Order Cheap Bosentan Aurobindo with No Prescription

Warnings

Bosentan comes with patient instructions about acceptable forms of birth control to use while taking this medicine. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Interactions

GlyBURIDE: May enhance the hepatotoxic effect of Bosentan. GlyBURIDE may decrease the serum concentration of Bosentan. Bosentan may decrease the serum concentration of GlyBURIDE. Avoid combination

Gemfibrozil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. See separate drug interaction monographs for agents listed as exceptions. Monitor therapy

Ulipristal: Bosentan may decrease the serum concentration of Ulipristal. Avoid combination

Food interaction

Take without regard to meals.

Pregnancy

• You are pregnant or plan to become pregnant.
• The antiepileptic treatment should be reviewed when a woman is planning to become pregnant.
• Learn about caffeine headache, caffeine during pregnancy, and caffeine pills.

Overview

Traklir (INN bosentan) - non-selective antagonist of endothelin receptors such as ETA and ETB. Vasodilator. Aurobindo best way endothelin-1 (ET-1) is one of the most powerful vasoconstrictors currently. It has the ability to induce fibrosis, cell proliferation, hypertrophy and myocardial remodeling and also exhibits pro-inflammatory activity. These effects are caused by endothelin when bound to the ETA and ETB receptors located in the endothelium and vascular smooth muscle cells. The concentrations of endothelin-1 in tissues and blood plasma increase with some cardiovascular diseases and pathologies of connective tissue, including with pulmonary arterial hypertension, scleroderma, acute and chronic heart failure, myocardial ischemia, systemic hypertension and atherosclerosis, which suggests the pathogenic role of ET-1 in the development of these diseases. Bozentan competitively blocks ET receptors and does not bind to other receptors, reduces the resistance of systemic and pulmonary vessels, which leads to an increase in cardiac output without increasing heart rate.

Pharmacokinetics
Suction. In healthy volunteers, the pharmacokinetics of bosentan depends on the dose and time. After oral administration, systemic exposure is proportional to a dose of up to 500 mg. When taking a higher dose, the increase in Cmax and AUC in relation to the dose occurs disproportionately and at a slower rate. The absolute bioavailability of bosentan after oral administration is approximately 50%, food intake does not affect this level. Cmax in blood plasma is reached after 3-5 hours.

Distribution and metabolism. Bosentan is 98% bound to plasma proteins. Bozentan is metabolized in the liver with the participation of CYP2C9 and CYP3A4 isoenzymes with the formation of 3 metabolites, and only one of them has pharmacological activity. In patients with symptoms of cholestasis, the systemic effect of this metabolite may increase. Bozentan there an inducer of CYP2C9 and CYP3A4, as well as possibly CYP2C19 and P-glycoprotein. In vitro bosentan inhibits the effectiveness of the BSEP there (Bile Salt Export Pump), which removes bile acids on hepatocyte cultures.

Breeding. Excreted in bile, less than 3% of the dose is found in urine.

Pharmacokinetics in special clinical cases
Based on studies of all parameters, it can be assumed that the pharmacokinet of bosentan in the adult population Bosentan not significantly affected by factors such as gender, body weight, race, or age of the patient.

In children with pulmonary arterial hypertension studies were conducted with the introduction of doses, the volume of which depended on body weight. The exposure of bosentan decreased over time according to the schedule characteristic of bosentan, since the substance is known for its properties to induce autoinduction of liver enzyme systems. Average AUC in children was lower than in adults with pulmonary arterial hypertension. In the stationary phase, systemic exposure in children with used treat body weight of 10-20 kg, 20-40 kg and more than 40 kg was 43%, 67% and 75%, respectively, of the level of systemic exposure in adults. The reasons for this ingredient have not been elucidated; the relationship of this phenomenon with hepatotoxicity has not been established. Gender and simultaneous iv administration of epoprostenol did not significantly affect the pharmacokinetics of bosentan. There is no data on the pharmacokinetics in children under 3 years.

In patients with mild natural impairment significant changes in pharmacokinetics are not marked. The pharmacokinetics of bosentan in patients with moderate to severe hepatic impairment has not been studied. Traclir is contraindicated in such patients.

In patients with severe renal impairment (creatinine clearance of 15-30 ml / min), Aurobindo concentration of bosentan in plasma decreased by about 10%. The plasma concentrations of bosentan metabolites increased approximately 2 times compared with patients who had normal renal function. For patients with impaired renal function, dose adjustment is not required. There is no specific clinical experience in the treatment of patients who are prescribed dialysis. Given the physicochemical properties of the substance and the high degree of protein binding, a significant elimination of bosentan from circulation during dialysis is not expected.

Indications for use: Pulmonary arterial hypertension, including: primary pulmonary arterial hypertension; scleroderma secondary pulmonary arterial hypertension.

Side effect
Side effects included Bosentan, hot flashes, fever, impaired liver function, swelling of the lower extremities, and anemia. All these phenomena were dose dependent. The table below shows the side effects that were observed in 3% or more of patients with a diagnosis of pulmonary arterial hypertension who received Traclir (125 mg and 250 mg 2 times / day) during a placebo-controlled clinical trial.
Side effects of Placebo (n = 80) Traklir (n = 165)
n% n%
Headache 16 20% 36 22%
Nasopharyngitis 6 8% 18 11%
Pneumonia 1 1% 5 3%
Swelling of the lower extremities 4 5% 13 8%
Palpitations 1 1% 8 5%
Upper respiratory tract infection 9 11% 20 12%
Edema 2 3% 7 4%
Dyspepsia - - 7 4%
Dry mouth 1 1% 5 3%
Tides 4 5% 15 9%
Arterial hypotension 3 4% 11 7%
Itchy skin - - 6 4%
Fatigue 1 1% 6 4%
Impaired liver function 2 3% 14 8%

The list includes only side effects noted from the start of therapy to 1 calendar day after its completion. One patient may have more than one adverse reaction.

Side effects that were noted in ≥1% and 3 x VGN) was 12.7% in the bosentan group (n = 165). This indicator was 11.6% in patients taking bosentan 125 mg 2 times / day, and 14.3% in patients taking bosentan 250 mg 2 times / day. An 8-fold increase was observed in 2.1% of patients with pulmonary arterial hypertension when taking a dose of 125 mg 2 times / day. and 7.1% of patients with pulmonary arterial hypertension when taking a dose of 250 mg 2 times / day.

Hemoglobin
The decrease in hemoglobin concentration at the final stage of the study compared with baseline in patients taking bosentan was 9 g / l, in the placebo group - 1 g / l. Reduction of 15% include more to the level of Contraindications
impaired liver function of moderate and severe severity;
the initial excess of the activity of liver enzymes (ACT and / or ALT) more than 3 times;
concomitant use of cyclosporin A;
pregnancy;
age up to 12 years (efficacy and safety not established);
hypersensitivity to bosentan or to any of the components of the drug.
The drug is contraindicated in women of reproductive age who do not use reliable methods of contraception.
With caution, the drug should be prescribed for impaired liver function.