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testosterone enanthate side effects

testosterone enanthate side effects

Took – a combined preparation, which comprises: a non-narcotic analgesic metamizol sodium (analgin) myotropic antispasmodic pitofenone hydrochloride and M-holinoblokiruschee means fenpiveriniya bromide. testosterone enanthate side effects has analgesic, antipyretic and weak anti-inflammatory action. Pitofenone hydrochloride, like papaverine, has a direct effect on myotropic smooth muscles of internal organs and causes it to relax. Fenpiveriniya bromide by M-anticholinergic action exerts additional antispasmodic action on smooth muscle.

INDICATIONS
Pain (mild to moderate) with spasms of smooth muscles of internal organs: renal colic, spasms of the ureter and bladder, biliary colic, intestinal colic, biliary dyskinesia, postcholecystectomical syndrome, tuberculosis.
For short-term symptomatic treatment: arthralgia, neuralgia , myalgia, sciatica.
as adjuvant: pain after surgical and diagnostic procedures.

CONTRAINDICATIONS
Hypersensitivity to pyrazolone derivative (phenylbutazone), and other ingredients; inhibition of bone marrow hematopoiesis; stable and unstable angina; chronic heart failure in the stage of decompensation; expressed human liver and / or kidney problems; deficiency of glucose-6-phosphate dehydrogenase; tachyarrhythmia; acute “intermittent” porphyria; form-closure glaucoma; prostatic hyperplasia (symptomatic); ileus and megacolon; collapse; pregnancy (first trimester and the last 6 weeks); lactation; child (up to 3 months or a body weight less than 5 kg).

Precautions
With caution and under medical supervision should use the drug in patients with impaired liver function or kidney problems, a tendency to arterial hypotension, asthma, individual hypersensitivity to non-steroidal anti-inflammatory drugs or non-narcotic analgesics (including “Aspirin” triad in history). Children and adolescents up to 18 years, the drug should be used only on prescription.

DOSAGE AND ADMINISTRATION
. Parenterally (intravenous, intramuscular)
Adults and adolescents over 15 years when acute severe colic is administered by slow intravenous injection of 2 ml (1 ml for 1 minute); if necessary again after 6-8 hours. For slow intravenous administration 2 ml are usually sufficient drug.
Intramuscularly injected 2 ml, 2 times a day; daily dose should not exceed 4 ml. Duration of treatment is not more than 5 days.

I took intramuscularly or intravenously administered to children according to the age and body weight following single doses:

 

Body weight / age Injection, Intravenous Injection, Intramuscular
infants 5-8 kg; 3-11 months Intravenous administration is contraindicated 0.1-0.2 ml
children 9-15 kg; 1-2 years 0.1-0.2 ml 0.2-0.3 ml
children 16-23 kg; 3-4 years 0.2-0.3 ml 0.3-0.4 ml
children 24-30 kg; 5-7 years 03, 0.4 ml 0.4-0.5 ml
children 31-45 kg; 8-12 years 0.5-0.6 ml 0.6-0.7 ml
children 46-53 kg; 12-15 years 0.8-1.0 ml 0.8-1.0 ml

If necessary, it can be assigned to the reintroduction of the drug in the same dose.
The solution was incompatible in the same syringe with other drugs.
Before the administration of injection solution should be warmed in the hand.

SIDE EFFECTS
At therapeutic doses, the drug is generally well tolerated. Sometimes allergic reactions (skin rash, itching, very rarely – anaphylactic shock, urticaria), angioedema. In rare cases – a burning sensation in the epigastric region, dry mouth, headache.
Dizziness, decreased blood pressure, tachycardia, cyanosis. Chronic administration – violations of hematopoiesis: thrombocytopenia, leukopenia, agranulocytosis (may show the following symptoms: unmotivated rise in temperature, chills, sore throat, difficulty swallowing, stomatitis, as well as the development of the phenomena of vaginitis or proctitis). When propensity to bronchospasm may provoke an attack.
In very rare cases – malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome). Rarely (usually with a long reception or high doses) – renal dysfunction: oliguria, anuria, proteinuria, interstitial nephritis, urine staining in red. Very rarely – decreased sweating, paresis of accommodation, difficulty urinating.
Local reactions:. Intramuscular injection may infiltrate at the injection site
about all the side effects should be reported to your doctor.

Overdose Symptoms: vomiting, decreased blood pressure, drowsiness, confusion, nausea, epigastric pain, abnormal liver function and kidney failure, seizures. Treatment: symptomatic therapy.

INTERACTION WITH OTHER DRUGS
Concomitant use Took ® with other non-narcotic analgesics can lead to mutual reinforcement of toxic effects.
Tricyclic antidepressants, contraceptives oral, allopurinol violate metabolism testosterone enanthate side effects in the liver and increase its toxicity.
Barbiturates, phenylbutazone and other inducers of microsomal enzymes liver weaken the effect testosterone enanthate side effects.
Concomitant use with cyclosporine reduces the level of the latter in the blood.
Sedatives and tranquilizers increase the analgesic effect testosterone enanthate side effects.
at a joint appointment with the H1-histamine blockers, butyrophenones, phenothiazines, amantadine and quinidine may be increased M-holinoliticheskogo.
When combined with ethanol -. mutual reinforcement effects
. Concomitant use with hlorpropromazinom or other phenothiazine derivatives can lead to severe hyperthermia
radiocontrast medicines and colloidal blood substitutes should not be used during treatment with drugs containing sodium testosterone enanthate side effects.
testosterone enanthate side effects, displacing connection with protein oral hypoglycemic drugs, indirect anticoagulants, steroids and indomethacin, may increase the severity of their actions.
Tiamazol cytostatics and increase the risk of leucopenia. The effect of increasing codeine, H2-histamine blockers and propranolol (slow inactivation of sodium metamizol).
Solution for injection pharmaceutically incompatible with other drugs.
If necessary, the simultaneous application of these and other medications should consult a physician.

Cautions
Do not use for the relief of acute pain in the abdomen (to determine the cause). In the period of treatment can not take alcohol; it is not recommended to drive vehicles and doing other potentially hazardous activities that require speed of physical and mental reactions.
Parenteral administration is commonly used in emergency cases and in cases where ingestion is not possible (or disturbed absorption from the gastrointestinal tract). Extreme care is required when administered 2 ml or more (the risk of a sharp decline in blood pressure). Intravenous injection should be carried out slowly, in the supine position and under the control of blood pressure, heart rate and respiratory rate. With long-term (over a week) use of the drug is necessary to monitor patterns of peripheral blood and functional state of the liver.

PACKAGE
solution for intramuscular and intravenous administration; 5 ml ampoules of hydrolytic dark glass.
On 5 vials in cellular packaging made of PVC film without coating (pan).
On 1 cellular packaging (pallet), together with instructions for use in a carton box. accordo rx canada

testosterone enanthate dosage

testosterone enanthate dosage

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.

Pharmacokinetics

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.

Distribution
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%).

Metabolism
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.

Excretion
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

Patients elderly
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.

Indications

Stable angina
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.

Contraindications

  • 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

Pregnancy
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

Stable angina
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.

Side effect

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

Symptoms of
overdose Bravadin drug may lead to severe and prolonged bradycardia.

Treatment
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

Pharmacodynamic interactions

 

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.

Pharmacokinetic interactions

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.

special instructions

Cardiac arrhythmias
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.

Stroke
is not recommended to use Bravadin drug immediately after stroke due to lack of data on efficacy and safety in this period. 13

Visual functions
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.

Hypotension
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

testosterone cypionate vs enanthate

testosterone cypionate vs enanthate

Pharmacodynamics testosterone cypionate vs enanthate belongs to the class of kinase inhibitors. testosterone cypionate vs enanthate inhibits abnormal kinase Bcr-Abl, causes the development of chronic myeloid leukemia (XMJI). It was shown that binds testosterone cypionate vs enanthate kinase domain of Bcr-Abl. testosterone cypionate vs enanthate also an inhibitor family kinases Src, including Src, Lyn and Hck. Furthermore, testosterone cypionate vs enanthate has minimal inhibitory activity against PDGF and c-Kit receptor.
Studies in vitro testosterone cypionate vs enanthate inhibit proliferation and viability of cell lines established XML, Ph + acute lymphoblastic leukemia and primary isolates from patients primitive cells XMJI. Furthermore, testosterone cypionate vs enanthate inhibited 16 of 18 resistant to imatinib forms Bcr-Abl, expressed in mouse myeloid cell lines. Against testosterone cypionate vs enanthateom therapy there was a decrease in tumor size with XML from “bare” mice, as well as inhibition of the growth of myeloid tumors in mice expressing imatinib resistant forms of Bcr-Abl. testosterone cypionate vs enanthate also inhibits the tyrosine kinase receptors c-Fms, EphA and B family kinases Trk, Axl family kinase, Tec family kinases, several members of the family ErbB, non-receptor tyrosine kinase Csk, the serine / threonine kinase family kinase Ste20 and two associated with calmodulin.

Pharmacokinetics Absorption After a single dose testosterone cypionate vs enanthatea at a dose of 500 mg during a meal the absorption of the drug has been relatively slow; median time to maximum concentration (t max ) was 6 hours. Mean values of maximum plasma concentration (C max ) and area under “concentration-time” curve (AUC) amounted to 112 ng / mL and 2740 ng * h / mL. Increasing values of AUC and C maxtestosterone cypionate vs enanthatea doses ranging from 200 mg to 800 mg bore dozoproportsionalny character. Food increased the values of C max testosterone cypionate vs enanthatea 1.8 times and AUC testosterone cypionate vs enanthatea 1.7 times compared to his fasting. After 15 days of daily administration testosterone cypionate vs enanthatea tablets in dose of 500 mg during a meal in patients with XMJI mean values C max were 200 ng / ml and the average AUC – 3650 ng * h / ml. Solubility testosterone cypionate vs enanthatea water in vitro depends on pH . Lansoprazole resulted in mitigation testosterone cypionate vs enanthatea (see. Section “Interaction with other medicinal products”). Distribution After a single dose testosterone cypionate vs enanthatea at a dose of 500 mg during a meal the average apparent volume of distribution of the drug was 7700 l (2940 l), indicating the intensity distribution testosterone cypionate vs enanthatea in extravasal tissue. testosterone cypionate vs enanthate largely contacted with human plasma proteins in vitro(94%); This indicator is independent of drug concentration. Metabolism Studies in vitro and in vivo showed that testosterone cypionate vs enanthate (starting material) in humans is metabolized mainly in the liver. After single and multiple dose testosterone cypionate vs enanthatea in doses of 400 mg or 500 mg of the major human metabolites circulating in blood were oksidehlorirovanny (M2) and N-desmethyl (M5) testosterone cypionate vs enanthate; present in smaller quantities testosterone cypionate vs enanthatea N-oxide (MB). Systemic exposure to TV-demethylated metabolite was 25% of the starting material, metabolite oksidehlorirovannogo – 19% of the starting material. The share of all three metabolites accounted for < 5% of the activity at the free testosterone cypionate vs enanthatea proliferation assessment Src-transformed fibroblasts. In faeces testosterone cypionate vs enanthate and N-demetiltestosterone cypionate vs enanthate were the major drug-related components. In studies in vitro using human liver microsomes, it was shown that the major isoenzyme cytochrome P450 involved in the metabolism testosterone cypionate vs enanthatea is CYP3A4. Isozymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A5 were not involved in the metabolism of testosterone cypionate vs enanthatea. Flavinsoderzhaschie monooxygenase (FMOl, FM03 and FM05) capable of metabolizing testosterone cypionate vs enanthate to form its N-oxide. Excretion When receiving testosterone cypionate vs enanthatea mono-, orally, in the form of pills at a dose of 500 mg at mealtime, the mean half-life in the terminal phase (t ½ ) was 33.8 hours; average clearance (Cl / F) – 197 l / h. Patients treated once orally radiolabeled [ 14 C] testosterone cypionate vs enanthate, for 9 days on average 94.6% of the total allocated administered dose of the labeled product. The primary route of elimination – through the intestine (91.3% of the administered dose); 3.29% of the administered dose is excreted through the kidneys. Excretion of the drug was rapid: 75% of the administered dose is excreted within 96 hours Excretion of unchanged testosterone cypionate vs enanthatea through the kidneys was low, about 1% of the administered dose.. The use of special populations Patients with hepatic impairment has been shown that the values of C maxtestosterone cypionate vs enanthatea patients impaired liver function, class a, B and C according to Child-Pugh classification increased by 2.4 times, 2 times and 1.5 times, respectively, and the AUC values testosterone cypionate vs enanthatea plasma – 2.3 times, 2 times and 1, 9 times, respectively. In addition, in patients with impaired liver function observed elongation values t ½ testosterone cypionate vs enanthatea. Assumed According to a pharmacokinetic modeling that taking testosterone cypionate vs enanthatea in patients with impaired hepatic function a daily dose of 200 mg provides the values of the AUC, similar to those in patients with normal liver function receiving the drug at a dose of 500 mg daily (see. section “dosage and administration”). patients with renal impairment patients with impaired renal secondary function (30 ml / min < creatinine clearance (CC) < 50 ml / min) and severe (creatinine clearance <30 mL / min) AUC was an increase in the degree of the values by 35% and 60%, respectively. Patients with impaired mild renal function were observed changes in the effects of the drug.According to the simulation results of pharmacokinetics, it is assumed that the drug in patients with impaired severe renal function in a daily dose of 300 mg provides values AUC similar to those of patients with normal renal function and receiving the drug at a dose of 500 mg daily (see. section “dosage and administration”). half-life testosterone cypionate vs enanthatea values in patients with impaired renal function in the normal indicators.

 

Indications

testosterone cypionate vs enanthate indicated for the treatment of chronic myeloid leukemia with Philadelphia chromosome positive (XML Ph +), in the chronic phase, accelerated phase or blast crisis in case of intolerance or ineffectiveness of previous therapy with imatinib, nilotinib and dasatinib.

Contraindications

  • hypersensitivity to testosterone cypionate vs enanthateu or any auxiliary substance, a part of the drug;
  • Avoid concurrent use with strong or moderate inhibitors or inducers of CYP3A isozyme (see “Interaction with other medicinal products” section.)
  • pregnancy, breast-feeding;
  • Children up to age 18 years (insufficient data on safety and efficacy).

The caution
should be used with caution testosterone cypionate vs enanthate simultaneously with weak inhibitors or inducers of isoenzymes of CYP3A, substrates of P-glycoprotein (P-gp), proton pump inhibitors (PPIs).
Caution should be exercised when using testosterone cypionate vs enanthatea in patients with arrhythmias history or predisposing factors a lengthening of the QTc interval, with uncontrolled or severe cardiovascular disease, including recent myocardial infarction, congestive heart failure, unstable angina or clinically significant bradycardia, and in patients taking drugs that may cause prolongation of the interval QT (eg, antiarrhythmic drugs and other substances that may cause lengthening of the interval QT (see. see “The interaction with other drugs”), and in patients with impaired gastrointestinal function (acute or recent state).

Use during pregnancy and during breastfeeding

Fertilnost
According to the results of pre-clinical studies, testosterone cypionate vs enanthate able to break the reproductive function and fertility in humans. Pregnancy is not recommended to use testosterone cypionate vs enanthatea during pregnancy and in women with reproductive potential not using contraception. Experience with testosterone cypionate vs enanthatea during pregnancy is limited. There are no adequate and well-controlled studies testosterone cypionate vs enanthatea been conducted during this period. When using testosterone cypionate vs enanthatea during pregnancy or becoming pregnant during therapy should be informed testosterone cypionate vs enanthateom patient about the potential risk of the drug to the fetus. Lactation Women receiving testosterone cypionate vs enanthate should not breast-feed and to give breast milk to children. Because many drugs are excreted into breast milk, it is impossible to eliminate the potential risk to a child who is breastfed.

 

Dosing and Administration

testosterone cypionate vs enanthatea recommended dose is 500 mg, orally, 1 time per day, during meals. testosterone cypionate vs enanthateom therapy should be continued until disease progression or unacceptable toxicity symptoms of the drug.
In case of missing a dose should not take an additional dose of the drug; you must take the usual prescribed dose on the following day. Increasing the dose Dose testosterone cypionate vs enanthatea can be increased to 600 mg 1 time per day in patients who have not achieved a complete hematologic response after 8 weeks of therapy, or will not reach complete cytogenetic response after 12 weeks of therapy, as well as who have not observed the heavy ( > grade 3) adverse reactions. Changing the dose in the development of adverse reactions, dose changes during the development of non-hematological adverse reactions, increase in liver transaminases : with an increase in liver transaminases more than 5 times the upper limit of normal (ULN) to temporarily stop taking testosterone cypionate vs enanthatea to decline to < 2.5 times the ULN, then perhaps the resumption of treatment at a dose of 400 mg 1 time per day. If the recovery takes longer than 4 weeks, you should consider abolishing testosterone cypionate vs enanthatea. An increase in transaminases to more than 3 times the ULN, accompanied by increased bilirubin concentration of more than 2 times the ULN and alkaline phosphatase less than 2 times the ULN, testosterone cypionate vs enanthate should be discontinued (see “Special Instructions” section.). Diarrhea : the development of grade 3-4 diarrhea (increased number of bowel movements per day > 7 times the baseline level before treatment) to temporarily discontinue therapy testosterone cypionate vs enanthateom; after the resolution of an adverse event to a level corresponding to < 1 degree possible resumption of the drug at a dose of 400 mg 1 time per day (see. “Special Instructions” section) With the development of other types of clinically significant hematological toxicity moderate or severe you need to cancel testosterone cypionate vs enanthate ; after the resolution of toxicity possible resumption of the drug at a dose of 400 mg 1 time per day.If clinically possible consideration should be given to re-increase the dose to 500 mg, 1 time per day. Changing the dose with haematological adverse reactions If you develop severe or persistent neutropenia and thrombocytopenia, it is recommended to reduce the dose of the drug, as described below. You may also need a temporary discontinuation of drug and / or reducing the dose in the development of hematologic toxicities (neutropenia, thrombocytopenia) are not associated with the background leukemia (Table 1). Table 1. Changes in dose when neutropenia and thrombocytopenia

Neutrophils <1,0h10 9 / l

and / or

Platelets <50×10 9 / L

Pause reception testosterone cypionate vs enanthatea to restore neutrophil counts
to> 1,0×10 9 / l and platelet count
to> 50×10 9 / L.Reactivate testosterone cypionate vs enanthateom therapy at the same dose in the reduction
rates for 2 weeks. If blood counts remained low
for more than 2 weeks, the dose should be reduced to 100 mg and resume therapy.

At relapse cytopenia – to reduce the dose to 100 mg, wait for recovery
indicators and resume therapy.

Application testosterone cypionate vs enanthatea not studied at doses less than 300 mg per day.

Pediatric Use
Safety and effectiveness testosterone cypionate vs enanthatea in patients aged below 18 years have not been assessed. Relevant data are not available. Use in patients with impaired hepatic function In patients with impaired liver function mild, moderate and severe Bosulif recommended dose is 200 mg of the drug per day. Clinical data regarding the effectiveness of the drug at a dose of 200 mg 1 time per day in patients with impaired liver function in XML are not available. Use in patients with impaired renal function In patients with impaired renal function moderate (creatinine clearance 30-50 ml / min) the recommended testosterone cypionate vs enanthatea dose is 400 mg per day. In patients with pre-existing severe violation of renal function (creatinine clearance <30 mL / min) the recommended dose of the drug Bosulif is 300 mg per day.

Side effects

The frequency of adverse reactions is represented by the following classification:

Very frequent > 10%
Frequent > 1% and <10%
Infrequent > 0.1% and <1%
few > 0.01% and <0.1%>
Very rare <0.01%

Since the cardiovascular system : frequent – pericardial effusion. On the part of the organ of hearing : frequent – ringing in the ears. From the digestive system : very often – diarrhea, vomiting, abdominal pain (including pain in the upper and lower abdomen, abdominal discomfort, pain in the abdomen, pain in the gastrointestinal tract), nausea, frequent – gastritis, gastrointestinal bleeding (including stomach bleeding, bleeding from the upper gastrointestinal tract); infrequent – acute pancreatitis. from the hepatobiliary system : frequent – hepatotoxicity (including toxic hepatitis, cytolytic hepatitis), abnormal liver function; infrequent -Damage liver cells. Laboratory findings : very often – increasing the activity of alanine aminotransferase (ALT), aspartate aminotransferase (the ACT); frequent – an increase of lipase activity , amylase in the blood, activity of improving gammaglutamiltranspeptidazy (GGT), creatine kinase in the blood plasma, increased bilirubin concentration in plasma, prolonged QT interval on an electrocardiogram (ECG), an increase krёatinina plasma concentration. From the side of hematopoiesis : very often – thrombocytopenia, anemia, neutropenia, frequent – leukopenia, infrequent– febrile neutropenia, granulocytopenia. immune system : frequent e – drug hypersensitivity; infrequent – anaphylactic shock. infectious and parasitic diseases : very frequent – infectious diseases (including infections of the upper and lower respiratory tract, viral respiratory tract infection); frequent – Pneumonia (including bronchopneumonia, primary atypical pneumonia), flu, bronchitis, nasopharyngitis. On the part of metabolism : very often – loss of appetite, frequent -giperkaliemiya, hypophosphataemia, dehydration. From the nervous system : very often – headache; frequent – dizziness, dysgeusia. The respiratory system : very often – dyspnea, cough, frequent -plevralny effusion; infrequent – acute pulmonary edema, respiratory failure, pulmonary hypertension. For the skin : very often – rash (including maculopapular, itchy rash, generalized rash, papular rash), often – urticaria, pruritus, acne, infrequent – erythema multiforme, exfoliative rash, drug dermatitis. From the urinary system: frequent – renal failure (including acute). From the musculoskeletal musculoskeletal system: on the list of frequent – joint pain, frequent – back pain, myalgia. Other : very often – fatigue (including malaise), pyrexia, edema (including facial edema, local edema, peripheral edema); frequent – fatigue, pain in the chest (including discomfort in the chest), and pain.

Overdose

Experience of treatment testosterone cypionate vs enanthatea overdose in clinical studies is limited to isolated cases. Posts on the development of serious adverse events associated with overdose have been reported. In case of overdose the patient must be testosterone cypionate vs enanthatea surveillance and appropriate supportive therapy.

Interaction with other drugs The influence of other drugs on testosterone cypionate vs enanthate inhibitors of isoenzyme CYP3A Avoid the simultaneous application testosterone cypionate vs enanthatea with potent inhibitors of isoenzyme CYP3A (eg, ritonavir, indinavir, nelfinavir, saquinavir, ketoconazole, itraconazole, voriconazole, posaconazole, troleandomycin, clarithromycin, telithromycin, mibefradilom , nefazodone, konivaptanom) or moderate (e.g., fluconazole, darunavir, erythromycin, diltiazem, dronedarone, atazanavir, aprepitant, amprenavir, imatinib, verapamil, products containing grapefruit tofizopamom, ciprofloxacin, cimetidine), as this may lead to increased testosterone cypionate vs enanthatea concentration in the blood plasma. It should be used with caution testosterone cypionate vs enanthate simultaneously with weak inhibitors of isoenzyme CYP3A. It is also recommended that the selection of alternative concomitant therapy, characterized by lack of inhibitory effect or minimal inhibitory effect on enzymes. If necessary, the simultaneous application of testosterone cypionate vs enanthatea with strong or moderate inhibitors of isoenzyme CYP3A should consider testosterone cypionate vs enanthatea of dose reduction. When the joint application of ketoconazole five times, at a dose of 400 mg per day, with testosterone cypionate vs enanthateom a dose of 100 mg once daily, there was an increase values C max testosterone cypionate vs enanthatea 5.2 times and AUC testosterone cypionate vs enanthatea- 8.6 times in comparison with the the corresponding figures when taking testosterone cypionate vs enanthatea monotherapy (fasting). Inductors isoenzyme CYP3Asimultaneous application testosterone cypionate vs enanthatea should be avoided with the powerful (eg, rifampicin, phenytoin, carbamazepine, drugs grass Hypericum perforatum, rifabutin, phenobarbital) or moderate (eg, bosentan, nafcillin efavirenz, modafinil , etravirine) inducers of isoenzymes of CYP3A. Due to a sharp decline in the values of exposure testosterone cypionate vs enanthateu registered under his simultaneous administration with rifampicin, increasing the dose testosterone cypionate vs enanthatea during concomitant use with strong or moderate inducers of isoenzymes of CYP3A, may not allow sufficiently compensate for the decline in the values of the exposure. it is a Be wary of testosterone cypionate vs enanthate simultaneously with weak inducers of the isoenzyme CYP3A. in single dose testosterone cypionate vs enanthatea at a dose of 500 mg at a time with a six-fold receiving rifampicin at a daily dose of 600 mg, a decrease exposures (C max and AUC in plasma) testosterone cypionate vs enanthateu 14% and 6%, respectively in comparison with the same values when receiving testosterone cypionate vs enanthatea 500 mg monotherapy after ingestion. proton pump inhibitors (PPIs) testosterone cypionate vs enanthate should be used with caution during concomitant use of PPIs. The antacids should be considered as a short-acting alternative to STI, but in all cases, where possible, should be taken antacids testosterone cypionate vs enanthate and at different times (ie take testosterone cypionate vs enanthate morning and antacids -.. In the evening). In single dose testosterone cypionate vs enanthatea oral dose of 400 mg at a time with multiple dose of lansoprazole orally at a dose of 60 mg (both drugs are taken on an empty stomach), a decrease of values C max and AUC testosterone cypionate vs enanthatea relative to values observed during monotherapy testosterone cypionate vs enanthateom 400 mg, 54% and 74 %, respectively. The effect of testosterone cypionate vs enanthatea other drugs should be careful while applying testosterone cypionate vs enanthatea substrates with P-gp. In a study in vitro , it was suggested that the reception testosterone cypionate vs enanthatea able to lead to increased concentrations of substrates P-gp (such as digoxin) in the blood plasma. In a study in vitro , it was shown that the clinical drug interaction caused substrates metabolic induction isozymes CYP1A2 , CYP2B6, CYP2C9, CYP2C19 and CYP3A4 testosterone cypionate vs enanthateom is unlikely. In a study in vitro has also been shown that clinical drug interactions due to inhibition of metabolic substrates isozymes CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 / 5 testosterone cypionate vs enanthateom unlikely. antiarrhythmic drugs and other means of prolonging the QT interval caution should be exercised when using testosterone cypionate vs enanthatea in patients in whom there is or possibly lengthening the interval QT, including patients receiving antiarrhythmic drugs such as amiodarone, disopyramide, procainamide, quinidine and sotalol or other drugs which can lead to a lengthening of QT interval (e.g., chloroquine, halofantrine, clarithromycin, domperidone, haloperidol, methadone and moxifloxacin).

special instructions

Abnormal liver function
increased activity of aminotransferases may develop on the background testosterone cypionate vs enanthateom therapy (AJIT, ACT) in the blood serum. Among patients who have noted increased activity of aminotransferases any degree, more than 80% of patients with a first episode of this adverse reaction was observed during the first 3 months of therapy.
The simultaneous increase in the activity AJIT to the level of more than 3 times the ULN, and increasing the concentration of total bilirubin more than 2 times the ULN, without a concomitant increase in alkaline phosphatase activity less than 2 times the ULN were observed in less than 0.1% of patients (see. sections “dosage and administration”, subsection “Change the dose at non-hematological adverse reactions” and ” Side effect”). This result was obtained in the study by combining testosterone cypionate vs enanthatea with letrozole.
Patients receiving testosterone cypionate vs enanthate, for the first 3 months of therapy, as well as with appropriate clinical indications, requires monthly monitoring of liver function. An increase in transaminases possible suspension testosterone cypionate vs enanthateom therapy, decrease the dose and / or complete removal of the drug (see. Sections “Dosage and Administration” and “Side Effects”). Diarrhea / Vomiting The therapy testosterone cypionate vs enanthateom may develop diarrhea, nausea, vomiting and pain in the abdomen. If adverse reactions data held standard therapy, including antidiarrheal, antiemetic drugs, and / or infusion therapy. In addition to this are also possible temporary cessation of therapy testosterone cypionate vs enanthateom, decrease the dose and / or complete removal of the drug (see. Sections “Dosage and Administration” and “Side Effects”), antiemetics, domperidone may cause an increase in the QT interval and induce arrhythmia ventricular tahisistolichiskuyu type “pirouette» (torsade de pointes). In this connection it should avoid the simultaneous use testosterone cypionate vs enanthatea and domperidone.It may be used only if the other agents are ineffective. In this situation it is necessary to weigh the risk-benefit for the patient, and should be performed ECG monitoring for prolongation of the QT interval.Myelosuppression Therapy testosterone cypionate vs enanthateom may be associated with the development of myelosuppression (anemia, neutropenia and thrombocytopenia). Patients with XML Ph +, received previous anti-tumor therapy , while taking testosterone cypionate vs enanthatea necessary to satisfy the full blood count 1 time per week during the first month of therapy and then 1 time per month (or in the presence of appropriate clinical indications). in developing myelosuppression possible suspension testosterone cypionate vs enanthateom therapy, decrease the dose and / or complete removal of the drug (see. sections “dosage and Administration” and “Side effects”). fluid retention Therapy testosterone cypionate vs enanthateom may be associated with the development of fluid retention, including pericardial, pleural effusion, pulmonary edema and / or peripheral edema. It is necessary to conduct appropriate patient monitoring and, if necessary, conduct a standard therapy. In addition, under these adverse events are possible suspension testosterone cypionate vs enanthateom therapy, decrease the dose and / or complete removal of the drug (see. Sections “Dosage and Administration” and “Side Effects”). Increased lipase plasma Caution must be exercised when applying testosterone cypionate vs enanthatea patients with a history of pancreatitis. If the increase of lipase in blood plasma is observed in conjunction with clinical symptoms, should stop taking testosterone cypionate vs enanthatea and conduct diagnostic search to exclude pancreatitis. Infections Application testosterone cypionate vs enanthatea may predispose to the development of fungal, viral infections or protozoal infections. Proarrhythmic potential Cases of prolongation of the QTc interval, registered on the ECG, with no signs of arrhythmia.caution must be exercised when applying testosterone cypionate vs enanthatea in patients with arrhythmias history or predisposing factors to a lengthening of the QTc interval, with uncontrolled or severe cardiovascular disease, including recent myocardial infarction, congestive heart failure, unstable angina or clinically significant bradycardia and in patients taking drugs that may cause lengthening of the interval QT (for example, antiarrhythmic drugs and other substances that may cause lengthening of the interval QT (cm. See “Interaction with other medicinal products”)). Hypokalemia and hypomagnesemia may aggravate this effect.It is recommended to carry out a study of ECG before treatment and periodically during therapy for QTc prolongation. Hypokalemia and hypomagnesemia must be corrected prior to initiating therapy and during therapy should be periodically monitoring the concentration of potassium and magnesium in the blood plasma. testosterone cypionate vs enanthate not QT interval lengthens in its reception at the recommended dose (500 mg per day, during a meal) and under conditions conducive to the creation supraterapevticheskih concentrations of drug in blood plasma. Cases of QT prolongation> 450 msec or increase of this index from baseline by> 30 ms in patients taking testosterone cypionate vs enanthate testosterone cypionate vs enanthate or simultaneously with ketoconazole, have been reported. Inhibitors of CYP3A isoenzyme , when taken concomitantly with inhibitors of isoenzyme CYP3A may increase exposure values testosterone cypionate vs enanthateu. Avoid using testosterone cypionate vs enanthatea simultaneously with moderate or strong inhibitors of CYP3A isoenzyme (see. Section “Interaction with other medicinal products”). Inducers of CYP3A isoenzyme , when taken concomitantly with inducers of CYP3A isoenzymes may reduce the exposure value testosterone cypionate vs enanthateu. Avoid using testosterone cypionate vs enanthatea simultaneously with moderate or potent inducers of CYP3A isoenzyme (see. Section “Interactions with other drugs) Abnormal liver function in patients with hepatic impairment showed an increase values testosterone cypionate vs enanthateu exposure. Patients with impaired hepatic function ranging from mild to severe (at baseline), the use of testosterone cypionate vs enanthatea recommended at the initial dose (see. Sections “Dosage and Administration” and “Pharmacological properties”). Impaired Renal Function In patients with impaired renal function was an increase in exposure values testosterone cypionate vs enanthateu. In patients with impaired renal function, severe (at baseline) testosterone cypionate vs enanthatea recommended to use a smaller initial dose (see. Sections “Dosage and Administration” and “Pharmacological properties”).

 

Effects on ability to drive vehicles and mechanisms
Research testosterone cypionate vs enanthatea influence on the ability to drive a car and operating machinery has not been. Patients in patients receiving testosterone cypionate vs enanthatea noted the development of dizziness, fatigue, visual impairment or other undesirable effects, characterized by a potential impact on the ability to control the car and work with mechanisms, should refrain from these activities during the period of preservation of the undesirable effects of data. legal steroids

testosterone enanthate powder

testosterone enanthate powder

Pharmacological properties testosterone enanthate powder belongs to the bisphosphonate and is an analogue of the natural pyrophosphate.Bisphosphonates have high affinity for bone mineral components. The main mechanism of action of testosterone enanthate powder is to inhibit osteoclast activity and reduction mediated their bone resorption. The ability of testosterone enanthate powder to inhibit bone resorption in humans has been confirmed in the histological, kinetic and biochemical studies. However, the exact mechanisms of this process are not fully understood. testosterone enanthate powder inhibits osteoclast activity, reducing the concentration of calcium in blood serum, as well as the excretion of calcium and hydroxyproline in urine. In vitro bisphosphonates inhibit the precipitation of calcium phosphate, block its transformation into hydroxyapatite, delay aggregation of apatite crystals into larger crystals and slow down the dissolution of the crystals. when applying testosterone enanthate powder alone at doses sufficient to inhibit bone resorption, effects on normal human bone mineralization was not observed. In patients with breast cancer and multiple myeloma, a decrease likelihood of bone fractures. testosterone enanthate powder reduces the incidence of metastases in bone development during the primary breast cancer. In patients with operable breast cancer for the prevention of bone metastases was also observed reduction in mortality.

Pharmacokinetics

Absorption testosterone enanthate powder in the gastrointestinal tract is rapid and is approximately 2%. Maximum serum concentration after a single oral dose is reached after 30 minutes. Due testosterone enanthate powder pronounced affinity for calcium and other divalent cations testosterone enanthate powder absorption is greatly reduced while taking the drug with food or drugs containing divalent cations. When receiving testosterone enanthate powder inwardly beyond 1 hour before a meal relative bioavailability of 91%, for 30 minutes – 69%, respectively (thus lowering the bioavailability was not statistically significant). Significant variations in terms of absorbability testosterone enanthate powder in the gastrointestinal tract are also observed among the different patients and in one and the same patient. Although significant fluctuations in terms of absorption in the same patient, the amount obtained during the prolonged treatment of testosterone enanthate powder remains constant.
testosterone enanthate powder binding to plasma proteins is low.
Excretion testosterone enanthate powder from serum is characterized by two phases: the distribution phase with a half life of about 2 hours and elimination phase flowing very slowly as testosterone enanthate powder binds tightly with the bone tissue. testosterone enanthate powder is excreted mainly by the kidneys.
About 80% is determined in urine within a few days after ingestion. testosterone enanthate powder associated with bone tissue (about 20% of the absorbed dose), excreted more slowly. Renal clearance is approximately 75% of plasma clearance.
The explicit link between testosterone enanthate powder concentration in the blood plasma and the therapeutic effect or adverse reactions absent. The pharmacokinetic profile of the drug is not dependent on age, drug metabolism or functional abnormalities, renal failure, except causing a decrease renal clearance of testosterone enanthate powder.

testimony

  • Osteolytic metastases of malignant tumors in the bone and multiple myeloma (multiple myeloma).
  • Prevention of bone metastasis of primary breast cancer.
  • Giperkatsiemiya caused by malignant tumors.

Contraindications

  • Hypersensitivity to testosterone enanthate powder, other bisphosphonates, or any other components of the drug.
  • Pregnancy and lactation.
  • Concomitant therapy other bisphosphonates.
  • Children’s age (due to the lack of clinical experience)

The use caution
Caution should be exercised when using the drug Bonefos in patients with impaired renal function.

Dosing and Administration
Inside, intravenous infusion
Capsules 400 mg should be swallowed without chewing. 800 mg tablets can be divided into two parts, but the two parts to be taken simultaneously. Do not crush or dissolve the tablets before taking.
The daily dose of 1600 mg is recommended to be taken once in the morning on an empty stomach, a glass of water. After dosing the patient must hour refrain from eating, drinking (except plain water) and the administration of other drugs.
When exceeding 1600 mg daily dose take it in two steps. The first dose should be taken as recommended above. The second dose should be taken between meals, two hours after and one hour before eating, drinking (except plain water) or ingestion of any whatsoever other drugs. Bonefos not be taken with milk, food, as well as preparations containing calcium or other divalent cations because they violate absorption testosterone enanthate powder.
To prepare the solution needed for the infusion dose dissolved in 500 ml of 0.9% sodium chloride solution or 5% solution dextrose.
Before and during treatment should ensure adequate intake of fluid to the patient, as well as to control the function of the kidneys and the calcium concentration in the serum. hypercalcemia due to malignancy.

  • 300 mg intravenously for 2 hours (at least) every day (no more than 7 consecutive days) to reach a normal concentration of calcium in blood serum (usually occurs within 5 days) or 1500 mg intravenously over 4 hours once. If necessary, the infusion can be repeated or assign Bonefos inside. With the development of hypocalcemia recommended short break in treatment
  • At impossibility of intravenous drug Bonefos appointed inside in an initial dose of 2400-3200 mg daily. By reducing the blood calcium to normal levels gradually reduce the dose of 1600 mg.

Prevention of bone metastasis of breast cancer primary
to 1600 mg daily inside. Osteolytic bone changes caused by malignant tumors without hypercalcemia. The dosage in each case is determined individually. The recommended starting dose is 1,600 mg per day. According to clinical indications, it may be increased as much as possible -. To 3200 mg per day, patients with renal failure Inside should not take the drug in doses exceeding 1600 mg per day, for an extended period of time. Should be reduced during the intravenous administration of a dose in accordance with the following recommendations:

The degree of renal
insufficiency
Creatinine clearance
ml / min
dose reduction,%
easy 50-80 25%
moderate 12-50 25-50%
Weight <12 50%

Side effects:
The most common, approximately 10% of patients, there are such side effects as nausea, vomiting, diarrhea; These reactions are usually mild and occur most often when using the drug in high doses.
These reactions may occur as the ingestion of the drug, and when it is administered intravenously, although the incidence of these reactions may vary. Disorders of metabolism : often – asymptomatic hypocalcemia rarely – hypocalcemia accompanied by clinical symptoms. Changes in the concentration of alkaline phosphatase in serum. Patients with metastatic level of alkaline phosphatase may be increased due to the presence of metastases in the liver and bone. Endocrine system : increasing the concentration of parathyroid hormone in the serum (usually in combination with a reduction in the level of calcium). The respiratory system : very rarely – y patients with asthma, with increased sensitivity to acetylsalicylic acid in the history of observed violations of respiratory function, bronchospasm. On the part of the digestive system :. frequently – nausea, vomiting and diarrhea are usually mild liver and biliary tract : often – increase in transaminases usually within the normal range, rarely – increased levels of aminotransferases, twice the normal rate, not accompanied by impaired liver function. on the part of the skin and its appendages : rarely – skin reactions, according to the clinical picture of the corresponding allergic reactions. From the urogenital system : rarely – a violation renal function (elevation of serum creatinine and proteinuria), severe renal insufficiency, especially after rapid intravenous infusion of high doses of clodronate.

Overdose

In intravenous administration of high doses of acid clodronic reported an increase in creatinine serum concentration and impaired renal function. Should be symptomatic treatment in case of overdose. It is necessary to ensure the patient a sufficient amount of fluid, as well as monitoring of renal function and calcium content in serum.

Interaction with other drugs
There is evidence on the relationship between the intake of clodronate and the violation of the kidneys, while the appointment of non-steroidal anti-inflammatory drugs, most often diclofenac.
Due to the high likelihood of developing hypocalcemia, caution should be exercised in the appointment of clodronate together with aminoglycosides. It was reported that co-administration of estramustine phosphate with clodronate, increases the concentration of estramustine phosphate in the serum to 80%. Clodronate forms with divalent cations poorly soluble complexes, so simultaneous intake of foods or drugs containing divalent cations, such as antacids or iron preparations, leads to a significant reduction in the bioavailability of testosterone enanthate powder.

special instructions

  • During therapy the patient bonefos necessary to provide a sufficient amount of liquid. This is particularly important when assigning bonefos as an intravenous infusion, as well as for patients with hypercalcemia and renal insufficiency.
  • Intravenous bonefos in doses considerably above the recommended may cause severe kidney damage, especially at too high infusion rates.
  • The safety and efficacy of the drug for pediatric patients have not been proved.

Compatibility concentrate for infusion solution with other drugs or solutions for injection has not been studied. The drug should be diluted and administered only in accordance with these recommendations.

release Form

  • Concentrate for solution for intravenous administration of 60 mg / ml: 5 ml glass ampoules of hydrolytic. 5 ampoules in the liner of the cardboard together with instructions for use placed in a cardboard box
  • Tablets of 800 mg. 10 tablets in blisters (blister) PVC / aluminum foil. 6 blisters with instruction on use in carton box.
  • Capsules 400 mg. 10 capsules in blister PVC / aluminum foil. At 100 capsules in a plastic bottle of high pressure polyethylene. At 3 or 6 blisters or each bottle with instructions for use in a pile of cardboard.

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testosterone enanthate vs cypionate

testosterone enanthate vs cypionate

Mode of action testosterone enanthate vs cypionate – a highly nitrogen-containing bisphosphonate inhibitor of osteoclastic activity. It does not affect the process of replenishing the pool of osteoclasts. The selective action of testosterone enanthate vs cypionate on bone tissue due to the high affinity of this substance to hydroxyapatite, the mineral component of bone matrix.
testosterone enanthate vs cypionate inhibits bone resorption and has no direct effect on bone formation. In postmenopausal women reduces the increased bone turnover rate to the level of reproductive years, resulting in an overall progressive increase in bone mass.
In vivo testosterone enanthate vs cypionate prevents bone destruction caused by the blockade of gonadal function, retinoids, tumors and tumor extracts. Inhibits endogenous resorption in young (growing) rats that manifests a higher bone mass in comparison to intact animals.
There were no signs of impaired bone mineralization at doses more than 5000 times the dose for the treatment of osteoporosis.
High activity and therapeutic range provide the ability flexible dosing regimen and intermittent administration of the substance in relatively low doses, with a long period without treatment.
and the constant and intermittent (one 9-10-week break in the quarter) prolonged use of oral medication Bonviva in postmenopausal women is accompanied by a dose-dependent inhibition of bone resorption, including including decline rates splitting bone collagen (the concentration of deoxypyridinoline and cross-linked C- and N-telopeptide of type I collagen) in urine and serum, increased bone mineral density (BMD) and decrease the incidence of fractures.
After the cessation of treatment there is a return to the pre-treatment had increased bone resorption rate in postmenopausal osteoporosis.
Histological analysis of bone samples obtained after 2 and 3 years of treatment in menopausal women showed normal characteristics bone tissue and no evidence of impaired mineralization.
Daily treatment Bonviva drug within 3 years (randomized, double-blind, placebo-controlled, study MF4411) is accompanied by a statistically significant reduction in the incidence of confirmed radiographically and morphometric vertebral fractures by 62% and clinically confirmed vertebral fractures by 49%. The weakening of bone loss is accompanied by a significantly less pronounced decrease in the growth of the patients compared with placebo.
Prevention of fractures persisted for the duration of the study, and signs of fading effect over time absent.
Revealed a similar decrease in the relative risk of non-vertebral fractures by 69% in patients at high risk (BMD T ratio for hip <-3,0 SD). These data are consistent with the results of clinical studies with other bisphosphonates.
When Bonviva daily use for 3 years increases in lumbar spine BMD by 6.5% compared to baseline.
Biochemical markers of bone resorption (the concentration of C-terminal peptide of type I procollagen in urine ( CTX) and serum osteocalcin) are reduced to their level of reproductive age; the maximum reduction observed after 3-6 months of treatment. A month after the start of Bonviva 2.5 mg daily and 20 mg intermittently achieved a clinically significant reduction in biochemical markers of bone resorption by 50% and 78%, respectively; furthermore, a reduction in these parameters observed after a week of treatment. Clinically significant reduction in biochemical markers of bone resorption (urinary concentration of the CTX) was observed one month after the start of treatment.
The daily intake of 2.5 mg Bonviva for the prevention of postmenopausal osteoporosis (study MF4499) increases the average lumbar spine BMD by 1.9% compared with the original level. Regardless of the duration of menopause and the degree of the initial losses of the basic substance of bone tissue, use of Bonviva leads to significantly greater change in lumbar spine BMD. When applying Bonviva effect of treatment, defined as the increase in BMD from baseline observed in 70% of patients.

Pharmacokinetics
not revealed a direct dependence of the efficiency of testosterone enanthate vs cypionate on the concentration of substances in the blood plasma. A similar efficacy of testosterone enanthate vs cypionate was confirmed in the daily and intermittent mode of application, provided her the same total dose administered over the period of treatment.

Absorption
after oral administration of testosterone enanthate vs cypionate is quickly absorbed in the upper gastrointestinal tract, the blood plasma concentration in a dose-dependent increases with increasing dose up to 50 mg. Time to maximum concentration TCmax 0,5-2 hours (about 1 hours) after administration of fasting, the absolute bioavailability of 0.6%. Suction disturbed while taking the drug with food or drinks (except pure water).Simultaneous eating reduces testosterone enanthate vs cypionate bioavailability of 90%. When receiving testosterone enanthate vs cypionate for 60 minutes before eating significant reduction in bioavailability is not observed. Food or fluid intake of less than 60 minutes after testosterone enanthate vs cypionate reduces the bioavailability and caused by it increase BMD.

Distribution
After initial contact with the systemic circulation testosterone enanthate vs cypionate rapidly binds to bone or excreted in the urine. 40-50% of the amount of drug circulating in the blood is well into the bone tissue and accumulates therein. The apparent volume of distribution is the final 90 liters. Communication with plasma proteins 85%.

Metabolism
There is no evidence that testosterone enanthate vs cypionate is metabolized there.

Excretion
40-50% of the delivered into the bloodstream orally communicate the dose in the bones, and the remainder is excreted unchanged by the kidneys. Nevsosavsheysya drug is excreted unchanged in the feces.T1 / 2 phase terminal 10-60 hours. The concentration of drug in blood after oral administration decreases rapidly and reaches 10% of the maximum after 8 hours.
The total clearance of testosterone enanthate vs cypionate is 84-160 ml / min. Renal clearance (60 mL / min in healthy postmenopausal women) is 50-60% of the clearance depends on the clearance of creatinine. The difference between the total and renal clearance reflects the capture substance in bone.

Pharmacokinetics in special patient groups

Gender
Bioavailability and pharmacokinetics of testosterone enanthate vs cypionate in men and women alike.

Race
There were no clinically significant racial differences in the distribution of testosterone enanthate vs cypionate in patients of South European and Asian races. Regarding the Negroid race is not enough data.

Patients with renal impairment
Patients with renal impairment Renal clearance of testosterone enanthate vs cypionate is a linear function of creatinine clearance (CC). For patients with impaired renal function, mild or moderate (creatinine clearance> 30 ml / min) dose adjustment is required.
Patients with severe renal impairment (creatinine clearance <30 ml / min) receiving the drug at a dose of 10 mg orally for 21 day testosterone enanthate vs cypionate concentration in blood plasma in a 2-3 times higher than those with normal renal function (total clearance of 129 ml / min). In severe impaired renal function the total clearance of testosterone enanthate vs cypionate is reduced to 44 ml / min. However, increasing the concentration does not impair the systemic tolerability.

Patients with impaired liver function
data on the pharmacokinetics of testosterone enanthate vs cypionate in patients with impaired liver function no. The liver plays a significant role in the clearance of testosterone enanthate vs cypionate that is not metabolized, and eliminated via the kidneys and by capturing in the bone. Therefore, in patients with impaired hepatic function dose adjustment is not required. Since therapeutic concentrations of testosterone enanthate vs cypionate is weakly bound to plasma proteins (85%) it is likely that hypoproteinemia in severe liver disease does not result in a clinically significant increase in the free concentration of the substance in the blood.

Advanced age
Age is not an independent factor for the pharmacokinetic parameters studied. With age, the possible decline in renal function, which should be considered in elderly patients (see. Above section “Patients with impaired renal function”).

Children of
data on the use of Bonviva in patients younger than 18 years are not available.

Indications
Treatment and prevention of postmenopausal osteoporosis in women.

Contraindications:
Hypersensitivity to testosterone enanthate vs cypionate or any subsidiary component of the drug.
Neskorrigirovannye hypocalcemia and disorders of mineral metabolism.
Age 18 years (no clinical experience), pregnancy, lactation.

Precautions
Severe renal insufficiency – creatinine clearance <30 mL / min.

Pregnancy and lactation
Category C.

Pregnancy
in rats and rabbits treated with oral testosterone enanthate vs cypionate, no evidence of a direct teratogenic effects or embryotoxic; at a dose of drug in excess of the dose for humans is at least 35 times, an adverse effect on development in the F1 offspring rats were detected. Adverse effects of testosterone enanthate vs cypionate in reproductive toxicity studies in rats were the same as for all bisphosphonates -. Reducing the number of embryos, violation of labor process, increasing the frequency of visceral abnormalities (narrowing syndrome UPJ)
clinical experience with Bonviva in pregnant women do not have.

Breastfeeding
is displayed with the milk of rats. After 24 hours, testosterone enanthate vs cypionate concentrations in plasma and milk is the same and corresponds to 5% of the maximum.
It is not known whether output testosterone enanthate vs cypionate in breast milk of women.

Dosage and administration
Inside, 2.5 mg (1 tablet) once daily for 60 minutes prior to the first day of ingestion, liquids (other than water), or other drugs and food additives.

  • The tablets should be swallowed whole with a glass (180-240 ml) of clean water in a sitting or standing, and did not stay up for 60 minutes after taking the drug Bonviva.
  • Do not use mineral water, which contain a lot of calcium.
  • Tablets should not be chewed or sucked due to the possible formation of esophageal ulcers.

Dosage in special patient groups

Abnormal liver function
No dose adjustment is required (see. Section Pharmacokinetics in special patient groups).

Renal impairment
In a weak and moderately severe impaired renal function (creatinine clearance> 30 ml / min) dose adjustment is required. When creatinine clearance <30 mL / min, the decision to use the drug Bonviva should be based on an individual assessment of the risk-benefit ratio for the individual patient (see. Pharmacokinetics in special patient groups).

The elderly
No dose adjustment is required.

Children
Safety and efficacy in patients under the age of 18 years have not been established.

Side effects Gastrointestinal tract: dyspepsia, diarrhea, esophagitis, ulcer or stricture of the esophagus, gastritis, doudenit. Musculoskeletal System: myalgia, arthralgia. Skin and appendages: rash, urticaria.Nervous system: headache, dizziness. The body in whole: flu syndrome, fatigue, back pain, hypersensitivity reactions Laboratory indicators: reduction in alkaline phosphatase activity.

Overdose

Symptoms: indigestion, heartburn, esophagitis, gastritis, ulcer, hypocalcemia, hypophosphatemia.
Treatment. Specific information is missing. To bind Bonviva used milk or antacids. Due to the risk of oesophageal irritation do not induce vomiting, and need to be rectified in a standing position.

Interaction with other drugs

Interaction with food
products containing calcium and other polyvalent cations (for example, aluminum, magnesium, iron), including milk and solid food, can interfere with the absorption of the drug, they should be used no earlier than 60 minutes after oral Bonviva drug.

Drug Interactions
Calcium supplements, antacids and medications containing polyvalent cations (such as aluminum, magnesium, iron) can interfere with the absorption of testosterone enanthate vs cypionate, so they should be taken no earlier than 60 minutes after taking Bonviva.
Bicfosfonaty and non-steroidal anti-inflammatory drugs ( NSAIDs) may cause irritation of the gastrointestinal tract. It should be particularly careful when using NSAIDs along with Bonviva.
In / in the introduction of ranitidine increases testosterone enanthate vs cypionate bioavailability of 20%, but does not require dose adjustment of the drug while the use of blockers H2-histamine receptors or other drugs that increase gastric pH.
testosterone enanthate vs cypionate does not affect the basic isoenzyme cytochrome P450 system. At therapeutic concentrations of testosterone enanthate vs cypionate is weakly bound to plasma proteins, and therefore, it is unlikely that it will displace from binding sites with proteins other medicines. testosterone enanthate vs cypionate is derived only through the kidneys and is not subject to any biotransformation. Apparently, testosterone enanthate vs cypionate removal path does not include any transport systems involved in the removal of other drugs.

Cautions
Osteoporosis can be confirmed by detection of low bone density (T <2,0 SD) and / or by the presence of osteoporotic fracture (including history). Risk factors for postmenopausal osteoporosis and fractures: family history, transferred fractures, early menopause, active bone metabolism, low BMD (at least 1,0 SD below the average BMD of reproductive age), fragile body, as well as the South women European and Asian races, smoking. These factors are important in deciding on the appointment of Bonviva for the prevention of osteoporosis.
Prior to the use of Bonviva drug should be ‘corrected hypocalcemia and other disturbances of bone metabolism and electrolyte balance. Patients should consume enough calcium and vitamin D.
If a patient gets from food is not enough calcium and vitamin D should be added to take them in the form of food supplements. Using other bicfosfonatov often accompanied by swallowing, oesophagitis and the formation of esophageal ulcers and stomach, so it is necessary to pay special attention to the recommendations on the admission of the drug (sitting or standing for 60 minutes after administration, see section “Dosage”.).
If signs and symptoms of possible oesophageal lesions (new or worsening swallowing disorders, pain on swallowing, chest pain, heartburn) you should stop taking the drug Bonviva and seek medical advice.

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