EFFEX Sildenafil - instructions for use, dose, side effects, contraindications

	50 mg	100 mg
Active substance:
Sildenafil citrate	- 70.25 mg	- 140.50 mg
(in terms of sildenafil)	(50.00 mg)	(100.00 mg)
Excipients:
Microcrystalline cellulose	- 126.37 mg	- 252.74 mg
Calcium hydrophosphate	- 41.25 mg	- 82.50 mg
Starch Pceloid	- 27.50 mg	- 55.00 mg
Magnesium stearate	- 4.13 mg	- 8.26 mg
Croscarmellose sodium	- 2.75 mg	- 5.50 mg
Silica colloidal dioxide	- 2.75 mg	- 5.50 mg
FROMshell left:
Hypromellose (hydroxypropylmethylcellulose)	- 4.71 mg	- 9.42 mg
Macrogol 4000 (polyethylene glycol 4000)	- 2.35 mg	- 4.70 mg
Titanium dioxide	- 2.83 mg	- 5.66 mg
Iron Oxide Red Dye Oxide	- 0.02 mg	- 0.04 mg
Dye iron oxide yellow	- 0.09 mg	- 0.18 mg

Description:

The tablets are round, biconvex, covered with a film coat from pale orange with pinkish scum to pale brown with pinkish color; on the cross-section the nucleus is from white to almost white.

Pharmacotherapeutic group:Erectile dysfunction remedy - PDE5-inhibitor

ATX: & nbsp

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

G.04.B.E.03 Sildenafil

Pharmacodynamics:

Sildenafil is a potent selective inhibitor of cyclic guanosine monophosphate (cGMP) -specific phosphodiesterase type 5 (PDE5).

The basis of the physiological mechanism of erection is the release of nitric oxide (NO) in the cavernous body during sexual stimulation. This, in turn, leads to an increase in the level of cGMP, resulting in relaxation of the smooth muscle tissue of the cavernous body and increased blood flow in the cavernous body.

Sildenafil does not have a direct relaxing effect on an isolated cavernous body, but enhances the relaxing effect of nitric oxide, causing oppression of PDE5, which is responsible for the disintegration of cGMP in the cavernous body.

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

Research in vitro showed that sildenafil selective for PDE5. Its activity against other known isoenzymes is much lower: PDE6 - 10 times, PDE1 - more than 80 times, PDE2, PDE4, FDE7-11 - more than 700 times. Sildenafil is 4000 times more active with respect to PDE5 than with FDES, which is of great importance, since FDEZ is one of the key enzymes in the regulation of myocardial contractility.

A mandatory condition for the effectiveness of sildenafil is sexual stimulation.

The use of sildenafil in doses up to 100 mg led to an easy short-term decrease in blood pressure. The hypotensive effect is associated with the vasodilating effect of sildenafil, associated with an increase in the level of cGMP in the smooth muscle cells of the vessels.

In some patients, an easy and transient impairment in the ability to distinguish between shades of color (blue / green) was detected 1 hour after taking the drug at a dose of 100 mg with the Farnsworth-Munssel test 100. After two hours, the color perception was restored. Disorder of color vision is caused by inhibition of PDE6, which is involved in the process of transmission of light in the retina. Sildenafil does not affect visual acuity, contrast perception, electro-retinogram, intraocular pressure or pupil diameter.

Pharmacokinetics:

Suction

After oral administration, it is rapidly absorbed.The maximum concentration in the blood plasma is reached within 30-120 minutes (an average of 60 minutes) when administered on an empty stomach. Bioavailability varies from 25 to 63%. When taken in combination with fatty foods, the rate of absorption decreases: C_mOh decreases by an average of 29%, and the time to reach the maximum concentration (T_mOh) is increased by 60 min, but the degree of absorption does not change significantly (the area under the pharmacokinetic concentration-time curve (AUC) is reduced by 11%).

Distribution

The volume of distribution of sildenafil in the equilibrium state averages 105 liters. Connection with plasma proteins of sildenafil and its main circulating N-detyl metabolite is approximately 96% and does not depend on the total drug concentration. Less than 0.0002% of the dose (an average of 188 ng) is found in the sperm 90 minutes after taking sildenafil.

Metabolism

Sildenafil is metabolized mainly in the liver by the action of microsomal isoenzymes of cytochrome P450: CYP3A4 (main path) and CYP2C9 (secondary path). The main circulating metabolite formed as a result of N-detylation of sildenafil, undergoes further metabolism.The selectivity of this metabolite on PDE is comparable to that of sildenafil, and its activity in relation to PDE5 in vitro is about 50% of the activity of sildenafil. The concentration of the metabolite in the blood plasma is about 40% of the concentration of sildenafil. N-detyl metabolite undergoes further metabolism; the final half-life is about 4 hours.

Excretion

The total clearance of sildenafil is 41 liters / hour, and the final half-life period is 3-5 hours. After oral administration sildenafil is excreted in the form of metabolites, mainly by the intestine (approximately 80% of the oral dose) and, to a lesser extent, by the kidneys (approximately 13% of the oral dose).

Pharmacokinetics in special gRUpp patientsthe

Elderly Patients

In healthy elderly patients (65 years and older), the clearance of sildenafil is reduced, and the concentration of free sildenafil in plasma is about 40% higher than in young (18-45 years). Age does not have a clinically significant effect on the incidence of side effects.

Renal impairment

In mild (creatinine clearance 50 to 80 ml / min) and moderate (KK 30-49 ml / min) degree of renal insufficiency, the pharmacokinetics of sildenafil after single ingestion at a dose of 50 mg does not change.In severe renal failure (CK <30 ml / min), the clearance of sildenafil decreases, which leads to an approximately twofold increase in the area under the pharmacokinetic concentration-time curve AUC (100%) and C_max(88%) in comparison with those for normal kidney function in patients of the same age group.

Dysfunction of the liver

In patients with cirrhosis of the liver (stages A and B according to the Child-Pugh classification), the clearance of sildenafil decreases, which leads to an increase AUC (84%) AND FROM_mOh (47%) by compared with those for normal liver function in patients of the same age group. The pharmacokinetics of sildenafil in patients with severe impairment of liver function (Stage C according to the Child-Pugh classification) has not been studied.

Indications:

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

EFFEX® Sildenafil is effective only with sexual stimulation.

Contraindications:

Hypersensitivity to sildenafil or to any other component of the drug.

Use in patients who receive permanently or intermittently donators of nitric oxide, organic nitrates or nitrites in any form, since EFFEX® Sildenafil strengthens the hypotensive effect of nitrates (see section "Interaction with other drugs").

Safety and efficacy of EFFEX® Sildenafil when combined with other treatment tools, erectile dysfunction has not been studied, so the use of such combinations is not recommended (see section "Special instructions").

Joint use with ritonavir.

Dysfunction of the liver.

Chronic renal failure of severe severity.

Severe heart failure, unstable angina, transferred during the last 6 months, stroke or myocardial infarction, life-threatening arrhythmias, hypertension (BP> 170/100 mm Hg), or hypotension (BP <90/50 mm Hg) (see section "Special instructions").

According to the registered indication, EFFEX® Sildenafil Not suitable for use in children under 18 years of age.

According to the registered indication, EFFEX® Sildenafil not suitable for use in women.

Carefully:

Anatomic deformation of the penis (angulation, cavernous fibrosis or Peyronie's disease) (see section "Special instructions").

Diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia) (see section "Special instructions").

Diseases accompanied by bleeding.

Exacerbation of peptic ulcer of stomach and duodenum.

Hereditary retinitis pigmentosa (see section "Special instructions").

Pregnancy and lactation:

Pon the registered indication the drug is not intended for use in women.

Dosing and Administration:

Inside.

The recommended dose for most adult patients is 50 mg of sildenafil for about 1 hour before sexual activity.

With regard to efficacy and tolerability, the dose can be increased to 100 mg. The maximum recommended dose is 100 mg. Maximum recommended multiplicity of application - 1 once a day.

Elderly patients

Correction of the dose of EFFEX® Sildenafil not required.

Renal impairment

For patients with mild or moderate severity of renal failure (CK 30-80 ml / min), dose adjustment is not required.

Joint use with other drugs

To minimize the risk of postural hypotension in patients,taking adrenoblockers, the use of sildenafil should be started only after achieving stabilization of hemodynamics in these patients. It should also consider the desirability of reducing the initial dose of sildenafil (see section "Interaction with other drugs" and "Special instructions").

Side effects:

The most common side effects were headache and "hot flashes".

Usually the side effects of EFFEX® Sildenafil weakly or moderately expressed and of a transient nature.

In studies using a fixed dose, it has been shown that the incidence of certain adverse events increases with increasing doses.

The frequency of adverse reactions is presented in the following classification:

Often	≥10%
Often	≥1% and < 10%
HOften	≥0,1% and < 1%
Rarely	≥0,01% and < 0,1%
Rarely	< 0,01%
Frequency unknown	HIt is impossible to determine from the available data

From the immune system: infrequently - reactions of hypersensitivity (including skin rash), allergic reactions.

From the side of the organ of vision: often - blurred vision, impaired vision, cyanopsy; infrequently - pain in the eyes, photophobia, photopsy, chromatopsy, red eyes / injections sclera,change in brightness of light perception, mydriasis, conjunctivitis, hemorrhage in the eye tissue, cataract, disruption of the tear apparatus; rarely - swelling of eyelids and adjacent tissues, dry eyes, the presence of iridescent circles in the field of view around the light source, increased eye fatigue, vision of objects in yellow color (xanthopsia), vision of objects in red (erythropsy), conjunctival hyperemia, irritation of the eye mucosa , unpleasant sensations in the eyes; frequency unknown - non-arterial anterior ischemic optic nerve neuropathy (NPINZ), retinal vein occlusion, visual field defect, diplopia *, temporary loss of vision or visual acuity, increased intraocular pressure, retinal edema, retinal vascular disease, vitreous humor / vitreous tract.

From the organ of hearing: infrequently - sudden decrease or loss of hearing, tinnitus, pain in the ears.

From the cardiovascular system: often - "tides"; infrequently - tachycardia, palpitations, decreased blood pressure, increased heart rate, unstable angina, atrioventricular block,myocardial ischemia, cerebral vascular thrombosis, cardiac arrest, heart failure, deviations in electrocardiogram indications, cardiomyopathy; rarely - atrial fibrillation.

From the side of the blood and lymphatic system: infrequently - anemia, and leukopenia.

From the side of metabolism and nutrition: infrequently - Thirst, swelling, gout, uncompensated diabetes mellitus, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemia, hypernatremia.

From the respiratory system: often - nasal congestion; infrequently - nosebleeds, rhinitis, asthma, dyspnoea, laryngitis, pharyngitis, sinusitis, bronchitis, increased volume of sputum, increased cough; rarely - a feeling of tightness in the throat, dryness of the mucous membrane of the nasal cavity, swelling of the nasal mucosa.

From the gastrointestinal tract: often - nausea, dyspepsia; infrequently gastroesophageal reflux disease, vomiting, abdominal pain, dryness of oral mucosa, glossitis, gingivitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, deviation of "liver" functional tests from normal, rectal bleeding; rarely - hyposthenia of the oral mucosa.

From the side of the musculoskeletal system: often - backache; infrequently - myalgia, pain in the extremities, arthritis, arthrosis, tendon rupture, tenosynovitis, bone pain, myasthenia gravis, synovitis.

From the genitourinary system: infrequently - cystitis, nocturia, enlargement of the mammary glands, urinary incontinence, hematuria, ejaculation, genital edema, anorgasmia, hematospermia, damage to the tissues of the penis; rarely - prolonged erection and / or priapism.

From the central and peripheral nervous system: Often - headache; often - dizziness; infrequently - drowsiness, migraine, ataxia, hypertonus, neuralgia, neuropathy, paresthesia, tremor, vertigo, depressive symptoms, insomnia, unusual dreams, increased reflexes, kinesthesia; rarely - convulsions *, repeated convulsions *, fainting.

From the skin and subcutaneous tissues: infrequently - skin rash, hives, herpes simplex, pruritus, increased sweating, skin ulceration, contact dermatitis, exfoliative dermatitis; frequency unknown - Stevens-Johnson syndrome, toxic epidermal necrolysis.

Other: infrequently - fever, facial edema, photosensitivity reaction, shock, asthenia, fatigue, pain of different locations, chills, accidental falls, pain in the chest, accidental trauma; rarely Irritability.

* Side effects identified during post-marketing research.

Cardiovascular complications

During the postmarketing use of sildenafil for the treatment of erectile dysfunction, adverse events such as severe cardiovascular complications (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension ) who had a temporary connection with the use of sildenafil, most of these patients, but not all of them, had risk factors for cardiovascular complications. Many of these adverse events were observed soon after sexual activity, and some of them were noted after taking sildenafil without subsequent sexual activity. It is not possible to establish the presence of a direct link between the observed undesirable phenomena and these or other factors.

Visual disorders

In rare cases, during the postemergence application of all PDE5 inhibitors, including sildenafil, non-arteritic anterior ischemic arthropathy neuropathy (NPEVN) was reported - a rare disease and the cause of a decrease or loss of vision. Most of these patients had risk factors, in particular, a reduction in the ratio of the diameter of the excavation and the optic disc ("stagnant disk"), age over 50 years, diabetes, hypertension, coronary heart disease, hyperlipidemia and smoking. In the observational study, it was assessed whether the recent use of preparations of the class of PDE5 inhibitors with the acute onset of NPINZH was related.

The results indicate an approximately 2-fold increase in the risk of NPIIV within 5 half-lives after the use of the PDE5 inhibitor. According to the published literature, the annual incidence of NPINZH is 2.5-11.8 cases per 100 000 men aged> 50 years in the general population.

It should be recommended to patients in the event of a sudden loss of vision to stop sildenafil therapy and immediately consult a doctor.Persons who already had a case of NPINZ have an increased risk of recurrence of NPINZN. Therefore, the physician should discuss this risk with such patients, and discuss with them the potential chance of adverse effects of PDE5 inhibitors. PDE5 inhibitors, including sildenafil, these patients should be used with caution and only in situations where the expected benefit outweighs the risk.

Overdose:

When using the drug EFFEX® Sildenafil in doses exceeding the recommended, undesirable phenomena were similar to those noted above, but were usually more frequent.

Treatment is symptomatic. Hemodialysis does not accelerate the excretion of the drug, since sildenafil strongly binds to blood plasma proteins and is not excreted by the kidneys.

Interaction:

The effect of other drugs on the pharmacokinetics of sildenafil

The metabolism of sildenafil occurs mainly under the action of cytochrome isoenzymes CYP3A4 (main path) and CYP2C9, therefore inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inductors, respectively, increase the clearance of sildenafil.

There was a decrease in clearance of sildenafil with simultaneous use of cytochrome isoenzyme inhibitors CYP3A4 (ketoconazole, erythromycin, cimetidine).

Cimetidine (800 mg), a nonspecific inhibitor of the cytochrome isoenzyme CYP3A4, with a joint admission with sildenafil (50 mg) causes an increase in the concentration of sildenafil in plasma by 56%.

A single dose of 100 mg of sildenafil together with erythromycin (500 mg / day 2 times a day for 5 days), a moderate inhibitor of the cytochrome isoenzyme CYP3A4, on the background of achieving a constant concentration of erythromycin in the blood, leads to an increase AUC sildenafil by 182%.

With the joint administration of sildenafil (once 100 mg) and saquinavir (1200 mg / day 3 times a day), an inhibitor of HIV protease and cytochrome isoenzyme CYP3A4, against the background of achieving a constant concentration of saquinavir in the blood C_mOhsildenafil increased by 140%, a AUC increased by 210%. Sildenafil does not affect the pharmacokinetics of saquinavir.

More potent inhibitors of cytochrome isoenzyme CYP3A4, such as ketoconazole and itraconazole, can cause and stronger changes in the pharmacokinetics of sildenafil.

Simultaneous use of sildenafil (once 100 mg) and ritonavir (500 mg 2 a day), an HIV protease inhibitor and a strong cytochrome inhibitor P450, on the background of achieving a constant concentration of ritonavir in the blood leads to an increase in C_mOhsildenafil by 300% (4 times), a AUC on 1000% (in 11 times). After 24 hours, the concentration of sildenafil in the blood plasma is about 200 ng / ml (after a single application of one sildenafil - 5 ng / ml).

If sildenafil use in recommended doses of patients receiving simultaneously strong inhibitors of the cytochrome isoenzyme CYP3A4, then C_mOh free sildenafil does not exceed 200 nM, and the drug is well tolerated.

A single dose of antacid (hydroxide / magnesium hydroxide, aluminum) did not affect the bioavailability of sildenafil.

In studies involving healthy volunteers with simultaneous use of an endothelin receptor antagonist, bosentan (isoenzyme inducer CYP3A4 (moderate), CYP2C9 and, possibly, CYP2C19) at an equilibrium concentration (125 mg twice in knots) and sildenafil at an equilibrium concentration (80 mg three times a day) there was a decrease AUC and C_max sildenafil by 62.6% and 52.4% respectively. Sildenafil increased AUC and C_mOh bosentan by 49.8% and 42% respectively. It is assumed that the simultaneous use of sildenafil with powerful isoenzyme inducers CYP3A4, such as rifampicin, can lead to a large decrease in the concentration of sildenafil in blood plasma.

Inhibitors of cytochrome isoenzyme CYP2C9 (tolbutamide, warfarin), cytochrome isoenzyme CYP2D6 (selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-like diuretics, ACE inhibitors and calcium antagonists have no effect on the pharmacokinetics of sildenafil.

Azithromycin (500 mg / day for 3 days) does not affect AUC, FROM_mOh, T_mOh, the rate constant of excretion and T_1/2 sildenafil or its main circulating metabolite.

Effect of sildenafil on other drugs

Sildenafil is a weak inhibitor of cytochrome isoenzymes P450 - 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IR₅₀> 150 μmol). When taking sildenafil in the recommended doses of its C_mOh is about 1 μmol, so it is unlikely that sildenafil can affect the clearance of the substrates of these isoenzymes.

Sildenafil enhances the hypotensive effect of nitrates both with prolonged use of the latter, and when they are prescribed for acute indications. In this regard, the use of sildenafil in combination with nitrates or donators of nitric oxide is contraindicated.

With the simultaneous administration of α-adrenoblocker doxazosin (4 mg and 8 mg) and sildenafil (50 mg and 100 mg) in patients with benign prostatic hyperplasia with stable hemodynamics, the mean additional decrease in systolic / diatonic blood pressure in the supine position was 9/5 mm Hg. Art. and 8/4 mm Hg. Art. respectively, and in the standing position 11/4 mm Hg. Art. and 4/5 mm Hg. Art. respectively. We report rare cases of development in these patients of symptomatic postural hypotension, manifested as dizziness (without syncope). Individual sensitive patients receiving α- adrenoblockers, simultaneous use of sildenafil can lead to symptomatic hypotension.

Signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the isoenzyme of cytochrome CYP2C9, have not been identified.

Sildenafil (100 mg) does not affect the pharmacokinetics of HIV protease, saquinavir and ritonavir inhibitors, which are substrates of the cytochrome isoenzyme CYP3A4, at their constant level in the blood.

Simultaneous use of sildenafil in an equilibrium state (80 mg three times a day) leads to an increase AUC and C_mOh bosentan (125 mg twice daily) by 49.8% and 12% respectively.

Sildenafil (50 mg) does not cause an additional increase in bleeding time when taking acetylsalicylic acid (150 mg).

Sildenafil (50 mg) does not increase the hypotensive effect of alcohol in healthy volunteers with a maximum blood alcohol concentration of 0.08% (80 mg / dl) on average.

In patients with arterial hypertension, signs of interaction between sildenafil (100 mg) with amlodipine was not detected. The average additional decrease in blood pressure in the prone position is 8 mm Hg. Art. (systolic) and 7 mm Hg. Art. (diastolic). The use of sildenafil in combination with antihypertensive drugs does not lead to additional side effects.

Special instructions:

To diagnose erectile dysfunction, determine their possible causes and choose an adequate treatment, you must collect a complete medical history and conduct a thorough physical examination.

Erectile dysfunction treatment agents should be used with caution in patients with anatomical deformation of the penis (angulation, cavernous fibrosis, Peyronie's disease) or in patients with risk factors for priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocythemia) (see section "C caution ").

During postmarketing studies, cases of development of prolonged erection and priapism were reported. If the erection persists for more than 4 hours, you should immediately seek medical help. If priapism therapy has not been performed immediately, it can lead to damage to the penile tissue and an irreversible loss of potency.

Drugs intended for the treatment of erectile dysfunction should not be prescribed to men for whom sexual activity is undesirable.

Sexual activity represents a certain risk in the presence of heart disease, so before starting any therapy for erectile dysfunction, the doctor should refer the patient to a cardiovascular system examination. Sexual activity is undesirable in patients with heart failure, unstable angina, transferred to the last 6 months with stroke or myocardial infarction, life-threatening arrhythmias, hypertension (BP> 170/100 mm Hg), or hypotension (BP <90/50 mm Hg) (see Contraindications section).

In clinical studies, there was no difference in the incidence of myocardial infarction (1.1 per 100 people per year) or mortality from cardiovascular disease (0.3 per 100 people per year)who received sildenafil, compared with patients receiving placebo.

Cardiovascular complications

During the postmarketing use of sildenafil, serious adverse events such as myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension, and hypotension were reported for the treatment of erectile dysfunction, such as serious cardiovascular complications ), which had a temporary connection with the use of sildenafil. Most of these patients, but not all of them, had risk factors for cardiovascular complications. Many of these adverse events were observed soon after sexual activity, and some of them were noted after taking sildenafil without subsequent sexual activity. It is not possible to establish the presence of a direct link between the observed undesirable phenomena and these or other factors.

Dapoptosis

Sildenafil has a systemic vasodilating effect, leading to a transient decrease in blood pressure, which is not clinically significant and does not lead to any consequences for most Nazis.Nevertheless, before the appointment of sildenafil, the doctor should carefully evaluate the risk of possible undesirable manifestations of vasodilating action in patients with the corresponding diseases, especially against the background of sexual activity.

Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with a rare syndrome of multiple systemic atrophy, manifested severe violation of the regulation of blood pressure from the autonomic nervous system.

Since the joint use of sildenafil and α- adrenoblockers can lead to symptomatic hypotension in selected sensitive patients, sildenafil should be administered with caution to patients taking α-blockers (see section "Interaction with other drugs"). To minimize the risk of postural hypotension in patients taking α-adrenoblockers, sildenafil should be taken only after stabilization of hemodynamic parameters in these patients has been achieved.It should also consider the desirability of reducing the initial dose of sildenafil (see section "Method of administration and dose"). The doctor should inform patients about what actions should be taken in case of symptoms of postural hypotension.

Visual disorders

In rare cases, during the post-marketing application of all PDE5 inhibitors, including sildenafil, non-arteritis anterior ischemic optic neuropathy (NPINZN) was reported - a rare disease and the cause of a decrease or loss of vision. Most of these patients had risk factors, in particular, a reduction in the ratio of the diameter of the excavation and the optic disc ("stagnant disk"), age over 50 years, diabetes, hypertension, coronary heart disease, hyperlipidemia and smoking. In the observational study, it was assessed whether the recent use of preparations of the class of PDE5 inhibitors with the acute onset of NPINZH was related. The results indicate an approximately 2-fold increase in the risk of NPIIV within 5 half-lives after the use of the PDE5 inhibitor. According to the published literature, the annual incidence of NPIH is 2.5-11.8 cases per 100 000 men aged ≥ 50 years in the general population.

It should be recommended to patients in the event of a sudden loss of vision to stop sildenafil therapy and immediately consult a doctor. Persons who already had a case of NPINZ have an increased risk of recurrence of NPINZN. Therefore, the physician should discuss this risk with such patients, and discuss with them the potential chance of adverse effects of PDE5 inhibitors. PDE5 inhibitors, including sildenafil, these patients should be used with caution and only in situations where the expected benefit outweighs the risk.

A small number of patients with hereditary pigment retinitis have genetically determined violations of the function of phosphodiesterases of the retina. Information on the safety of sildenafil in patients with retinitis pigmentosa absent, so the drug should be used with caution (see section "With caution").

Hearing impairment

Some post-marketing and clinical studies report cases of sudden deterioration or hearing loss associated with the use of all PDE5 inhibitors, including sildenafil, most of these patients had risk factors for sudden deterioration or loss of hearing.The causal relationship between the use of PDE5 inhibitors and sudden deterioration of hearing or loss of hearing is not established. In the event of a sudden deterioration in hearing or hearing loss, taking sildenafil should immediately consult a doctor.

Bleeding

Sildenafil enhances the antiplatelet effect of sodium nitroprusside, a donator of nitric oxide, on human platelets in vitro. Data on the safety of sildenafil in patients with a tendency to bleeding or exacerbation of peptic ulcer of the stomach and duodenum are absent, therefore sildenafil these patients should be used with caution (see "With caution").

The frequency of nasal bleeding in patients with pulmonary hypertension associated with diffuse connective tissue diseases was higher (sildenafil 12.9%, placebo 0%) than in patients with primary pulmonary hypertension (sildenafil 3.0%, placebo 2.4%). In patients who received sildenafil in combination with a vitamin K antagonist, the incidence of nasal bleeding was higher (8.8%) than in patients who did not take a vitamin K antagonist (1.7%).

Application in conjunction with other treatments for erectile dysfunction

The safety and efficacy of sildenafil together with other PDE5 inhibitors or other drugs for the treatment of pulmonary hypertension containing sildenafil (such as Revacio®) or other means of treating erectile dysfunction have not been studied, so the use of such combinations is not recommended (see section "Ppotand quotations).

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

Since the use of sildenafil may develop dizziness, lower blood pressure, the development of chromatopsy, blurred vision, and the like. side effects, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions. Also, you should carefully consider the individual effect of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.

Form release / dosage:

Tablets, film-coated, 50 mg and 100 mg.

Packaging:

1 tablet in a bag (sachets) made of a film combined on the basis of polymer films and aluminum foil.

For 15 tablets (for a dosage of 100 mg) in a contour mesh package made of a polyvinylchloride film and flexible packaging made on the basis of aluminum foil.

For 1, 2, 4, 10 bags (sachets) or 1 contour pack, along with the instruction for use, is placed in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 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-004039

Date of registration:22.12.2016

Expiration Date:22.12.2021

The owner of the registration certificate:EVALAR, CJSC EVALAR, CJSC Russia

Manufacturer: & nbsp

EVALAR, CJSC Russia

Representation: & nbspEVALAR CJSC EVALAR CJSC Russia

Information update date: & nbsp24.01.2017

Illustrated instructions

Instructions

EFFEX® Sildenafil (EFFAX® Sildenafil)