primobolan side effects

The frequency is unknown – according to available data to set the frequency of occurrence was not possible.Violations of the blood and lymphatic system rare: primobolan side effects anemia (including haemolytic), thrombocytopenia, eosinophilia. Disorders of the nervous system Rare: dizziness, headache, paresthesia, peripheral neuropathy ; very rare: sleep disorders (insomnia, “nightmarish” dream), depression, loss or memory loss, blurred vision. violations of the respiratory system, organs, thoracic and mediastinal disorderscommon: upper respiratory tract infection, the frequency is unknown: interstitial lung disease ( . especially with prolonged use), bronchitis, sinusitis Violations of the heart often: atrial fibrillation.

Disorders of the digestive system often: gastritis rare: constipation, abdominal pain, nausea, vomiting, diarrhea, flatulence, pancreatitis. Violations of the liver and biliary tract rare: hepatitis, jaundice, very rarely fatal and non-fatal hepatic failure.

Disorders of the skin and subcutaneous tissue disorders rare: rash, itching skin, alopecia, photosensitivity. Violations of the musculoskeletal and connective tissue disorders rare:myopathy * (including myositis), rhabdomyolysis (with or without acute renal failure), myalgia, muscle cramps, polymyositis, very rare: arthralgia, arthritis, the frequency is unknown: . tendinopathy, possibly with tendon rupture * in clinical trials of myopathy was observed more frequently . in patients treated with simvastatin 80 mg / day, as compared to patients applying the dose of 20 mg / day (1.0% vs. 0.02%, respectively) Violations of the kidneys and urinary frequency is unknown: acute renal failure (due to rhabdomyolysis), urinary tract infection. violations of the genital and breast frequency is not known: erectile dysfunction, gynaecomastia.

General disorders and injection site rarely . weakness Allergic primobolan side effects reactions are rare: angioedema, polymyalgia rheumatica, vasculitis, an increase in the erythrocyte sedimentation rate (ESR), a positive antinuclear antibody titers, facial flushing, lupus syndrome, dyspnea, malaise; Frequency not known: immune-mediated necrotizing myopathy, toxic epidermal necrolysis (Lyell’s syndrome), erythema multiforme, including Stevens-Johnson syndrome. Laboratory and instrumental data rare: increased activity of “liver” transaminases, alkaline phosphatase and creatine kinase in the blood plasma; Frequency not known: an increased concentration of glycated hemoglobin hyperglycemia. The following additional adverse events have been reported with the use of other statins: • Memory loss • cognitive impairment • diabetes. The incidence of diabetes mellitus is dependent on the presence of risk factors (fasting blood glucose concentration of more than 5.6 mmol / L, body mass index greater than 30 kg / m², an increased concentration of thyroglobulin (TG) in blood plasma, a history of hypertension). Children and adolescents (10-17) according to a study duration of 1 year in children and adolescents (boys Tanner stage II and above and girls, at least one year after the first menstrual period), aged 10-17 years, with heterozygous familial hypercholesterolemia (n = 175 ), in the group employing simvastatin, it was similar to the profile of the group, placebo applying safety and tolerability profile. The most frequently reported side effects are upper respiratory tract infection, headache, abdominal pain, nausea. The long-term effects on physical, intellectual and sexual development is not known. At this time (a year after treatment) there is insufficient safety data.

To date, specific symptoms of overdose (maximum dose taken 3.6 g) were detected. Treatment: symptomatic therapy. A primobolan side effects specific antidote is not known.

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oral primobolan

Precautions should use the oral primobolan drug in patients with severe renal insufficiency (creatinine clearance less than 30 mL / min); with hereditary muscular diseases; with hypertension; with expressed metabolic and endocrine disorders (including untreated hypothyroidism); high risk of developing diabetes; alcohol abuse; elderly patients (65 years); while the use of nicotinic acid in the lipid-lowering doses (more than 1 g / day), amiodarone, amlodipine, verapamil, diltiazem, colchicine, fusidic acid, ranolazine, dronedarone (increased risk of myopathy and rhabdomyolysis), grapefruit juice.

Application of pregnancy and during breastfeeding

Due to the fact that inhibitors of oral primobolan reductase inhibitors inhibit the synthesis of cholesterol and cholesterol and other products of its synthesis are essential in fetal development including synthesis of steroids and cell membranes, simvastatin may adversely affect the fetus when administered in pregnant women (women of childbearing age should avoid conception). If in the course of treatment became pregnant, the drug should be withdrawn and the woman warned of the possible danger to the fetus.
Cancel lipid-lowering drugs during pregnancy has no significant impact on the long-term treatment of primary hypercholesterolemia.
No data on the allocation of simvastatin in breast milk, therefore the application of the drug during lactation should stop breastfeeding.

Dosing and Administration

The recommended daily doses ranging from 5 mg to 80 mg.
Titration dose It should be carried out at intervals of 4 weeks.
The dose of 80 mg may be used only in patients with severe hypercholesterolemia and high cardiovascular risk. patients with homozygous familial hypercholesterolemia: the recommended daily dose is 40 mg per day, once in the evening. The dose of 80 mg per day is recommended only if the expected benefit of therapy outweighs the potential risk. In such patients, is used in combination with other lipid-lowering treatments (e.g., plasmapheresis) or without such treatment, if it is available. Patients with coronary artery disease or high risk of cardiovascular complicationsstandard initial dose rhigh risk patients with hyperlipidemia or without (if diabetes, stroke or other cerebrovascular diseases in history, peripheral vascular diseases), as well as for patients with coronary heart disease is 40 mg per day. The patients with hyperlipidemia, without the above risk factors: standard starting dose is 20 mg once a day in the evening. patients  concentration in blood serum, a 45% excess of normal values, the initial dose may be 40 mg / day. Patients with mild to moderate hypercholesterolemia therapy with  can begin with an initial dose of 10 mg / day. Concomitant therapy: preparation oral primobolancan be used as monotherapy, or in combination with bile acid sequestrants. For patients taking concomitant fibrates addition fenofibrate , the maximum daily dose is 10 mg of simvastatin. Concomitant use of gemfibrozil is contraindicated. In patients taking concomitant verapamil, diltiazem and dronedarone, the maximum daily dose is 10 mg / day.

For patients, while taking amiodarone, amlodipine, ranolazine, the maximum daily dose of simvastatin 20 mg. Patients with chronic renal failure: in patients with impaired renal and mild to moderate severity function (creatinine clearance 30 mL / min) dose adjustment is required. Patients with impaired-severe renal function (creatinine clearance less than 30 mL / min) or receiving simultaneously fibrates or nicotinic acid (in a dose of 1 g / day), starting dose is 5 mg and the maximum permitted daily dose – 10 mg. In elderly patients (over 65 years) dosage adjustment is necessary. Use in children and adolescents 10 – 17 years with heterozygous familial hypercholesterolemia: the recommended starting dose is 10 mg per day in the evening. The recommended dosing regimen is 10 – 40 mg per day, the maximum recommended dose is 40 mg per day. Selection of oral primobolan doses held individually in accordance with the objectives of the treatment. In the case of the current dose skip the drug should be taken as soon as possible. If it is time for your next dose, do not double the dose.

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primobolan

It is a decrease in plasma concentrations of triglycerides , low density lipoproteins , very low density lipoproteins  and total cholesterol . (with heterozygous familial and non-familial hypercholesterolemia, in mixed hyperlipidemia where the increased concentration of cholesterol in blood plasma is a risk factor)
Increasing the concentration of high density lipoprotein and reduces the ratio  cholesterol and total primobolan ratio in the blood plasma.
Starting manifestations effect – 2 weeks from the start of application, the maximum therapeutic effect is achieved after 4 – 6 weeks of therapy. Action is maintained with continued treatment, at the termination of treatment cholesterol concentration in blood plasma is gradually returning to its original value.  Simvastatin is well absorbed from the gastrointestinal tract. Food does not affect the absorption of simvastatin. After oral administration the maximum concentration is reached about 1-2 hours in the blood plasma and reduced by 90% after 12 h. Binding to plasma proteins is greater than 95%.Not accumulates. Extensively metabolized in the liver (hydrolyzed to form primary active derivative – beta-hydroxyacids and four other active metabolites). Excreted mainly as metabolites intestine (60%) for 4 days, 13% of kidney in an inactive form.

Patients with renal impairment Because primobolan simvastatin is excreted by kidneys in small numbers, there is no need for dose adjustment in patients with impaired renal and mild to moderate severity function. However, in patients with severe renal impairment (creatinine clearance of less than 30 ml / min), simvastatin should be used with caution. The initial dose of the drug in such cases should be 5 mg per day. It should be used with caution in doses above 10 mg / day, and if any doses deemed necessary, patients should be under close medical supervision. Patients of advanced age (over 65) The need for dose adjustment is not available.

 

Indications

Hypercholesterolemia (for patients older than 18 years):
• as an adjunct to diet when diet alone, and other non-pharmacological treatments is not enough to:
– reduce elevated concentrations of total cholesterol,  cholesterol, triglycerides, apolipoprotein B (apo B);
– increasing  cholesterol in patients with primary hypercholesterolaemia, including heterozygous familial hypercholesterolaemia (hyperlipidemia IIa type classification Fredrickson) or mixed hypercholesterolaemia (hyperlipidemia, type IIb Fredrickson classification);
• hypertriglyceridemia (hyperlipidemia type IV classification Frederickson);
• an adjunct to diet and other methods of treating patients with homozygous familial hypercholesterolemia to reduce elevated concentrations of total cholesterol;
• the primary disbetalipoproteinemiya (hyperlipidemia type III classification Fredrickson). patients with coronary heart disease  or high risk of cardiovascular complications (for patients older than 18 years) patients with a high risk of cardiovascular complications (if hyperlipidemia and without it), for example, patients with ischemic heart disease or predisposition to coronary artery disease, diabetes, stroke or other cerebrovascular disease history, patients with peripheral vascular disease is shown for the purpose of: • reducing the risk of total mortality by reducing as a result of coronary heart disease mortality; • reduce the risk of serious cardiovascular and coronary events:    – non-fatal myocardial infarction    – coronary death;    – stroke ;    – revascularization procedures. • reducing the risk of the need for operations to restore coronary blood flow; • reducing the risk of the need for recovery operations in peripheral blood flow and other non-coronary revascularization; • reduction in the risk of hospitalization due to primobolan angina. Use in children and adolescents 10 – 17 age with heterozygous familial hypercholesterolemia: t simultaneously with diet shown to reduce elevated concentrations of total cholesterol,  cholesterol, triglycerides, apo B in boys 10 – 17 years and girls 10 – 17 years at least 1 year after menarche, with heterozygous familial hypercholesterolemia.

 

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primobolan cycle

It is recommended to gradually reduce the dose before stopping treatment is not recommended strongly to cancel treatment.
In case of insufficient efficacy or exceeding the maximum recommended necessary to reconsider the tactics of treatment. Sudden and progressive deterioration in control of the symptoms of asthma or primobolan cycle is potentially life-threatening condition and requires immediate medical intervention. In this situation, you should consider increasing the dose of glucocorticoids. The appointment course of oral corticosteroids, or antibiotic treatment in the event of the accession of infection

It should be noted, the patient’s attention to the need for regular maintenance dose of Symbicort reception turbuhaler in accordance with the chosen therapy, even in the absence of symptoms. Inhalation Symbicort turbuhaler cupping should be performed only when symptoms occur, but are not shown for regular prophylactic use, ie before exercise. In such cases, shows the use of a separate short-acting bronchodilator.
If asthma symptoms are manageable, you can gradually reduce  turbuhaler, it is important to continuously monitor the patient’s condition. It is necessary to assign the lowest effective dose of  turbuhaler (see; “Dosage and Administration” section).
Treatment  should not be initiated during an exacerbation or significant worsening of asthma.
During  turbuhaler can celebrate exacerbation and development of serious adverse events associated with asthma. Patients should continue treatment but to seek medical care in the absence of control over the symptoms of asthma, or in the case of deterioration after initiation of therapy.
As with any other inhalation therapy, paradoxical bronchospasm may occur with an immediate intensification of wheezing after taking the dose. In this connection, primobolan cycle discontinue therapy treatment policy review and, if necessary, to assign an alternative therapy.
Systemic action may occur at any reception inhaled glucocorticosteroids, especially when high doses of drugs over a long period of time. The manifestation of systemic effects are less likely during inhalation therapy than with oral corticosteroids. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma.
It is recommended to regularly monitor the growth of children receiving long-term glucocorticoid therapy in inhalable form. In the case of established growth retardation, therapy should be reviewed with the aim of reducing the dose of inhaled glucocorticosteroid. It should be carefully weighed against the benefits of glucocorticosteroid therapy to a possible risk of growth retardation. When selecting therapy is recommended to apply to the children’s lung specialist.
Based on the limited research data on the chronic administration of corticosteroids, one can assume that the majority of children and adolescents receiving therapy with inhaled budesonide ultimately achieve normal adult growth rates. However reported slight momentary delay in growth mainly during the first year of treatment. Because of the potential actions of inhaled corticosteroids on bone mineral density should pay particular attention to patients taking high doses over a long period with the presence of risk factors for osteoporosis. Studies have long-term use of inhaled budesonide in children at mean daily doses of 400 micrograms (metered dose) or adults in a daily dose of 800 micrograms (metered dose) have not shown significant effects on bone mineral density. No data on the effect of high doses of Symbicort turbuhaler on bone mineral density. If there is reason to believe that against the background of previous systemic therapy primobolan cycle corticosteroids adrenal function has been compromised, you should take precautions when transferring patients to treatment Symbicort.
The benefits of inhalation therapy with budesonide, as a rule, minimize the need for acceptance of oral corticosteroids, but in patients discontinuing therapy oral corticosteroids for a long time can be maintained insufficient function of the adrenal glands. Patients who are in urgent need of past reception of high doses of corticosteroids or receiving long-term treatment with inhaled corticosteroids at high doses, may also be in this risk. It is necessary to provide for the appointment of additional corticosteroids during times of stress or surgery.
It is recommended to instruct the patient about the need to rinse your mouth with water after maintenance doses of inhaled to prevent the risk of candidiasis of the mucous membranes of the mouth and pharynx. It is also necessary to rinse your mouth with water after inhalation for the relief of symptoms in the case of candidiasis of the mucous membranes of the mouth and throat.
Observe the precautions in the treatment of patients with prolonged QTc-interval. Acceptance of formoterol may cause lengthening of the QTc-interval. It is necessary to reconsider the need for, and dose of inhaled glucocorticosteroid in patients with active or inactive forms of pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system.
The joint appointment β 2 -adrenomimetikov with drugs that can cause or exacerbate hypokalemic effect, for example, xanthine derivatives, steroids or diuretics may increase gipokaliemicheskogo effect of β2 -adrenomimetikov. It is necessary to take special precautions in patients with unstable asthma who use short-acting bronchodilators, for the removal of heavy attacks during exacerbation of asthma, since the risk of hypokalemia increased by hypoxia and in other conditions when the increased probability of developing gipokaliemicheskogo effect. In such cases it is advisable to control the content of potassium in serum.
Reception primobolan cycle of patients with acute bronchial obstruction formoterol in a dose of 90 mg for 3 hours safe. The treatment should monitor the concentration of blood glucose in patients with diabetes.
Generally, such amount does not cause problems in patients with lactose intolerance.

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primobolan results

Special patient groups: no need for special dose selection for elderly patients drug. No data on the admission of primobolan results in patients with renal or hepatic insufficiency. As budesonide and formoterol are mainly derived with the participation of hepatic metabolism, the patients with severe cirrhosis of the liver can be expected to slow the rate of excretion of the drug. Children under 6 years: Symbicort Turbuhaler is not recommended for children under 6 years old.

Instructions for proper use turbuhaler :

The mechanism of action turbuhaler: inhalation by the patient through the mouthpiece of the drug enters the respiratory tract. It is necessary to instruct the patient:
• carefully review the instructions for use turbuhaler
• breathe heavily and deeply through the mouthpiece to ensure getting the optimal dose of the drug to the lungs
• never to breathe out through the mouthpiece
• rinse your mouth with water after inhalation maintenance doses to reduce the risk of developing oral mucosal candidiasis and pharynx. It is also necessary to rinse your mouth with water after inhalation for the relief of symptoms in the case of candidiasis of the mucous membranes of the mouth and throat.
The patient may not taste primobolan results or feel the medication after using turbuhaler, due to a small amount of the substance to be delivered.

Overdose

Symptoms of overdose of formoterol:. Tremor, headache, palpitations
In some cases, it was reported on the development of tachycardia, hyperglycemia, hypokalemia, lengthening , arrhythmia, nausea and vomiting. Can be assigned to supportive and symptomatic treatment.
If necessary, cancel primobolan results turbuhaler due to overdose of formoterol, which is part of a combined drug, should consider the appointment of an appropriate glucocorticosteroid.
In acute overdose of budesonide, even in large doses, is not expected clinically significant effects. In chronic receiving excessive doses can manifest systemic effects of glucocorticoids such as hypercortisolism and adrenal suppression.

Interaction with other drugs

Receiving 200 mg ketoconazole once daily increases in the plasma concentration of oral budesonide (3 mg single dose) with their concomitant use, on average, 6 times. When assigning ketoconazole by 12 hours after administration of budesonide in the plasma concentration of the latter was increased an average of 3 times. Information about such interactions with inhaled budesonide is not, however, expect a noticeable increase in the plasma concentration of the drug. Since the data for recommendations on the selection of doses available, to avoid the above combination of drugs. If this is not possible, the time interval between administration of ketoconazole and budesonide should be maximized. You should also consider reducing the dose of budesonide. Other potent inhibitors of , probably also can significantly increase the plasma concentration of budesonide. Not recommended the appointment of  as maintenance therapy and cupping to patients receiving strong  inhibitors.
Receptors may attenuate the effect of formoterol. Should not be administered simultaneously with β-blockers (including eye drops) unless required cases.
turbuhaler and quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), monoamine oxidase inhibitors primobolan results and tricyclic antidepressants can prolong the interval QTc and increase the risk of ventricular arrhythmias.
in addition, levodopa, levothyroxine, oxytocin and alcohol may reduce the tolerance of the heart muscle to β 2 -adrenomimetikam.
Co-administration  inhibitors and drugs with similar properties such as furazolidone and procarbazine, may cause increased blood pressure. There is an increased risk of arrhythmias in patients receiving general anesthesia drugs halogenated hydrocarbons.
In a joint reception and  turbuhaler other β-adrenergic drugs may increase the side effects of formoterol.
As a result of .beta. 2 -adrenomimetikov hypokalemia can occur, which may be aggravated by concomitant medication xanthine derivatives, mineral derivatives of corticosteroids or diuretics.
hypokalemia may enhance susceptibility to the development of arrhythmias in patients receiving cardiac glycosides.
There was no interaction primobolan results of budesonide and formoterol with other drugs used to treat asthma.