active ingredient: sildenafil;
1 tablet contains 50 mg sildenafil citrate in terms of 100% sildenafil;
auxiliary substances: lactose, magnesium gluconate, powdered sugar, calcium stearate, flavor "Lemon", colouring agent tartrazine (E 102).
The main physical and chemical properties: biconvex yellow interspersed with a notch on the one hand and the company logo on the other.
Remedies used for erectile dysfunction.
ATC code G04B E03.
Pharmacodynamics. ERGOS is a preparation for oral administration intended for the treatment of erectile dysfunction. When sexual excitation of the drug is reduced restores erectile function by increasing blood flow to the penis.
ERGOS is a citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE-5).
The physiological mechanism that leads to erection is the release of nitric oxide (NO) in the cavernous bodies during sexual arousal. The released nitric oxide activates the enzyme guanylate cyclase, which causes an increase in the level of cyclic guanosine monophosphate (cGMP), which, in turn, causes relaxation of the smooth muscles of the muscles of the cavernous body and increase in blood flow in them.
Sildenafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effectiveness of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the cavernous body.
When sexual stimulation causes local release of NO, inhibition of PDE5 with sildenafil causes an increase in the level of cGMP in the cavernous body, resulting in relaxation of smooth muscles and increased blood flow to the cavernous body.
The use of sildenafil in recommended doses is ineffective in the absence of sexual stimulation.
In vitro studies have shown that sildenafil is selective relative to PDE-5. Its effect on PDE5 is stronger than other known PDE (ten times stronger than ФДЭ6, 80 times than ФДЕ1, 700 times than ФДЕ2, PDAS, ФДЕ4, ФДЕ7-ФДЕ11). In particular, sildenafil has 400 times better selectivity relative to PDE-5 than PDES, cGMP specific PDE isoforms, which takes part in processes of regulation of heart rate.
Efficiency. The effectiveness of sildenafil, which was assessed by the ability of the drug to provide offensive and maintaining an erection sufficient for intercourse, has been demonstrated and persisted with long-term use of the drug (1 year).
In the study, when taking sildenafil at doses of 25 mg or 50 mg, 100 mg improvement of erection was observed in 62%, 74%, 82% respectively. In addition to improving erectile function, ICEF analysis (international erectile function index) has shown that treatment with sildenafil also enhances orgasm and sexual satisfaction.
In the treatment of sildenafilom improvement was noted in 59% of patients with diabetes in patients who underwent radical prostatectomy, 43%, patients with spinal cord injury - 83%.
Pharmacokinetics. Within the recommended dose range, the pharmacokinetics of sildenafil is proportional to the dose. The drug is excreted mainly by biotransformation in the liver (mainly with the participation of cytochrome P450 3A4) with the formation of an active metabolite with properties similar to sildenafil.
Absorption. Sildenafil is rapidly absorbed after ingestion with absolute bioavailability in the environment 41% (25% - 63%). Sildenafil inhibits PDE5 enzyme in vitro by up to 50% at a concentration of 3.5 nm. The average concentration in the blood plasma after the use of sildenafil in a dose of 100 mg is approximately 18 ng/ml or 38 nm. The maximum concentrations, which were observed in blood plasma, were recorded after 30-120 min (average 60 min) after oral administration of fasting. In cases where the drug is taken with very fatty foods, the rate of absorption decreases, and the delay of Tmax is an average of 60 minutes, and the reduction in Cmax - an average of 29%, but the degree of absorption is not violated (AUC decreased by 11%).
Distribution. The average volume of distribution of sildenafil at steady state (Vss) is 105 liters, which indicates its penetration into the tissue. How sildenafil and its major circulating N-dimitrovi metabolite approximately 96% bound to plasma proteins the blood. Protein binding is independent of total concentrations. In healthy volunteers, receiving sildenafil (1 time in a dose of 100 mg), 90 minutes after taking the drug in the ejaculate was less than 0.0002% of the substance (an average of 188 ng) of the dose.
Metabolism. Sildenafil is metabolized isoenzymes liver, localized in microsomes, CYP 3A4 (major route) and CYP2C9 (minor route). The main circulating metabolite is formed as a result Of n-dimethylation of sildenafil. This metabolite is characterized by selectivity to PDE-5, similar to sildenafil, but its activity against PDE5 in vitro is approximately 50% of the selectivity of the initial drug. The concentrations of this metabolite in blood plasma are approximately 40% of the corresponding concentrations of sildenafil. N-dimitrovi metabolite is metabolized further, its ultimate half-life is approximately 4:00.
Breeding. The total clearance of sildenafil is 41 l/h, with an end half-life of 3-5 hours. In oral administration, sildenafil is excreted as metabolites, mainly with feces (about 80% of the dose) and to a lesser extent with urine (13% of the dose).
Pharmacokinetics in special groups of patients.
Patients of advanced age. Healthy elderly volunteers 65 years of age had reduced performance in clearance of sildenafil, and the concentrations of sildenafil and its N-dimetilovogo metabolite was about 90% higher than in healthy individuals (18-45 years). Given the age dependence in protein binding, the corresponding increase in the concentration of free sidenafilu plasma was almost 40%.
Patients with renal insufficiency. In volunteers with mild (creatinine clearance 50-80 ml/min) and moderate (creatinine clearance 30-49 ml/min) renal impairment, the pharmacokinetics of sildenafil were not altered after oral administration at a dose of 50 mg in volunteers with severe (creatinine clearance
Patients with insufficiency of liver function. In volunteers with mild to moderate liver cirrhosis (child-Pugh a and B), sildenafil clearance decreased, which was the reason for the increase in AUC (84%) and Cmax (47%), compared with the same volunteers, the same age, in which liver failure was diagnosed. Pharmacokinetics of sildenafil in patients with severe hepatic impairment (child-Pugh C) have not been studied.
Data from preclinical studies, which were based on conventional studies of safety, toxicity of doses of recurrent genotoxicity, Carcinogenicity and toxic effects on reproduction, showed no particular risk to humans.
ERGOS is recommended for men with erectile dysfunction, defined as how to achieve and maintain the penis erection necessary for successful sexual intercourse. For effective action of the ERGOS need sexual arousal.
The simultaneous use of ERGOS with nitric oxide donators (such as amyl nitrile) or nitrates in any form is contraindicated, since it is known that sildenafil affects the metabolism of nitric oxide/cyclic guanosinmonophosphate (cGMP) and potentiates the hypotensive effect of nitrates.
The drug should not be prescribed to patients for whom sexual activity is undesirable (for example, patients with unstable angina, with severe heart failure). - Patients with loss of vision by one eye due to nonarterial anterior ischemic neuropathy of the optic nerve, regardless of whether this pathology is associated with the previous use of PDE-5 inhibitors, or not.
The use of ERGOS is contraindicated in persons with increased individual sensitivity to the components of the drug.
Patients with the following diseases: severe liver dysfunction, arterial hypotension (blood pressure below 90/50 mm Hg.recent stroke or myocardial infarction and known hereditary degenerative retinal diseases, such as pigment retinitis (a small number of such patients have genetic disorders of retinal PDE), because the insanity of sildenafil has not been studied in such subgroups of patients.
Interaction with other medicinal products and other forms of interactions
The effect of other drugs on sildenafil.
In vitro studies: sildenafil metabolism is mediated mainly by cytochrome P450 (CYP), namely his ZA4 isoforms (major route) and 2C9 (minor route). Thus, inhibitors of these isoenzymes may reduce sildenafil elimination, inducers of these isoenzymes may increase its output.
In vivo studies: population pharmacokinetic analysis of clinical study results demonstrated a reduced clearance of sildenafil at its simultaneous application with inhibitors of CYP ZA4 (such as ketoconazole, erythromycin, cimetidine), although simultaneous use of sildenafil and inhibitors of CYP 3A4 increase in the frequency of side effects was observed, you should consider using an initial dose of sildenafil 25 mg. Cimetidine (800 mg), a cytochrome P450 inhibitor and non-specific inhibitor of CYP 3A4, while receiving sildenafil at a dose of 50 mg to healthy volunteers resulted in an increase in its plasma concentration by 56%.
When prescribed a single dose of 100 mg sildenafil with erythromycin, specific inhibitor CYP 3A4 (500 mg twice a day for 5 days), the dose of sildenafil (AUC) increased by 182%. Concomitant use of protease inhibitors HIV of saquinavir (1200 mg three times a day), which also is an inhibitor of CYP 3A4, resulted in an increase in sildenafil C Max 140%, AUC by 210%. Sildenafil. did not affect the pharmacokinetics of saquinavir. Strong CYP ZA4 inhibitors, such as ketoconazole and Itraconazole, can show more pronounced effects. Concomitant use of HIV protease inhibitor which is highly specific inhibitor of P450, in equilibrium (500 mg twice a day) sildenafilo (100 mg once) leads to a 300% (4 times) the maximum concentration of sildenafil Cmax and a 1000% (11-fold) AUC sildenafil in blood plasma. Given these pharmacokinetic data, the simultaneous use of sildenafil and ritonavir is not recommended. After 24 hours the concentration of sildenafil in plasma was approximately 200 ng/ml, while in the application of sildenafil concentration was 5 ng/ml. This is due to ritonavir on isozymes P450. Sildenafil does not affect the pharmacokinetics of ritonavir. When the dose of sildenafil for subjects that receive the CYP 3A4 inhibitor was used according to the recommendations, the concentration of sildenafil in blood plasma did not exceed 200 nm for any patient, and the drug had good tolerance. Grapefruit juice is a weak inhibitor of CYP 3A4 in the intestinal wall and can cause a moderate increase in the level of sildenafil in blood plasma.
Nicorandil is a hybrid of calcium channel activator and nitrate. Efrati component somabluewe the possibility of serious interaction with sildenafilom.
There are no data on the interaction of sildenafil and such nonspecific phosphodiesterase inhibitors like theophylline and dipyrimadole.
The simultaneous use of sildenafil and blockers of ?-adrenoreceptors may lead to symptomatic hypotension in some predisposed patients. This reaction often occurred within 4:00 after the application sildenafilo (see "Method of application and dosage" and "peculiarities of use").
Patients who used sildenafil, were observed no differences of the side profile of side effects compared to placebo while the use of such classes of antihypertensive drugs, like diuretics, blockers ?-adrenergic receptors, ACE inhibitors, angiotensin II antagonists, antihypertensive medicinal products (vasodilator and centrally acting ), adrenergic neuron blockers, calcium channel blockers, and blockers of ?-adrenergic receptors.
In healthy male volunteers use sildenafil at steady state (80 mg three times daily) resulted in AUC and Cmax of bosentan (125 mg twice a day) 49.8%; 42%, respectively.
A single dose of antacid (magnesium hydroxide/aluminium hydroxide) did not affect the bioavailability of sildenafil.
CYP 2C9 inhibitors (such as tolbutamide, warfarin), CYP 2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazides and related diuretics, ACE inhibitors and calcium channel blockers did not affect sildenafil pharmacokinetics.
The study involving healthy volunteers-men, the simultaneous use of the endothelin antagonist bosentan (a moderate inducer of CYP3A4, CYP2C9 and possibly 2C19) at steady state (125 mg twice a day) and sildenafil at steady state (80 mg three times PA day) resulted in a decrease in AUC and Cmax for sildenafil 62.6% and 55.4%, respectively. Therefore, the simultaneous use of such powerful inductors CYP3A4, as rifampicin, can lead to a more pronounced decrease in the concentration of sildenafil in blood plasma. In healthy volunteers has not been proven effect of azithromycin (500 mg daily for 3 days) on the AUC, Cmax, Tmax, clearance and half-life of sildenafil and its main metabolites.
The effects of sildenafil on other drugs.
In vitro studies: sildenafil is a weak inhibitor of cytochrome P450 isoforms, namely 1A2, 2C9, 2C19, 2D6, 2E1 and ZA4 (IC 50 > 150 µm). When used in recommended doses, the maximum concentration of sildenafil in blood plasma reaches about 1 microns, therefore it is unlikely that sildenafil is able to change the excretion of substrates of these isoferments.
In vivo studies: sildenafil enhances the hypotensive effect at short-term and long-term use of nitrates, so a one-time or course application of nitric oxide donors, organic nitrates or organic nitrites in any form is contraindicated with sildenafilom.
When sildenafil (25 mg, 50 mg and 100 mg) was used in patients with benign prostatic hyperplasia simultaneously with therapy with ?-blockers by doxazosin (4 mg and 8 mg), which was maintained at a stable level, there was an additional decrease in blood pressure by 7/7 RT. article, 9/5 RT.article 8/4 and RT.art. respectively, and the average additional reduction in AD 6/6 RT.article, 11/4 RT.article and 4/5 RT.the article under. When sildenafil and doxazosin was administered simultaneously to patients resistant to doxepin therapy, was observed rare cases of symptomatic postural hypotension. Her symptoms included dizziness and loss of coordination under the action of light, but not loss of consciousness. Concomitant treatment sildenafilom patients taking alpha adrenoblokatora therapy may lead to symptomatic hypotension in some patients.
Any significant signs of interaction of sildenafil (50 mg) with tolbutamide (250 mg) or warfarin (40 mg), each of which is metabolized by CYP 2C9 have not been identified.
Sildenafil (100 mg) does not change the equilibrium pharmacokinetics of the HIV protease inhibitors, savinar and ritonavir are inhibitors of CYP ZA4.
Sildenafil (50 mg) does not increase the duration of bleeding caused by acetylsalicylic acid (150 mg).
Sildenafil (50mg) did not reinforce the hypotensive effect of alcohol in healthy volunteers who had the maximum level of blood alcohol of 0.08% (80 mg/DL).
There was no interaction between sildenafil (100 mg) and amlodipine in patients with hypertension.
The average value of an additional decrease in blood pressure was 8 mm Hg.art. systolic and 7 mm Hg.art. - Diastolic.
Safety analysis showed no difference in the profile of adverse reactions in patients taking sildenafil separately and with antihypertensive drugs.
To diagnose erectile dysfunction, determine the possible causes of the disease and prescribe adequate treatment, it is necessary to carefully study the patient's medical history and conduct medical examinations. For the effectiveness of the ERGOS should sexual stimulation.
Risk factors for cardiovascular disease. Since sexual activity is accompanied by a certain risk from the heart, before any treatment of erectile dysfunction, the doctor should assess the state of the cardiovascular system of patients. Sildenafil has a vasodilating effect, manifested by a slight and short-term decrease in blood pressure (see section "Pharmacological"). Prior to sildenafil's appointment, the physician should carefully consider whether such an effect can adversely affect patients with certain major diseases, especially in combination with sexual activity. To patients with hypersensitivity to vasodilators include patients with obstruction of the excretory tract of the left ventricle (eg aortic stenosis, hypertrophic obstructive cardiomyopathy), or patients with rare sinprobom Multisystem atrophy, one manifestation of which is severe dysregulation of blood pressure the autonomic nervous system.
Sildenafil potentiates the hypotensive effect of nitrates (see Section "Contraindications).
In post-marketing period have reported serious adverse reactions from the cardiovascular system, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, arterial hypertension and arterial hypotension, which coincided with the drug ERGOS . In most patients, but not all, there was the risk factors of cardiovascular diseases. A lot of these polichni reactions were observed during or immediately after intercourse and only a few shortly after use of the drug ERGOS without sexual activity. Therefore, it is impossible to determine whether the development of such adverse reactions is directly related to risk factors, or their development is due to other factors.
Priapism. Treatment for erectile dysfunction, including sindenafil must be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernous fibrosis or Peyronie's disease) or patients who have diseases that can lead to the development of priapism (such as sickle cell anemia, multiple myeloma, or leukemia).
After entering the market, cases of prolonged erection and priapism were reported. In cases where the erection lasts more than 4:00, patients should immediately seek medical help. In the absence of neginho treatment priapism can damage the penis tissues and permanent loss of potency.
The simultaneous use with other inhibitors of PDE5 or to other drugs for the treatment of erektilnoy dysfunction. The safety and efficacy of combinations of sildenafil with other inhibitors of PDE5 or to other drugs used to treat hypertension of the pulmonary artery containing sildenafil or with other medicines to treat erectile dysfunction has not been studied. Therefore, the use of such combinations is not recommended.
Effect on vision. Spontaneous reports of the occurrence of the defect came to the eye associated with the use of sildenafil and other inhibitors of FDE-5 (see section "Adverse reactions"). Cases of non-arterial anterior ischemic optic neuropathy, which is a rare condition, were reported spontaneously and were reported in a Supervisory study associated with the use of sildenafil and other PDE-5 inhibitors (see section "Adverse reactions"). Patients should be warned that in case of sudden visual impairment of ERGOS should be discontinued and immediately consult a doctor (see section"Contraindications").
In patients with age-related retinal degeneration, sildenafil at a dose of 100 mg once a day was well-tolerated and had no clinical effect in the study of visual fuctions in tests (visual acuity, Amsler grid, color recognition, "artificial light flux", Humphrey perimeter and photostress).
Some patients with congenital pigmented retinitis marked genetic defects PDE retina. There is no information about the safety of the appointment of sildenafil in patients with pigment retinitis, so this group of patients sildenafil should be administered with caution.
Concurrent use with ritonavir. The simultaneous use of sildenafil and ritonavir is not recommended (see "Interaction with other medicinal products and other forms of interaction").
The simultaneous use of blockers ?-adrenergic receptors. Sildenafil is recommended to be used with caution in patients who concurrently use of ?-blockers, because in some cases this can lead to symptomatic hypotension. In order to minimize the risk of postural hypotension, it is necessary to achieve stabilization of blood pressure with the help of ?-blockers for the use of sildenafil. Should start apply sildenafil with low doses. In addition, doctors should tell patients what to do in case of symptoms of postural hypotension. Symptomatic hypotension usually occurs within 4: 00 after the use of sildenafil.
Effect on bleeding. Studies of human platelets in vitro indicate that sildenafil enhances the antiplatelet effect of sodium nitroprusside (donator NO). There is no safety information regarding the appointment of sildenafil to patients with a tendency to bleeding or with acute gastric ulcer, so this group of patients sildenafil should be prescribed with caution.
The drug contains lactose, therefore patients with rare hereditary forms of intolerance of galactose, lactase deficiency or malabsorption syndrome of glucose-galactose should not use the drug.
After taking a single dose of 100 mg of sildenafil, there was no effect on the mobility and morphological properties of sperm in healthy volunteers.
Hearing loss. Physicians should advise patients to stop use of inhibitors of PDE5, including drug ERGOS and immediately seek medical help in cases of sudden decrease or loss of hearing. These phenomena, which may also be accompanied by tinnitus and dizziness, have been reported to the Association over time with the use of PDE-5 inhibitors, including ERGOS . To determine these effects directly associated with the use of inhibitors of PDE5 or to other factors.
The simultaneous use of antihypertensive drugs. ERGOS has systemic vasodilatory effect and can further reduce blood pressure in patients using antihypertensive drugs. In a separate study of drug interaction, the simultaneous use of amlodipine (5 mg or 10 mg) and ERGOS (100 mg) was orally observed an average additional reduction in systolic pressure by 8 mm of Hg.station and diastolic-7 mm
Sexually transmitted diseases. The use of the drug ERGOS does not protect against sexually transmitted diseases. Consideration should be given to instructing patients on the necessary precautions to protect against sexually transmitted diseases, including human immunodeficiency virus.
Application during pregnancy and lactation
The drug ERGOS is not intended for zastosuvannya women.
The ability to influence the reaction rate when driving motor transport or operating other mechanisms
The study of the effect of the drug on the ability to drive a car and work with the mechanisms were not carried out. Since during clinical studies of sildenafil were observed dizziness and blurred vision, patients should know their reaction to the reception of ERGOS before you drive or operate machinery.
Method of application and doses
The drug is administered orally. In each case, the dose is set individually. For the development of the effect of the drug needs sexual arousal. The use of the drug on an empty stomach contributes to the development of an erection after an average 25-30 minutes (12-37 minutes). To start taking the drug recommended a dose of 50 mg Given efficacy and tolerability, the dose can be increased to 100 mg or reduced to 25 mg. With caution should use the drug in patients with severe renal insufficiency, patients with arterial hypotension (BP <90/50 mm Hg.art.). The maximum daily dose is 100 mg.
Use in patients with impaired renal function. For patients with renal insufficiency of mild and moderate severity (creatinine clearance 30-80 ml/min) dosing regimen does not change. Because in patients with severe renal failure (creatinine clearance
Application to patients with impaired liver function. Since in patients with hepatic insufficiency sildenafil clearance is reduced, for example, in cirrhosis, the use of the drug should begin with a dose of 25 mg.
Application to patients who undergo other types of treatment. Given the degree of interaction in patients receiving therapy with ritonavir, it is recommended not to exceed a maximum single dose of 25 mg sildenafil within 48 hours. A starting dose of 25 mg should be advised in patients receiving concomitant treatment with CYP3A4 inhibitors (e.g. erythromycin, saquinavir, ketoconazole, Itraconazole). In order to reduce the risk of postural hypotension should be achieved stabilization of patients on the background of therapy with ?-blockers for ERGOS . In addition, the appointment of the drug should begin with small doses.
Use in elderly patients. For elderly patients (? 65 years) dose adjustment is not required.
The drug is indicated for use in children.
In clinical studies involving volunteers in the application of a single dose of sildenafil to 800 mg, adverse reactions were similar to those observed when using sildenafil at lower doses, but met often and were more severe. The use of sildenafil at a dose of 200 mg led to increased efficiency, but caused an increase in the number of cases of adverse reactions (headache, blood spills, dizziness, dyspepsia, nasal congestion, visual impairment).
In case of overdose, if necessary, resort to the usual supportive measures. Acceleration of clearance of sildenafil in hemodialysis is unlikely due to the high degree of binding of the drug with plasma proteins and the lack of elimination of sildenafil with urine.
The safety profile of the drug is based on data obtained from 9570 patients from 74 double-blind placebo-controlled clinical trials. This files most often reported adverse reactions such as headache, flushing, dyspepsia, nasal congestion, back pain, dizziness, nausea, cyanopsia and blurred vision. Information on adverse reactions in the framework of post-marketing surveillance has been gathered over a period of more than 10 years. Since not all adverse reactions have been reported, the relationship between the use of PDE-5 inhibitors and the occurrence of adverse reactions cannot be reliably determined.
All clinically significant adverse reactions, which were observed in clinical studies more often than in placebo, are shown in the table in accordance with the classification "System-organ-class" and frequency: very often (?1/10), often (?1/100 - <1/10), infrequently (?1000 - <1/100) and rarely (?1/10000 - <1/1000). In addition, the frequency of clinically significant adverse reactions reported in the post-market experience has been identified as unknown. Within each frequency group, adverse reactions are listed in order of decreasing severity.
Infectious and invasive diseases.
Rarely has rhinitis.
From the immune system.
From the nervous system.
Very often a headache.
Rarely drowsiness, hypesthesia.
Rarely stroke, transient ischemic attack, seizures * recurrence of court *, syncope.
From the side of organs of vision.
Often, violation of color perception **, visual disturbances, blurred vision.
Rare disorders lacrimation *, eye pain, photophobia, redness of the eyes, clarity of vision, conjunctivitis, photopsia.
Rarely partitially anterior ischemic neuropathy of the optic nerve * occlusion of the vessels of the retina * retinal hemorrhage, arteriosclerotic retinopathy, disorders of the retina, glaucoma, visual field defects, diplopia, decreased visual acuity, myopia, asthenopia, disturbance from the side of the iris, mydriasis, the appearance of glowing circles around the light source ( "halo") in the field of view, eye swelling, swelling of the eyes, disorders of the eyes, redness, conjunctly, eye irritation, abnormal sensation in eyes, swelling of the eyelids, discoloration of the sclera.
From the facet of the hearing and vestibular apparatus.
Rarely dizziness, ringing in the ears.
From the heart.
Infrequently, tachycardia, palpitations.
Rarely myocardial infarction, ventricular arrhythmia*, atrial fibrillation, unstable angina.
From the vessels.
Often, hot flashes, fever.
Not often hypertension, hypotension.
From the respiratory system, chest and mediastinum.
Often nasal congestion.
Rarely epistaxis, congestion of the sinuses.
Rarely does the sensation of compression in the throat, swelling of the nasal mucosa, dryness in the nose.
The gastro-intestinal tract.
Often nausea, dyspepsia.
Infrequently gastroesophageal reflux disease, vomiting, pain in the upper abdomen, dry mouth.
Rarely, hypoesthesia oral cavity.
On the part of the skin and subcutaneous tissue:
Not often rashes.
Rarely Stevens-Johnson syndrome * , toxic epidermal necrolysis *.
From the side of musculoskeletal system and connective tissue.
Infrequently myalgia, pain in the limbs.
From the urinary system.
On the part of the reproductive system and mammary glands.
Rarely bleeding from the penis, priapism * hematospermia, prolonged erection.
General disorders and reactions at the injection site.
Infrequently chest pain, fatigue, a sense of heat.
Rarely cause irritation.
Infrequently increased heart rate.
* - Reported only in the study after the drug is on the market.
** Violation of color perception: chloropeta, cyanopsia, eritropenia, xanthopsia.
*** - Violation of lacrimation: dry eyes, violation of lacrimation and increased lacrimation.
The following events occurred in <2% of patients in controlled clinical trials; a causal relationship was not determined. The communication included phenomena that were likely to be associated with the use of the drug. The phenomena that were not listed were easy and the messages were very inaccurate to make a difference.
General: face edema, photo - sensitivity reactions, shock, asthenia, pain, loss of balance, abdominal pain, sudden damage.
From the side of cardiovascular system: angina pectoris, AV block, migraine, progressive hypotension, myocardial ischemia, thrombosis of cerebral vessels, sudden cardiac arrest, violation results in ECG, cardiomyopathy.
From the gastrointestinal tract: glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, violation of the results of liver tests, rectal bleeding, gingivitis.
From the blood and lymphatic systems: anemia, leukopenia.
Metabolic disorders and nutritional: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral phenomena, hyperuricemia, hypoglycemia, hypernatremia.
From the musculoskeletal system: arthritis, arthrosis, tendon rupture, tenosinovitis, bone pain, myasthenia gravis, synovitis.
From the nervous system: ataxia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, abnormal dreams, decreased reflexes.
From the respiratory system: asthma, shortness of breath, laryngitis, pharyngitis, sinusitis, bronchitis, increased salivation, increased cough.
From the skin: urticaria, herpes, itching, sweating, skin ulcers, contact dermatitis, exfoliative dermatitis.
Specific sensations: sudden decrease or loss of hearing, pain in the ears, hemorrhage in the eye, cataract, dry eyes.
On the part of the urogenital system: cystitis, nicturia, increased frequency of urinations, breast enlargement, urinary incontinence, ejaculation disorders, genital edema, anorgasmia.
Experience in the use of the drug after release to Ryn