The instruction for medical use
of Silmelt Torgovoye medicine a name
the International unlicensed
name Sildenafil Lekarstvennaya
the Tablet form of 50 mg and 100 mg dispersed in an oral cavity
One tablet contains
active agent – a sildenafil of citrate of 70.240 mg or 140.480 mg
(it is equivalent to a sildenafil of 50 mg or 100 mg respectively),
excipients: calcium carbonate, sodium of a kroskarmelloz
(Ac-Di-Sol), Mannitolum 60 (Pearlitol 160), povidone (Plasdon K-29/32), krospovidon (Poliplasdon XL), Mannitolum (Pearlitol 200), aspartame, silicon dioxide colloidal, talc, mint fragrance DC 50117, dye indigo carmine GA223919 E (132) varnish, dye diamond blue GA216176 varnish (E 133), magnesium stearate.
of the Tablet of round shape, with a biconvex surface, is spotty – blue color with mint taste, smooth on both sides
Drugs for treatment of urological diseases. Other drugs for treatment of urological diseases, including spasmolysants. Drugs for treatment of disturbances of an erection. Sildenafil
ATH G04BE03 code
Sildenafil is quickly soaked up. Concentration of drug in plasma after reception it inside on an empty stomach reaches peak within 30-120 min. (on average 60 min.). The absolute bioavailability at intake on average is 41% (25-63%).
At reception of a sildenafil with food the speed of absorption decreases with an average delay of time of Tmax equal to 60 minutes at average lowering of Cmax by 29%.
The volume of distribution (V) sildenafil in an equilibrium state averages 105 l that indicates its distribution in fabrics. At reception of a single oral dose of 100 mg the average maximum general concentration of a sildenafil in plasma makes about 440 ng/ml (coefficient of variation is 40%). Sildenafil and his main metabolite circulating M-desmetilovy approximately for 96% contact proteins of plasma. As a result of such binding the average maximum concentration of a sildenafil in free plasma makes 18 ng/ml (38 nanometers). Linking with proteins does not depend on the general concentration of drug.
Sildenafil is metabolized mainly in a liver under the influence of microsomal isoenzymes of P450 cytochrome: CYP3A4 (main way) and CYP2C9. The main circulating active metabolite which is formed as a result of N-demethylation of a sildenafil is exposed to further metabolism. On selectivity of action on PDE5 the metabolite is comparable with sildenafily, and its activity concerning PDE5 is about 50% of activity of the drug. Concentration of a metabolite in blood plasma makes about 40% of concentration of a sildenafil. N-demetilmetabolit is exposed to further metabolism, the final period of its semi-removal is equal about 4 hours.
The general clearance of a sildenafil is of an organism 41 l/hour, and final elimination half-life – 3-5 hour. After intake sildenafit it is removed in the form of metabolites generally with a stake (about 80% of a dose) and to a lesser extent with urine (about 13% of a dose).
At elderly patients (65 years are also more senior) the clearance of a sildenafil is reduced, and concentration of a free sildenafil in blood plasma is about 40% higher, than at young patients (18-45 years).
The renal failure
At easy (clearance of creatinine of 50-80 ml/min.) and moderated (clearance of creatinine of 30-49 ml/min.) degrees of a renal failure pharmacokinetics of a sildenafil after single dose in 50 mg does not change. In a heavy renal failure (clearance of creatinine & lt, 30 ml/min.) the clearance of a sildenafil decreases that leads to approximately double increase in AUC (126%) and Cmax (73%).
The liver failure
At patients with cirrhosis (Chayld-Pyyu And yes C) clearance of a sildenafil decreases that also Cmax for 47% leads to increase in AUC for 84%.
of Silmelt – drug for treatment of disturbances of an erection. Sildenafil citrate is selection inhibitor of tsGMF-specific phosphodiesterase of type 5 (FDE5). The physiological mechanism of an erection of a penis assumes release of nitrogen oxide (NO) in a cavernous body at sexual stimulation.
Nitrogen oxide activates enzyme guanylate cyclase that leads to increase in level of the cyclic guanozinmonofosfat (tsGMF), relaxation of unstriated muscles of a cavernous body and strengthening of a blood-groove in a penis. At sexual excitement, local release NO under the influence of a sildenafil leads to oppression of FDE5 and increase in the tsGMF level in a cavernous body therefore there is a relaxation of unstriated muscles and strengthening of a blood-groove in a cavernous body. Use of a sildenafil in the recommended doses is inefficient in the absence of sexual stimulation.
Silmelt does not influence visual acuity, perception of contrast, electroretinogram indicators, intraocular pressure or diameter of a pupil.
Drug in a dose of 100 mg does not affect physical activity or morphology of spermatozoa at its single dose.
– treatment of the disturbances of an erection which are characterized by inability to achievement or preservation of an erection of a penis sufficient for satisfactory sexual intercourse
of Silmelt it is effective only in the presence of sexual stimulation.
To apply a route of administration and doses in order to avoid complications strictly on doctor’s orders!
The recommended dose for most of patients – 50 mg inside approximately in 1 hour prior to sexual intercourse. Taking into account efficiency and shipping the dose can be increased up to 100 mg. The maximum recommended dose – 100 mg and frequency rate of use – once a day.
The renal failure
At easy and medium-weight degree of insufficiency of function of kidneys (clearance of creatinine of 30-80 ml/min.) correction of a dose is not required, at heavy (clearance of creatinine & lt, 30 ml/min.) – the dose is reduced to 25 mg.
A liver failure
At patients with easy and medium-weight insufficiency of function of a liver Silmelt’s dose can be lowered to 25 mg.
Combined use with other medicines
At combined use with ritonaviry the maximum single dose of Silmelt has to make 25 mg not more often than 1 time during the 48th hour.
At combined use with inhibitors of P450 3A4 cytochrome (such as erythromycin, sakvinavir, ketokonazol, itrakonazol) the single dose of Silmelt makes 25 mg. It is necessary to consider the possibility of use of Silmelt along with these drugs.
For reduction of risk of developing orthostatic hypotension, the condition of the patients accepting alpha adrenoblockers has to be stable before Silmelt’s use. Decrease in a single dose is recommended.
Correction of a dose is not required.
Very often (& gt, 1/10)
– a headache
– a vazodilatation (inflows of blood to the person)
it is frequent (& gt, 1/100, & lt, 1/10)
– change of sight (the obscured sight, change of light sensitivity)
– a chromatopsia (easy and passing, mainly change of perception
of shades of color)
– a cardiopalmus
– rhinitis (congestion of a nose)
Infrequently (≥1/1000 & lt, 1/100)
– skin rash
– a stethalgia, myalgia, the general weakness, drowsiness
– a giposteziya
Seldom (≥1/10000 & lt, 1/1000)
– decrease or a hearing loss
– a myocardial infarction, fibrillation of auricles
– hypertensia, hypotension
– nasal bleeding
– decrease or loss of sight owing to not arterial front ischemic optical neuropathy
– a spasm, a recurrence of spasms
– serious cardiovascular events, including a myocardial infarction, a sudden cardiac death, ventricular arrhythmia, the cerebrovascular hemorrhagic and tranzitorny ischemic attacks associated with reception of a sildenafil
of the Contraindication
– hypersensitivity to a sildenafil or any component of drug
– a concomitant use of drugs, being donators of nitrogen oxide,
organic nitrates or nitrites in any forms
– a heavy liver failure
– heart failure
– unstable stenocardia,
the myocardial infarction postponed to the last 6 months, a stroke or zhizneugrozhayushchy arrhythmias
– arterial hypertension (the arterial blood pressure (ABP) & gt, 170/100 mm Hg)
or arterial hypotonia (the ABP & lt, 90/50 mm Hg)
– the established congenital degenerative diseases of a retina
(pigmentary retinitis, congenital defect of retinal phosphodiesterases)
– children’s and teenage age up to 18 years
– is not intended for use for women
anatomic deformation of a penis (including, an angulation, cavernous fibrosis or Peyroni’s disease)
the diseases contributing to development of a priapism (such as it is crescent – cellular anemia, a multiple myeloma, a leukosis, a trombotsitemiya)
the diseases which are followed by bleeding
exacerbation of a peptic ulcer
a hereditary pigmentary retinitis
of the Research in vitro Metabolism of a Sildenafil it is generally mediated by isoforms 3A4 (main way) and 2C9 (a minor way) P450 (CYP) cytochrome. For this reason inhibitors of these isoenzymes can lower, and inductors of these isoenzymes to increase clearance of a sildenafil.
The researches in Vivo
the Population pharmacokinetic analysis of these clinical trials confirms decrease in clearance of a sildenafil at a concomitant use with CYP3A4 inhibitors (such as ketokonazol, erythromycin and Cimetidinum).
Cimetidinum (800 mg) which is inhibitor of P450 cytochrome and nonspecific CYP3A4 inhibitor caused increase in concentration of a sildenafil in plasma for 56% at simultaneous use with sildenafily (in a dose of 50 mg) in healthy volunteers.
At reception of a sildenafil in a single dose of 100 mg together with erythromycin, specific CYP3A4 inhibitor, in the set mode (500 mg twice a day within 5 days), increase in system influence of a sildenafil by 182% was observed (on AUC). Besides, the concomitant use of inhibitor of HIV protease of the sakvinavir which is CYP3A4 inhibitor in the set mode (three times a day) with sildenafily (100 mg a single dose) led 1200 mg to increase in Cmax of a sildenafil by 140% and also increase in AUC of a sildenafil by 210%. Sildenafil did not influence pharmacokinetics of a sakvinavir. Stronger CYP3A4 inhibitors, such as ketokonazol and itrakonazol as believe, would have more significant effect.
The concomitant use of inhibitor of HIV protease of the ritonavir which is strong inhibitor of P450 cytochrome in the set mode (twice a day) with sildenafily (100 mg a single dose) led 500 mg to increase in Cmax of a sildenafil by 300% (4-multiply) and also to increase in AUC of a sildenafil in plasma for 1000% (11-multiply). In 24 hours the levels of a sildenafil in plasma still were about 200 ng/ml in comparison with about 5 ng/ml after reception only sildenafit. On these data it will be agreed with the significant effects of a ritonavir on a wide range of P450 substrates. Sildenafil did not influence pharmacokinetics of a ritonavir.
At reception according to the recommendations of a sildenafil by the patients receiving strong CYP3A4 inhibitors, the maximum concentration of a free sildenafil in plasma did not exceed 200 nanometers at one of persons, and drug was well transferred. Single reception of antiacid means (hydroxide aluminum hydroxide magnesium) did not affect bioavailability of a sildenafil.
The pharmacokinetic data obtained in clinical trials indicate lack of influence of inhibitors of an isoenzyme of CYP2C9 cytochrome (tolbutamide, warfarin), CYP2D6 cytochrome isoenzyme inhibitors (selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and tiazidopodobny diuretics, inhibitors of the angiotensin-converting enzyme (ACE) and antagonists of calcium on pharmacokinetics of a sildenafil.
At combined use at male normal healthy volunteers of signs of influence of azithromycin (in a dose of 500 mg a day within 3 days) on indicators of AUC, Cmax, Tmax, a constant of speed of elimination or the subsequent elimination half-life of a sildenafil or its main circulating metabolite it is not revealed.
Silmelt’s influence on other medicines
of the Research in vitro
Sildenafil is weak inhibitor of isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 of P450 cytochrome (IK50 & gt, 150 microns).
Provided that peak concentration of a sildenafil in plasma make about 1 micron after reception of the recommended drug doses, it is improbable that sildenafit will change clearance of substrates of these isoenzymes.
The researches in Vivo
It was shown that sildenafit strengthens hypotensive effect of nitrates both at prolonged use of the last, and at their appointment according to sharp indications. Therefore its reception is contraindicated to the patients receiving constantly or with breaks treatment by donors of nitrogen oxide, organic nitrates or organic nitrites in any form.
During three special researches of interaction of medicines, alpha adrenoblocker docsazozin (in a dose of 4 mg and 8 mg) also sildenafit (in a dose of 25 mg, 50 mg or 100 mg) applied at the same time at patients with the benign hyperplasia of a prostate (BHP) which course was stabilized by means of therapy docsazoziny. In these studied groups of patients the average additional lowering of arterial pressure in a dorsal decubitus on 7/7 mm Hg., 9/5 mm Hg was observed. and 8/4 mm Hg., and the average additional lowering of arterial pressure in a standing position made 6/6 mm Hg., 11/4 mm Hg. and 4/5 mm Hg., respectively. At simultaneous use of a sildenafil and docsazozin for the patients stabilized by means of therapy docsazoziny it was reported about exceptional cases of emergence at patients of symptomatic postural arterial hypotension. These messages also included cases of dizziness and a preunconscious state, but not a faint. Simultaneous use of a sildenafil for the patients receiving treatment by alpha adrenoblockers can lead to developing of symptomatic arterial hypotension at some sensitive patients.
At simultaneous use of a sildenafil (in a dose of 50 mg) with tolbutamide (in a dose of 250 mg) or warfarin (in a dose of 40 mg), both from which are metabolized by CYP2C9, considerable interactions it was revealed not.
Silmelt (100 mg) did not influence pharmacokinetics in steady state of inhibitors of HIV protease, a sakvinavir and ritonavir, both from which are CYP3A4 substrates.
Silmelt (50 mg) did not promote increase in the bleeding time caused by intake of aspirin (in a dose of 150 mg).
Silmelt (50 mg) did not promote strengthening of hypotensive effect of alcohol at healthy volunteers at the average maximum levels of alcohol in blood of 0.08% (80 mg/dl).
At patients with arterial hypertension of signs of interaction of a sildenafil (100 mg) with amlodipiny it is not revealed. The average additional lowering of arterial pressure in a dorsal decubitus made 8 mm Hg. for systolic and 7 mm Hg. for diastolic.
The analysis of the database on safety did not reveal differences in a profile of side effects at the patients accepting sildenafit in combination with antihypertensive drugs and without them.
For diagnosis of erectile dysfunction, definition of its possible reasons and the choice of adequate treatment need to be collected the full medical anamnesis and to perform careful physical examination.
The sexual activity represents a certain risk in the presence of heart diseases therefore before any therapy concerning erectile dysfunction the doctor should perform examination of a cardiovascular system.
Men to whom the sexual activity is undesirable should not appoint the drugs intended for treatment of erectile dysfunction.
During the post-registration period, cases of serious cardiovascular complications, including a myocardial infarction, a sudden cardiac death, ventricular arrhythmia, cerebrovascular bleeding and the tranzitorny ischemic attack were registered, during use of a sildenafil for treatment of erectile dysfunction. The majority, but not everything, from these patients had the previous risk factors of cardiovascular diseases. Many of these phenomena were registered in time or soon after completion of sexual intercourse and also several phenomena were registered soon after reception of a sildenafil without sexual activity. Others took place in several hours or days after use of a sildenafil and sexual activity. There is no opportunity to define whether these phenomena were connected directly with reception of a sildenafil, with sexual activity, with the available cardiovascular disease, with a combination of these factors or with other factors.
Clinical trials showed that sildenafit has the systemic vasodilating action leading to a passing lowering of arterial pressure. At most of patients it has insignificant consequences or has no consequences. However before purpose of a sildenafil the doctors should check carefully the probability of undesirable consequences of vasodilating effect of this drug for a condition of patients with certain background diseases, especially in their combination to sexual activity. To group of hypersensitivity to vasodilators patients treat with narrowing of output department of a left ventricle (for example, a stenosis of the aortal valve, a hypertrophic subaortic stenosis) and also patients with a rare syndrome of the multiple system atrophy which is shown in the form of heavy extent of disturbance of regulation of the ABP from the autonomic nervous system.
In rare instances during post-registration use of all FDE-5 inhibitors, including sildenafit, reported about not arterial front ischemic optical neuropathy of an optic nerve (NPINZN), a rare disease and the reason of decrease or loss of sight. At most of these patients had risk factors, such as: the age is more senior than 50 years, a papilledema (a stagnant disk), diabetes, a hypertension, coronary heart disease, a lipidemia and smoking. In an observation research estimated whether recent use of drugs of a class of FDE5 inhibitors is connected with acute onset of NPINZN. Results demonstrate approximately 2-fold increase in risk of NPINZN during an interval of time equal to 5 elimination half-life of FDE5 inhibitor. In case of unexpected deterioration or loss of sight, patients are recommended to stop Silmelt’s reception and to consult immediately with the doctor. Persons who already had NPINZN case have the increased risk of a recurrence of NPINZN. Therefore doctors should discuss this risk with such patients and also to discuss the probability of an adverse effect of FDE5 inhibitors on them. Such patients have FDE5 inhibitors, including Silmelt, it is not recommended.
It is recommended to apply with care sildenafit at the patients taking the drug of group of alpha adrenoblockers as their simultaneous use can lead to symptomatic arterial hypotension at some sensitive patients. For reduction of risk of development of postural arterial hypotension the condition of the patients receiving alpha adrenoblockers has to be stable prior to treatment sildenafily. It is necessary to consider expediency of an initiation of treatment low doses of a sildenafil. Besides, doctors should recommend to patients that to do to them in case of symptoms of postural hypotension.
The small number of patients with a hereditary pigmentary retinitis has genetically determined disturbances of functions of phosphodiesterases of a retina of an eye. Data on safety of use of a sildenafil for patients with a pigmentary retinitis are absent therefore sildenafit it is necessary to apply with care.
The researches in vitro with use of thrombocytes of the person demonstrate that sildenafit enhances anti-aggregation effect of Sodium nitroprussidum (donor of nitrogen oxide). Data on safety of use of a sildenafil for patients with disturbances of blood clotting or an active round ulcer are absent therefore sildenafit it is necessary to apply with care.
Medicines for treatment of erectile dysfunction should be used with care at patients with anatomic deformation of a penis (such as angulation, cavernous fibrosis or Peyroni’s disease) and also at patients with the diseases contributing to development of a priapism (such as sickemia, multiple myeloma or leukemia).
Safety and efficiency of use of a sildenafil in a combination with other methods of treatment of erectile dysfunction was not investigated and use of such combinations of drugs is not recommended.
In some post-market and clinical trials with use of all FDE-5 inhibitors, including sildenafit, it was reported about sudden decrease or a hearing loss at patients. Most of these patients had risk factors of developing this pathology. Relationship of cause and effect between use of FDE-5 inhibitors and sudden decrease or a hearing loss was not revealed. To patients it is necessary to recommend to stop in case of sudden decrease or a hearing loss therapy sildenafily and to consult immediately with the doctor.
Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms
Considering side effects of medicine, it is necessary to be careful at control of motor transport or other potentially dangerous mechanisms.
Symptoms: strengthening of side effects.
Treatment: symptomatic. The hemodialysis is not effective.
The form of release and packing
of the Tablet dispersed in an oral cavity of 50 mg and 100 mg.
On 2 tablets place in blister strip packaging from aluminum foil from one party and aluminum printing foil on the other hand.
On the 2nd blister strip packagings together with the instruction for medical use in the state and Russian languages place in a pack from cardboard.
To Store storage conditions in the dry, protected from light place, at a temperature not over 25C.
To store out of children’s reach!
not to use a period of storage after an expiration date.
According to the prescription
MSN Laboratories Private Limited Plot No 42, Anrich Industrial Estate, Bollaram, Medak District Producer – 502,325. A. P., India