Active substanceSildenafilSildenafil
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  • Dosage form: & nbspfilm coated tablets
    Composition:

    1 tablet, film-coated, contains: active substance sildenafil citrate - 35.12 mg, 70.24 mg or 140.48 mg (in terms of sildenafil - 25.00 mg, 50.00 mg or 100.00 mg respectively); Excipients: microcrystalline cellulose 102.88 mg, 205.76 mg or 411.52 mg, croscarmellose sodium 5.25 mg, 10.50 mg or 21.00 mg, giprolose 4.50 mg, 9.00 mg or 18.00 mg , silicon dioxide colloidal anhydrous 0.75 mg, 1.50 mg or 3.0 mg; magnesium stearate 1.50 mg, 3.00 mg or 6.0 mg; film sheath: Opadrai II 31F58914 white (hypromellose, lactose monohydrate, titanium dioxide (E171), macrogol-4000, sodium citrate) 5.955 mg, 11.91 mg or 23.82 mg, indigocarmine (E2) 0.045 mg, 0.09 mg or 0.18 mg.

    Description:

    dosage 25 and 50 mg: round biconvex tablets, covered with a film coating of blue color;

    dosage of 100 mg: oval biconvex tablets, covered with a film coating of blue color, with a risk on both sides.

    Pharmacotherapeutic group:treatment of erectile dysfunction PDE5-inhibitor
    ATX: & nbsp

    G.04.B.E   Drugs for the treatment of erectile dysfunction

    G.04.B.E.03   Sildenafil

    Pharmacodynamics:

    The drug for the treatment of erectile dysfunction, restores impaired erectile function in conditions of sexual stimulation by increasing the blood flow in the penis. The physiological mechanism of erection includes the release of nitric oxide (N0) in the cavernous body due to sexual arousal .. N0 activates the enzyme guanylate cyclase, which leads to an increase in the concentration of cyclic guanosine monophosphate (cGMP). In turn, cGMP causes relaxation., Smooth muscles of blood vessels and, accordingly, the flow of blood into the cavernous body of the penis.

    Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which causes the disintegration of cGMP in the cavernous body of the penis. It does not have a direct relaxing effect on the smooth muscles of the cavernous body, but enhances the relaxing effect of nitric oxide on this. tissue and increases blood flow in the penis. When the chain is activated NO cGMP, observed with sexual stimulation,oppression PDE-5 leads to an increase in cGMP in the cavernous body.

    The pharmacological effect is achieved only with the presence of sexual stimulation.

    The activity of sildenafil with respect to PDE5 exceeds activity in relation to other known isoenzymes of phosphodiesterase: PDE6 - 10 times, PDE1 - more than 80 times; PDE2 - PDE4, PDE7-FDE11 - more than 700 times. Sildenafil is 4000 times more selective with respect to PDE5, compared with FDHD, which is of great importance, since FDEZ is one of the key enzymes in the regulation of myocardial contractility.

    Sildenafil has a mild and short-term hypotensive effect, in most cases not having a clinical manifestation when taken in the recommended doses. The hypotensive effect is associated with the vasodilating effect of sildenafil due to an increase in cGMP content in the smooth muscle shell of the vessels.

    Pharmacokinetics:

    Suction

    After ingestion quickly, absorbed. Maximum concentration in blood plasma (Cmax) when taken on an empty stomach is achieved within 0.5-2 hours, bioavailability cleaves in ceat it ~ 41 %~(25-63%). At reception with food Cmax is replaced by 20-40%, and is achieved after 1.5-3 hours.

    Distribution

    The apparent volume of distribution in the equilibrium state is 105 liters. The association of sildenafil and its main active metabolite with plasma-blood proteins is 96% of the administered dose and is not dose-dependent.

    Metabolism

    Sildenafil is metabolized, mainly by isozymes -, CYP3A4 (main path) and CYP2C9 (an additional pathway) of microsomal isoenzymes of the liver. The main circulating active metabolite is N-detylmetabolite, whose activity with respect to phosphodiesterase is 50% of the activity of sildenafil, and its concentration in the plasma reaches, 40% concentration of sildenafil N-detyl methyl metabolite undergoes a further metabolism with a half-life of 4 hours.

    Excretion

    The total clearance of sildenafil is 4 g / h. The half-life (T1 / 2) of sildenafil is 3-5 hours. Inactive metabolites are excreted by the intestine (80%) and kidneys (13%).

    Pharmacokinetics in special groups of patients.

    Patients over 65 years of age Cmax sildenafil and its active metabolite is increased by approximately 90% compared with patients aged 18-45 due to reduced clearance of sildenafil.The concentration of sildenafil in blood plasma, not associated with proteins is 40%.

    In patients with moderate renal insufficiency (creatinine clearance 30-80 ml / min), the pharmacokinetics of sildenafil does not change with admission of 50 mg, and Stach and the area under the concentration-time curve (AUC) for N-metalmetabolite increased by 73% and 126%, respectively. In patients with severe renal failure (creatinine clearance less than 30 ml / min) Cmax and AUC increased by '88% and 100% respectively, Cmax and AUC N-detylmetabolite increased by 79% and 200%, respectively.

    In patients with cirrhosis of the liver (classes A and B on the Child-Pugh scale) Cmax and AUC increased by 47% and 84% respectively.

    Indications:

    Treatment of erectile dysfunction characterized by an inability to achievement or preservation of penile erection, sufficient for a satisfactory sexual intercourse.

    Effective only with sexual stimulation.

    Contraindications:

    Hypersensitivity to sildenafil or any other component of the drug; simultaneous reception, donators of nitric oxide or organic nitrates or nitrates in. any medicinal forms;

    simultaneous reception of ritonavir;

    patients who are sexually active: activity is undesirable including with severe cardiovascular diseases such as unstable angina, severe heart failure, life-threatening arrhythmias, arterial hypotension (blood pressure (BP) less than .90 / 50 mmHg) , , arterial hypertension. (Blood pressure more than 170/100 mm Hg) recently transferred, cerebral circulation or myocardial infarction; patients with loss of vision to one eye due to anterior ischemic-optic neuropathy of non-arterial genesis (regardless of whether it was due to the intake of the PDE5 inhibitor or not); hereditary degenerative diseases of the retina, c. including retinitis pigmentosa (a minority of these patients have a genetic PDE of the retina); severe hepatic impairment; female; age to 18 years.

    Carefully:

    Syndrome of multiple systemic atrophy; obstruction of the left ventricular outflow tract, including aortic stenosis, hypertrophic obstructive cardiomyopathy; anatomical deformation of the penis; priapism;

    multiple myeloma; leukemia; simultaneous reception alpha-adrenergic blockers;
    lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

    Dosing and Administration:

    Inside, about 1 hour before the planned sexual activity.

    50 mg once a day. With regard to efficacy and tolerability, the dose can be increased to 100 mg or reduced to 25 mg.

    For patients with mild or moderate renal insufficiency (creatinine clearance (CK) 30-80 ml / min), dose adjustment is not required.

    For patients with severe renal insufficiency (QC less than 30 ml / min), the first dose is 25 mg. With good tolerability, the dose can be increased to 50 or 100 mg.

    For elderly patients, the first dose is 25 mg. With good tolerability, the dose can be increased to 50 or 100 mg.

    For patients with mild or compensated, hepatic insufficiency, the first dose is 25 mg. With good tolerability, the dose can be increased to 50 or 100 mg.

    For patients; taking alpha-adrenoblockers, the first dose. 25 mg. With good tolerability, the dose can be increased to 50 or 100 mg.

    Side effects:
    The incidence of side effects is classified according to recommendations - the World Health Organization: very often - at least 10%; often - not, less than 1%, but less than 10%; infrequently - not less than 0,1%,but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%, including isolated cases!
    From the nervous system: very often - headache ;, often, - dizziness; infrequently - drowsiness, hypoesthesia; rarely - a stroke, a faint; frequency unknown - transient ischemic attack, convulsions, c. including recurrent.
    From the cardiovascular system: often - "hot flashes"; infrequent - a feeling of palpitations, tachycardia; rarely - increase or decrease in blood pressure, myocardial infarction, atrial fibrillation; frequency; unknown - ventricular arrhythmia, unstable angina, sudden death. , From the side of the organ of vision: often - visual impairment, violation of color perception; * infrequent - conjunctival damage, lacrimation, increased perception of light, impaired vision, transient chromatopsy; rarely reddening of the scleral in the eyes of apples; frequency unknown - anterior ischemic optic neuropathy, retinal vascular occlusion, narrowing of the visual fields.
    From the side of the organ of hearing: infrequently - vertigo, noise in the ears; rare, deaf
    On the part of the respiratory system: - often - nasal congestion; rarely - nasal - d bleeding. .
    From the gastrointestinal tract: often - dyspepsia; infrequently - vomiting, nausea, dryness of the oral mucosa.
    Allergic reactions: infrequent - skin rash; frequency unknown - Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).
    On the part of the genitals: the frequency is unknown - priapism, prolonged erection. .
    Other: rarely - chest pain, fatigue.

    Overdose:
    Symptoms: 'with a single dose of the drug in a dose of up to 800 mg are undesirable; reactions (headache, "hot flashes", dizziness, dyspepsia, nasal congestion, visual impairment) were more pronounced and more common than with normal doses; doses up to 200 mg increase the frequency, but not the severity; undesirable reactions.
    Treatment: symptomatic therapy. Hemodialysis is ineffective.

    Interaction:

    Inhibitor inhibitors CYP3A4 and CYP2C9 (ketoconazole, erythromycin, tsimitidin) reduce metabolism and increase the concentration of sildenafil in the blood. In this case, the treatment with sildenafil begins with a dose of 25 mg.

    Simultaneous use with ritonavir Cmax sildenafil increases by 300%, AUC by 1000% and remain at a high level even a day after taking sildenafil.

    Simultaneous application with saquinavir Cmax sildenafil increased by 140%, AUC by 210%.

    The pharmacokinetics of ritonavir and saquinavir does not change with the use of sildenafil.

    Sildenafil enhances the antiaggregant effect of sodium nitroprusside.

    Nicorandil because of the nitrate component when interacting with sildenafil can lead to severe arterial hypotension.. Simultaneous reception sildenafil and. organic, nitrate and so on. donators, nitric oxide can lead to a fatal outcome due to the mutual enhancement of effects. .

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

    With simultaneous application increases the effectiveness of hypoglycemic agents.

    Azithromycin does not affect the pharmacokinetics of sildenafil. '

    With the simultaneous use of sildenafil and alpha-adrenoblockers, in the number of doxazosin, especially in the first 4 hours after taking sildenafil, there may be a pronounced decrease in blood pressure and orthostatic hypotension.

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

    Special instructions:

    Before using sildenafil, a thorough examination of the patient should be carried out in order to diagnose erectile dysfunction and to determine the causes of its occurrence.It is necessary to assess the risk of developing serious adverse reactions, due to sexual activity, in patients with cardiovascular diseases, as well as concomitant medication.

    Sildenafil causes a soft decrease in blood pressure. Particularly susceptible to hypotensive effect of sildenafil patients with left ventricular obstruction or with a rare syndrome of multiple atrophy. Before using sildenafil in such patients, it is necessary to exclude the risk of adverse effects of low blood pressure. the time of sexual activity. Most adverse reactions from the cardiovascular system develop, immediately after intercourse - or a short time after it, in single cases, adverse reactions can develop before sexual intercourse.

    He It is recommended simultaneous use of several different drugs before the treatment of erectile dysfunction.

    Sildenafil should be used with caution in patients with anatomical deformities of the genital: (angulation, cavernous-fibrosis or Peyronie's disease), as well as patients with diseases predisposing to priapism (sickle cell anemia, myeloma, leukemia).If a visual impairment occurs, consult a doctor immediately.

    Doses of more than 200 mg do not increase efficacy, but increase the frequency and severity of dose-related side effects.

    Effect on the ability to drive transp. cf. and fur:

    In case of development of adverse reactions from the nervous system and sensory organs, it is recommended that patients refrain from driving the car and controlling the mechanisms, and also take care when engaging in activities, requiring concentration of attention and speed of psychomotor reactions.

    Form release / dosage:
    Tablets, film-coated 25 mg, 50 mg, 100 mg. / .
    For 1 or 4 tablets in a blister of PVC / PVDC / aluminum foil or from OPA / aluminum foil / PVDC / aluminum foil. -
    1 blister with instructions for use in a cardboard box.,

    Packaging:
    For 1 or 4 tablets in a blister of PVC / PVDC / aluminum foil or from OPA / aluminum foil / PVDC / aluminum foil. -
    1 blister with instructions for use in a cardboard box.
    Storage conditions:
    At a temperature of no higher than 25 ° C.
    Keep out of the reach of children.

    Shelf life:
    3 years.
    Do not use after the expiry date printed on the package. '

    Terms of leave from pharmacies:On prescription
    Registration number:LP-000129
    Date of registration:11.01.2011
    The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia
    Manufacturer: & nbsp
    Information update date: & nbsp10.12.2012
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