supplements side effects

primobolan enanthate

Penile erection is a hemodynamic process based on the relaxation of smooth muscles of cavernous bodies and located in its arterioles. During sexual stimulation of the nerve endings of the cavernous bodies released nitric oxide (N0), activating the enzyme guanylate cyclase, resulting in increased content in the cavernous bodies of cyclic guanosine monophosphate (cGMP). The result primobolan enanthate is relaxation of smooth muscles of cavernous bodies, which increases blood flow to the penis. CGMP level is adjusted, on the one hand, the synthesis of guanylate cyclase, and on the other hand, – splitting cGMP hydrolysis by phosphodiesterases (PDEs). The best-known PDE is the cGMP-specific phosphodiesterase type 5 (PDE5). By blocking PDE5, which participates in the cleavage of cGMP, thereby vardenafil enhances the local action of endogenous nitric oxide (NO) in the cavernous bodies during sexual stimulation. Increasing the level of cGMP by inhibiting PDE5 leads to relaxation of smooth muscles of the corpus cavernosum and increases blood flow to them.This effect leads to the ability of Levitra ® enhances the natural response to sexual stimulation. Vardenafil is a potent and highly selective inhibitor of PDE5 (mean inhibitory concentration with respect to PDE5 – 0.7 nM). Inhibitory activity vardenafil on PDE5 is more pronounced than in other known PDE, (15 times more than FDEb, 130 times greater than FDE1, 300 times greater than FDE11 and 1000 times greater than for PDE -2,3,4,7,8,9,10). Reception of vardenafil 20 mg can cause an erection (enough for penetration) in 15 minutes. A complete response is achieved after 25 minutes.

Indications for Use

Erectile dysfunction (inability to achieve and maintain an erection necessary for sexual intercourse).

Contraindications

  • hypersensitivity to any component of the drug;
  • simultaneous use with nitrates or drugs, which are nitric oxide donators;
  • simultaneous application of a moderately active and potent inhibitors of CYP3A4, such as ketoconazole, itraconazole, ritonavir, indinavir, erythromycin and clarithromycin;
  • drugs to treat erectile dysfunction, should not be used in men who do not show sexual activity (eg, patients with underlying cardiovascular disease such as unstable angina or severe cardiac failure [class III or IV according to the classification of the New York Heart Association]) ;
  • Safety Levitra ® has not been studied and is not obtained relevant data, its use is not recommended in patients with the following conditions:
    • severe liver function abnormalities,
    • kidney disease in the terminal stage, requiring dialysis,
    • hypotension (systolic blood pressure at rest <90 mm Hg. Art.)
    • recent myocardial infarction or stroke (within the last 6 months)
    • unstable angina and hereditary degenerative retinal disorders such as retinitis pigmentosa.

Precautions   should use the drug in patients with anatomical deformation of the penis (curved, cavernous fibrosis, Peyronie’s disease), diseases predisposing to priapism (sickle-cell anemia, multiple myeloma, leukemia). In patients with a tendency to bleeding and exacerbation of peptic ulcer disease, the drug should be used only after assessment of the benefit-risk.

Pregnancy during breastfeeding
The drug is not indicated for use in women, newborns and children.

Dosing and Administration
The drug is taken by mouth with or without food. At the beginning of treatment the recommended dose is 10 mg (approximately 25-60 minutes before sexual intercourse). However, it was shown that the drug Levitra ® effective and reception for 4-5 hours before sexual activity. The maximum frequency of the drug – 1 times per day. Depending on the efficacy and tolerability of treatment dose can be increased to 20 mg or decreased to 5 mg per day. The maximum recommended dose is 20 mg 1 time per day. In order to ensure an adequate response to treatment requires sexual stimulation.
P atsienty elderly (over 65 years)
dose adjustment in elderly patients is not required. Children (under 18 years) use of the drug Levitra ® is not indicated in patients in this age group. Abnormal liver function have patients with minor hepatic impairment (step a by Child-Pugh) changes in the dosing regimen is required. In patients with moderate hepatic impairment (stage B by Child-Pugh), the initial dose is 5 mg per day. In the future, depending on the efficacy and tolerability of treatment dose can be increased to a maximum of 10 mg. In patients with severe hepatic impairment (stage C according to Child-Pugh), the pharmacokinetics of vardenafil has not been studied. Renal dysfunction Change dosing regimen is required in patients with minor (CC> 50-80 mL / min), moderate (K> 30-50 mL / min) and severe (creatinine clearance <30 mL / min) decrease in renal function. Patients with concomitant CYP3A4 inhibitors intake may need to adjust the dose of Levitra pills, film-coated, in patients taking certain inhibitors of cytochrome P450 (CYP) 3A4 with moderate or severe activity (eg, ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, and indinavir (see. sections “Special instructions” and “Interaction with other drugs.” in a joint application Levitra with CYP3A4 inhibitors ketoconazole or itraconazole their dose should not exceed 200 mg per day. If the dose ketoconazole and itraconazole greater than 200 mg per day, Levitra should not be used. in a joint application with the CYP3A4 inhibitors erythromycin or clarithromycin, the dose of Levitra should not exceed 5 mg. Contraindicated sharing ingibitoramiproteazy with HIV, such as indinavir and ritonavir (see. sections “Contraindications”, “Special Instructions”, “Interaction with other drugs”). Patients with concomitant intake of alpha-blockers in connection with the vasodilating effect of alpha-blockers and vardenafil, co-administration of tablets, film-coated, Levitra with alpha-blockers may cause some patients to symptomatic hypotension. Joint reception can only be started if the patient has a stable condition in the treatment of alpha-blockers (see. Section ” Interaction with other medicinal products “). Levitra can be taken at any time with tamsulosin or alfuzosin. B. case of a joint appointment Levitra with terazosin and other alpha-blockers should be observed the necessary interval between doses of Levitra and these alpha-blockers (see. Section ” Interaction with other medicinal products “). For patients who are already taking the optimal dose of Levitra pills, coated film shell, treatment of alpha-blockers should be started with the lowest dose. The gradual increase in the dose of alpha-blocker may be followed by a subsequent decrease of blood pressure in patients taking phosphodiesterase inhibitors (PDE5), including vardenafil.

 

Side effects
Adverse reactions (HP), which have been reported in connection with the use of Levitra ® are shown in the table. In each group, undesirable effects are given in order of decreasing severity. The frequency is defined as “very common ( > 1/10),” “often (by > 1/100 to <i / 10),” “infrequent (from > 1/1 000 to <1/100),” “rarely ( by > 1/10 000 and <000 1/1) “,” very rare (<1/10 000). ”
it was not possible to estimate that the frequency of the HP, which have been recorded only during post-marketing observations are designated as” frequency not known ”
the HP, found in patients in all clinical trials around the world, including those considered to be related to the drug in > 0.1% of patients, or rare and serious in their nature.

Reported cases of myocardial infarction associated in time with taking vardenafil and with sexual activity, but not installed, if the occurrence of the disease directly using vardenafil related, sexual activity, comorbidities, or a combination of these factors.
There are rare reports of cases of anterior ischemic optic neuropathy (PINZN) leading to impaired vision (including permanent loss of vision), associated in time with taking PDE5 inhibitors, including the drug Levitra ® , patients, many of whom have concomitant risk factors for this condition, such as an anatomical defect optic disc, age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. Not installed, connected whether development PINZN directly using PDE5 inhibitors with existing patient concomitant vascular risk factors and anatomical defects, the combination of these factors, or other causes.
Reported cases of visual disturbances, including temporary or permanent loss of vision, which are linked in time with taking PDE5 inhibitors, including Levitra ® . It not determined whether these cases directly with PDE5 inhibitors reception or concomitant cardiovascular risk factors, or other reasons.
It is noted few cases sudden deafness or hearing loss with preparations from the group of PDE5 inhibitors, including primobolan enanthate . Not established whether these cases directly with the use  , associated risk factors for hearing loss, a combination of these factors, or other causes.

Overdose
A study in healthy volunteers was conducted to test vardenafil single doses as high as 120 mg per day. Single doses of vardenafil 80 mg and multiple doses up to 40 mg of vardenafil assigned once a day for 4 weeks tolerated without the occurrence of serious adverse reactions.
However, when using vardenafil 40 mg 2 times a day had apparent pain without signs toxic action on the muscular and nervous systems.
should be a standard maintenance therapy in cases of overdose.
since vardenafil is highly bound to plasma proteins, and only a small amount of the drug is excreted by the kidneys, dialysis efficiency is unlikely.

The incidence of syncope in this study and in previous studies with tamsulosin or terazosin was not. The combined use of the drug and alpha-blockers is permissible only in the presence of stable indicators of blood pressure in patients receiving alpha-blockers, and the drug should be appointed in the minimum recommended dose of 5 mg. Should not take Levitra  at the same time with an alpha-blocker, with the exception of tamsulosin which reception can coincide with the reception Levitra. Between taking vardenafil and other alpha-blockers should be observed time interval. When concomitant administration of terazosin and the drug  is necessary to comply with 6-hour interval between doses of drugs. The simultaneous use of digoxin (0.375 mg), and the drug  every other day for 14 days is not accompanied by their interaction. A single dose of the drug  (antacid: magnesium hydroxide / aluminum hydroxide) did not affect the performance AUC and C max of vardenafil. The bioavailability of the drug Levitra® (20 mg) was also not affected when it is combined with antagonists H 2 -receptor ranitidine (150 mg 2 times a day) and cimetidine (400 mg, 2 times a day). Levitra ® (10 mg and 20 mg) did not affect the duration of bleeding when used as monotherapy and in combination with acetylsalicylic acid at a low dose (2tabletki on 82 mg). Levitra ® (20 mg) did not potentiate the hypotensive effect of alcohol (0.5 g / kg body weight), the pharmacokinetics of vardenafil has not been violated. Aspirin, ACE inhibitors, beta-blockers, diuretics, and antidiabetic drugs (sulfonylureas and metformin), weak CYP3A4 inhibitors are not affect the pharmacokinetics of vardenafil.

Special instructions:

The drug is taken orally. Can be taken regardless of meals. To be effective, treatment requires a sufficient level of sexual stimulation.
Before prescribing drugs used to treat erectile dysfunction, the physician should evaluate the state of the cardiovascular system, as there is a risk of developing complications from the heart during sexual activity. Vardenafil has vasodilator properties, which may be accompanied, minor or moderate decrease in blood pressure. Patients with obstruction of outflow paths from the left ventricle, for example, aortic stenosis, idiopathic hypertrophic subaortal stenosis may be sensitive to the action of vasodilators, including PDE5 inhibitors.
When using primobolan enanthate therapeutic (10 mg) and sverhterapevticheskih (80 mg) doses marked lengthening of the interval QT. In this regard, the appointment of the drug  should be avoided in patients with congenital prolongation of the QT interval and in patients taking anti-arrhythmic drugs class IA (quinidine, procainamide), or class III (amiodarone, sotalol).
The safety and efficacy of  in combination with other treatments for erectile dysfunction has not been studied, so their combined use is not recommended.
In patients receiving the drug and other PDE5 inhibitors have been reported cases of transient visual loss and nearteriitnoy ischemic optic neuropathy. In the event of a sudden loss of vision should stop taking  and immediately consult your doctor.
Combined therapy of alpha-blockers  . It can be accompanied by the development of arterial hypotension with the appropriate clinical picture, because these drugs have vasodilating effects.Combined appointment of vardenafil and alpha-blockers is permissible only in the presence of stable rates of blood pressure in patients receiving alpha-blockers, and the drug Levitra ® should be administered in the minimum recommended dose of 5 mg. Do not take the drug Levitra ® at the same time with the alpha-blockers, except for tamsulosin intake which may coincide with the intake of Levitra ® . Between taking vardenafil and other alpha-blockers should be observed time interval. In the case of receiving selected dose of vardenafil therapy of alpha-blockers should be started with the lowest dose. The gradual increase in the dose of alpha-blockers in patients receiving drugs from the group of PDE5 inhibitors, may lead to a further decrease in blood pressure.
The dose of  should not exceed 5 mg when it is combined with the use of erythromycin, clarithromycin, ketoconazole, itraconazole. The dose of ketoconazole and itraconazole at the same time must not exceed 200 mg. Simultaneous treatment with indinavir iritonavirom contraindicated. Because the drug  is not used in patients with a tendency to bleeding, and in patients with acute exacerbation of peptic ulcer disease, its purpose in these cases is possible only after a thorough evaluation of the relation benefit-risk. The drug  does not affect the duration of bleeding, as it does not affect the rate in the combined use with acetylsalicylic acid. vardenafil does not increase platelet aggregation induced by various drugs. In concentrations above the therapeutic vardenafil causes a slight increase in antiplatelet effect of sodium nitroprusside, which is a donor of nitric oxide. In studies on rats with concomitant appointment of vardenafil and heparin are not marked effect on bleeding time, however, the use of this combination in humans has not been studied. safety data obtained from preclinical studies not identified toxic (including reproductive toxicity), genotoxic and carcinogenic effects.