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Voriconazole concentrations in plasma may be reduced when combined with darunavir / ritonavir.Voriconazole should not be used in conjunction with darunavir / ritonavir, simultaneous use is possible only if the potential benefits from the use of voriconazole outweighs the potential risk.

ClotrimazoleInteraction combinationbuy primobolan depot ritonavir has not been studied with clotrimazole. With simultaneous use of clotrimazole and darunavir, and low-dose ritonavir may experience an increase in darunavir plasma concentrations. With simultaneous use of a combination ritonavir and clotrimazole should be careful and conduct clinical monitoring. Beta-blockers (metoprolol, timolol) Combined use of beta-blockers and the combination   ritonavir may result in increased concentrations of beta-blockers. With the simultaneous use of these drugs and the combination ritonavir should be careful and conduct a careful clinical monitoring may also be necessary to decrease the dose of beta-blockers. Methadone In a study of the effect of the combination  ritonavir (600/100 mg 2 times a day) on a stable methadone maintenance therapy was shown to decrease by 16% R-methadone concentration in plasma. Based on the pharmacokinetic and clinical results, methadone dose correction at the beginning of therapy  r is not required. However, clinical monitoring is recommended, as some patients require maintenance therapy correction.

Buprenorphine / naloxoneThe study of interaction of a combination  ritonavir with buprenorphine / naloxone showed no effect  ritonavir, the concentration of buprenorphine in their joint application. The concentration of the active metabolite of buprenorphine – norbuprenorfina increased by 46%. Dose adjustment of buprenorphine is not required. In a joint receptionbuy primobolan depotritonavir, and buprenorphine is recommended to conduct a careful clinical monitoring. The estrogen-containing oral contraceptives results of the study on the interaction between the combination  ritonavir (600/100 mg 2 times a day) and ethinyl estradiol and norethisterone show that constant plasma concentration of ethinyl estradiol and norethisterone, respectively reduced by 44% and 14%. Therefore, it is recommended to use alternative non-hormonal contraception. Inhibitors of phosphodiesterase type 5 (PDE-5) In the treatment of erectile dysfunction One study investigated sildenafil concentrations after a single dose of the drug (100 mg), and after taking 25 mg of Sildenafil simultaneously combination with darunavir / ritonavir (400 mg / 100 mg twice a day). Sildenafil concentrations were similar in both situations. Caution must be exercised with concomitant use of PDE-5 inhibitors for the treatment of erectile dysfunction and combinations ritonavir. If necessary, use  and ritonavir simultaneously with sildenafil, vardenafil or sildenafil tadalafil single dose not exceed 25 mg for 48 hours, a single dose of vardenafil should not exceed 2.5 mg per 72 hours, and a single dose of tadalafil should not exceed 10 mg within 72 hours. in the treatment of pulmonary arterial hypertension safe and effective dose of sildenafil for treating pulmonary hypertension is not established. There is an increased risk of side effects of sildenafil (including blurred vision, decreased arterailnogo pressure, prolonged erection, and syncope).

Thus, the simultaneous use of a combination ritonavir and sildenafil in pulmonary hypertension therapy is contraindicated. For the treatment of pulmonary arterial hypertension tadalafil while the use of a combination of Prezista ® / ritonavir is required change doses of tadalafil. For patients receiving the combination of Prezista ® / ritonavir for at least one week, the initial dose of tadalafil should be 20 mg 1 time per day with a possible increase to 40 mg 1 time per day based on individual tolerability. For patients receiving tadalafil and beginners combination therapy  ritonavir should be discontinued tadalafil at least 24 hours prior to initiation of therapy, a combination  ritonavir and should avoid the simultaneous use of tadalafil during initiation of therapy, a combination of Prezista ® / ritonavir.

After 1 week after initiation of therapy, a combination of  ritonavir should resume tadalafil at a dose of 20 mg 1 time per day with a possible increase to 40 mg 1 time per day based on individual tolerability. Rifabutin Rifabutin is a substrate of theisoenzymes of cytochrome. In studying the interaction / ritonavir (600/100 mg 2 times daily) and rifabutin (150 mg every other day) increase the concentration of darunavir was observed in 57%. Based on the safety profile ritonavir, the increase in the concentration of darunavir in the presence of rifabutin does not require dose adjustment for  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.

When assigning such combination to patients required a dose reduction of rifabutin is 75% of the usual dose of 300 mg per day and increased control of side effects of rifabutin. Selective serotonin reuptake inhibitors Investigation of the interaction between paroxetine (20 mg once daily) or sertraline (50 mg once per day) and combination ritonavir (400 mg / 100 mg twice a day) showed that the plasma concentration of darunavir not dependent upon the presence of paroxetine or sertraline. On the other hand, in the presence of a combination buy primobolan depot 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 of ritonavir, it is necessary to closely monitor the severity of the primary effect of the antidepressant.

Cautions
Patients should be informed that modern antiretroviral drugs do not cure HIV infection or prevent the transmission of HIV. Patients should clarify the need to observe the appropriate precautionary measures.
Elderly patients: Information about the treatment of the combination of ritonavir in patients aged 65 years and older is very limited, caution should be exercised when treating such patients the drug buy primobolan depot, because they have more common liver dysfunction and they often suffer from concomitant diseases or receive concomitant 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 drug Prezista ® must be taken only in combination with low dose ritonavir.
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.

Skin reactions severe
in 0.4% of patients taking  were reported skin reactions to severe, which may be accompanied by fever and / or an increase in liver transaminases. Stevens-Johnson syndrome was reported rarely (<0.1%). In the post-marketing period, toxic epidermal necrolysis has been recorded very rarely (<0.01%). If you have any signs or symptoms of skin reactions to severe (rash severe course or rash accompanied by fever, general malaise, muscle pain or joint pain, blisters, oral lesions, conjunctivitis, hepatitis and / or eosinophilia) receiving  should be discontinued immediately.
rash (all species) was observed in 10.3% of patients taking. 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 of  ritonavir.
Darunavir contains a sulfonamide group. Appointment  in patients with allergy to sulfonamides should be done with caution. In clinical studies, ritonavir, the degree and frequency of eruptions were similar in patients with allergy to sulfonamides history without it.

Patients with concomitant diseases Patients with liver disease data on the use of ritonavir in patients with severe hepatic impairment are not available. Based on the data that stable pharmacokinetic parameters in the application of darunavir in patients with mild to moderate hepatic impairment compared with parameters in healthy subjects, dose adjustment in patients with mild to moderate hepatic impairment is not required. steroiden kaufen

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