Maxigra tabs 100mg #4

Maxigra instruction for use

You can buy Maxigra here

Composition

One tablet contains:
the active substance is sildenafil citrate 70.24 mg or 140.48 mg (equivalent to sildenafil) 50.00 mg or 100.00 mg, respectively,
excipients: mannitol, crospovidone (type A), povidone (K 25), silicon dioxide, colloidal starch, magnesium stearate, sodium lauryl sulfate,
shell composition: hypromellose (15 mPas), macrogol6000, titanium dioxide E171, talc, indigo carmine E132.
Packaging - In the package 1.4 pcs.

pharmachologic effect

Medication for the treatment of erectile dysfunction. Restores impaired erectile function and provides a natural response to sexual arousal.
Sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for the breakdown of cGMP in the cavernous body. Sildenafil has no direct relaxing effect on the corpus cavernosum, but actively enhances the relaxing effect of nitric oxide on this tissue. During sexual arousal, the local release of NO under the influence of sildenafil leads to the inhibition of PDE5 and an increase in the level of cGMP in the cavernous body, resulting in the relaxation of smooth muscles and increased blood flow in the cavernous body.
Sildenafil can cause a mild and transient disturbance in color (blue / green). A supposed mechanism of color vision impairment is the inhibition of PDE6, which is involved in the process of transmitting light in the retina. In vitro studies have shown that the effect of sildenafil on PDE6 is 10 times less than its activity on PDE5.
In vitro studies indicate that the activity of sildenafil in relation to PDE5 is 10–10,000 times greater than its activity against other phosphodiesterase isoforms (PDE 1, 2, 3, 4, and 6). In particular, the activity of sildenafil in relation to PDE5 is 4000 times greater than its activity in relation to PDE3, a cAMP-specific phosphodiesterase involved in cardiac contraction.

Suction

Sildenafil is rapidly absorbed. The maximum concentration in plasma after oral administration of Maxigra on an empty stomach is reached within 30 to 120 minutes. The average absolute bioavailability prioral intake is 41% (range 25 -63%). After oral administration of sildenafil, AUC and Cmax increase in proportion to the dose when taking the recommended dose range (50-100 mg).
When taking sildenafil with food, the rate of absorption decreases, while the average delay Tmax is 60 minutes and the average decrease in Cmax is 29%.

Distribution

The average distribution of sildenafil in the state of equilibrium concentration (Vd) is 105 liters, which indicates its distribution in the tissues. After a single oral dose of 100 mg, the average maximum total concentration of sildenafil in plasma is approximately 440 ng / ml. Since sildenafil (and its main circulating metabolite, N-desmethyl) is 96% bound to plasma proteins, the average maximum concentration of free sildenafil in plasma is 18 ng / ml (38 nM). Binding with a clue does not affect the total concentration of the drug.
In healthy volunteers receiving sildenafil (single dose in a dose of 100 mg), less than 0.0002% (average 188 ng) of the administered dose was determined 90 minutes after the injection in the seminal fluid.

Metabolism

Sildenafil is metabolized by predominantly microsomal liver isoenzymes CYP3A4 (primary pathway) and CYP2C9 (secondary pathway). The major circulating metabolite is formed from isildenafil by N-demethylation. This metabolite has a profile of phosphodiesterase similar to that of sildenafil, and its activity against PDE5 in vitro is approximately 50% of the activity of the original preparation. The concentration of this metabolite in plasma is approximately 40% of the concentration of sildenafil. In the future, the metabolite N-desmethylmetabolized, while its half-life is about 4 hours

Removal

The total clearance of sildenafil is 41 l / h, while the terminal half-life is 3-5 hours. After oral or intravenous administration, sildenafil is excreted as metabolites, mainly with feces (approximately 80% of the oral dose) and in smaller quantities with urine (approximately 13% of oral doses).

Pharmacokinetics

drug in separate groups of patients

Elderly

In healthy elderly volunteers (over 65 years), there was a decrease in the clearance of sildenafil, which led to an increase in the concentration of sildenafil and the active metabolite N-desmethyl in the plasmedo 90% compared with healthy volunteers of younger age (18-45 years). Due to age differences in plasma protein binding, the corresponding increase in plasma concentration of free sildenafil was approximately 40%.

Patients with renal failure

In volunteers with impaired renal-lung function and moderate severity (creatinine clearance = 30-80 ml / min) after repeated oral administration of sildenafil at a dose of 50 mg, its pharmacokinetic parameters did not change. The mean AUC and Cmax values ​​of metabolite N-desmethyl increased to 126% and 73%, respectively, compared to volunteers of the same age without impairing renal function. However, due to the high inter-individual variability, these differences were not statistically significant. In volunteers with severe impaired renal function (clearance of <30 ml / min), the clearance of sildenafil decreased, leading to an increase in mean AUC and Cmax values ​​of up to 100% and 88%, respectively, compared to volunteers of the same age without impairing renal function. In addition, the AUC and Cmax values ​​for the N-desmethyl metabolite were significantly increased to 79% and 200%, respectively.

Patients with liver failure

Volunteers with mild and moderate degrees of liver cirrhosis (A and B class Child-Pugh classification) showed a decrease in clearance of sildenafil, which led to an increase in AUC (84%) and Cmax values ​​(47%) compared with volunteers of the same age without impairing hepatic function The pharmacokinetic parameters of sildenafil in patients with severely impaired liver function have not been studied.

Pharmacodynamics

Sildenafil is an oral medication for the treatment of erectile dysfunction. In vivo, for example, sexual stimulation, Maxigra restores impaired erectile function by increasing blood flow to the penis.
The physiological mechanism by which the erection of the penis occurs is the release of nitric oxide (NO) in the veins of the body during sexual stimulation. Further, nitric oxide activates the enzyme guanylate cyclase, which leads to an increase in the level of cyclic guanosine monophosphate (cGMP), which causes relaxation of smooth muscles in the veral body and promotes blood flow. Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5) in the cavernosum, where PDE5 is responsible for the breakdown of cGMP. Sildenafil has a peripheral type of action on an erection. Sildenafil has no direct relaxing effect on the isolated cavernous body of a person, but actively enhances the relaxing effect of NO on the cavernous tissue. When the pathway NO / cGMP is activated, as in the case of sexual stimulation, inhibition of PDE5 under the influence of sildenafil leads to an increase in the level of cGMP in the cavernous body. Therefore, in order for sildenafil to produce the expected effective pharmacological effect, sexual stimulation is necessary. Sildenafil is selective for PDE5, which is involved in the erection process. Its activity against PDE5 surpasses that of other known phosphodiesterases. The activity is 10 times greater than the activity with respect to PDE6, which is involved in the process of transmitting light in the retina. Sildenafil causes a slight and transient decrease in blood pressure, which in most cases does not manifest clinically. The average maximum decrease in systolic blood pressure in the supine position after oral administration of sildenafil at a dose of 100 mg was 8.4 mm Hg. The corresponding change in diastolic arterial pressure in the supine position was 5.5 mmHg. Such a decrease in blood pressure is consistent with the vasodilating action of sildenafil, probably associated with an increase in cGMP levels in vascular smooth muscle. A single oral administration of sildenafil up to 100 mg did not have a clinically significant effect on ECG parameters.
After a single dose of sildenafil in a dose of 100 mg, there was no effect on motility or sperm morphology.

Maxigra, indications for use

Treatment of erectile dysfunction, characterized by the inability to achieve or maintain an erection of the penis, sufficient for satisfactory sexual intercourse.

Contraindications

Simultaneous intake of donators of nitric oxide or nitrates in any form, hypersensitivity to sildenafil.
    hypersensitivity to sildenafil or to any of the components of the drug;
    diseases of the cardiovascular system (for example, unstable angina, severe heart failure);
    Maxigra should not be used in patients undergoing treatment;
    nitratami and other drugs that release the oxidase;
    severe liver failure;
    arterial hypotension (blood pressure below 90/50 mm Hg. Art.);
    recent myocardial infarction or brain stroke;
    hereditary degenerative diseases of the retina such as retinitispigmentoza);
    loss of vision in one eye due to anterior ischemic neuropathy of the optic nerve, not associated with inflammation of artery, regardless of whether this episode was associated with the previous use of the PDE5 inhibitor or not;
    children and adolescents up to 18 years.

Dosage and administration

For oral administration

Adults

The recommended starting dose is 1 tablet 50 mg of sildenafil. The maximum daily recommended dose is 100 mg.
The drug Maxigra should be taken approximately 60 minutes before the start of sexual activity.

Elderly patients

Selection of the dose is carried out by an individual doctor.

Use in patients with impaired renal function

In patients with severe renal impairment (creatinine clearance <30 ml / min), reduction of the dose to 25 mg is recommended. The dose can be increased to 50 mg and 100 mg, depending on the effectiveness and tolerability of Maxigra.

Use in patients with impaired liver function

In patients with impaired liver function (for example, in cirrhosis), the metabolism of sildenafil is reduced. Therefore, in patients with slightly and moderately impaired liver function, it is recommended to reduce the dose to 25 mg, taking into account the effectiveness and tolerability, the dose can be increased to 50 mg and 100 mg.

Use during pregnancy and lactation

Maxigra is not intended for use in women.

Side effects of Maxigra

From the side of the central nervous system: possible headache, flushing, dizziness, insomnia.
On the part of the digestive system: possible dyspepsia, asthenia, diarrhea, abdominal pain, nausea.
On the part of the musculoskeletal system: arthralgia, myalgia, increased muscle tone.
On the part of the respiratory system: nasal congestion, pharyngitis, rhinitis, sinusitis, respiratory tract infections, respiratory failure.
On the part of the organ of vision: a change in vision (mild and transient; mainly a change in the color of objects, as well as enhanced light perception and impaired visual clarity), conjunctivitis.
Other: possible flu-like syndrome, the development of infectious diseases, symptoms of vasodilation, back pain, rash, urinary tract infections, dysfunction of the prostate gland; in isolated cases - priapism.

special instructions

It is necessary to use with caution the preparation of patients with concomitant anatomical pathology of the penis (for example, cavernous fibrosis, Peyronie's disease), in patients with diseases of the cardiovascular system (the drug has a vasodilating property, which can cause a short-term reduction in arterial pressure), as well as in patients which have factors predisposing to the onset of priapism (for example, sickle cell anemia, leukemia, multiple myeloma).
It is not recommended to use sildenafilno with other methods of treating erectile dysfunction due to the lack of studies confirming the safety and efficacy of such therapy.
For the onset of therapeutic action of sildenafil, prior sexual stimulation is necessary.
Given the lack of data regarding the safety of using sildenafil in patients with impaired hemostasis, as well as in patients with acute gastric ulcer and duodenal ulcer, in these patients, Maxigra should be used only when the treatment of erectile dysfunction exceeds the potential risk of bleeding.
Since sexual activity poses a certain risk in heart disease, before starting any therapy with an erectile dysfunction surgeon, the doctor should examine the condition of the cardiovascular system of patients. Sildenafil has vasodilator properties, which leads to a slight and transient reduction in arterial pressure. Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular output tract (for example, aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as rarely occurring multiple systemic atrophy syndrome, manifested by a severe violation of autonomic regulation of arterial pressure.
Sildenafil enhances the hypotensive effects of nitrates.
Postmarketing phenomena on the part of the cardiovascular system included myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebral hemorrhage, transient ischemic attack, hypertension and hypotension, and had a time association with sildenafil. Most, but not all, of these patients had pre-existing cardiovascular risk factors. It was reported that many phenomena occurred during or immediately after the sex action, while some were observed immediately after taking sildenafla without sexual activity. It is impossible to establish whether these phenomena are directly related to these factors, or they are related to other factors.
There are reports of rare cases of development of nonarterial anterior ischemic optic neuropathy, which leads to visual impairment when sharing Maxigira and other PDE5 inhibitors. In the event of a sudden visual impairment, the patient should be advised to stop taking sildenafil and consult with a doctor immediately.
Sildenafil should be administered with caution to patients taking alpha-blockers, because using them together can lead to clinically severe hypotension in individual sensitive patients. This effect is most likely to develop within 4 hours after taking sildenafil. In order to minimize the possibility of developing orthostatic hypotension in patients taking alpha blockers, treatment with sildenafil should begin after stabilization of hemodynamics in these patients. The attending physician should inform patients what actions should be taken in case of symptoms of orthostatic hypotension.
Studies show that the sildena phyla strengthens the antiplatelet effect of sodium nitroprusside on human invitro platelets.
Features of the influence of Maxigra ability to drive a vehicle or potentially dangerous machinery
After taking the drug Maxigra should be careful when driving and potentially dangerous mechanisms, due to the possibility of side effects - dizziness, visual disturbances.

Interaction

Sildenafil potentiates hypotensive drugs that release nitric oxide (for example, nitrates, molsidomine, sodium nitroprusside).
The simultaneous use of sildenafil (once at a dose of 100 mg) and HIV protease inhibitor saquinavir, which is an inhibitor of CYP3A4, under conditions of equilibrium concentration (at a dose of 1200 mg 3 times a day) led to an increase in Cmax of sildenafil by 140%, and AUC of sildenafil by 210%. Sildenafil had no effect on saquinavir pharmacokinetics. More robust inhibitors of the isoenzyme CYP3A4, such as ketoconazole and itraconazole, can have a more pronounced effect.
Grapefruit juice is a weak inhibitor of the metabolism of the CYP3A4 isoenzyme in the wall of the gastrointestinal tract and can cause a moderate increase in the level of sildenafil in the blood plasma.
A single antacid (magnesium hydroxide / aluminum hydroxide) does not affect the bioavailability of sildenafil.
Although studies of specific interactions for all drugs have not been carried out, population-based pharmacokinetic analysis has demonstrated that the combined use of other drugs, such as CYP2C9 inhibitors (for example, tolbutamide, warfarin, phenytoin), CYP2D inhibitors (for example, selective inhibitors of serotonin inverse, inhibitors of seroponin reuptake inhibitors, tripartite inhibitors of serotonin, for example, selective inhibitors of serotonin recurring seizures, tripartite inhibitors of CYP2D (for example, selective inhibitors of serotonin reuptake inhibitors, tripartite inhibitors of serotonin, for example, selective inhibitors of serotonin reuptake inhibitors, tripartite inhibitors of serotonin, for example, selective inhibitors of serotonin inverse, inhibitors of seroponin reuptake serotonin inhibitors, tripartic inhibitors of CYP2D (for example, selective inhibitors of serotonin reuptake inhibitors, trifluoride, serotonin, phenytoin), inhibitors of CYP2D) , loop and potassium-sparing diuretics, inhibitors angiotensin-converting enzyme, calcium blockers channels, antagonists, adrenergic receptors, or inducers of CYP450 metabolism (for example, rifampicin, barbiturates) do not affect the pharmacokinetic parameters of sildenafil.
Nicorandil is an activator of potassium channels and nitrate. Interaction with sildenafil is possible due to the presence of the nitrate component.
Interaction of sildenafil (50 mg) with combined use with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by CYP2C9, has not been identified.
Sildenafil (50 mg) did not cause an additional increase in bleeding time caused by taking acetylsalicylic acid (150 mg).
Sildenafil (50 mg) did not potentiate the hypotensive effects of alcohol in healthy volunteers with an average level of alcohol in the blood of an average of 80 mg / dl.
With the combined use of sildenafil with CYP3A4 suppressive drugs (for example, ketoconazole, erythromycin, cimetidine), the metabolism of sildenafil is reduced. In the case of simultaneous use of sildenafil and CYP3A4 inhibitors, it is recommended to reduce the initial dose of sildenafil to 25 mg.
The simultaneous use of sildenafilas ritonavir (HIV protease inhibitor) is not recommended, since the metabolism of sildenafil is significantly reduced.
The simultaneous use of sildenafil and HIV protease inhibitor saquinavir causes an increase in plasma concentration of syldenafil.
Sildenafil should be used with caution by patients taking α-adrenolytic drugs (especially at a dose of> 25 mg); symptomatic hypotension may occur within 4 hours after taking sildenafil.
With the simultaneous use of amlodipine isildenafil at a dose of 100 mg, the hypotensive effect of amlodipine increases (decrease in systolic and diastolic pressure, respectively, by 8 mm. Hg and 7 mm. Hg. Art.).

Overdose

Symptoms: increased symptoms of side effects.
Treatment: symptomatic. Unknown specific antidote for sildenafil. Dialysis does not accelerate the elimination of sildenafil.
Shelf life - 4 years.
Do not use Maxigra after the expiration date.

Storage conditions

    At a temperature not higher than 30 ° C.
    Keep out of the reach of children.

Terms of sell

You don't need a prescription to buy Maxigra.