Instructions for Viagra film-coated tablets 50 mg No. 4
Composition
active ingredient: sildenafil;
1 tablet contains 70.225 mg of sildenafil citrate, which is equivalent to sildenafil 50 mg;
excipients: ludiflash (mannitol (E 421), crospovidone, polyvinyl acetate, povidone), croscarmellose sodium, microcrystalline cellulose, colloidal anhydrous silicon dioxide, sucralose (E 955), indigo carmine aluminum lake 30-36% (E 132), sweet taste enhancer, special natural component, lemon flavoring, magnesium stearate.
Dosage form
Orodispersible tablets.
Main physicochemical properties: blue, diamond-shaped tablets, engraved with "V50" on one side and without engraving on the other side.
Pharmacotherapeutic group
Drugs used for erectile dysfunction. Sildenafil. ATX code G04B E03.
Pharmacological properties
Pharmacodynamics
Mechanism of action: Sildenafil is an oral drug used to treat erectile dysfunction. During sexual arousal, the drug restores impaired erectile function by increasing blood flow to the penis.
The physiological mechanism that causes an erection involves the release of nitric oxide (NO) in the corpora cavernosa during sexual arousal. The released nitric oxide activates the enzyme guanylate cyclase, which stimulates an increase in cyclic guanosine monophosphate (cGMP), which in turn causes relaxation of the smooth muscle of the corpora cavernosa, facilitating blood flow.
Sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for the breakdown of cGMP. The effects of sildenafil on erection are peripheral in nature. Sildenafil does not cause a direct relaxant effect on isolated human corpus cavernosum, but potently enhances the relaxant effect of NO on this tissue. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, sildenafil's inhibition of PDE5 leads to an increase in cGMP levels in the corpus cavernosum. Thus, sexual arousal is required for sildenafil to produce the desired pharmacological effect.
Pharmacodynamic effects. In vitro studies have shown that sildenafil is selective for PDE5, which is actively involved in the erection process. The effect of sildenafil on PDE5 is more potent than on other known phosphodiesterases. This effect is 10 times more potent than the effect on PDE6, which is involved in photoconversion processes in the retina. When using the maximum recommended doses, the selectivity of sildenafil for PDE5 is 80 times higher than its selectivity for PDE1, 700 times higher than for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10 and PDE11. In particular, the selectivity of sildenafil for PDE5 is 4000 times higher than its selectivity for PDE3 - a cAMP-specific isoform of phosphodiesterase involved in the regulation of cardiac contractility.
Pharmacokinetics
Absorption. Sildenafil is rapidly absorbed. Peak plasma concentrations are reached within 30-120 minutes (median 60 minutes) after oral administration in the fasted state. The mean absolute oral bioavailability is 41% (range 25-63%). Over the recommended dose range (25-100 mg), the AUC and Cmax of sildenafil increase proportionally with dose after oral administration.
When sildenafil is taken with food, the extent of absorption is reduced with a mean prolongation of Tmax to 60 minutes and a mean decrease in Cmax by 29%.
Distribution. The mean steady-state volume of distribution (Vd) is 105 liters, indicating distribution of the drug into body tissues. After a single oral dose of 100 mg sildenafil, the mean maximum total plasma concentration of sildenafil is approximately 440 ng/mL (the coefficient of variation is 40%). Since the binding of sildenafil and its major N-desmethyl metabolite to plasma proteins reaches 96%, the mean maximum plasma concentration of free sildenafil reaches 18 ng/mL (38 nmol). The extent of binding to plasma proteins is independent of the total concentrations of sildenafil.
In healthy volunteers who used sildenafil once at a dose of 100 mg, less than 0.0002% (average 188 ng) of the administered dose was detected in the ejaculate after 90 minutes.
Elimination: The total clearance of sildenafil is 41 l/h, resulting in a half-life of 3-5 hours. After both oral and intravenous administration, sildenafil is excreted as metabolites primarily in the feces (approximately 80% of the administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose).
Pharmacokinetics in special patient groups.
Elderly patients: In healthy elderly volunteers (aged 65 years and older), a decrease in sildenafil clearance was observed, which resulted in an increase in plasma concentrations of sildenafil and its active N-demethylated metabolite by approximately 90% compared with the corresponding concentrations in healthy younger volunteers (18-45 years). Due to age-related differences in plasma protein binding, the corresponding increase in plasma concentrations of free sildenafil was approximately 40%.
Renal impairment. In volunteers with mild to moderate renal impairment (creatinine clearance 30-80 ml/min), the pharmacokinetics of sildenafil were unchanged after a single oral dose of 50 mg. The mean AUC and Cmax of the N-desmethyl metabolite were increased by 126% and 73%, respectively, compared with those in age-matched volunteers without renal impairment. However, due to high interindividual variability, these differences were not statistically significant. In volunteers with severe renal impairment (creatinine clearance below 30 ml/min), sildenafil clearance was reduced, resulting in a mean increase in AUC and Cmax of 100% and 88%, respectively, compared with age-matched volunteers without renal impairment. In addition, the AUC and Cmax values of the N-demethylated metabolite were significantly increased by 79% and 200%, respectively.
Hepatic impairment: In volunteers with mild to moderate liver cirrhosis (Child-Pugh class A and B), sildenafil clearance was reduced, resulting in increased AUC (84%) and Cmax (47%) compared to age-matched volunteers without hepatic impairment. The pharmacokinetics of sildenafil in patients with severe hepatic impairment have not been studied.
Indication
VIAGRA® ODT is recommended for use in men with erectile dysfunction, which is defined as the inability to achieve or maintain a penile erection necessary for successful sexual intercourse.
Sexual arousal is required for VIAGRA® ODT to be effective.
Contraindication
– Hypersensitivity to the active substance or any of the excipients of the drug.
– Concomitant use with nitric oxide donors (such as amyl nitrite) or nitrates in any form is contraindicated, as sildenafil is known to affect nitric oxide/cyclic guanosine monophosphate (cGMP) metabolic pathways and potentiate the hypotensive effect of nitrates.
– Conditions in which sexual activity is not recommended (e.g. severe cardiovascular disorders such as unstable angina or severe heart failure).
– Loss of vision in one eye due to non-arteritic anterior ischemic optic neuropathy, regardless of whether this pathology is associated with previous use of PDE5 inhibitors or not.
– Presence of 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 retinitis pigmentosa (a small number of such patients have genetic disorders of retinal phosphodiesterases), as the safety of sildenafil has not been studied in the presence of such diseases.
Interaction with other medicinal products and other types of interactions
Effects of other drugs on sildenafil.
In vitro studies.
Sildenafil is metabolized primarily by cytochrome P450 (CYP) isoform 3A4 (major pathway) and isoform 2C9 (minor pathway). Therefore, inhibitors of these isoenzymes may decrease sildenafil clearance, and inducers of these isoenzymes may increase sildenafil clearance.
In vivo studies.
Co-administration of the HIV protease inhibitor ritonavir, a very potent P450 inhibitor, at steady state (500 mg once daily) with sildenafil (single dose of 100 mg) resulted in a 300% (4-fold) increase in sildenafil Cmax and a 1000% (11-fold) increase in sildenafil plasma AUC. After 24 hours, plasma sildenafil levels were still approximately 200 ng/ml, compared to approximately 5 ng/ml with sildenafil alone, consistent with the significant effect of ritonavir on a wide range of P450 substrates. Sildenafil does not affect the pharmacokinetics of ritonavir. Based on these pharmacokinetic data, co-administration of sildenafil and ritonavir is not recommended (see section 4.4); In any case, the maximum dose of sildenafil should under no circumstances exceed 25 mg within 48 hours.
Co-administration of the HIV protease inhibitor saquinavir, a CYP3A4 inhibitor, at a steady-state dose (1200 mg three times daily) with sildenafil (100 mg once daily) resulted in a 140% increase in sildenafil Cmax and a 210% increase in sildenafil systemic exposure (AUC). Sildenafil had no effect on the pharmacokinetics of saquinavir (see section 4.2). More potent CYP3A4 inhibitors such as ketoconazole and itraconazole are expected to have a greater effect.
When sildenafil (100 mg once daily) was administered with erythromycin, a moderate CYP3A4 inhibitor, at steady state (500 mg twice daily for 5 days), a 182% increase in sildenafil systemic exposure (AUC) was observed. In healthy male volunteers, there was no effect of azithromycin (500 mg daily for 3 days) on the AUC, Cmax, Tmax, elimination rate constant, and subsequent half-life of sildenafil or its major circulating metabolite. Cimetidine (a cytochrome P450 inhibitor and non-specific CYP3A4 inhibitor) at a dose of 800 mg when co-administered with sildenafil at a dose of 50 mg in healthy volunteers resulted in a 56% increase in plasma concentrations of sildenafil.
Grapefruit juice is a weak inhibitor of CYP3A4 in the intestinal wall and may cause a modest increase in plasma levels of sildenafil.
Single administration of antacids (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of sildenafil.
Although specific drug interaction studies have not been conducted, population pharmacokinetic analysis suggests that sildenafil pharmacokinetics were not altered by concomitant use of drugs belonging to the CYP2C9 inhibitor group (tolbutamide, warfarin, phenytoin), CYP2D6 inhibitor group (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-like diuretics, loop and potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, calcium antagonists, β-adrenoceptor antagonists, or inducers of CYP450 metabolism (such as rifampicin, barbiturates).
In a study in healthy male volunteers, co-administration of the endothelin antagonist bosentan (a moderate inducer of CYP3A4, CYP2C9 and possibly CYP2C19) at steady state (125 mg twice daily) with sildenafil at steady state (80 mg three times daily) resulted in a 62.6% and 55.4% decrease in sildenafil AUC and Cmax, respectively. Therefore, co-administration of potent CYP3A4 inducers such as rifampin may result in a more pronounced decrease in sildenafil plasma concentrations.
Nicorandil is a hybrid of a calcium channel activator and a nitrate. The nitrate component makes it possible for it to have a serious interaction with sildenafil.
Effects of sildenafil on other drugs.
In vitro studies.
Sildenafil is a weak inhibitor of cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 > 150 μM). Since peak plasma concentrations of sildenafil are approximately 1 μM, the effect of VIAGRA® ODT on the clearance of substrates of these isoenzymes is unlikely.
There are no data on the interaction of sildenafil and non-specific phosphodiesterase inhibitors such as theophylline and dipyridamole.
In vivo studies.
Concomitant use of sildenafil and α-adrenergic blockers may lead to symptomatic hypotension in some susceptible patients. This reaction most often occurred within 4 hours of sildenafil administration (see sections 4.2 and 4.4). In 3 specific drug interaction studies, the α-adrenergic blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) were administered concomitantly to patients with benign prostatic hyperplasia who were stabilized on doxazosin. In these populations, mean additional reductions in supine blood pressure of 7/7 mmHg, 9/5 mmHg and 8/4 mmHg and mean reductions in standing blood pressure of 6/6 mmHg, 11/4 mmHg and 11/4 mmHg were observed. Art., 4/5 mm Hg. Art., respectively. With the simultaneous use of sildenafil and doxazosin in patients whose condition was stabilized on doxazosin, the development of symptomatic orthostatic hypotension has sometimes been reported. These reports included cases of dizziness and fainting, but without syncope.
No significant interactions were observed with the concomitant use of sildenafil (50 mg) and tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by CYP2C9.
Sildenafil (50 mg) did not prolong bleeding time induced by acetylsalicylic acid (150 mg).
Sildenafil (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers at mean maximum blood ethanol levels of 80 mg/dL.
In patients taking sildenafil, no differences in the side effect profile compared to placebo were observed when such classes of antihypertensive drugs as diuretics, β-blockers, ACE inhibitors, angiotensin II antagonists, antihypertensive drugs (vasodilators and centrally acting), adrenergic neurone blockers, calcium channel blockers and α-adrenergic blockers were used concomitantly. In a specific interaction study, when sildenafil (100 mg) was co-administered with amlodipine in hypertensive patients, an additional reduction in supine systolic blood pressure of 8 mm Hg was observed. The corresponding reduction in diastolic blood pressure was 7 mm Hg. These additional reductions in blood pressure were comparable to those observed with sildenafil alone in healthy volunteers (see section 5.1).
Sildenafil at a dose of 100 mg did not affect the pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, which are CYP3A4 substrates.
In healthy male volunteers, administration of sildenafil at steady state (80 mg three times daily) resulted in an increase in the AUC and Cmax of bosentan (125 mg twice daily) by 49.8% and 42%, respectively.
Application features
Before starting therapy, the patient's medical history should be collected and a physical examination should be performed to diagnose erectile dysfunction and determine its possible causes.
Cardiovascular risk factors. Since sexual activity carries a certain cardiac risk, the physician should assess the patient's cardiovascular status before initiating any treatment for erectile dysfunction. Sildenafil has a vasodilating effect, manifested by a mild and transient decrease in blood pressure (see section 5.1). Before prescribing sildenafil, the physician should carefully consider whether this effect may adversely affect patients with certain underlying diseases, especially in combination with sexual activity. Patients with increased sensitivity to vasodilators include patients with left ventricular outflow tract obstruction (e.g. aortic stenosis, hypertrophic obstructive cardiomyopathy) and patients with the rare syndrome of multiple system atrophy, one of the manifestations of which is severe dysregulation of blood pressure by the autonomic nervous system.
VIAGRA® ODT potentiates the hypotensive effect of nitrates (see section "Contraindications").
Serious cardiovascular adverse reactions, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, and hypotension, have been reported in postmarketing experience in patients receiving VIAGRA® ODT. Most, but not all, patients had risk factors for cardiovascular disease. Many of these adverse reactions occurred during or immediately after sexual intercourse, and only a few occurred shortly after VIAGRA® ODT use in the absence of sexual activity. Therefore, it is not possible to determine whether these adverse reactions are directly related to the risk factors or whether they are caused by other factors.
Cases of prolonged erection and priapism have been reported in post-marketing experience. Patients should seek immediate medical attention if an erection lasts more than 4 hours. If not treated promptly, priapism can lead to penile tissue damage and permanent loss of potency.
Concomitant use with other PDE5 inhibitors or other drugs for the treatment of erectile dysfunction. The safety and efficacy of concomitant use of sildenafil with other PDE5 inhibitors or other drugs for the treatment of pulmonary arterial hypertension that contain sildenafil (e.g. Revatio) or with other drugs for the treatment of erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended.
Effects on vision.
Spontaneous reports of visual defects have been reported in association with the use of sildenafil and other PDE5 inhibitors (see section 4.8). Cases of non-arteritic anterior ischemic optic neuropathy, a rare condition, have been reported spontaneously and in an observational study in association with the use of sildenafil and other PDE5 inhibitors (see section 4.8). Patients should be advised that in the event of sudden visual impairment, VIAGRA® ODT should be discontinued and a physician should be consulted immediately (see section 4.8).
Concomitant use with ritonavir.
The simultaneous use of sildenafil and ritonavir is not recommended (see section "Interaction with other medicinal products and other types of interactions").
Concomitant use with α-adrenergic blockers.
Sildenafil should be used with caution in patients taking α-adrenergic blockers, as the combination may lead to symptomatic hypotension in some susceptible patients. Symptomatic hypotension usually occurs within 4 hours of sildenafil administration. In order to minimize the potential for postural hypotension, the patient should be hemodynamically stable on α-adrenergic blockers before starting sildenafil. A starting dose of 25 mg of sildenafil should be considered (see section 4.2). Patients should also be advised what to do if they develop symptoms of orthostatic hypotension.
Effects on bleeding. Studies in human platelets have shown that sildenafil potentiates the antiaggregatory effects of sodium nitroprusside in vitro. There is no information on the safety of sildenafil in patients with coagulation disorders or acute peptic ulcer. Therefore, sildenafil should only be used in these patients after careful consideration of the benefit-risk ratio.
Hearing Loss. Physicians should advise patients to discontinue use of PDE5 inhibitors, including VIAGRA® ODT, and seek immediate medical attention if they experience sudden hearing loss or hearing loss. These events, which may also be accompanied by tinnitus and dizziness, have been reported in temporal association with the use of PDE5 inhibitors, including VIAGRA® ODT. It is not possible to determine whether these events are directly related to the use of PDE5 inhibitors or to other factors.
Concomitant use with antihypertensive drugs. VIAGRA® ODT has a systemic vasodilator effect and may further reduce blood pressure in patients taking antihypertensive drugs. In a separate drug interaction study, concomitant administration of amlodipine (5 mg or 10 mg) and VIAGRA® ODT (100 mg) orally resulted in a mean additional reduction in systolic blood pressure of 8 mm Hg and diastolic blood pressure of 7 mm Hg.
Sexually Transmitted Diseases. Use of VIAGRA® ODT 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.
Fertility: No effects on sperm morphology or motility were observed after administration of a 100 mg dose to healthy volunteers (see section 5.1).
Use during pregnancy or breastfeeding
VIAGRA® ODT is not intended for use by women.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies have been conducted on the effect of the drug on the ability to drive vehicles and work with other mechanisms.
Since dizziness and visual disturbances have been reported in clinical trials with sildenafil, patients should be aware of their individual reaction to VIAGRA® ODT before driving or operating machinery.
Method of administration and doses
The drug is administered orally.
The drug should be used immediately after removing the tablet from the blister. The tablet should be placed on the tongue, allowed to disintegrate, and then swallowed. The drug can be taken with or without water.
It is recommended to use the drug on an empty stomach, since when the drug is used simultaneously with fatty food, there is a significant delay in absorption compared to taking the tablets on an empty stomach.
Adults. If necessary, VIAGRA® ODT should be taken 1 hour before sexual activity. The recommended dose is 50 mg. Since simultaneous use of the drug with food delays absorption and slows down the effect of the drug (see section "Pharmacokinetics"), it is recommended to use the drug on an empty stomach.
Depending on efficacy and tolerability, the dose may be increased to 100 mg. The maximum recommended dose is 100 mg. If a dose of 100 mg is required, 2 tablets of 50 mg should be taken consecutively.
The maximum recommended frequency of use of the drug is 1 time per day.
If a dose of 25 mg is required, it is recommended to use sildenafil 25 mg.
Elderly patients: No dose adjustment is required for elderly patients (≥ 65 years).
Patients with renal impairment: For patients with mild to moderate renal impairment (creatinine clearance 30-80 ml/min), the recommended dose is the same as given above in the Adults section.
Since sildenafil clearance is reduced in patients with severe renal impairment (creatinine clearance < 30 ml/min), a dose of 25 mg should be considered. Depending on efficacy and tolerability, the dose may be gradually increased to 50 mg and 100 mg if necessary.
Patients with hepatic impairment: Since sildenafil clearance is reduced in patients with hepatic impairment (e.g. cirrhosis), a dose of 25 mg should be considered. Depending on efficacy and tolerability, the dose may be gradually increased to 50 mg and 100 mg if necessary.
Patients taking other medications.
If patients are concomitantly taking CYP3A4 inhibitors (see section 4.5), a starting dose of 25 mg should be considered (except for ritonavir, the use of which with sildenafil is not recommended, see section 4.4).
To minimise the potential for postural hypotension in patients taking α-adrenergic blockers, their condition should be stable before starting sildenafil. A starting dose of 25 mg should also be considered (see sections 4.4 and 4.5).
Children
The drug is not indicated for use by persons under the age of 18.
Overdose
In clinical trials involving volunteers, when using a single dose of sildenafil up to 800 mg, adverse reactions were similar to those observed with sildenafil at lower doses, but were more frequent and more severe. The use of sildenafil at a dose of 200 mg did not lead to increased efficacy, but caused an increase in the number of cases of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, visual disturbances).
In case of overdose, usual supportive measures should be employed if necessary. Acceleration of sildenafil clearance during hemodialysis is unlikely due to the high degree of binding of the drug to plasma proteins and the lack of elimination of sildenafil in the urine.
Adverse reactions
The safety profile of VIAGRA® ODT is based on data from 74 double-blind, placebo-controlled clinical trials (9570 patients). The most frequently reported adverse reactions were headache, flushing, dyspepsia, nasal congestion, back pain, dizziness, nausea, hot flushes, visual disturbances, cyanopsia and blurred vision. Post-marketing data on adverse reactions were collected over a period of more than 10 years. As not all adverse reactions were reported to the applicant and not all adverse reactions were included in the safety database, the frequency of such reactions cannot be reliably estimated.
All clinically significant adverse reactions observed in clinical trials at an incidence greater than placebo are listed below by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 - < 1/10), uncommon (≥ 1,000 - < 1/100) and rare (≥ 1/10,000 - < 1/1,000). The frequency of clinically significant adverse reactions reported during post-marketing experience is defined as unknown. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Infectious and invasive diseases.
Uncommon: rhinitis.
Immune system disorders.
Uncommon: hypersensitivity.
Nervous system disorders.
Very common: headache.
Common: dizziness.
Uncommon: drowsiness, hypoesthesia.
Rare: stroke, transient ischemic attack, convulsions*, recurrent convulsions*, syncope.
Disorders of the organs of vision.
Common: color perception disorders**, visual disturbances, blurred vision.
Rare: non-arteritic anterior ischemic optic neuropathy*, retinal vascular occlusion*, retinal haemorrhage, arteriosclerotic retinopathy, retinal disorders, glaucoma, visual field defects, diplopia, visual acuity reduced, myopia, asthenopia, floating vitreous opacities, iris disorders, mydriasis, halos, eye oedema, eye swelling, eye disorders, conjunctival hyperaemia, eye irritation, abnormal eye sensation, eyelid oedema, sclera discolouration.
Disorders of the hearing and vestibular system.
Uncommon: dizziness, tinnitus.
Rare: deafness.
Heart disorders.
Uncommon: tachycardia, palpitations.
Rare: sudden cardiac death*, myocardial infarction, ventricular arrhythmia*, atrial fibrillation, unstable angina.
Vascular disorders.
Common: flushing, hot flushes.
Uncommon: hypertension, hypotension.
Respiratory, thoracic and mediastinal disorders.
Common: nasal congestion.
Uncommon: epistaxis, sinus congestion.
Rare: feeling of tightness in the throat, swelling of the nasal mucosa, dry nose.
Gastrointestinal disorders.
Common: nausea, dyspepsia.
Uncommon: gastroesophageal reflux disease, vomiting, upper abdominal pain, dry mouth.
Rare: oral hypoesthesia.
Skin and subcutaneous tissue disorders.
Uncommon: rash.
Rare: Stevens-Johnson syndrome*, toxic epidermal necrolysis*.
Musculoskeletal and connective tissue disorders.
Uncommon: myalgia, pain in extremity.
Disorders of the urinary system.
Uncommon: hematuria.
Disorders of the reproductive system and mammary glands.
Rare: penile bleeding, priapism*, hematospermia, prolonged erection.
General disorders and administration site reactions.
Uncommon: chest pain, fatigue, feeling hot.
Rare: irritation.
Examination.
Uncommon: increased heart rate.
*Reported only during post-marketing surveillance.
** Color perception disorders: chloropsia, chromatopsia, cyanopsia, erythropsia, xanthopsia.
*** Lacrimation disorders: dry eyes, lacrimation disorders and lacrimation increased.
The following adverse reactions were observed in < 2% of patients in controlled clinical trials; their causal relationship to the use of VIAGRA® ODT is uncertain. Adverse reactions that had a probable relationship to the use of the drug were reported. At the same time, adverse reactions of mild severity were not reported. Also, adverse reactions that were reported too imprecisely to be of significance were not reported.
General: facial edema, photosensitivity reactions, shock, asthenia, pain, sudden fall, abdominal pain, sudden injury.
Cardiovascular system: angina pectoris, AV block, migraine, postural hypotension, myocardial ischemia, cerebral thrombosis, sudden cardiac arrest, ECG abnormalities, cardiomyopathy.
Gastrointestinal disorders: glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, liver function test abnormalities, rectal bleeding, gingivitis.
From the blood and lymphatic system: anemia, leukopenia.
Metabolism and nutrition disorders: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemia, hypernatremia.
Musculoskeletal disorders: arthritis, arthrosis, tendon rupture, tenosynovitis, bone pain, myasthenia gravis, synovitis.
Nervous system disorders: ataxia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, abnormal dreams, decreased reflexes.
Respiratory system disorders: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, increased salivation, increased cough.
Skin disorders: urticaria, herpes, itching, sweating, skin ulcers, contact dermatitis, exfoliative dermatitis.
Specific sensations: sudden decrease or loss of hearing, earache, hemorrhage in the eye, cataract, dry eyes.
Urogenital system disorders: cystitis, nocturia, increased urinary frequency, breast enlargement, urinary incontinence, ejaculation disorders, swelling of the genitals, anorgasmia.
Post-marketing Experience. The following adverse reactions have been identified during post-marketing experience. Because these reactions are reported voluntarily and from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions were considered in light of the following factors: seriousness, frequency of reporting, lack of a clear alternative relationship, and a combination of these factors.
Cardiovascular and cerebrovascular events: Serious cardiovascular, cerebrovascular and vascular events have been reported, including cerebrovascular haemorrhage, subarachnoid and intracerebral haemorrhage and pulmonary haemorrhage.
