22 Sep

halotestin reviews

Data on the use of the drug halotestin reviewsin patients  infection receiving antiretroviral therapy are limited. The results of the study of the interaction in the combined use of bosentan and lopinavir + ritonavir in healthy volunteers have shown that bosentan concentration increases, reaching a maximum value for 4 days. Requires control tolerance therapy  in patients receiving ritonavir in combination with protease inhibitors, increased activity, especially at the beginning of the treatment, since it is possible decrease in blood pressure, as well as changes in the activity of liver transaminases.With long-term use  and antiretroviral drugs may increase the risk of adverse effects on liver function and blood count indices. In view of possible interactions associated with bosentan induction of cytochrome isoenzymes , antiretroviral activity may decrease, these patients need to carefully monitor the effectiveness of  treatment.

 resulting in severe chronic obstructive pulmonary disease

Efficacy and safety of bosentan studied in search of 12-week study involving 11 patients with secondary  resulting in severe . The study results show an increase in minute ventilation rate and halotestin reviews reduce oxygen saturation; of the side effects most commonly noted shortness of breath, which decreases the severity of the abolition of bosentan.

The simultaneous use of other drugs

Glibenclamide: not recommended the simultaneous use and glibenclamide in connection with the risk of increased activity of “liver” transaminases. For the treatment of diabetes mellitus in patients who  , should be used other hypoglycemic agents for ingestion or injection of insulin. Fluconazole: the simultaneous use of the drug fluconazole and halotestin reviewsis not recommended. Combination therapy has not been studied, but while the application may bosentan significant increase in plasma concentration. Rifampicin: simultaneous administration and rifampicin is not recommended. Applications drug combination  and inhibitors  isozyme to be avoided.

22 Sep

fluoxymesterone 10mg diazepam

Use  in women of reproductive age is only possible when pre-treatment no pregnancy is confirmed negative test and matched reliable methods of contraception.
Before starting treatment should conduct a survey confirming the absence of pregnancy, and, on doctor’s advice to women of reproductive age Gynecology-, they should use reliable methods of contraception.
it is necessary to inform patients that due to the use of the drug pharmacokinetic interaction fluoxymesterone 10mg diazepam may reduce the efficacy of oral hormonal contraceptives. For this reason, women of childbearing age must not use a hormonal contraceptive method, as the sole; you must use an additional or an alternative reliable method of contraception (oral, injectable, and transdermal therapeutic systems, implantable intrauterine devices). Please refer to a gynecologist for individual selection of a reliable means of contraception. Given the decline in the effectiveness of hormonal contraception, and the possible negative impact of pregnancy on the course of the Arab League, during therapy wit is recommended 1 time per month to carry out a pregnancy test for the earliest possible diagnosis of pregnancy.

Possible effects on spermatogenesis in adult

In study investigated the effect of the drug on spermatogenesis when taken at a dose of 62.5 mg 2 times a day for 4 weeks, and then – 125 mg per day for 5 months. The study included 25 adult men  and IV at baseline unchanged spermogramme; conducted analysis of data obtained in 23 patients, two patients were excluded due to the side effects that are not related to changes in spermatogenesis. The majority of patients after 6 months of treatment, the total number of sperm were observed in the normal range, do not set the morphology changes, sperm motility, changes in hormonal status. Only one patient in spermogramme marked signs oligospermia after 3 months of treatment  , the total number of sperm was reduced at two subsequent analyzes over the next 6 weeks. After 2 months after the abolition  total number of sperm in this patient has returned to baseline to study. The significance of the described observations to be determined, especially given the high interindividual variability of the total number of sperm in patients. Nevertheless, the data does not allow to eliminate the possibility of endothelin receptor antagonists, which include preparation  , spermatogenesis in men and no systematic effect of long-term use is not contrary to the results of toxicological studies of the drug.

Venookklyuzionnaya pulmonary disease

It is necessary to consider the possibility of concomitant diseases venookklyuzionnogo if the intake of the drug Traklir ® in patients with PAH, there are signs of pulmonary edema.

Fluid retention and worsening

Peripheral edema – one of the clinical symptoms of fluoxymesterone 10mg diazepam, at the same time when applying endothelin receptor antagonists  deterioration often occurs. In 20 placebo-controlled studies conducted on the testimony  and digital ulcers, peripheral edema and fluid retention in the body have been observed in 13.2% of patients receiving bosentan and 10.9% -. Placebo
In addition, in the post-marketing period we received numerous reports of fluid retention in patients during the first weeks of preparation  . Therefore, patients administered receiving diuretics, conduct liquid consumption control and diuresis, when deterioration of a heart failure requiring hospitalization.
If indicated clinically severe fluid retention, whether accompanied by it increases in body weight or not, should be carried out examination for clarify the causes of fluid retention in the body (the use or heart failure) as well as to assess the need for continued treatment with fluoxymesterone 10mg diazepam or its cancellation.


22 Sep

anabolic halo side effects

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.

special instructions

liver function

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.

22 Sep

halo steroid

Bosentan applied in a single dose of 2400 mg in healthy volunteers, and 2000 mg / day for 2 months in patients with other diseases, in addition . The most common symptoms of overdose was headache of mild or moderate intensity. Overdose can lead to a marked decrease in blood pressure, which may require medical treatment. Joined case bosentan overdose teenage boy after taking 10,000 mg, which halo steroid resulted in marked nausea, vomiting, marked reduction in blood pressure, dizziness, sweating, a violation of sharpness of vision. State fully returned to normal within 24 hours, while the correction of pronounced reduction in blood pressure. Bosentan is not removed by hemodialysis.

Interaction with other drugs

Bosentan is metabolized with participation of cytochrome  isoenzymes . Inhibition  increase the plasma concentration of bosentan (see. Ketoconazole). Effect of inhibition  isoenzymes at concentrations of bosentan plasma have not studied. The combined use with caution. Concomitant use with fluconazole, which basically has an inhibitory effect on the  isozyme and only a small – on the isoenzyme bosentan may cause a higher concentration in plasma. This combination is not recommended. For the same reason it is not recommended the simultaneous use  and potent inhibitors  isoenzyme (such as ketoconazole, itraconazole or ritonavir) and an inhibitor isoenzymes (such as voriconazole).

Bosentan is an inducer  isoenzymes . According to a study in vitro it assumed the role of inductor isoenzyme . Therefore, while use  and drugs the metabolism of which is mediated by these isoenzymes, their concentration in the blood plasma decreases. Keep in mind the possibility of reducing the effectiveness of drugs, the metabolism of which is carried out with the participation of these same isoenzymes. You may need a dosage adjustment simultaneously used drugs after you start taking , change the dose or withdrawal.

Cyclosporine: the simultaneous use halo steroid and cyclosporine (a calcineurin inhibitor) is contraindicated. With this combination of drugs bosentan minimum the initial concentration in the blood plasma increased 30 times as compared to using bosentan in monotherapy. Bosentan equilibrium concentration in plasma increased 3-4 times as compared with the concentration of bosentan in monotherapy. Possible mechanism of this interaction is inhibited by cyclosporin transport protein responsible for the delivery of bosentan in hepatocytes. Plasma concentration of cyclosporin thus reduced by approximately 50%.

Tacrolimus, Sirolimus: simultaneous application  in clinical trials have not been studied, but it is assumed that bosentan plasma concentration can be increased by analogy with cyclosporine.Plasma concentrations of tacrolimus and sirolimus may be reduced when combined . In this regard,  not be used simultaneously with the tacrolimus or sirolimus. If necessary, the application of this combination control is required and the patient’s condition tacrolimus and sirolimus concentration in the blood plasma.

Glibenclamide: while  at a dose of 125 mg 2 times / day. for 5 days reduces the concentration of glibenclamide  by 40% in blood plasma, which may be accompanied by a significant decrease hypoglycemic effect of glibenclamide. Bosentan concentration in plasma is also reduced by 29%. In addition, patients receiving concomitant treatment, the risk of increased activity of “liver” transaminases. Both active compounds, glibenclamide and bosentan, have an inhibitory effect on the transport pump bile salts, thereby enhancing the activity can be explained by “liver” transaminases. In connection with this, Traklir ® should not be used in conjunction with glibenclamide. No information about possible drug interactions with other sulfonyl-urea derivatives.

Hormonal contraceptives: while the application for 7 days drug halo steroid125 mg 2 times / day. and an oral contraceptive for a single dose – combination product containing 1 mg norethisterone and 35 mcg ethinyl estradiol, noted reduction in AUC for its components by 14% and 31%, respectively. For some patients norethisterone and ethinyl estradiol exposure reduction reached 56% and 66%, respectively.Thus, hormonal contraception can not be considered effective, regardless of the route of administration -Inside drug injection, transdermally or in the form of implants.

Warfarin: while the application in healthy volunteers with  at a dose of 500 mg 2 times / day. for 6 days decreased the concentration  in blood plasma by 29% and 38%, respectively. Experience the simultaneous use and warfarin in patients  was not accompanied by clinically significant changes in the international normalized ratio and warfarin (at the end of the study compared with baseline). In addition, the frequency adjustment of warfarin dose during the study  changes or due to side effects were not different in patients treated with bosentan or placebo. You do not need dose adjustment of warfarin or other oral anticoagulants at the beginning of therapy  . However, we recommend mandatory control , especially at the beginning and stages of increasing the dose.

Simvastatin: while the application  2 times / day. reduced concentration of simvastatin  and its active form beta-hydroxy acids in blood plasma by 34% and 46%, respectively. The simultaneous use of simvastatin has no effect on the concentration in the blood plasma of bosentan. In a joint application of the drug simvastatin and  it is recommended to control the concentration of cholesterol in the blood plasma, with subsequent correction of the dose of simvastatin.

Ketoconazole: simultaneous application dose of 62.5 mg 2 times a day. and ketoconazole, a potent inhibitor of  isoenzyme, accompanied by a twofold increase in bosentan plasma concentrations. Correction dose  is not carried out.
Increase bosentan plasma concentrations is also expected, while the use of itraconazole and ritonavir, despite the lack of confirmation in studies in vivo. However, in combination with bosentan inhibitor of halo steroid, patients with reduced metabolism  isozyme exists a significant increase in the risk of bosentan concentration that may increase the frequency and severity of side effects of the drug.

22 Sep


In 20 placebo-controlled studies conducted in various indications, 2486 patients were treated with bosentan at doses ranging from 100 mg to 2000 mg and 1,838 patients were treated with placebo. Treatment fluoxymesterone duration was 45 weeks on average.

The most frequently (at 1% or more receiving bosentan and 0.5% placebo) reported headache (11.5% vs. 9.8%), edema of lower limbs and / or fluid retention (13.2% vs. 10 9%), increased activity of “liver” transaminases aspartate aminotransferase and / or alanine aminotransferase (10.9%) versus 4.6%) and anemia / hemoglobin decrease (9.9% vs. 4.9%).

The use of bosentan is associated with a dose-dependent increase in the activity of “liver” transaminases and decreased hemoglobin.

Adverse reaction reports have been received in the postmarketing phase of the drug are included with the frequency of occurrence of specified during the 20 placebo-controlled studies, and are marked in italics.

Frequency categories do not account for factors such as the duration of the use of bosentan, the data history, initial clinical data. In each group, the side reactions listed in decreasing order of severity.Clinically significant differences in adverse reactions listed in a common database and separately registered indications were observed.

Frequency can not be estimated from the available data. fluoxymesterone reactions were reported in 9.9% of patients who received bosentan, and 9.1% -. Placebo 3 Headache noted 11.5% of patients who received bosentan and 9.8% – placebo. 4 These reactions may be due to the underlying disease. 5 The appearance of peripheral edema and fluid retention observed 13.2% of patients who received bosentan and 10.9% – placebo.

In post-marketing period there have been reports of rare cases of liver cirrhosis of unknown etiology with long-term use  in patients with serious underlying medical conditions while applying multiple medications. Also noted rare cases of liver failure function. These cases raise the importance of strict adherence to the monthly monitoring of liver function during the entire treatment period .


The safety profile of the use of bosentan in children (BREATH-3: n = 19, bosentan 2 mg / kg, 2 times / day .; for 12 weeks) did not differ from the corresponding safety profile in adult patients with PAH in the supporting studies. The most frequently observed in children “tides” of blood to the skin of the face (21%), headache, and increased activity of “liver” transaminases (16% for each adverse reaction).

Changes in laboratory parameters

Changes in the activity of “liver” transaminases
In the clinical program, dose-dependent increase in “liver” transaminases were observed for 26 weeks of treatment, developed gradually, usually asymptomatic. In post-marketing period have been reports of rare cases of patients with liver cirrhosis and liver failure function.
The mechanism of occurrence fluoxymesterone of adverse reactions mentioned above is unclear. The activity of “liver” transaminases may spontaneously decrease with continued treatment without modifying  or after the reduction, however, discontinuation of treatment or brief interruption in therapy may still be required.
In 20 conducted studies noted increased activity of “liver” transaminases 3 times or more in 11.2% of patients receiving bosentan and 2.4% -platsebo. Increase in 8 or more times the upper limit of normal (ULN) were observed in 3.6% of patients on bosentan and 0.4% – placebo. It is noted that the increase in “liver” transaminases are associated with increased bilirubin plasma levels (of 2 or more times higher than the ULN) patients in the absence of biliary obstruction in 0.2% of cases (5 cases), and receiving bosentan 0 3% of patients (6 patients) – placebo.