Bisoprolol Plus HCT 5/6.25 Savi medicine for hypertension from mild to medium (3 blisters x 10 tablets)

Bisoprolol Fumarate (B) and Hydrochlorothiazide (HCT) have been used individually or combined to treat hypertension. The hypotension effect of these active ingredients is Hiep force, HCT 6.25mg significantly increases the hypotension effect of Bisoprolol Fumarate. The rate of hypotension of bisoprolol fumarate and HCT 6.25mg (b/h) is significantly lower than HCT 25mg. In the clinical trials of Bisoprolol Fumarate and Hydrochlorothiazide, the average change of serum potassium content in patients is treated with combination of bisoprolol fumarate and hydrochlorothiazide 2.5mg/6.25mg - 5mg/6.25mg - 10mg/6.25mg or placebo is less than ± 0.1 MEQ/L. The average change of the serum potassium content of patients treated with any Bisoprolol dose combined with HCT 25mg changes from -0.1 to -0.3 Meq/l.

Bisoprolol Fumarate is a block-selected blockbuster (cardioselec-tive) that has no significant membrane stability or has no effect of intrinsic sympathetic nerve within the scope of treatment. At high doses (20mg), Bisoprolol Fumarate also inhibits the beta2 receptor located in the muscular system and blood vessels. To keep the relative selection, it is important to use the lowest dose effectively.

Hydrochlorothiazide is a benzothiadiazine diuretic. Thiazide affects the renal tubular mechanism of electrolyte reabsorption and increases the secretion of sodium and chloride with similar amounts of grace. Sodium-sodium (sodium) will lose secondary potassium.

bisoprolol

Bisoprolol is a selective blockbuster Beta1 (β1) but has no membrane stability and has no effect like intrinsic sympathetic nerve when used within the scope of treatment. With low doses, selective Bisoprolo inhibits the adrenalin stimulation of the β1 adrenalin receptor blocker of the heart, but has little effect on the beta2 receptor (β2) Adrenalin of bronchial muscles and vascular walls. With high doses (for example, 20mg or more), the selective properties of bisoprolol on receptors β1 usually decrease and the drug will compete inhibiting both receptors β1 and β2.

Bisoprolol is used to treat hypertension. Bisoprolol's effectiveness is equivalent to other beta blockers. The mechanism of lowering the hypotension of Bisoprolol may include factors such as reducing heart flow, renal inhibitors releasing renin and reducing the impact of sympathetic nerve from vasomotor centers in the brain. But the most prominent effect of Bisoprolol is to reduce the heart frequency, both resting and at exertion. Bisoprolol reduces the flow of the heart at a break and when exertion, accompanied by few changes in the volume of blood expeled in every heart, and only increases the right atrial pressure or the pulmonary capillary pressure at rest and exertion. Unless there is contraindications or the patient is not tolerated, beta blockers have been used in combination with enzyme inhibitors, diuretic and heart glycosides to treat heart failure due to left ventricular dysplasia, to reduce progressive heart failure. The good effect of beta blockers in the treatment of congestive heart failure is mainly due to inhibition of the effects of sympathetic nervous system. Long -term beta blockers, as well as conversion inhibitors, can reduce heart failure symptoms and improve clinical status of people with chronic heart failure. These good effects have been shown in people who are taking a transferred inhibitor, showing the inhibition of the coordination of the Renin-Anotensin system and the sympathetic nervous system are plus effects.

In control clinical trial, Bisoprolol Fumarate is used as a single dose every day proving to be an effective active ingredient that is effective when used alone or simultaneously with thiazide diuretic.

The mechanism of hypotension of Bisoprolol Fumarate has not been completely set. The elements can be involved include:

Electrical research in humans has shown that Bisoprolol Fumarate significantly reduces the heart rate, increases the recovery time of the sinus button, prolongs the rest time of AV AI button (Atriovovicular) and the atrial stimulation, extending the atrial transmission time.

hydrochlorothiazide

hydrochlorothiazide and thiazide diuretics increase the excretion of sodium chloride and water attached to the mechanism of inhibiting the reabsorption of sodium and chloride ions in the distance. The excretion of other electrolytes also increases, especially potassium and magnesi, and calcium decreases.

Hydrochorothiazide also reduces the activity of carbon dioxide enzyme, so it increases the secretion of bicarbonate but this effect is usually small compared to the effect of Cl- secretion and does not significantly change the urine pH. Thiazide has a moderate diuretic effect, because about 90% of sodium ions have been reabsorbed before arriving in the distance is the main position of the drug.

hydrochlorothiazide has the effect of lowering blood pressure, which is probably due to a decrease in plasma volume and extracellular fluid related to sodium urine. Then, during the use of the drug, the effect of lowering blood pressure depends on the decrease in peripheral resistance, through the gradual adaptation of blood vessels from the reduction of Na+concentration. Therefore, the hypotension effect of hydrochlorothiazide is shown slowly after 1-2 weeks, while diuretic effects occur quickly and can be seen right after a few hours.

hydrochlorothiazid increases the effects of other antihypertensive drugs. Sodium-sodium (sodium) will cause secondary potassium loss.

Dynamic pharmacokinetics

bisoprolol fumarate (B) combined Hydrochlorothiazide (HCT)

In healthy volunteers, both Bisoprolol Fumarate and Hydrochlorothiazide are well absorbed after drinking. There is no vendor for each substance when drinking together in the same pill.

The absorption of Bisoprolol Fumarate and Hydrochlorothiazide is not affected whether used with food. The average peak concentration in the plasma of Bisoprolol Fumarate is about 9 nano grams/ml, 19nanogam/ml and 36ng/ml occurring about 3 hours after taking doses of 2.5mg/6.25mg, 5mg/6.25mg and 10mg/6.25mg of combined, corresponding. The average peak concentration in the plasma of hydrochlorothiazide reaches 30nanogam/ml that occurs about 2.5 hours after the combination of pills. Increasing the dose increases the plasma concentration ratio of Bisoprolol Fumarate has been observed between 2.5 mg and 5mg dose, as well as between 5mg and 10mg dose. Half-life excreted T1/2 of Bisoprolol Fumarate within 7 hours to 15 hours and hydrogen-chlorothiazide from 4 to 10 hours. The percentage of dosage in urine is about 55% for bisoprolol fumarate and about 60% with hydrochlorothiazide.

bisoprolol fumarate

Bisoprolol Fumarate is almost completely absorbed through the digestive tract. And only through the initial metabolism is very little, so orally via oral about 90%. After drinking, the peak concentration in plasma is reached from 2 to 4 hours. About 30% of the drug attaches to plasma proteins. Food does not affect the absorption of the drug. Half life eliminated in plasma from 10 to 12 hours. Bisoprolol dissolves moderate in lipid. Metabolic drugs in the liver and excretion in urine, about 50% in constant form and 50% in the form of metabolites.

In the elderly, half -life eliminated in plasma is slightly longer than young people, although the average plasma concentration in a stable state increases, there is no difference in the level of accumulation of Bisoprolol among young people and the elderly. In people with creatinine clearing coefficient below 40 ml/min, half -life plasma increases about 3 times higher than normal people. In people with cirrhosis, Bisoprolol elimination speed is more and lower than that of normal people (8.3 - 21.7 hours).

Absolute bioavailability after oral dose 10mg Bisoprolol Fumarate is about 80%. The first metabolism of Bisoprolol Fumarate is about 20%. The pharmacokinetic records of Bisoprolol Fumarate have been tested after a single dose and in a stable state. Linking with serum protein is about 30%. Plasma peak concentration occurs within 2-4 hours after taking the drug in doses from 2.5mg to 20mg and the average peak value is from 9nanogam/ml at the dose of 2.5mg to 70nogam/ml at the dose of 20 mg. When taking Bisoprolol Fumarate with a one -time standard daily, the result is a less than twice -changing plasma peak concentration. The concentration is proportional to oral dose ranges from 2.5mg to 20mg.

Half of the lifetime of plasma is about 9 - 12 hours and a bit longer in elderly patients, partly due to the reduced renal function. Stable state is achieved within 5 days with a dose once a day. In both young and elderly groups, the accumulation of plasma is low, the factor accumulates from 1.1 to 1.3 and is what has been expected from half a lifetime and standard for a daily use of the drug. Bisoprolol Fumarate is excreted equally by the kidney and no kidney, with about 50% of the dosage appears in urine in the form of constant and 50% in the form of inactive metabolites. In humans, metabolites are known to be unstable or have no pharmacological activity. There are less than 2% of the dose is excreted in the feces. The dynamic characteristics of the two enamfiomers are similar. Bisoprolol is not metabolized by cytochrome P450 II D6 (Debrisoquin hydroxylase).

With objects with creatinine clearance below 40ml/min, half -life plasma increases about 3 times higher than healthy people. In patients with cirrhosis, Bisoprolol elimination rate is often significantly changed and significantly slower than healthy objects, accompanied by a different half -life of plasma, from 8 hours to 22 hours.

In the elderly people, the average plasma concentration in a stable state has been increased, partly due to decreasing creatinine clearance. However, there is no significant difference in the accumulation level of Bisoprolol found between the young group and the elderly.

hydrochlorothiazide (HCT)

Hydrochlorothiazide is well absorbed (65% - 75%) after drinking. The absorption of hydrochlorothiazide decreases in patients with congestive heart failure.

The concentration of the maximum of the mulch is observed within 1-5 hours after taking the drug and is within 70 nanogam - 490 nanogam/ml after the oral dose from 12.5mg to 100mg. The plasma concentration is linearly related to the dose. The concentration of hydrochlorothiazide in the whole blood is 1.6 - 1.8 times higher than the plasma. Linking with serum protein has been reported about 40% to 68%. Half lifetime of plasma excretion is reported about 6-15 hours. Hydrochlorothiazide is eliminated mainly by kidney.

After the oral dose of 12.5mg to 100mg, about 55% - 77% of the dose appears in the urine and more than 95% of the absorption dose is excreted through the unchanged urine. HCT's plasma concentration increases and half -life eliminates for patients with kidney disease.

bisoprolol fumarate

Bisoprolol is well tolerated in most patients. Most unwanted effects are mild and temporary. The percentage of patients who have to stop treatment due to unwanted effects is 3.3% for patients using bisoprolol and 6.8% for patients using Placebo.

In clinical trials worldwide or experience after bringing the drug to the market, a series of other side effects (AES), in addition to the side effects listed above, have been reported. While in many cases, whether it is a causal relationship between Bisoprolol and AES, but still listed to warn the doctor about the possible relationship.

When ADR occurs with the above manifestations, it can be treated as cases of overdose symptoms (see item: overdose).

Notify the physician the unwanted effects when using the drug.

Be cautious when using

bisoprolol

heart failure

Parasma stimulation is an essential component that supports circulatory function in the beginning of congestive heart failure and beta blockers can lead to further decline in heart muscle contraction and promote more severe heart failure. However, in some patients with congested heart failure, compensation may need this medication. In this case, the medication must be used carefully. The drug is only added when it has been treated for heart failure with basic drugs (diuretics, digitalis, inhibiting enzymes) under the strict control of a specialist.

Humanity does not have a history of heart failure

In some patients with beta blockers can continue to cause heart muscle (pinch) and promote heart failure. Based on the first signs or symptoms of heart failure, it is necessary to consider stopping bisoprolol fumarate and hydrochlorothiazide. In some cases, the treatment with bisoprolol fumarate and hydrochlorothiazide can be continued while heart failure is treated with other drugs.

Sudden stop treatment

Exacections of angina and in some cases, myocardial infarction or ventricular arrhythmia have been observed in patients with coronary artery disease determined after suddenly stopping treatment with beta blockers. Therefore, these patients need to be warned that they are not interrupted or stopped without the doctor's advice. Even in patients without coronary artery disease can be recommended for treatment with Bisoprolol Fumarate and Hydrochlorothiazide for more than a week provided that patients must be carefully monitored. If the symptoms occur, it is necessary to re -establish treatment with beta blockers, at least temporarily. If the symptoms of cessation occur, the drug should be used at least for a period of time.

Peripheral vascular disease

Beta blockers can promote or aggravate the symptoms of artery failure in patients with peripheral vascular disease. Caution should be used for these patients.

Bronchospasm

In general, patients with bronchospasm should not use beta blockers. Because it is associated with the selection of Beta1 of Bisoprolol Fumarate, Bisoprolol Fumarate + Hydrochlorothiazide can be used in patients with bronchospasmic spasms who do not respond to drugs or those who cannot tolerate other antihypertensive drugs. Due to the absolute beta1 selection (selective selection decreases when increasing the dose), the lowest dose is needed by bisoprolol fumarate and hydrochlorothiazide. Beta2's ownership effect (bronchodilator) can also be effective.

Anesthesia and surgery

If Bisoprolol Fumarate and Hydrochlorothiazide are still continued treatment during the pre -surgical period, it is necessary to perform special care because anesthetics impaired myocardial function, such as using Ether, Cyclopropane and Trichlorethylene.

Diabetes and hemiasis blood

Beta blockers can cover the manifestations of hypoglycemia, especially tachycardia. Unstolant beta blockers may increase the level of hypoglycemia caused by insulin and slow down the recovery of serum glucose concentrations. Due to the selective nature of Beta1, this is less likely to occur with Bisoprolol Fumarate. However, a patient should be warned or hypoglycemia or diabetes patients taking insulin or blood glucose medications for these possibilities and must be used carefully.In addition, potential diabetes can become a manifestation and diabetes because Thiazide may require adjusting their insulin dose. Due to the low dosage of hydrochlorothiazide, this may be less likely to happen with a combination of bisoprolol fumarate and hydrochlorothiazide.

thyroid poisoning

The beta-adrenergic blocker can cover the clinical signs of hyperthyroidism (hyperthyroidism), such as tachycardia. The sudden stopping of beta blockers can worsen the symptoms of hyperthyroidism or may promote the storm.Kidney disease

Need to adjust Bisoprolol dose carefully for patients with kidney failure or liver failure. The accumulation of thiazide can develop in patients with impaired renal function. In these patients, Thiazide can cause blood nitrogen. The statue has a creatinine clearance below 40ml/minute, half -life of bisoprolol fumarate plasma increased by tripling than healthy people. If the renal failure progresses, it is necessary to stop the bisoprolol fumarate and hydrochlorothiazide.

Liver disease

Bisoprolol Fumarate and Hydrochlorothiazide should be used carefully in patients with impaired liver function or progressive liver disease. Thiazide can change the balance of fluid and electrolytes, which can cause liver coma. In addition, the elimination of Bisoprolol Fumarate is significantly slower in patients with cirrhosis than healthy people.

hydrochorothiazide

Acute myopia and closing angle of pressure angle (glaucoma): Hydrochlorothiazide, a sulfonamide that can cause its own specific reaction, leading to acute myopia and closed angle of acute angle. Symptoms include an acute impulsive or visual reduction of pain and often occur within hours to a few weeks when starting to take the drug. The angle hypertrophy of the angle if left untreated can lead to permanent eyesight. Work

The main treatment is to stop hydrochlorothiazide as quickly as possible. Suggestions for treatment or surgery may need to be considered if the intraocular pressure is still uncontrolled. Risk factors for developing an angle of glaucoma may include a history of sulfonamide or penicillin allergy.

Cautions

The condition of the fluid and electrolyte balance

Warning signs or symptoms of fluid imbalance and electrolytes include dry mouth, thirst, weakness, indifference, drowsiness, restlessness, muscle pain or cramps, muscle fatigue, hypotension, ureter, tachycardia and digestive disorders such as nausea and vomiting.

Hypotension can develop, especially with rapid diuretic during serious cirrhosis, during use simultaneously with corticosteroids or epidemic hormones (ACTH) or after prolonged treatment. Interventions with adequate oral electrolytic will also contribute to hypokalemia. Hypotension and decreased blood magnesium can cause ventricular arrhythmia or increase sensitivity or increase the heart response of the heart with the toxic effects of digitalis. Hypotension can be avoided or treated with potassium or increased consumption of potassium -rich foods.

Reducing blood hyponemia may occur in patients with edema in hot weather, appropriate treatment is to limit water rather than drinking salt water, except for a rare case of hypoglycemia that threatens life. In reality of salt decline, the appropriate choice is to replace therapy.

Hyper uric acid hyperkemosis

Hyperglycemia or acute gout can occur in some patients using thiazide bisoprolol fumarate diuretics, used alone or in combination with HCT, are associated with uric acid hypertrophy, but in clinical trials in the United States, the rate of wear must increase high uric acid -related acid -related acid -related acid in hydrochlorothiazide. With b/HCT 6.25mg (10%). Because of the very low dosage of HCT, hyperuricemiaemiasis can be less likely to occur with a combination of bisoprolol fumarate + hydrochlorothiazide.

Hyperglycemia

Hyperglycemia can occur with thiazide diuretics. Therefore, potential diabetes can show when treated with Thiazide.

Other effects

The hypotension effects of the drug can increase in patients with surgery to remove sympathetic nerve.

Armor disease

Thiazide reduces calcium secretion and changes the pathology of parathyroid glands, hypercalcemia and hypoglycemia has been observed in some prolonged thiazide patients. Thiazide can cause continuous and mild hypertopic growth in the absence of calcium metabolic disorders. Marking for hypercalcemia may be evidence of hidden hyperthyroidism. Thiazide should be stopped before performing the adjacent function test. The increase in cholesterol and neutral fat levels may be related to thiazide diuretics.

kidney failure

If the renal failure progresses clearly, it is necessary to consider reducing the dose or not to continue treating with diuretics. Thiazide has been shown to increase the secretion of urine magnesium, which can lead to decreased magnesium (hypomagnesemia).

Thiazide should be used cautiously in severe kidney disease. In patients with renal disease, Thiazide can cause urea-meteor. The accumulation of drugs can develop in patients with impaired renal function.

The effect of drugs on driving and operating machinery

Experience shows that the treatment does not affect the ability to drive or use the patient's machines. However, some beneficial reactions such as dizziness, headache, and drowsiness are still rare but still occur; Hence can affect the ability to drive or operate machinery.

Using drugs for women during pregnancy and lactation

Case of pregnancy

Thiazide passes through the placenta and appears in the umbilical cord blood. The use of thiazide in pregnant women requires predicting benefits compared to the risks for the fetus. These dangers include jaundice for fetuses or babies, pancreatitis, thrombocytopenia and may have other adverse reactions that have occurred in adults.

Breastfeeding case

Bisoprolol Fumarate used mono or combined with HCT has not been studied in mothers who are breastfeeding. Thiazide is excreted through breast milk. A small amount of bisoprolol fumarate ( Drug interaction

bisoprolol fumarate (B) and hydrochlorothiazide (HCT)

Bisoprolol Fumarate + Hydrochlorothiazide can increase the effect of other antihypertensive drugs when used simultaneously. Bisoprolol Fumarate and hydrochlorothiazide should not be used in combination with other beta blockers. Patients who receive drugs decrease/consume catecholamine, such as reserpine or guanethidine, should be closely monitored because of the increase in beta-adrener-gic blocking effect that can cause excessive decline in sympathetic activity. In patients treated simultaneously with clonidine, if needed to stop treatment, bisoprolol fumarate and hydrochlorothiazide should be discontinued a few days before stopping clonidine.

Bisoprolol Fumarate + Hydrochlorothiazide should be cautious when used with myocardial inhibitors or inhibitors of atrial conduction or depression, such as identified calcium antagonistic drugs (especially phenylalkylamine [Verapamil] and benzothiazepine [DiltIAZEM]) disopyramide.

Both digitalis glycosides and beta blockers slow down the atrial transmission and heart rate decreases. Simultaneous use may increase the risk of slow heart rate.

bisoprolol

Simultaneously used with rifampin increases the clearance of bisoprolol fumarate, shortening half -life of elimination. However, it is not necessary to change the starting risk. Research documents on pharmacokinetics do not show clinical interactions related to other simultaneous substances, including thiazide and cimetidine diuretics. Bisoprolol Fumarate does not affect Pro-Thrombin time in patients with stable warfarin doses.

Risk of anaphylactic reaction

While taking beta blockers, patients with a serious history of allergies with different allergens have a stronger reaction to the use of repeated drugs or by accident or due to treatment. These patients may not respond to the dose of epinephrine often used to treat allergic reactions.

hydrochlorothiazide

When simultaneously with the following drugs, there may be interaction with thiazide diuretics including alcohol, sedative or addictive sleeping pills: There may be an increase in vertical potential.