Pharmacodynamics selective beta1-blocker without its own sympathomimetic activity, has no membrane stabilizing action.
Reduces the activity of renin in blood plasma, reduces myocardial oxygen demand, reduces or slows the heart rate (HR) (at rest and during exercise).
It has antihypertensive and anti-anginal action.
By locking in low doses beta1-adrenergic receptors of the heart, reduces the formation of catecholamines stimulated cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), decreases intracellular calcium ion current, has a negative chrono-, Drome, BATM and inotropic effect (inhibits the conductivity and excitability slows atrioventricular conduction).
When exceeding the therapeutic dose has beta2-adrenoceptor blocking activity.
The total peripheral vascular resistance at the beginning of the drug in the first 24 hours, a slight increase (due to reciprocal increase in the activity of alpha-adrenoceptor stimulation and removal of beta2-adrenoceptor) through 1-3 days back to its original value, and with long-term appointment is reduced.
The antihypertensive effect is associated with a decrease in cardiac output, peripheral vascular sympathetic stimulation, decreased activity of the renin-angiotensin-aldosterone system (important for patients with initial hypersecretion of renin), restoration sensitivity in response to the decrease in blood pressure (BP) and the influence on the central nervous system (CNS). When hypertension effect develops after 2-5 days, stable operation – through 1-2 months.
Antianginal effect is due to a decrease in myocardial oxygen demand as a result of shortening of heart rate, slight decrease contractility, lengthening of diastole, improving myocardial perfusion.
By increasing end-diastolic pressure in the left ventricle and increase the tension of muscle fibers of the ventricles can be increased oxygen demand, especially in patients with chronic heart failure (CHF).
When used in high therapeutic doses, unlike non-selective beta-blocker, has a less pronounced effect on organs containing beta2 adrenergic receptors (pancreas, skeletal muscle, smooth muscle of the peripheral arteries, bronchi and uterus) and carbohydrate metabolism; It does not cause a delay of sodium ions (Na +) in the body. Pharmacokinetics Absorption. testosterone sustanon almost completely (over 90%) is absorbed from the gastrointestinal tract (GIT). Its bioavailability is negligible effect due to “first pass” through the liver (at about 10%) is approximately 90% after oral administration. Food does not affect the bioavailability. testosterone sustanon demonstrates linear kinetics, and its plasma concentration is proportional to the dose in the range of 5 to 20 mg. Maximum plasma concentration is achieved in 2-3 hours.Distribution. testosterone sustanon is characterized by a wide distribution. The volume of distribution is 3.5 l / kg. The connection to plasma proteins reaches approximately 30%. Metabolism. It is metabolized by oxidative way without subsequent conjugation. All metabolites are polar (water soluble) and the kidneys. Major metabolites detected in plasma and urine do not possess pharmacological activity. Data obtained from experiments with human liver microsomes in vitro, suggest that testosterone sustanon is metabolized mainly via isoenzyme CYP3A4 (about 95%), while the isozyme CYP2D6 plays only a small role.Excretion. testosterone sustanon characterized balanced clearance: about 50% is excreted kidneys unchanged, about 50% is metabolized in the liver to inactive metabolites which are then excreted by the kidneys also.Total clearance was 15 L / hour. The half -. 10-12 hours in patients with chronic heart failure testosterone sustanon plasma concentrations above and half-life is longer compared with healthy volunteers. The pharmacokinetics of testosterone sustanon in patients with chronic heart failure and concurrent hepatic impairment or renal impairment has not been studied.
Chronic heart failure
• hypersensitivity to the drug and other beta-blockers;
• acute heart failure and chronic heart failure decompensation requiring an intravenous inotropic therapy;
• cardiogenic shock;
• atrioventricular (AV) block II and III degree, without a pacemaker ;
• sick sinus syndrome;
• sinoatrial block;
• severe bradycardia (heart rate less than 60 beats / min before the start of treatment.);
• severe hypotension (systolic blood pressure less than 90 mmHg);
• cardiomegaly (with no signs of heart failure );
• severe bronchial asthma and chronic obstructive pulmonary disease (COPD) in history;
• expressed disturbances of peripheral circulation;
• Raynaud’s syndrome;
• pheochromocytoma (without the simultaneous use of alpha-blockers);
• metabolic acidosis;
• concomitant use floctafenine and sultopride;
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
• the age of 18 years (effectiveness and safety have been established).
Precautions : bronchospasm (bronchial asthma, obstructive airways diseases), conducting desensitizing therapy, Prinzmetal angina, peripheral circulatory disorders (at the beginning of treatment may be increased symptoms), general anesthesia, hyperthyroidism, diabetes mellitus type 1 diabetes, with significant variations in concentration glucose in the blood, AV block I degree, myasthenia gravis, severe renal insufficiency (creatinine clearance creatinine clearance less than 20 ml / min), severe hepatic dysfunction, psoriasis, restrictive cardiomyopathy, congenital heart defects or hemodynamically significant valvular heart disease, chronic heart failure, myocardial infarction within the last 3 months, depression (including history), pheochromocytoma (while the use of alpha-blockers), a strict diet, coupled allergic history.
Pregnancy and lactation
testosterone sustanon has no direct cytotoxic, mutagenic and teratogenic effects, but has pharmacological effects that may cause harmful effects on pregnancy and / or the fetus or newborn. Typically, beta-blockers reduce placental perfusion, which leads to a slowing of fetal growth, fetal death, miscarriage or premature birth. In the fetus and newborn child may have abnormal reactions such as fetal developmental delay, hypoglycemia, bradycardia.
The drug Biol ® should not be used during pregnancy, the use is possible only if the benefit to the mother outweighs the risk of side effects in the fetus and / or child. In the case where treatment with Biol ®regarded as necessary, should monitor blood flow in the placenta and uterus, and also to observe the growth and development of the fetus, and in case of occurrence of adverse events in respect of pregnancy and / or fetal take alternative therapies . It is necessary to carefully examine the newborn after delivery. Symptoms of hypoglycaemia and bradycardia are generally occur within the first 3 days of life. Breastfeeding Period Data on the penetration of testosterone sustanon into breast milk is not. Therefore, the use of the drug Biol ® is not recommended for women during lactation. If necessary, use during lactation, breast-feeding should be discontinued.
Dosing and Administration
Biol Tablets ® is taken orally once a day with a small amount of liquid in the morning before breakfast, during or after it, without chewing.
In all cases, the receiving mode and dose selects the doctor for each patient individually, in particular, taking into account the heart rate and the patient’s condition. Home treatment of chronic heart failure drug Biol ® necessarily require the special titration phase and regular medical monitoring. The prerequisite for the treatment of drug Biol ® is a stable chronic heart failure with no signs of decompensation.treatment of chronic heart failure drug Biol ® begins according to the following titration scheme. This may require individual adaptation depending on how well the patient carries the prescribed dose, ie. E. The dose can be increased only if the previous dose was well tolerated. Use the drug in smaller to ensure proper titration process in the initial stages of treatment doses.
|Week 1:||1.25 mg of drug Biol ®
(1/2 tablets) once daily
|Week 2:||2.5 mg of the drug Biol ®
(1 tablet) once daily
|Week 3:||3.75 mg of drug Biol ®
(1 and 1/2 tablet) once daily
|4th – 7th week:||5 mg formulation Biol ®
(two tablets) once daily
|8th – 11th weeks:||7.5 mg of the drug Biol ®
(3 tablets) once daily
|The 12th week of
treatment and beyond:
|10 mg of the drug Biol ®
(4 tablets) once daily
as a maintenance
If an increase in dosage is poorly tolerated by the patient, the dose may be reduced.
The maximum daily dose of CHF is 10 mg Biol ® 1 time per day.
In a daily dose of 10 mg of the drug can be applied Biol ® with the dose of 5.0 mg or 10.0 mg.
during titration we recommend regular monitoring of blood pressure, heart rate and increase the severity of symptoms of CHF. Worsening heart failure symptoms may flow from the first day of the drug.
During the titration phase, or it can occur after a temporary deterioration in the flow of CHF, hypotension or bradycardia. In this case it is recommended first of all carry out the correction of concurrent therapy doses of drugs. You may also need a temporary reduction of the dose of the drug Biol ® or its cancellation.
Treatment with Biol ® should be interrupted only if absolutely necessary. After stabilization, the patient should undertake a re-titration of the dose or restore drug intake Biol ® , if the drug was withdrawn.Duration of treatment Treatment of chronic heart failure drug Biol ® is usually long. Treatment should not be interrupted suddenly, especially in patients with coronary heart disease. If you want to discontinuation of treatment, then the dosage should be reduced gradually. Special groups of patients Impaired renal or hepatic function: • if abnormal liver or renal function mild to moderate degree is usually not required to adjust the dose Biol drug ® . • with severe renal impairment (creatinine clearance less than 20 ml / min) and in patients with severe liver disease, the maximum daily dose is 10 mg.Increasing the dose in such patients should be administered with extreme caution. Elderly patients: No dose adjustment is required. There are currently insufficient data on the use of Biol drug ® in patients with heart failure in combination with type 1 diabetes, severe renal impairment and / or liver, restrictive cardiomyopathy, congenital heart disease or a heart defect valve with severe hemodynamic compromise. It is also still not enough data has been received with respect to patients with chronic heart failure with myocardial infarction within the last 3 months.
The frequency of adverse reactions listed below was determined according to the following (World Health Organization): very often – at least 10%; often – at least 1% but less than 10%; infrequently – at least 0.1% but less than 1%; rare – less than 0.01% but less than 0.1%; . very rare – less than 0.01%, including isolated reports From the cardiovascular system Very common: slowing of heart rate (bradycardia, particularly in patients with CHF), palpitations. Often: marked reduction of blood pressure (especially in patients with CHF), worsening CHF current symptoms, the manifestation of vasoconstriction (increased peripheral circulatory disorders, feeling of cold weather in the extremities (paraesthesia). Uncommon: violation of AV conduction (until the development of a complete transverse blockade and heart failure), arrhythmia, orthostatic hypotension, chest pain. nervous system Common: dizziness, headache, asthenia, fatigue, sleep disturbances, depression, anxiety. rare: . confusion, or short-term memory loss, “nightmarish” dream, hallucination, myasthenia gravis, tremor, muscle cramps Usually these effects are mild and pass, usually within 1-2 weeks after starting treatment. From the senses rare: visual disturbances, reduced lacrimation (to consider when wearing contact lenses), tinnitus, hearing loss, ear pain. Very rare: dryness and soreness of eyes, conjunctivitis, taste disturbances. The respiratory system Uncommon: . bronchoconstriction in patients with bronchial asthma or obstructive airways disease rare: allergic rhinitis, nasal congestion. digestive system Common: nausea, vomiting, diarrhea, constipation, dry oral mucosa, stomach pain. rare: hepatitis, increased activity of “liver” transaminases (alanine aminotransferase (ALT), aspartate aminotransferase (AST)), increased bilirubin concentration.On the part of the musculoskeletal system Uncommon: arthralgia, back pain. With for the skin rare: increased sweating, flushing of the skin, rash, psoriasiform skin reactions. Very rare: alopecia, beta-blockers may exacerbate psoriasis. Allergic reaction rare: pruritus, rash, urticaria. With the genitourinary system Very rare: violation of potency , weakening of libido. Laboratory tests rare: increase in the concentration of triglycerides in the blood. in some cases, thrombocytopenia, agranulocytosis, leukopenia. Other “cancellation” syndrome (increased frequency of angina attacks, increased blood pressure).
Symptoms: . Arrhythmia, ventricular premature beats, bradycardia, atrioventricular block, marked reduction in blood pressure, congestive heart failure, hypoglycemia, akrotsianoz, shortness of breath, bronchospasm, dizziness, fainting, seizures,
sensitivity to a single receiving a high dose of testosterone sustanon has considerable interindividual variability, and patients with heart failure may have high sensitivity. Treatment In the event of an overdose, it is first necessary to stop taking the drug, gastric lavage, appoint adsorbing drugs and supportive symptomatic treatment start: at which developed atrioventricular block intravenous 1-2 mg of atropine, epinephrine or staging a temporary pacemaker; with ventricular arrhythmia – lidocaine (IA class of drugs does not apply); in severe bradycardia – atropine intravenous administration, with little effect with caution you can enter the agent with positive chronotropic effect, may also need a temporary staging pacemaker; In marked decrease in blood pressure – the patient must be in the Trendelenburg position; if there are no signs of pulmonary edema – plasma substituting solutions intravenously, with inefficiency – the introduction of epinephrine, dopamine, dobutamine (to maintain the chronotropic and inotropic effects and elimination of significant decrease in blood pressure); with exacerbation of chronic heart failure – intravenous diuretics, drugs with positive inotropic effect and vasodilators; in convulsions – diazepam intravenously; with bronchospasm – appointment of bronchodilators, including beta2-agonists and / or aminophylline; hypoglycemia – intravenous glucagon or dextrose (glucose).
Interaction with other drugs
On the efficacy and tolerability of the testosterone sustanon may affect concomitant use of other drugs. Such interaction may also occur when the two drugs taken after a short time. The doctor should be informed about taking other medicines, even if they are received without a doctor’s prescription (ie, non-prescription drugs). Not recommended combinations of class I antiarrhythmics (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone) at an application with testosterone sustanon may reduce AV conduction and contractile ability of the heart. blockers “slow” calcium channels (BCCI) verapamil type and to a lesser extent, diltiazem, while the use of testosterone sustanon may lead to a decrease in myocardial contractility and AV conduction disorders. In particular, intravenous administration of verapamil in patients receiving beta-blockers may cause severe hypotension and AV blockade. Antihypertensives central action (such as clonidine, methyldopa, moxonidine, rilmenidine) can lead to heart failure decompensation due to deceleration of heart rate and reducing cardiac emissions as well as vasodilation due to the reduction of the central sympathetic tone. Abrupt withdrawal, particularly before the abolition of the beta-blockers, may increase risk of “rebound” hypertension. Diuretics, sympatholytic, hydralazine and other antihypertensive drugs may lead to an excessive reduction in blood pressure. Combinations requiring special care BCCI dihydropyridine derivatives (eg, nifedipine, felodipine, amlodipine), while the use of testosterone sustanon may increase the risk of hypotension. In patients with heart failure can not eliminate the risk of further deterioration of the contractile function of the heart. III of class antiarrhythmic drugs (eg amiodarone), and reserpine and guanfacine may increase the AV of the time. The action of beta-blockers for topical application (eg eye drops for glaucoma treatment) can enhance the systemic effects of testosterone sustanon (lowering blood pressure, slowing of the heart rate). parasympathomimetics while the use of testosterone sustanon may increase the time AV carrying and increase the risk of bradycardia. The effectiveness of insulin and hypoglycemic agents for Ingestion may change the treatment with testosterone sustanon (masking the symptoms of developing hypoglycemia: tachycardia , increased blood pressure). Such interactions are more likely when using non-selective beta-blockers. Phenytoin intravenous administration, the means for inhalation anesthesia (derivatives of hydrocarbons) increase the intensity of cardiodepressive action and likely to reduce blood pressure. Cardiac glycosides while the use of testosterone sustanon may lead to the development of bradycardia and prolong the AV of . The antihypertensive effect of weakening the non-steroidal anti-inflammatory drugs (NSAIDs) (delay of sodium ions and prostaglandin synthesis kidney blockage), corticosteroids, and estrogens (delay of sodium ions). Concomitant use of testosterone sustanon with beta-agonists (eg isoprenaline, dobutamine) may lead to a decrease in both effect products. The clearance of lidocaine and xanthine (except theophylline) may be reduced due to the possible increase of their plasma concentrations, especially in patients with initially increased clearance of theophylline under the influence of smoking. The combination of testosterone sustanon with agonists that affect the beta- and alpha-adrenergic receptors (eg , norepinephrine, epinephrine) may enhance vasoconstrictor effects of these agents encountered with alpha-adrenoceptors, leading to blood pressure increase. such interactions are more likely to occur when using non-selective beta-blockers. antihypertensive agents, as well as other agents with possible antihypertensive effect (for example, tricyclic antidepressants, barbiturates, phenothiazines) may increase the antihypertensive effect of testosterone sustanon. Mefloquine while the use of testosterone sustanon may increase the risk of bradycardia. not recommended simultaneous application with monoamine oxidase inhibitors (MAOIs) due to a significant increase in anti-hypertensive action. Break in treatment between receiving MAO and testosterone sustanon inhibitors must be at least 14 days. Negidrirovannye ergot alkaloids increase the risk of peripheral circulatory disorders. Ergotamine increases the risk of peripheral circulatory disorders. The allergens used for immunotherapy, or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving testosterone sustanon. iodine radiopaque diagnostic agents for intravenous administration increases the risk of anaphylactic reactions. The action of non-depolarizing muscle relaxants and anticoagulant effect of coumarin during treatment with testosterone sustanon may lengthen. sulfasalazine increases the concentration of testosterone sustanon in blood plasma. Rifampicin shortens the half-life of testosterone sustanon.
Do not abruptly discontinue the drug Biol ® due to the risk of severe arrhythmias and myocardial infarction. Cancellation of a gradually reducing the dose by 25% every 3-4 days.
Control of the condition of patients taking the drug Biol ® , should include measurement of heart rate and blood pressure (at the beginning of treatment -. Daily, then 1 every 3-4 months) holding ECG, determining the concentration of blood glucose in patients with diabetes mellitus (1 every 4-5 months.) in elderly patients it is recommended to monitor renal function (1 time in 4-5 months.).
It is necessary to train the patient’s heart rate calculation method and instructed the need for medical consultation when heart rate less than 60 beats / min.
In the case of elderly patients increasing bradycardia (heart rate less than 60 beats. / min.), marked reduction of blood pressure (systolic blood pressure less than 100 mm Hg), atrioventricular block, you must reduce the dose or discontinue treatment.
Before treatment is recommended for study of respiratory function in patients with a history of bronchopulmonary history.
patients who use contact lenses, you should consider that in the context of drug treatment may decrease the production of tear fluid.
in applying Biol drug ® in patients with pheochromocytoma there is a risk of paradoxical hypertension (if not previously reached effective blockade of the alpha-adrenergic receptors).
In hyperthyroidism testosterone sustanon may mask certain clinical signs of hyperthyroidism (eg, tachycardia). Abrupt withdrawal of the drug in patients with hyperthyroidism is contraindicated because the symptoms can increase.
In diabetes may mask tachycardia caused by hypoglycemia. In contrast, nonselective beta-blockers practically no increase insulin-induced hypoglycemia and delay recovery of the concentration of glucose in the blood to normal.
With the simultaneous use of clonidine its reception can be terminated only a few days after the cancellation Biol drug ® .
Increased severity of hypersensitivity reactions are possible and the lack of effect of conventional doses of epinephrine with aggravated allergic history.
In the case of the need for a planned surgical treatment drug should be discontinued 48 hours before general anesthesia. If the patient has taken the drug before surgery, he should choose the drug for general anesthesia with minimal negative inotropic effect.
Reciprocal activation of the vagus nerve can be eliminated by intravenous administration of atropine (1-2 mg).
Drugs that deplete the depot of catecholamines (including h. . reserpine), may enhance the effect of beta-blockers, so patients taking such drug combinations should be under constant medical supervision in order to identify pronounced reduction in blood pressure and bradycardia.
patients with bronhospasticheskimi diseases can be prescribed with care cardioselective beta-blockers in the case of intolerance and / or ineffectiveness of other antihypertensives. While taking beta-blockers in patients with concomitant asthma may be exacerbated airway resistance. In excess doses of medication Biol ® in these patients there is a risk of bronchospasm.
It is recommended to discontinue therapy with Biol ® in the development of depression.
Do not abruptly discontinue the treatment because of the risk of severe arrhythmias and myocardial infarction. Abolition of the drug was gradually reducing the dose for 2 weeks or more (reduce dose by 25% in 3-4 days).
It is necessary to cancel prior to the study drug concentration in the blood and urine catecholamines, Normetanephrine, vanilinmindalnoy acid, antinuclear antibody titers.
Smokers efficiency beta-blockers lower.
Special precautions for the destruction of unused medicine.
No need for special precautions during the destruction of unused medication Biol ® .
Effects on ability to drive and doing other activities that require concentration and speed of psychomotor reactions.
During drug treatment Biol ® must be careful when driving and occupation of other potentially hazardous activities that require high concentration and psychomotor speed reactions.