Ravenell-125 Davipharm medicine for hypertension pulmonary pressure (4 blisters x 14 tablets)

Dosage form Box of 4 blisters x 14 tablets
Specifications Bosentan

Ingredient

Composition information	Content
Bosentan	125mg

Uses

Indications

Ravenell drug contains the main ingredient with pharmacological effects of Bosentan, in the form of Bosentan monohydrate, which inhibits natural hormone called endothelin-1 (Et-1), this enzyme causes vascular contractions. Therefore, Bosentan has vasodilation effect.

Ravenell is used for treatment:

Hypertension of pulmonary artery (PAH): increased pulmonary artery pressure is a serious narrowing of pulmonary blood vessels leading to increased pressure in the pulmonary artery (pulmonary artery is the blood artery from the heart to the lungs). At that time, the amount of blood oxygen taken from the lungs decreased, making it difficult for physical activity.

Bosentan relaxes the pulmonary artery, blood from the heart to the pulmonary artery. Lower blood pressure and reduce symptoms.

Bosentan is used for treatment in patients with lung pressure III to improve exertion (ability to perform physical activity) and symptoms of the disease.

The drug is also effective in patients with increased pulmonary artery pressure II.

"degree" shows the severity of the disease:

"level III": increased pulmonary artery pressure significantly limits energy activity.

Tien Phat (unknown cause or family). The nucleus is sclerotic. Bosentan reduces the number of new ulcers of fingers/ feet.

Pharmacokology

Pharmacological group: other anti -hypertension drugs.

ATC code: C02KX01.

Bosentan is the dual receptor -endorin -shipping owner with affinity on both endothelin A and B (ETA and ETB) receptors.

Bosentan reduces pulmonary vascular resistance and the whole body leads to an increase in heart rate without increasing heart rate.

Endothelin-1 neuroscience (ET-1) is one of the strong vascular contraction substances that can promote atherosclerosis, cell proliferation, hypertrophy and heart restructuring, and inflammation.

Intermediate effects by Endothelin bonds ETA and ETB receptors located in endothelial and muscular cells. ET-1 concentration in tissue and plasma increases in some cardiovascular diseases and connective tissue diseases, including pulmonary hypertension, sclerosis, acute and chronic heart failure, myocardial ischemia, systemic hypertension and atherosclerosis, showing the pathological role of ET-1 in these diseases.

In pulmonary hypertension and heart failure, when there is no antagonistic resettlin endothelin, ET-1 concentration increases closely with the severity and prognosis of these diseases.

Bosentan competes with ET-1 and other ET peptides in connecting with ETA and ETB receptors. Agreement with ETA receptors (ki = 4.1 - 43 nanomol) is slightly higher than the ETB receptors (Ki = 38 - 730 Nanomol). Bosentan is specialized with ET receptors and does not bind to other receptors.

Dynamic pharmacokinetics

Bosentan pharmacokinetics are mainly researched on healthy people.

Clinical data is limited to show that Bosentan concentration in adult patients with pulmonary artery pressure is about 2 times higher than healthy people. In healthy people, Bosentan's pharmacokinetics depend on the dose and time.

Semi -selling time and distribution volume decrease when increasing intravenous dose and increasing over time. After oral, the body exposure is proportional to the dose of up to 500 mg. At higher doses, CMAX and AUC are less proportional to the dose.

absorption:

In healthy people, absolute bioavailability is about 50% and not affected by food. The maximum plasma concentration is achieved after about 3-5 hours.

Distribution:

Bosentan bound a lot (> 98%) with plasma proteins, mainly albumin. The distribution volume (VSS) is about 18 liters after an intravenous injection of 250 mg.

Metabolism and elimination:

After an intravenous injection of a dose of 250 mg, the clearance is 8.2 l/h. The reduction of this concentration may be due to the automatic touch of the metabolic enzyme in the liver.

Stable state is achieved after 3-5 days. Bosentan is eliminated through bile after being metabolized in the liver by the isenzyme CYP450, CYP2C9 and CYP3A4. Less than 3% of the dosage dosage except for urine.

Bosentan has 3 metabolites and only one of which has pharmacological activity. This metabolite is eliminated mainly without conversation. In adult patients, the amount of metabolites is more active than healthy people.

In patients with evidence and the presence of cholestasis, the amount of metabolites with activity may increase. Bosentan is the touch substance of CYP2C9 and CYP3A4 and also possible of CYP2C19 and PGlycoprotein. In vitro, bosentan inhibit honey secretion in liver cells.

In vitro data shows that Bosentan has no inhibitory effect with testing ISOENZYM (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2D6, 2E1, 3A4). Therefore, Bosentan does not increase the plasma concentration of metabolic drugs by these isenzymes.

pharmacokinetics on special subjects

Patients with liver failure:

In patients with mild liver failure (Child-Pugh A), there is no pharmacokinetic change. AUC in the stable state of Bosentan is 9% higher, and the AUC of metabolites is 33% higher in patients with mild liver failure compared to healthy patients.

Patients with renal failure:

In patients with severe renal failure (Creatinin clearance 15 - 30 ml/min), Bosentan concentration decreases by about 10%. There is no specialized clinical experience in patients with hemolysis.

Before taking Ravenell-125 Davipharm medicine for hypertension pulmonary pressure (4 blisters x 14 tablets)

How to use

The drug is used orally, taken in the morning or afternoon, can be the same or not with food.

film bags should be taken whole with water.

Dosage

Pulmonary pressure increased

Should only start treatment and monitoring by a doctor with experience in pulmonary hypertension treatment.

Adults:

In adult adults, it is recommended to start Bosentan treatment at a dose of 62.5 mg x 2 times/day for 4 weeks and then increase the maintenance dose of 125 mg x 2 times/day.

Dynamic data in children shows that plasma bosentane concentrations in children from 1 to 15 years old have PAH with lower average value than adults, and the concentration does not increase when increasing the dose of bosentan to 2 mg/ kg of weight, or increasing the frequency of use from 2 to 3 times/ day. These pharmacokinetic results, when used for children with PAH from 1 year of age and older, the recommended and maintained starting dose is 2 mg/ kg in the morning and evening. There is no recommended dose for this patient.

Clinical condition worsens:

In the case of more severe illness (for example: 10% reduction of walking distance 6 minutes compared to the results before treatment) despite being treated with Bosentan for at least 8 weeks (at least 4 -week target dose), consider other treatments. again. Depending on the dose.

Stop treatment:

Clinical data is still limited when the sudden stopping of Bosentan in patients with pulmonary hypertension. There is no evidence that the reverse reaction is acute. If you decide to stop using Bosentan, you should stop slowly while taking another replacement.

Should only start treatment and monitored by a doctor with experience in therapy.

Adults:

In adult adults, Bosentan should start at a dose of 62.5 mg x 2 times/day for 4 weeks and then increase the maintenance dose of 125 mg x 2 times/day. And the need to continue treatment.

There is no safe and effective data for patients under 18 years old.

Patients with liver failure: Bosentan is contraindicated to patients with medium and severe liver failure. It is not necessary to adjust the dose for patients with mild liver failure (Child-Pough a). 2,400 mg in healthy people and 2,000 mg/ day for 2 months in patients only increased pulmonary artery pressure.

Unwanted effect is a mild headache.

Overdose of Bosentan can lead to a clear hypotension that requires positive cardiovascular support.

There has been a report on male patients in adolescents using 10,000 mg Bosentan.

Patients with symptoms of nausea, vomiting, hypotension, dizziness, sweating and blurred vision. The patient recovers completely within 24 hours thanks to blood pressure support.

Bosentan cannot be excluded by dialysis.

What to do when you forget a dose? However, if close to the next dose, skip the forgotten dose and take the next dose at the time as planned. Note that it should not be used double the prescribed dose.

Side Effects

When using Ravenell 125mg, you may experience unwanted effects (ADR).

Unjust unwanted effects are headache (11.5%), edema/ fluid (13.2%), abnormal liver function (10.9%) and anemia/ decrease in haemoglobin (9.9%).

When treated with bosentan, liver aminotransferase and blood haemoglobin decrease depending on the dose.

Very common (ADR ≥ 1/10):

Nervous system: headache

Hematology system: Anemia, hemoglobin. Skin and subcutaneous tissue: Red rash.

Hematology system: thrombocytopenia, neutropenia, leukopenia.

The immune system: anaphylaxis and/or angioedema.

Hematology system: Anemia or hemoglobin decrease needs red blood cell transmission.

The drug can cause other unwanted effects. It is necessary to closely monitor and recommend the patient to notify the doctor with unwanted effects when using the drug.

Warnings

Before using the drug you need to read the instructions carefully and refer to the information below.

contraindicated

Ravenell 125mg contraindications in the following cases:

Hypersensitivity to Bosentan or any ingredients of the drug.

Pregnant women.

Be cautious when using

Before using this medication, the doctor will give you the following tests:

Liver function testing blood tests.

Some patients after using Bosentan have abnormal liver function test results and anemia.

While taking the drug, the doctor will give you the following tests:

While treating Bosentan, the doctor will give you a periodic blood test to monitor liver function and Haemoglobin concentration. Liver function tests are done monthly during treatment with Bosentan. Haemoglobin concentration tests are done monthly in the first 4 months of treatment, then every 3 months because the patient using Bosentan may have anemia.

If the test results are abnormal, the doctor will decide to reduce the dose or stop treatment with Bosentan and do many other tests to find the cause.

Warning about excipients: Drugs containing castor oil can cause abdominal pain, diarrhea, nausea, vomiting.

Do not use this medication for children with stiffness in the system and finger/ feet ulcer.

Driving and operating machinery

No specialized research on the impact of Bosentan on the ability to drive and operate machinery.

However, Bosentan can lower blood pressure, with symptoms of dizziness or fainting, which can affect the ability to drive and operate machinery.

Pregnant or lactating women

Pregnant women:

If you are pregnant, or think that you are pregnant, or plan to get pregnant, do not use Bosentan.

Bosentan can affect the fetus. If you are a woman of reproductive age, the doctor will give you pregnancy test before treatment and during treatment with Bosentan.

breastfeeding women:

Notify the doctor immediately if you are breastfeeding.

Interactive drug

bosentan is the Cytochrom P450 (CYP), isoenzyme CYP3A4 and CYP2C9.

In vitro data also shows the ability to touch CYP2C19. Therefore, plasma concentrations of metabolites by these isenzymes will decrease when used with bosentan.

Consider the ability to change the effectiveness of metabolic drugs by these isenzymes. The dose of these drugs should be adjusted at the beginning of treatment, change the dose or stop using Bosentan.

Bosentan is metabolized by CYP2C9 and CYP3A4. Inhibiting these isenzymes can increase the concentration of Bosentan. The impact of CYP2C9 inhibitors on Bosentan concentration has not been studied. Should be careful when coordinating.

fluconazole and inhibitors of both isenzyme CYP2C9 and CYP3A4:

Used with fluconazole, the main inhibitor CYP2C9, but a certain extent also inhibits CYP3A4, which can lead to significantly increasing the concentration of Bosentan. Ritonavir) and CYP2C9 (e.g. Voriconazole) with Bosentan is not recommended.

cyclosporin A:

Contraindicated to use bosentan with cyclosporin A (Calcineurin inhibitor). Interactive processing may be due to the inhibition of the absorption through bosentan's transportation protein intermediaries into liver cells by cyclosporin.

tacrolimus, syrolimus:

Using Tacrolimus or Sirolimus with Bosentan has not been studied, but used with Bosentan may increase the plasma concentration of Bosentan when extracted from cyclosporin a. Therefore, bosentan should not be used with syrolimus and tacrolimus.

glibenclamid:

General use of Bosentan 125 mg x 2 times/ day for 5 days reduces the plasma concentration of glibenclamid (substrate of CYP3A4) 40%, can significantly reduce hypoglycemic effects. In addition, increasing the frequency of increasing aminotransferase enzyme has observed in patients using these two drugs. There is no drug interactive data - drugs with other sulfonylura drugs.

rifampicin:

Research in 9 healthy people using Bosentan for 7 days at a dose of 125 mg twice a day with rifampicin, the substance has the ability to touch CYP2C9 and CYP3A4, plasma concentrations of Bosentan decrease by 58%, and in some cases can be reduced to nearly 90%. Rifampicin. It is not recommended to use rifampicin with bosentan. John, but the common use can reduce Bosentan's concentration and can lead to clinical effectiveness.

lopinavir + ritonavir (and other protease inhibitors increase other ritonavir effects):

Used with Bosentan 125 mg 2 times/ day and Lopinavir + Ritonavir 400 + 100 mg x 2 times/ day for 9.5 days in a healthy volunteer for the first bottom concentration of Bosentan 48 times higher than using Bosentan alone. Me. When used with Bosentan for 9.5 days, Lopinavir concentration decreased by 14% and Ritonavir decreased by 17%. However, it may not be completely touched by Bosentan and therefore the concentration of protease inhibitors can continue to decrease. The same effect may occur when using other protease inhibitors.

Other anti -Retrovirus drugs:

Lack of data, therefore, there is no recommendation for other anti -Retrovirus drugs.

Hormone contraceptives:

General use of Bosentan 125 mg 2 times/ day for 7 days with 1 dose of oral contraceptives containing 1 mg + Ethinyl estradiol 35 mcg reduces the AUC of Norethisteron 14% and Ethinyl estradiol 31%. Therefore, hormone contraception methods with all lines (oral, injection, subcutaneous or transplant), are not considered a safe contraceptive method.

warfarin:

Used with Bosentan 500 mg twice a day for 6 days reduces the plasma concentration of s-warfarin (substrate of CYP2C9) 29% and R-Warfarin (substrate of CYP3A4) 38%. The common use of bosentan and warfarin clinically in patients with pulmonary hypertension does not show changes in international normalization index (INR) or Warfarin dose. There is no need to adjust the Warfarin dose and oral anticoagulants when using Bosentan, but it is recommended to closely monitor Inr, especially when starting to treat or increase the dose of bosentan.

simvastatin:

Used with Bosentan 125 mg 2 times/ day for 5 days to make Simvastatin concentration (the substrate of CYP3A4) decreased by 34% and ß-hydroxy acid metabolites with its activity decreased by 46%. Monitor cholesterol levels and consider adjusting the dose.

ketoconazole:

Use Bosentan 62.5 mg x 2 times/ day for 6 days with ketoconazole, CYP3A4 inhibitor, increasing Bosentane concentration to about 2 times. No need to adjust the dose of Bosentan. Increasing higher Bosentan concentration and the risk of side effects is also higher.

EPPROSTENOL:

When combining EPPROSTENOL with single -dose or multi -dose bosentan, CMAX and AUC of Bosentan are similar in patients with or non -transmission of EPPROSTENOL continuously.

Sildenafil:

Used with Bosentan 125 mg 2 times/ day (stable state) with Sildenafil 80 mg x 3 times/ day (stable state) within 6 days in healthy volunteers showing reducing AUC Sildenafil 63% and reducing AUC Bosentan by 50%. Precautions when used together.

digoxin

Used with Bosentan 500 mg twice a day with digoxin for 7 days reducing AUC Digoxin by 12%, CMAX decreased by 9%and CMIN decreased by 23%. The mechanism of interaction may be due to PGLYCOPREIN induction.

This interaction may not mean clinically.

Storage

Leave a cool place, avoid light, temperature below 30⁰C.

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