pharmacodynamics testosterone enanthate dosage – a drug that slows down the heart rate, the mechanism of action which is selective and specific inhibition of I of f sinus channels, controlling the spontaneous diastolic depolarization of sinus node and regulating heart rate (HR). testosterone enanthate dosage has a selective effect on the sinus node, without affecting the duration of the pulses intraatrial, atrioventricular and intraventricular conduction paths, as well as myocardial contractility and ventricular repolarization. testosterone enanthate dosage can also interact with the I h channel retina, similar to the I f channel of the heart involved in causing a temporary change of visual perception of the system due to changes in the retinal response to bright light stimuli. The triggering conditions (sharp change in brightness) is a partial inhibition of testosterone enanthate dosage I of h channels, which causes a transient change in the brightness in a limited area of the visual field (photopsia). The main pharmacodynamic property of testosterone enanthate dosage is dose-dependent slowing of the heart rate. Analysis of the dependence of the deceleration in heart rate of the dose of testosterone enanthate dosage was conducted by gradually increasing the dose to 20 mg twice daily and showed a tendency to achieve a “plateau” effect when there is no increase therapeutic effect with higher doses, it reduces the risk of severe bradycardia (heart rate less than 40 beats / min).
At recommended doses, heart rate slowing is about 10-15 beats / min at rest and during exercise. This leads to a reduction of the load on the myocardium due to a decrease in myocardial oxygen demand.testosterone enanthate dosage does not influence intracardiac conduction, myocardial contractility (no negative inotropic action) or ventricular repolarisation:
- in electrophysiological studies, testosterone enanthate dosage had no effect on the time of the pulses on the atrioventricular or intraventricular routes, as well as the corrected interval QT;
- in patients with left ventricular dysfunction (left ventricular ejection fraction (LVEF) of 30 to 45%), testosterone enanthate dosage did not have a negative influence on LVEF.
testosterone enanthate dosage is the S-enantiomer shows no biological conversion in studies in vivo. N-desmetilirovannoe testosterone enanthate dosage derivative is the major active metabolite.
Absorption and bioavailability
testosterone enanthate dosage is rapidly and almost completely absorbed from the gastrointestinal tract after ingestion fasting with achieving maximum concentration (C max ) in plasma after about 1 hour. The absolute bioavailability of approximately 40% due to the effect of “first pass” through the liver.
Eating increases the absorption of testosterone enanthate dosage time about 1 hour and increases the concentration in plasma from 20 to 30%. It is recommended to take the tablets during meals in order to reduce the concentration variability.
testosterone enanthate dosage binds to plasma proteins, about 70%, volume of distribution in patients at steady state is about 100 liters. C max testosterone enanthate dosage plasma after prolonged use of an oral dose of 5 mg twice daily is 22 ng / ml (coefficient of variation (CV) = 29%). The average equilibrium concentration in plasma is 10 ng / mL (CV = 38%).
testosterone enanthate dosage largely metabolized in the liver and intestine by oxidation with cytochrome P450 ZA4 (isoenzyme CYP3A4). The main active metabolite is a derivative of N-desmetilirovannoe (S 18982) at a concentration of about 40% relative to the concentration of the starting material. The metabolism of this active metabolite also occurs with the participation of isoenzyme CYP3A4. testosterone enanthate dosage has low affinity for the isoenzyme CYP3A4, shows no clinically significant isoenzyme inhibition or induction of CYP3A4, or so metabolic change isoenzyme CYP3A4 substrate concentrations in the plasma under the action of testosterone enanthate dosage is unlikely. Conversely, strong inducers and inhibitors of cytochrome P450 can significantly affect the concentration of testosterone enanthate dosage plasma.
half-life (T 1/2 ) is testosterone enanthate dosage, on average, 2 chasa (70-75% relative to the area under the curve “concentration / time» (AUC) in plasma), the effective T T 1/2 – 11 hours . The total clearance is about 400 ml / min, renal clearance – 70 ml / min. Excretion of metabolites occurs equally through the intestines and kidneys. About 4% of an oral dose is excreted unchanged by the kidneys.
Linearity / nonlinearity
Pharmacokinetics testosterone enanthate dosage is linear in the dose range 0.5-24 mg.
Special patient groups
pharmacokinetic indices (AUC and the C max ) were not significantly different in patients 65 years and older, 75 years or older and the general population of patients.
Impaired renal function
Changing the kinetics of testosterone enanthate dosage in patients with renal insufficiency (creatinine clearance (CC) of 15-60 mL / min) is minimal, since only about 20% of testosterone enanthate dosage and its active metabolite S 18982 excreted by the kidneys.
Abnormal liver function
in patients with mild hepatic insufficiency (up to 7 points on a scale Child-Pugh) AUC of testosterone enanthate dosage and its metabolite by 20% higher than in patients with normal liver function. Data on the use of testosterone enanthate dosage in patients with moderate hepatic insufficiency (7-9 points on a scale Child-Pugh) are limited and do not allow to draw a conclusion about the features of the pharmacokinetics of testosterone enanthate dosage in this group of patients, and in patients with severe hepatic insufficiency (more than 9 points on a scale Child -Pyu) no.
The relationship between the pharmacokinetic and pharmacodynamic properties of
slowing the heart rate is directly proportional to the increase in the blood plasma concentration of testosterone enanthate dosage and the active metabolite S 18982 when taken in doses of 15-20 mg twice daily. At higher doses, slowing the heart rate of the drug is not proportional to the testosterone enanthate dosage plasma concentration and is characterized by a tendency to achieve the effect of the “plateau”.
High concentrations of testosterone enanthate dosage in blood plasma, which can be achieved with the simultaneous use of testosterone enanthate dosage with potent inhibitors isoenzyme CYP3A4, can lead to a marked slowing of the heart rate, however, this risk is reduced while the use of a moderate inhibitor of CYP3A4.
Treatment of stable angina in adults with normal sinus rhythm:
- in case of intolerance or contraindications to the use of beta-blockers;
- in combination with beta-blockers with inadequate control on a background of stable angina optimal dose of beta-blocker.
Chronic heart failure
to reduce the incidence of cardiovascular events (death from cardiovascular disease and hospitalization due to increased symptoms of chronic heart failure (CHF)) in patients with chronic heart failure patients in sinus rhythm and heart rate of not less than 70 beats / min.
- Hypersensitivity to testosterone enanthate dosage or any ancillary components of the formulation.
- Bradycardia (resting heart rate less than 60 beats / min (before treatment)).
- Cardiogenic shock.
- Acute myocardial infarction.
- Severe hypotension (systolic blood pressure (BP) of less than 90 mm Hg and diastolic blood pressure less than 50 mmHg).
- Severe hepatic insufficiency (more than 9 points on a scale Child-Pugh).
- sick sinus syndrome.
- Sinoatrial block.
- Unstable or acute heart failure.
- The presence of pacemaker operating in a mode of constant stimulation.
- Unstable angina.
- Atrioventricular block (AV) III degree.
- The simultaneous use of strong inhibitors of the cytochrome P450 ZA4, such as antifungal agents group of azoles (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin for oral, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone.
- Pregnancy and breast-feeding.
- Age 18 years (effectiveness and safety of the drug in this age group has not been studied).
- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.
Precautions: moderately severe hepatic impairment (less than 9 points on a scale Child-Pugh), severe renal impairment (creatinine clearance less than 15 ml / min), congenital lengthening of the interval QT, the simultaneous use of medicines (drugs), prolonging the interval the QT, the simultaneous use of moderate inhibitors and inducers of CYP3A4 and grapefruit juice, asymptomatic left ventricular dysfunction, AV block II degree, recent stroke, retinitis pigmentosa (retinitis pigmentosa), hypotension, heart failure functional class IV according to NYHA classification, simultaneous application of blockers “slow” calcium channels (BCCI), slows heart rate (verapamil or diltiazem), the simultaneous application of nekaliysberegayuschimi diuretics.
Application of pregnancy and during breastfeeding
Animal studies have demonstrated the presence of reproductive toxicity, embryotoxicity and teratogenicity.
The drug Bravadin ® is contraindicated for use during pregnancy due to an insufficient number of safety data.
The period of breast-feeding
Use of the drug Bravadin ® during breastfeeding is contraindicated.
It is not known whether testosterone enanthate dosage penetrates into breast milk.
If necessary, use Bravadin during lactation should stop breastfeeding.
Dosing and Administration
Inside, twice a day (morning and evening) during food intake. 6
recommended starting dose is 10 mg per day (5 mg 1 tablet twice a day). After 3-4 weeks of therapy, the dose may be increased to 15 mg per
day (7.5 mg one tablet twice a day), depending on the therapeutic effect. If, during the use of the drug Bravadin ® resting heart rate slows less than 50 beats / min, or the patient has symptoms associated with bradycardia (dizziness, fatigue or pronounced reduction in blood pressure), the dose of the drug Bravadin ® should be reduced to 2.5 mg (on 1L tablets 5 mg) twice daily.
Treatment with Bravadin should be discontinued if a lower dose Bravadin heart rate remains below 50 beats / min or symptoms of bradycardia persist.
Chronic heart failure
recommended starting dose is 10 mg per day (5 mg 1 tablet twice a day).
After 2 weeks of therapy, the dose may be increased to 15 mg per day (7.5 mg one tablet twice a day), if resting heart rate is stable for more than 60 beats / min, or reduced to 2.5 mg (1L at 5 mg tablets) twice a day, stable if the heart rate less than 50 beats / min or the patient has symptoms associated with bradycardia (dizziness, fatigue or pronounced reduction in blood pressure).
If the heart rate is in the range of 50-60 beats / min, recommended Bravadin drug at a dose of 5 mg twice a day.
If, during the application of HR Bravadin drug alone slows less than 50 beats / min or the patient has symptoms associated with bradycardia, patients receiving the drug Bravadin ® in a dose of 5 mg twice daily or 7.5 mg twice a day, the dose should be reduced.
If the patients receiving the drug Bravadin ® dose 2.5 mg (2.1 by 5 mg tablets) twice daily or 5 mg twice a day, resting heart rate is stable for more than 60 beats / min, Bravadin dose preparation may be increased.
If the heart rate is less than 50 beats / min or the patient has saved the symptoms associated with bradycardia, therapy with Bravadin ® should be discontinued.
Patients older than 75 years,
patients aged 75 years and older treatment should be started at a lower dose.
The recommended starting dose is 2.5 mg (1/2 tablets of 5 mg) twice a day.
In the future, the dose may be increased. 7
Impaired renal function,
patients with impaired renal function (creatinine clearance greater than 15 mL / min) dose adjustment is required.
The recommended initial dose – 10 mg per day (1 tablet of 5 mg twice a day). After 3-4 weeks of therapy, the dose may be increased to 15 mg per day (7.5 mg 1 tablet twice a day).
Due to lack clinical data Bravadin drug should be used with caution in patients with CC less than 15 ml / min .
Abnormal liver function No dose adjustment is required in patients with mild hepatic insufficiency (up to 7 points on a scale Child-Pugh). Caution should be exercised when using the drug Bravadin in patients with moderate hepatic impairment (7- 9 points on a scale Child-Pugh). Patients with severe hepatic insufficiency (more than 9 points on a scale Child-Pugh) Bravadin use of the drug “is contraindicated.
Children and adolescents
The safety and efficacy of testosterone enanthate dosage in children and adolescents under the age of 18 years have not been established.
The use of testosterone enanthate dosage has been studied in clinical trials involving almost 14,000 patients. The most common side effects were dose-dependent and have been associated with the mechanism of action of testosterone enanthate dosage.
Classification of the incidence of side effects of the World Health Organization (WHO):
very common ≥ 1/10
often from ≥ 1/100 to <1/10
uncommon ≥ 1/1000 of to <1/100
rarely ot≥ 1/10000 to <1/1000
rarely from <1/10000
frequency not known – can not be estimated from the available data.
in each group, undesirable effects are presented in order of decreasing seriousness.
Violations of the organ of vision:
very often: change svetovospriyatiya (photopsia) *;
common: blurred vision. Violations of the organ of hearing and labyrinth disorders: Uncommon: vertigo. Violations of the heart and blood vessels: common: uncontrolled blood pressure, bradycardia ** AV block of I degree (long interval PQ on the electrocardiogram (ECG)), ventricular premature beats; rare: palpitations, supraventricular arrhythmias, marked reduction of blood pressure may be associated with bradycardia; very rare: atrial fibrillation, AV blockade II and III extent syndrome sinus. Disorders of the nervous system: common: headache (especially in the first month of treatment), dizziness, possibly related to bradycardia, the frequency is not known: syncope, possibly related to bradycardia. Violations of the respiratory system, the chest and mediastinum: uncommon: shortness of breath. Violations of the skin and subcutaneous tissue disorders: uncommon: angioneurotic edema, skin rash, rarely pruritus, erythema, urticaria. Violations of the gastrointestinal tract: uncommon: nausea, constipation, diarrhea.from Violations musculoskeletal and connective tissue disorders: uncommon: muscle cramps. General disorders and at the injection site: uncommon: asthenia, fatigue, possibly related to bradycardia, rarely. malaise, possibly related to bradycardia Laboratory and instrumental data: uncommon: hyperuricemia, eosinophilia, elevated serum creatinine concentration in blood plasma, lengthening QT interval on the electrocardiogram.
* Change svetovospriyatiya (photopsia) was observed in 14.5% of patients and was described as a transient change in the brightness in a limited area of the visual field. Usually, such events provoked a sharp change in light intensity in the area of the visual field. Basically photopsia appeared during the first two months of therapy, followed by repetition. Intensity photopsias usually been mild or moderate.Photopsia stopped against the background of continued therapy (77.5% of cases) or after its completion. Less than 1% of patients photopsias appearance caused the failure of the therapy.
** Bradycardia was observed in 3.3% of patients, especially in the first 2-3 months of therapy in 0.5% of patients developed severe bradycardia with a heart rate less than or equal to 40 beats / min.
overdose Bravadin drug may lead to severe and prolonged bradycardia.
Treatment is symptomatic and severe bradycardia should be carried out in a specialized hospital departments. In the case of a combination of bradycardia with impaired hemodynamic necessary use of beta-agonists (isoprenaline). If necessary – to set the pacemaker.
Interaction with other drugs
Concomitant use is not recommended
PM, lengthening the interval the QT:
– antiarrhythmics, lengthening the interval QT (eg, quinidine, disopyramide, bepridil, sotalol, Ibutilide, amiodarone);
– drugs, lengthening the interval the QT, non-antiarrhythmic drugs (such as pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, erythromycin for intravenous administration).Concomitant use of testosterone enanthate dosage and drugs prolonging the QT interval, it is not recommended, because the slowing of the heart rate can cause further elongation of the QT interval. If necessary, the simultaneous application requires careful monitoring of ECG.
Concomitant use requiring caution
Nekaliysberegayuschie diuretics (thiazide and “loop”)
Hypokalemia may increase the risk of arrhythmia. Since the use of testosterone enanthate dosage may cause bradycardia, hypokalemia, and a combination of bradycardia is a predisposing factor for the development of severe arrhythmias, especially in patients with the syndrome of the extended interval QT, both congenital and caused by the use of drugs.
Cytochrome P450 ZA4 (isoenzyme CYP3A4)
testosterone enanthate dosage is metabolised by the liver with the participation only of CYP3A4 and is a very weak inhibitor of this cytochrome. It does not affect the metabolism and the blood plasma concentration of other substrates (strong, moderate and weak inhibitors) isoenzyme CYP3A4. Inhibitors and inducers of CYP3A4 isozyme can react with testosterone enanthate dosage and exert a clinically significant effect on its metabolism and pharmacokinetic properties.
Inhibitors of CYP3A4 isoenzyme increased, and inducers of CYP3A4 isoenzyme testosterone enanthate dosage reduce the concentration in the blood plasma. Increasing testosterone enanthate dosage plasma concentrations can cause a risk of severe bradycardia (see. “Special Instructions” section).
Concomitant use is contraindicated
The simultaneous use of potent inhibitors isoenzyme CYP3A4, such as antifungal agents group of azoles (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin for oral, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone, contraindicated ( see. “Contraindications”). Strong inhibitors isoenzyme CYP3A4 – ketoconazole (200 mg once daily) or josamycin (1 g twice a day) increased average plasma concentration of testosterone enanthate dosage 7-8 times.
Concomitant use is not recommended
Moderate inhibitors of CYP3A4
Concomitant use of testosterone enanthate dosage and diltiazem or verapamil (drugs that slows the heart rate) in healthy volunteers and patients was accompanied by an increase in AUC 2-3 times and an additional heart rate slowing to 5 beats / min.
Concomitant use requiring caution
Moderate inhibitors of CYP3A4
Concomitant use of testosterone enanthate dosage with other moderate inhibitors of CYP3A4 (eg, fluconazole) is possible if resting heart rate is 60 beats / min. The recommended starting dose of testosterone enanthate dosage 2.5 mg twice daily.
Is necessary to control heart rate.
Grapefruit juice is
an application with grapefruit juice was an increase testosterone enanthate dosage plasma concentrations twice. When using testosterone enanthate dosage drinking grapefruit juice is not recommended.
Inducers of CYP3A4
11 inducers of CYP3A4 (eg, rifampicin, barbiturates, phenytoin, and drugs containing St. John’s wort) may reduce plasma concentrations of testosterone enanthate dosage and activity and require the selection of a higher dose of testosterone enanthate dosage. Concomitant use of testosterone enanthate dosage 10 mg twice daily, and drugs containing St. John’s wort reduces AUC of testosterone enanthate dosage in 2 times. The simultaneous use of medicines containing St. John’s wort, and testosterone enanthate dosage is not recommended.
Concomitant use with other medicines
No clinically significant effect on the pharmacodynamics and pharmacokinetics of testosterone enanthate dosage while the use of proton pump inhibitors (omeprazole, lansoprazole), inhibitors of phosphodiesterase-5 (sildenafil), inhibitors of HMG-CoA reductase inhibitors (simvastatin), BCCI (amlodipine, lacidipine) , digoxin and warfarin.
testosterone enanthate dosage has no clinically meaningful effect on the pharmacokinetics of simvastatin, amlodipine, lacidipine, pharmacokinetics and pharmacodynamics of digoxin, warfarin and on the pharmacodynamics of aspirin.
Concomitant use of testosterone enanthate dosage and angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, beta-blockers, diuretics, aldosterone antagonists, nitrates short and prolonged action, inhibitors of HMG-CoA reductase inhibitors, fibrates, proton pump inhibitors, hypoglycemic agents for oral administration, acetylsalicylic acid, and other antiplatelet agents are not accompanied by a change in the profile of the therapy safety.
drug Bravadin ® is ineffective in the treatment or prevention of arrhythmia, its effectiveness decreases with tachyarrhythmia occurs (eg, ventricular or supraventricular tachycardia). Application Bravadin drug is not recommended in patients with atrial fibrillation (atrial fibrillation) or other types of arrhythmias associated with the function of the sinus node.
When using Bravadin drug ® is recommended clinical monitoring of patients in order to identify atrial fibrillation (paroxysmal or persistent form), including research ECG if clinically indicated (eg, worsening of angina, occurrence of palpitations, irregular heart rhythm).
The risk of developing atrial fibrillation may be increased in patients with chronic heart failure taking the drug Bravadin. Atrial fibrillation is more common among patients taking testosterone enanthate dosage simultaneously with amiodarone or antiarrhythmic drugs of class I.
Patients with chronic heart failure and intraventricular conduction disorders (blockade of the left or right bundle branch) and ventricular dyssynchrony should be monitored carefully.
AV blockade II degree of
use of the drug Bravadin ® is not recommended in patients with AV blockade II degree.
Use in patients with bradycardia,
use of the drug Bravadin is contraindicated in patients with a heart rate less than 60 beats / min at rest before the start of therapy.
If the use of the drug Bravadin ® resting heart rate slows less than 50 beats / min or patients experienced symptoms associated with bradycardia (dizziness , fatigue or pronounced reduction in blood pressure), the dose should be reduced.
If the lower dose Bravadin ® heart rate remains below 50 beats / min or stored symptoms associated with bradycardia, drug therapy should be discontinued Bravadin.
The combined use of a part of antianginal therapies
Concomitant use of drug Bravadin ® with BCCI, slows heart rate (verapamil, diltiazem) is not recommended. In an application with nitrates or BCCI, dihydropyridine derivatives (amlodipine), changes in the safety profile of the therapy were observed. Not established that the simultaneous application of BCCI, dihydropyridine derivatives, povppaet effectiveness of testosterone enanthate dosage.
Chronic heart failure
The possibility of using the drug Bravadin ® is considered only in patients with stable heart failure. In applying the drug Bravadin “in patients with chronic heart failure functional class IV of NYHA classification should be careful due to the limited number for use in this group of patients.
is not recommended to use Bravadin drug immediately after stroke due to lack of data on efficacy and safety in this period. 13
The drug Bravadin ® affects the function of the retina eyes. Currently, there was no evidence of toxic effects on the retina, but the effects of the drug
on the retina Bravadin long-term use (more than 1 year) is currently unknown.
In the event of any violation of visual perception that are not described in this manual, use Bravadin drug ® should be discontinued. In applying the drug Bravadin “in patients with retinitis pigmentosa should be careful.
drug Bravadin should be used with caution in patients with arterial hypotension (insufficient clinical data).
Use of the drug Bravadin contraindicated in patients with severe hypotension (systolic blood pressure less than 90 mm Hg and diastolic blood pressure less than 50 mmHg ).
Atrial fibrillation (atrial fibrillation) – abnormal heart rhythm
Do not proven to increase the risk of severe bradycardia during treatment with the drug Bravadin in restoring sinus rhythm during pharmacological cardioversion. However, due to lack of sufficient data, with the possibility to postpone the planned electrical cardioversion, the use Bravadin drug should be discontinued 24 hours prior to its holding.
Use in patients with congenital syndrome of elongated QT interval or in patients taking drugs, QT-prolonging
drug Bravadin ® is not used in patients with congenital QT syndrome elongated interval, and in patients taking drugs prolonging the QT interval. If necessary, the simultaneous application requires strict ECG monitoring.
Slowing of heart rate as a result of the drug Bravadin “may exacerbate QT prolongation and trigger the development of severe arrhythmias, in particular the polymorphic ventricular tachycardia type” pirouette “.
Patients with hypertension who need a change of antihypertensive therapy
in a clinical trial cases of increase in blood pressure were more frequent in the group of patients treated with testosterone enanthate dosage (7.1%) compared with the placebo group (6.1%).
These cases are particularly frequent immediately after changes in antihypertensive therapy, were temporary in nature and do not affect the effectiveness of testosterone enanthate dosage therapy 14. If you change the antihypertensive therapy in patients with CHF taking the drug Bravadin ® , blood pressure should be monitored at regular intervals.
Moderate hepatic insufficiency
Caution should be exercised when applying the drug Bravadin ® in patients with moderate hepatic insufficiency patients (less than 9 points on a scale Child-Pugh).
Severe renal impairment
Caution must be exercised when applying the drug Bravadin “in patients with severe renal insufficiency (creatinine clearance less than 15 ml / min).
Specific information on excipients
drug Bravadin ® contains lactose, so the drug is contraindicated in patients with lactase deficiency, lactose intolerance, glucose-galactose syndrome malabsorption.
Effects on ability to road management and other technical devices
A study was conducted to assess the possible influence of testosterone enanthate dosage on driving ability in healthy volunteers, the results of which did not change the ability to drive. However, in the post-marketing period, cases have been reported worsening ability to drive vehicles as a result of the symptoms associated with visual impairment. Bravadin drug can cause a temporary change svetovospriyatiya (mainly in the form photopsias) that must be taken into account when driving or operating other mechanisms with a sharp change in light intensity, especially at night. steroids for building muscle steroid online uk where can i buy steroid cream