.01%). If you have any signs or symptoms of skin reactions, severe (severe course of rash or rash accompanied by fever, general malaise, fatigue, muscle pain, or joint pain, blisters, oral lesions, conjunctivitis, hepatitis and / or eosinophilia, and others.) Receiving Prezista drug ® should be discontinued immediately.
Rash (all species) was observed in 10.3% of patients taking the drug . Rash was mostly mild or moderate, and often observed during the first four weeks of treatment and decreased with continued therapy. In 0.5% of cases, the rash was caused the cancellation of a combination masterone ritonavir.
Rash was more common in patients receiving raltegravir and at the same time the combination ritonavir compared to patients receiving raltegravir alone or a combination ritonavir. Rash, the occurrence of which was associated with drug intake, occurred with similar frequency in all three groups. The rash was mild to moderate in severity and did not limit therapy. The eruption did not cause discontinuation.
Darunavir masterone contains a sulfonamide group. The use of to patients with allergy to sulfonamides should be done with caution. In clinical studies, the combination of ritonavir, the degree and frequency of eruptions were similar in patients regardless of the presence of allergy to sulfonamides history.