medicalmeds.eu Medicines Remedy for erectile dysfunction – FDE5-inhibitor Dinamiko

Dynamics

Producer: Teva (Tev) Israel

Code of automatic telephone exchange: G04BE03

Release form: Firm dosage forms. Tablets.

Indications to use: Erectile dysfunction (Impotence).

General characteristics. Structure:

1 tablet, film coated, contains active agent: sildenafit citrate of-35,12 mg, 70,24 mg or 140,48 mg (in terms of sildenafit - 25,00 mg, 50,00 mg or 100,00 mg respectively); excipients: cellulose of microcrystallic 102,88 mg, 205,76 mg or 411,52 mg, croscarmellose sodium of 5,25 mg, 10,50 mg or 21,00 mg, gipromelloza of 4,50 mg, 9,00 mg or 18,00 mg, silicon dioxide of colloid anhydrous 0,75 mg, 1,50 mg or 3,00 mg; magnesium stearate of 1,50 mg, 3,00 mg or 6,00 mg; film cover: Опадрай II 31F58914 white (gipromelloza, lactoses monohydrate, titanium dioxide, macrogoal-4000, sodium citrate) 5,955 mg, 11,91 mg or 23,82 mg, indigo carmine E 132 0,045 of mg, 0,09 mg or 0,18 mg.

Description:

dosages of 25 and 50 mg:
round biconvex tablets, film coated blue color;

dosage of 100 mg:
oval biconvex tablets, film coated blue color, with risky on both sides.

Pharmacological properties:

Pharmacodynamics. Drug for treatment of erectile dysfunction, recovers in the conditions of sexual stimulation the broken erectile function by increase in a blood-groove in a penis.

The physiological mechanism of an erection includes release of nitrogen oxide (NO) in a cavernous body owing to sexual excitement. NO activates enzyme guanylate cyclase that leads to increase in concentration of a cyclic guanozinmonofosfat (tsGMF). In turn, tsGMF causes relaxation of unstriated muscles of blood vessels and, respectively, inflow of blood to a cavernous body of a penis.

Sildenafil represents the selection inhibitor of tsGMF-specific phosphodiesterase of the 5th type (FDE5) which causes disintegration of tsGMF in a cavernous body of a penis. It has no the direct weakening effect on unstriated muscles of a cavernous body, but strengthens the weakening effect of nitrogen oxide on this fabric and increases a blood stream in a penis. At activation of a chain of NO - tsGMF which is observed at sexual stimulation oppression of FDE5 leads to increase in tsGMF in a cavernous body. The pharmacological effect is reached only in the presence of sexual stimulation.

Activity of a sildenafil concerning FDE5 surpasses activity concerning other known isoenzymes of phosphodiesterase: FDE6 - by 10 times, FDE1 - more than by 80 times; FDE2 - FDE4, FDE7-FDE11 - more than by 700 times. Sildenafil by 4000 times more селективен concerning FDE5, in comparison with FDEZ that is of great importance as FDEZ is one of key enzymes of regulation of contractility of a myocardium.

Sildenafil possesses the easy and short-term hypotensive action which in most cases does not have clinical implication at reception in the recommended doses. Hypotensive action is connected with vazodilatiruyushchy effect of a sildenafil because of increase in maintenance of tsGMF in a smooth muscle cover of vessels.

Pharmacokinetics. Absorption

After intake it is quickly soaked up. The maximum concentration in a blood plasma (Cmax) at reception is on an empty stomach reached within 0,5-2 hours, bioavailability averages 41% (25-63%). At reception with Cmax food decreases by 20-40% and it is reached in 1,5-3 hours.

Distribution

The seeming distribution volume in an equilibrium state makes 105 l. Communication sildenafit and its main active metabolite with proteins of a blood plasma makes 96% of the entered dose and is not dozozavisimy.

Metabolism

Sildenafil is metabolized, mainly, under the influence of CYP3A4 isoenzymes (the main way) and CYP2C9 (an additional way) of microsomal isoenzymes of a liver. The main circulating active metabolite is N-demetilmetabolit which activity concerning phosphodiesterase makes 50% of activity of a sildenafil, and its concentration in plasma reaches 40% of concentration of a sildenafil. N-demetilmetabolit is exposed to further metabolism with an elimination half-life of 4 h.

Removal

The general clearance of a sildenafil is equal to 41 l/h. The elimination half-life (Ti/2) of a sildenafil makes 3-5 hours. Inactive metabolites are removed by intestines (80%) and kidneys (13%).

Pharmacokinetics at special groups of patients.

At patients 65 years of Cmax of a sildenafil are more senior and its active metabolite it is increased approximately by 90% in comparison with patients of 18-45 years because of reduced clearance of a sildenafil. Concentration sildenafit in a blood plasma, not connected with proteins makes 40%.

At patients with a moderate renal failure (clearance of creatinine of 30-80 ml/min.) the pharmacokinetics of a sildenafil does not change at reception of 50 mg, and Cmax and the area under a curve "concentration time" (AUC) for N-demetilmetabolita is increased by 73% and 126% respectively. At patients with a heavy renal failure (clearance of creatinine less than 30 ml/min.) Cmax and AUC are increased by 88% and 100% respectively, Cmax and AUC N-demetilmetabolita are increased by 79% and 200% respectively.

At patients with cirrhosis (classes A and B on a scale of Chayld-Pyyu) Cmax and AUC are increased by 47% and 84% respectively.

Indications to use:

Treatment of the erectile dysfunction which is characterized by inability to achievement or preservation of an erection of a penis sufficient for satisfactory sexual intercourse. It is effective only at sexual stimulation.

Route of administration and doses:

Inside, approximately in 1 hour prior to the planned sexual activity.

On 50 mg of 1 times a day. Taking into account efficiency and portability the dose can be increased to 100 mg or is lowered to 25 mg.

For patients with a slight or moderate renal failure (the clearance of creatinine (CC) of 30-80 ml/min.) of dose adjustment it is not required.

For patients with a heavy renal failure (KK less than 30 ml/min.) the first dose makes 25 mg. At good tolerance the dose can be increased to 50 or 100 mg.

For elderly patients the first dose makes 25 mg. At good tolerance the dose can be increased to 50 or 100 mg.

For patients with the slight or compensated liver failure the first dose makes 25 mg. At good tolerance the dose can be increased to 50 or 100 mg.

For the patients accepting alpha adrenoblockers, the first dose makes 25 mg. At good tolerance the dose can be increased to 50 or 100 mg.

Features of use:

Before use of a sildenafil it is necessary to conduct careful examination of the patient for the purpose of diagnosis of erectile dysfunction and definition of the reasons of its emergence. It is necessary to estimate risk of development of the serious side reactions caused by sexual activity at patients with cardiovascular diseases, and also the accompanying reception of medicines. Sildenafil causes soft decrease in the ABP. Patients with obstruction of a left ventricle or with a rare syndrome of a multiple atrophy are especially subject to hypotensive effect of a sildenafil. Before use of a sildenafil for such patients it is necessary to exclude risk of adverse influence of the low ABP during sexual activity. The majority of side reactions from cardiovascular system develop directly after sexual intercourse or later short time after it, in isolated cases side reactions can develop before sexual intercourse.

Simultaneous use of several various medicines for treatment of erectile dysfunction is not recommended.

Sildenafil it is necessary to apply with care at patients with anatomic deformations of a penis (an angulation, cavernous fibrosis or Peyroni's disease), and also to patients with the diseases contributing to a priapism (a sickemia, a multiple myeloma, a leukosis).

When developing a visual impairment it is necessary to see a doctor immediately.

Doses more than 200 mg do not increase efficiency, however increase, the frequency and expressiveness of dozozavisimy side effects.

Influence on ability to driving of motor transport and to control of mechanisms

In case of development of side reactions from a nervous system and sense bodys patients are recommended to refrain from driving of the car and control of mechanisms, and also to be careful at occupation the types of activity demanding concentration of attention and speed of psychomotor reactions.

Side effects:

Frequency of development of side effects is classified according to recommendations of World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; seldom - not less than 0,01%, but less than 0,1%; very seldom - less than 0,01%, including isolated cases. From a nervous system: very often - a headache; often - dizziness; infrequently - drowsiness, a hypesthesia; seldom - a stroke, a faint; frequency is unknown - the tranzitorny ischemic attack, spasms, including recurrent.

From cardiovascular system: often - "inflows"; infrequently - a heart consciousness, tachycardia; seldom - increase or a lowering of arterial pressure, a myocardial infarction, fibrillation of auricles; frequency is unknown - ventricular arrhythmia, unstable stenocardia, sudden death. From an organ of sight: often - a vision disorder, disturbance of color perception; infrequently - defeat of a conjunctiva, disturbance of dacryagogue, the strengthened light perception, disturbance of clearness of sight, a passing chromatopsia; seldom - reddening of scleras, pain in eyeglobes; frequency is unknown - front ischemic optical neuropathy, occlusion of vessels of a retina, narrowing of fields of vision. From an acoustic organ: infrequently - вертиго, a sonitus; seldom - deafness. From a respiratory organs: often - a nose congestion; seldom - nasal bleeding.

From digestive tract: often - dyspepsia; infrequently - vomiting, nausea, dryness of a mucous membrane of an oral cavity.

Allergic reactions: infrequently - skin rash; frequency is unknown - Stephens-Johnson's syndrome, a toxic epidermal necrolysis (Lyell's disease). From generative organs: frequency is unknown - a priapism, the prolonged I erection. Other: seldom - a stethalgia, fatigue.

Interaction with other medicines:

Inhibitors of isoenzymes of CYP3A4 and CYP2C9 (кетоконазол, erythromycin, Cimetidinum) reduce metabolism and increase concentration of a sildenafil in blood. In this case treatment sildenafily begin 25 mg with a dose.

Simultaneous use with ritonaviry Cmax of a sildenafil increases by 300%, AUC for 1000% and remain at the high level even days later after reception of a sildenafil.
Simultaneous use with sakvinaviry Cmax of a sildenafil increases by 140%, AUC for 210%.
The pharmacokinetics of a ritonavir and sakvinavir does not change at use of a sildenafil.

Sildenafil strengthens antiagregantny effect of Natrium nitroprussicum.

Nikorandil because of a nitrate component at interaction with sildenafily can lead to heavy arterial hypotension.

The concomitant use of a sildenafil and organic nitrates, etc. can lead donators of nitrogen oxide to a lethal outcome because of mutual strengthening of effects.

Sildenafil strengthens hypotensive effects of blockers of "slow" calcium channels, beta adrenoblockers, inhibitors of an angiotensin-converting enzyme.

At simultaneous use increases efficiency of hypoglycemic means.

Azithromycin does not exert impact on pharmacokinetics of a sildenafil.

At simultaneous use of a sildenafil and alpha adrenoblockers, including the doksazozina, especially in the first 4 hours after reception of a sildenafil, can be observed the expressed decrease in the ABP and orthostatic hypotension.

Grapefruit juice can moderately increase concentration of a sildenafil in blood.

Contraindications:

Hypersensitivity to a sildenafil or any other component of drug; a concomitant use of donators of nitrogen oxide or organic nitrates or nitrates in any dosage forms; concomitant use of a ritonavir; to patients to whom sexual activity is undesirable, including with a serious cardiovascular illness, such as unstable stenocardia, heavy heart failure, life-threatening arrhythmias, arterial hypotension (the arterial pressure (AP) less than 90/50 mm of mercury.), arterial hypertension (ABP more than 170/100 mm of mercury.), recently postponed disturbances of cerebral circulation or a myocardial infarction; to patients with loss of sight on one eye owing to front ischemic optical neuropathy of not arterial genesis (irrespective of whether there was it owing to reception of FDE5 inhibitor or not); hereditary degenerative diseases of a retina, including pigmental retinitis (a smaller part of such patients has a genetic disease of FDE of a retina); heavy liver failure; female; age up to 18 years.

With care

Syndrome of a multiple system atrophy; obstruction of an output path of a left ventricle, including aortal stenosis, hypertrophic subaortic stenosis; anatomic deformation of a penis; priapism; multiple myeloma; leukosis; concomitant use of alpha adrenoblockers; lactose intolerance, deficit of lactase, glyukozo-galaktozny malabsorption.

Overdose:

Symptoms: at a single dose of drug in a dose to 800 mg undesirable reactions (a headache, "inflows", dizziness, dyspepsia, a nose congestion, a vision disorder) were expressed stronger and met more often than at reception of usual doses; doses to 200 mg increase frequency, but not expressiveness undesirable reactions Treatment: symptomatic therapy. The hemodialysis is inefficient.

Storage conditions:

At a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 3 years. Not to apply after the period of validity specified on packaging.