Dosages 25 and 50 mg:
round biconvex, blue film-coated tablets;
100 mg dosage:
oval biconvex, blue film-coated tablets, with a ridge on both sides.
ATX code: G04BE03
Pharmacodynamics. Dynamogen for treatment of erectile dysfunction, restores under sexual stimulation impaired erectile function by increasing blood flow in the penis.
The physiological mechanism of erection involves the release of nitric oxide (NO) in the cavernous body due to sexual arousal. NO activates the enzyme guanylate cyclase, which leads to an increase in cyclic guanosine monophosphate (cGMP). The cGMP in turn relaxes the smooth muscles of the blood vessels and this leads to an increase in the blood supply to the cavernous body of the penis.
Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which causes cGMP breakdown in the penile cavernous body. It does not have a direct relaxing effect on the smooth muscles of the cavernous body, but enhances the relaxing effect of nitric oxide on this tissue and increases blood flow in the penis. During activation of NO – cGMP circuit, observed during sexual stimulation, inhibition of FDE5 results in increase of cGMP in cavernous body. The pharmacological effect is only achieved in the presence of sexual stimulation.
Sildenafil activity regarding FDEF5 is superior to other known phosphodiesterase isoenzymes: FDEF6 – 10 times, FDEF1 – more than 80 times; FDEF2 – FDEF4, FDEF7-FDEF11 – more than 700 times. Sildenafil is 4,000 times more selective against FDE5 than FDEZ, which is important because FDEZ is one of the key enzymes regulating myocardial contractility.
Sildenafil has mild and short-lived hypotensive effect, in most cases without clinical manifestation when taken in recommended doses. The hypotensive effect is due to the vasodilatory effect of sildenafil by increasing the content of cGMP in the vascular smooth muscle membrane.
After oral administration it is rapidly absorbed. Maximal plasma concentration (Cmax) is reached during fasting period (0.5-2 hours), bioavailability is on average 41% (25-63%). Cmax decreases by 20-40% when taken with food and is reached after 1.5-3 hours.
The apparent volume of distribution in equilibrium is 105 litres. Binding of sildenafil and its main active metabolite to plasma proteins is 96% of the administered dose and is not dose dependent.
Sildenafil is metabolised mainly by the CYP3A4 (main pathway) and CYP2C9 (complementary pathway) microsomal liver isoenzymes. The main circulating active metabolite is N-demethylmetabolite, which has phosphodiesterase activity of 50% of sildenafil activity and its plasma concentration reaches 40% of sildenafil concentration. N-demethylmetabolite is further metabolised with a half-life of 4 hours.
Total sildenafil clearance is 41 l/h. The half-life (Ti/2) of sildenafil is 3-5 hours. Inactive metabolites are eliminated by the intestine (80%) and the kidneys (13%).
Pharmacokinetics in special patient groups.
Cmax of sildenafil and its active metabolite is increased by approximately 90% in patients older than 65 years old due to decreased clearance of sildenafil. Plasma concentration of sildenafil not bound to proteins is 40%.
In patients with moderate renal impairment (creatinine clearance 30-80 ml/min) the pharmacokinetics of sildenafil is not altered when taking 50 mg, while Cmax and area under the concentration-time curve (AUC) for N-demethylmetabolite are increased by 73% and 126% respectively. In patients with severe renal insufficiency (creatinine clearance less than 30 ml/min) Cmax and AUC are increased by 88% and 100%, respectively; Cmax and AUC of N-demethylmetabolite are increased by 79% and 200%, respectively.
In patients with hepatic cirrhosis (Child-Pugh grades A and B) Cmax and AUC are increased by 47% and 84%, respectively.
Treatment of erectile dysfunction characterized by the inability to achieve or maintain a penile erection sufficient for satisfactory intercourse. Effective only with sexual stimulation.
Hypersensitivity to sildenafil or any other component of the drug; simultaneous use of nitric oxide donators or organic nitrates or nitrates in any dosage form; simultaneous use of ritonavir; Patients for whom sexual activity is undesirable, including those with severe cardiovascular diseases such as unstable angina pectoris, severe heart failure, life-threatening arrhythmias, arterial hypotension (blood pressure (BP) less than 90/50 mmHg). arterial hypertension (blood pressure less than 90/50 mm Hg). ), arterial hypertension (BP over 170/100 mmHg). ), recent cerebrovascular events or myocardial infarction; patients with single-eye vision loss due to nonarterial anterior ischemic optical neuropathy (whether or not due to an FDE5 inhibitor); hereditary retinal degenerative diseases, including retinitis pigmentosa (a minority of these patients have retinal FDE genetic disease); severe hepatic impairment; female sex; under 18 years of age.
Multiple systemic atrophy syndrome; left ventricular outflow tract obstruction, including aortic stenosis, hypertrophic obstructive cardiomyopathy; anatomical penile deformity; priapism; multiple myeloma; leukaemia; concomitant use of alpha-adrenoblockers; lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
Dosage and administration
Orally, about 1 hour before the planned sexual activity.
50 mg once daily. Depending on efficacy and tolerability, the dose may be increased to 100 mg or decreased to 25 mg.
No dose adjustment is required for patients with mild to moderate renal impairment (creatinine clearance (CK) 30-80 ml/min).
For patients with severe renal impairment (CKR less than 30 ml/min), the first dose is 25 mg. If tolerated well, the dose can be increased to 50 or 100 mg.
In elderly patients, the first dose is 25 mg. If well tolerated, the dose may be increased to 50 or 100 mg.
For patients with mild or compensated hepatic impairment, the first dose is 25 mg. If well tolerated, the dose may be increased to 50 or 100 mg.
For patients taking alpha-adreno-blockers, the first dose is 25 mg. The dose may be increased to 50 or 100 mg if well tolerated.
Frequency of side effects is classified according to the World Health Organization recommendations: very frequently – at least 10%; frequently – at least 1%, but less than 10%; infrequently – at least 0.1%, but less than 1%; rarely – at least 0.01%, but less than 0.1%; very rarely – less than 0.01%, including occasional cases. Nervous system: very common – headache; common – dizziness; infrequent – somnolence, hypoesthesia; rare – stroke, fainting; common unknown – transient ischemic attack, seizures, including recurrent ones.
Cardiovascular system: frequent – “hot flashes”; infrequent – palpitations, tachycardia; rare – increase or decrease in blood pressure, myocardial infarction, atrial fibrillation; common unknown – ventricular arrhythmia, unstable angina, sudden death. Eye: often – visual disturbances, colour perception disorders, infrequent – conjunctival damage, tear production disorders, enhanced perception of light, visual clarity problems, transient chromatopsia; rarely – redness of sclerae, pain in the eyeballs; frequency unknown – ischemic anterior optical neuropathy, retinal vascular occlusion, narrowing of the visual fields. Hearing organ: infrequent – vertigo, tinnitus; rarely – deafness. Respiratory system: often – nasal congestion; rarely – nasal bleeding.
Gastrointestinal tract: frequent – dyspepsia; infrequent – vomiting, nausea, dry oral mucosa.
Allergic reactions: infrequent – skin rash; frequency unknown – Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome). Genital disorders: frequency unknown – priapism, prolonged I erection. Other: rarely – chest pain, fatigue.
Symptoms: after a single dose of up to 800 mg, the adverse reactions (headache, “hot flashes”, dizziness, dyspepsia, nasal congestion, visual disturbances) were stronger and more frequent than in usual doses; doses up to 200 mg increased the frequency, but not the severity of adverse reactions Treatment: symptomatic therapy. Haemodialysis is ineffective.
Interaction with other drugs
The inhibitors of CYP3A4 and CYP2C9 isoenzymes (ketoconazole, erythromycin, cimitidine) reduce the metabolism and increase the blood concentration of sildenafil. In this case, start sildenafil treatment with a dose of 25 mg.
Concomitant use with ritonavir increases sildenafil Cmax by 300% and AUC by 1000% and remains high even 24 hours after sildenafil administration.
Concomitant use with saquinavir increases sildenafil Cmax by 140% and AUC by 210%.
The pharmacokinetics of ritonavir and saquinavir are not altered by sildenafil administration.
Sildenafil enhances the antiplatelet effect of sodium nitroprusside.
Nicorandil due to its nitrate component may cause severe arterial hypotension when interacting with sildenafil.
Simultaneous use of sildenafil and organic nitrates and other nitric oxide donors may be fatal due to mutually reinforcing effects.
Sildenafil enhances the hypotensive effects of “slow” calcium channel blockers, beta-adrenoblockers, angiotensin-converting enzyme inhibitors.
Simultaneous use increases the effectiveness of hypoglycemic agents.
Azithromycin has no effect on the pharmacokinetics of sildenafil.
Simultaneous use of sildenafil and alpha-adrenoblockers, including doxazosin, especially in the first 4 hours after sildenafil administration, may result in marked BP lowering and orthostatic hypotension.
Grapefruit juice may increase sildenafil blood concentration moderately.
Before using sildenafil, a thorough examination of the patient should be carried out in order to diagnose erectile dysfunction and to determine the cause of the dysfunction. The risk of serious adverse reactions due to sexual activity should be assessed in patients with cardiovascular disease and concomitant medication. Sildenafil causes a mild decrease in blood pressure. Patients with left ventricular obstruction or rare multiple atrophy syndrome are particularly susceptible to the hypotensive effects of sildenafil. Before using sildenafil in such patients the risk of adverse effects of low BP during sexual activity should be excluded. Most adverse cardiovascular reactions develop immediately after sexual intercourse or shortly thereafter, in single cases adverse reactions may develop before sexual intercourse.
The simultaneous use of several different medicines for the treatment of erectile dysfunction is not recommended.
Sildenafil should be used with caution in patients with anatomical deformities of the penis (angulation, cavernous fibrosis or Peyronie’s disease) and in patients with diseases that predispose to priapism (sickle cell anaemia, myeloma, leukaemia).
If visual defects occur, seek medical attention immediately.
Doses higher than 200 mg do not increase the efficacy, but the frequency and severity of dose-dependent side effects do increase.
Effect on driving and operating machinery
In case of adverse reactions of nervous system and sense organs, patients should abstain from driving motor transport and operating mechanisms as well as to be careful during activities requiring concentration and quick psychomotor reactions.
In the process of treatment it is important to be distracted by something pleasant. For example, you can buy clothes here: