Composition, form of production and packaging
The tablets covered with a film cover of blue color, oval, biconcave, with engraving "SL25" on one side.
1 tab.
sildenafil citrate 35.12 mg,
which corresponds to the content of sildenafil 25 mg
Excipients: lactose monohydrate - 62.38 mg, microcrystalline cellulose - 19.5 mg, povidone K29-32 - 6.5 mg, croscarmellose sodium - 5.2 mg, magnesium stearate - 1.3 mg.
The composition of the film shell: opadray 03F20404 blue - 2.6 mg (hypromellose-6cP - 1.65 mg, titanium dioxide - 0.53 mg, macrogol-6000 - 0.3 mg, indigo carmine (dye indigo carmine aluminum varnish) - 0.12 mg).
1 PC. - blisters (1) - packs of cardboard.
1 PC. - blisters (2) - packs of cardboard.
4 things. - blisters (1) - packs of cardboard.
4 things. - blisters (2) - packs of cardboard.
4 things. - blisters (3) - packs of cardboard.
The tablets covered with a film cover of blue color, oval, biconcave, with engraving "SL50" on one side.
1 tab.
sildenafil citrate 70.24 mg,
which corresponds to the content of sildenafil 50 mg
Excipients: lactose monohydrate - 124.76 mg, microcrystalline cellulose - 39 mg, povidone K29-32 - 13 mg, croscarmellose sodium - 10.4 mg, magnesium stearate - 2.6 mg.
The composition of the film shell: opadray 03F20404 blue - 5.2 mg (hypromellose-6cP - 3.3 mg, titanium dioxide - 1.06 mg, macrogol-6000 - 0.59 mg, indigo carmine (dye indigo carmine aluminum varnish) - 0.25 mg).
1 PC. - blisters (1) - packs of cardboard.
1 PC. - blisters (2) - packs of cardboard.
4 things. - blisters (1) - packs of cardboard.
4 things. - blisters (2) - packs of cardboard.
4 things. - blisters (3) - packs of cardboard.
The tablets covered with a film shell of blue color, oval, biconcave, with engraving "SL100" on one side.
1 tab.
sildenafil citrate 140.48 mg,
which corresponds to the content of sildenafil 100 mg
Excipients: lactose monohydrate - 249.52 mg, microcrystalline cellulose - 78 mg, povidone K29-32 - 26 mg, croscarmellose sodium - 20.8 mg, magnesium stearate - 5.2 mg.
The composition of the film shell: opadray 03F20404 blue - 10.4 mg (hypromellose-6cP - 6.6 mg, titanium dioxide - 2.11 mg, macrogol-6000 - 1.19 mg, indigo carmine (dye indigo carmine aluminum varnish) - 0.5 mg).
1 PC. - blisters (1) - packs of cardboard.
1 PC. - blisters (2) - packs of cardboard.
4 things. - blisters (1) - packs of cardboard.
4 things. - blisters (2) - packs of cardboard.
4 things. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
The drug for the treatment of erectile dysfunction, inhibitor PDE5. Sildenafil is a potent selective inhibitor of cyclic guanosine monophosphate (cGMP), a specific PDE5. The realization of the physiological mechanism of erection is associated with 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, subsequent relaxation of the smooth muscle tissue of the cavernous body and an increase in blood flow.Sildenafil does not have a direct relaxing effect on an isolated cavernous body in humans, but enhances the effect of NO by inhibiting PDE5, which is responsible for the degradation of cGMP. The use of sildenafil in recommended doses is ineffective in the absence of sexual stimulation.
Sildenafil is selective for PDE5 in vitro, its activity against PDE5 is significantly superior to that of other known phosphodiesterase isozymes.
PHARMACOKINETICS
The pharmacokinetics of sildenafil in the recommended dose range is linear.
Suction
After taking the drug, sildenafil is rapidly absorbed. Absolute bioavailability averages 40% (25-63%). In vitro, sildenafil at a concentration of about 1.7 ng / ml (3.5 nM) suppresses human PDE5 by 50%. After a single intake of sildenafil in a dose of 100 mg orally, the average C max of free sildenafil in blood plasma is 18 ng / ml (38 nM) and is achieved with fasting on average during 60 minutes (30-120 min). When taken in combination with fatty foods, the suction rate decreases: C maxdecreases by an average of 29%, and T max increases by 60 min, but the degree of absorption does not change significantly (AUC decreases by 11%).
Distribution
V d of sildenafil in the equilibrium state averages 105 liters.
The binding to plasma proteins of sildenafil and its main circulating N-desmethyl metabolite is about 96% and does not depend on the total concentration of sildenafil. Less than 0.0002% of the dose (an average of 188 ng) is found in the semen 90 minutes after taking sildenafil.
Metabolism
Sildenafil is metabolized mainly in the liver with the participation of CYP3A4 isoenzymes (the main pathway) and CYP2C9 (a secondary pathway). The main circulating metabolite, which is formed as a result of N-demethylation of sildenafil, undergoes further metabolism. By the selectivity of action on PDE, the metabolite is comparable with sildenafil, and its activity in relation to PDE5 in vitro is approximately 50% of the activity of sildenafil. The concentration of the metabolite in the blood plasma is approximately 40% of the concentration of sildenafil. The N-desmethyl metabolite undergoes further metabolism. Its T 1/2 is about 4 hours.
Excretion
The total clearance of sildenafil is 41 l / h, and the final T 1/2 is 3-5 hours. After oral administration, as well as after intravenous administration, sildenafil is excreted as metabolites, mainly by the intestine (about 80% of the oral dose) and, to a lesser extent, kidneys (about 13% of the oral dose).
Pharmacokinetics in special clinical cases
In healthy elderly people (over 65 years), the clearance of sildenafil is reduced, and the concentration of free sildenafil in blood plasma is approximately 40% higher than in young (18-45 years). Age does not have a clinically significant effect on the incidence of side effects.
With renal insufficiency of mild (CC is 50-80 ml / min) and average (QC is 30-49 ml / min), the degree of pharmacokinetics of sildenafil after single ingestion in a dose of 50 mg does not change. In patients with severe renal insufficiency (CC <30 ml / min), the clearance of sildenafil decreases, which leads to approximately a twofold increase in AUC (100%) and Cmax (88%) compared with those in normal kidney function in patients of the same age group.
In patients with cirrhosis of the liver (grades A and B on the Child-Pugh scale), the clearance of sildenafil decreases, which leads to an increase in AUC (84%) and Cmax (47%) 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 (class C on the Child-Pugh scale) has not been studied.
INDICATIONS
- treatment of erectile dysfunction, characterized by the inability to achieve or maintain an erection penis sufficient for a satisfactory sexual intercourse.
The drug is effective only with sexual stimulation.
DOSING MODE
The drug is taken orally.
The recommended dose for most patients is 50 mg approximately 1 hour before sexual activity. With regard to efficacy and tolerability, the dose can be increased to 100 mg or reduced to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended frequency of application is 1 time / day.
Older patients do not need a dose adjustment.
With renal insufficiency of mild and moderate severity (CK 30-80 ml / min) dose adjustment is not required, with renal failure of severe degree (CK <30 ml / min) the recommended dose is 25 mg.
In patients with impaired liver function, the dose should be reduced to 25 mg.
Simultaneous use with other drugs
When combined with ritonavir, the maximum single dose of the drug is 25 mg not more than, 1 time in 48 hours .
When combined with inhibitors of the isoenzyme CYP3A4 (such as erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose is 25 mg.
To minimize the risk of postural hypotension in patients taking alpha-blockers , start taking Olmax Strong should only after hemodynamics stabilization in these patients has been achieved. In addition, one should consider the desirability of reducing the initial dose of sildenafil to 25 mg.
SIDE EFFECT
The frequency of unwanted adverse reactions (NDP): very often (? 10%), often (? 1% and <10%), infrequently (? 0.1% and <1%), rarely (? 0.01% and <0.1%), very rarely (<0.01%). Frequency (NDP), reported in the post-registration period, is listed as "unknown".
From the cardiovascular system: often - vasodilation ("hot flashes"); infrequent - a feeling of palpitations, tachycardia; rarely - myocardial infarction, atrial fibrillation, increase or decrease in blood pressure; unknown - ventricular arrhythmias, unstable angina, sudden cardiac arrest.
From the nervous system: very often - headache; often - dizziness; infrequently - drowsiness, hypoesthesia; rarely - a stroke, a faint; unknown - transient ischemic attack, convulsions, incl. recurrent.
From the side of the organ of vision: often - impaired vision, violation of color perception; infrequently - damage to the organ of vision, incl. defeat of the conjunctiva, violation of lacrimation; unknown - anterior non-artery ischemic neuropathy of the optic nerve, occlusion of the retinal vessels, narrowing of the visual fields.
From the side of the organ of hearing and labyrinthine disturbances: infrequently - vertigo, noise in the ears; rarely - deafness (sudden decrease or loss of hearing).
From the respiratory system: often - nasal congestion; rarely - epistaxis.
From the side of the digestive system: often - indigestion; infrequently - vomiting, nausea, dryness of the oral mucosa.
From the skin and subcutaneous tissues: infrequently - skin rash.
From the osteomuscular and connective tissue: infrequently - myalgia.
From the immune system: rarely - hypersensitivity.
On the part of the reproductive system: infrequently - hematospermia and hemorrhage from the penis; it is not known - priapism, prolonged erection.
General disorders: infrequent - chest pain, fatigue.
CONTRAINDICATIONS
- hypersensitivity to the components of the drug;
- severe violations of the liver (class C on the scale Child-Pugh);
- use in combination with donators of nitric oxide (for example, amyl nitrite), nitrates or nitrites in any form;
- joint use with other drugs to treat erectile dysfunction (safety and efficacy of combination therapy not studied);
- a joint use with the HIV-1 and HIV-2 inhibitor of ritonavir protease;
- use in women;
- patients with rare hereditary diseases of galactose intolerance, lactase insufficiency or glucose-galactose malabsorption (contains lactose monohydrate);
- age under 18 years (efficiency and safety not established).
Carefully:
- anatomical deformation of the penis (angulation, cavernous fibrosis or Peyronie's disease);
- diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocytopenia);
- diseases accompanied by bleeding;
- exacerbation of peptic ulcer of the stomach and duodenum;
- Severe cardiovascular disorders (life-threatening arrhythmias, unstable angina or severe heart failure, stroke or myocardial infarction), transferred during the last 6 months;
- arterial hypotension (blood pressure less than 90/50 mm Hg);
- arterial hypertension (blood pressure more than 170/100 mm Hg);
- hereditary degenerative diseases of the retina, including
hereditary retinitis pigmentosa;
- violations of the liver (classes A and B on the scale Child-Pugh);
- renal failure of severe degree (CK <30 ml / min);
- patients with episodes of development of anterior non-artery ischemic neuropathy of the optic nerve in the anamnesis.
PREGNANCY AND LACTATION
According to the registered indication the drug is not intended for use in women.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution: violations of the liver (classes A and B on the scale Child-Pugh);
Contraindicated: severe violations of the liver (class C on the scale Child-Pugh);
SPECIAL INSTRUCTIONS
Before starting any treatment for erectile dysfunction, the doctor must determine the cardiovascular status of the patient, since there is a certain degree of risk associated with sexual activity. Drugs intended for the treatment of erectile dysfunction should not be prescribed to men for whom sexual activity is undesirable.
Sildenafil has vasodilator properties, resulting in insignificant transient decreases in blood pressure. However, increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (eg, aortic stenosis, hypertrophic obstructive cardiomyopathy), or in patients with a rare syndrome of multiple systemic atrophy, manifesting a severe violation of blood pressure regulation from the autonomic nervous system.
During the post-marketing period, serious cardiovascular events including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmias, cerebrovascular bleeding, transient ischemic attack, increase or decrease in blood pressure, which were in a temporary connection with the use of sildenafil, were reported during the post-marketing period. Most of these patients had cardiovascular risk factors. It was reported that many of the phenomena occurred during or soon after intercourse, and only a small amount occurred shortly after taking sildenafil without sexual activity, so it is impossible to determine whether these phenomena are directly related to these or other factors.
Since the combined use of sildenafil and alpha-blockers can lead to symptomatic hypotension in selected sensitive patients, sildenafil should be used with caution in patients taking alpha-blockers. In order to minimize the risk of postural hypotension in patients taking alpha-adrenoblockers, the initiation of sildenafil should be started only after hemodynamics stabilization in these patients has been achieved. Consider the desirability of reducing the initial dose of sildenafil. In addition, the doctor should inform the patients about what actions should be taken in case of symptoms of postural hypotension.
Sildenafil enhances the antiplatelet effect of sodium nitroprusside (a donor of nitric oxide) on human platelets in vitro. Information about the safety of the drug in patients with internal bleeding or active peptic ulcers of the stomach is not available, so in such cases, the drug should be used with caution.
A small number of patients with hereditary pigment retinitis have hereditary disorders of the phosphodiesterase of the retina and, since there is no information on the safety of sildenafil, the drug should be used with caution.
The doctor should inform the patient about the increased risk of developing anterior ischemic optic neuropathy of non-arterial genesis, if previously this condition was already noted. There have been rare cases of development of anterior ischemic optic neuropathy of non-arterial genesis as a cause of impairment or loss of vision against the background of the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors, such as excavating the optic nerve head, age over 50, diabetes, hypertension, IHD, hyperlipidemia, smoking. The causal relationship between the intake of PDE5 inhibitors and anterior ischemic optic neuropathy of non-arterial genesis has not been revealed.
In some post-marketing and clinical trials using all PDE5 inhibitors, including sildenafil, sudden depression or hearing loss in patients was reported. However, in most cases, these patients had risk factors for this pathology, and there was no correlation between
use of PDE5 inhibitors and sudden decrease or loss of hearing. The patient should be warned that in the event of a sudden decrease or loss of hearing, stop sildenafil therapy and consult a doctor immediately.
Impact on the ability to drive vehicles and manage mechanisms
Since it is possible to reduce blood pressure, the development of chromatopsy, blurred vision, you should carefully consider the individual effect of the drug, especially in the beginning of treatment and when changing the dosage regimen and to be careful when driving vehicles and engage in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: with a single dose of the drug in a dose of up to 800 mg, adverse reactions were the same as in the case of lower doses, but were more common.
Treatment: In case of an overdose, if necessary, standard supportive measures should be taken. Treatment is symptomatic. Dialysis does not accelerate clearance, because sildenafil is largely associated with plasma proteins and is not excreted by the kidneys.
DRUG INTERACTION
Metabolism of sildenafil occurs mainly in the liver under the action of cytochrome isozymes CYP3A4 (the main pathway) and CYP2C9, so inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inductors, respectively, increase the clearance of sildenafil. With the simultaneous use of inhibitors of the isoenzyme CYP3A4 (such as ketoconazole, erythromycin, cimetidine), a decrease in the clearance of sildenafil was noted. Cimetidine (800 mg), which is a non-specific inhibitor of the isoenzyme CYP3A4, when taken with sildenafil (50 mg) causes an increase in the concentration of sildenafil in plasma by 56%. A single dose of sildenafil 100 mg concurrently with erythromycin, a specific inhibitor of the isoenzyme CYP3A4 (when taking erythromycin 2 times / day for 500 mg for 5 days), against the background of achieving a constant concentration of erythromycin in the blood, leads to an increase in the AID of sildenafil by 182%.
With the simultaneous use of sildenafil (once in a dose of 100 mg) and saquinavir, which is both an inhibitor of the HIV protease, and an inhibitor of the isoenzyme CYP3A4 (with the administration of saquinavir 3 times / day at a dose of 1200 mg), against the background of C ss saquinavir in the blood, C max sildenafil in the blood increased by 140%, and the AUC increased by 210%. Sildenafil had no effect on the pharmacokinetic parameters of saquinavir. More potent inhibitors isoenzyme CYP3A4, such as ketoconazole or itraconazole, may cause more pronounced changes sildenafil pharmacokinetics.
With simultaneous use of sildenafil (single dose 100 mg) and ritonavir is an inhibitor of HIV protease and a potent inhibitor of isoenzymes of cytochrome P450 (at reception of ritonavir of 500 mg of 2 times / day), against the backdrop of C ss of ritonavir in the blood, C max sildenafil increased by 300% (4 times), a AUC 1000% (11 times). After 24 h of sildenafil plasma concentration was approximately 200 ng / ml (a single application of sildenafil - 5 ng / ml).
If sildenafil is taken at the recommended doses, patients receiving both potent inhibitors of isoenzyme CYP3A4, C max free sildenafil less than 200 nM, and the preparation well tolerated.
A single dose of antacid (hydroxide / magnesium hydroxide, aluminum) did not affect the bioavailability of sildenafil.
Inhibitors of the isoenzyme CYP2C9 (such as tolbutamide, warfarin) isoenzyme CYP2D6 (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazides and thiazide diuretics, ACE inhibitors and calcium antagonists have no effect on the pharmacokinetic parameters of sildenafil.
Simultaneous treatment with azithromycin (500 mg / day for 3 days) did not affect the AUC, C max , T max, Elimination rate constant and T 1/2 sildenafil or its main circulating metabolite.
Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes - 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC 50 > 150 mM). It is unlikely that sildenafil can affect the clearance of substrates of these isoenzymes.
Sildenafil enhances the hypotensive effects of nitrates, as a long-term use, and when used on acute indications. In this regard, the use of sildenafil in combination with nitrates or nitric oxide donators contraindicated.
When simultaneous administration of alpha-adrenergic blocker doxazosin (4 mg and 8 mg) and sildenafil (50 mg and 100 mg) in patients with benign prostatic hyperplasia with stable haemodynamics average additional reduction in systolic / diastolic blood pressure in the supine position was 9/5 mm Hg and 8/4 mm Hg respectively, and a standing position - 11/4 mmHg and 4/5 mm Hg respectively. It reported rare cases of such patients symptomatic postural hypotension, manifested in the form of dizziness (without fainting). In certain sensitive patients treated with alpha-adrenergic blockers, the simultaneous use of sildenafil may result in symptomatic hypotension.
No evidence of significant interaction with sildenafil tolbutamide (250 mg) or warfarin (40 mg) that are metabolized isoenzyme CYP2C9, is not revealed.
Sildenafil 100 mg no effect on the pharmacokinetic parameters of HIV protease inhibitors at its constant concentration in the blood, such as saquinavir and ritonavir simultaneously are substrates isoenzyme CYP3A4.
Sildenafil (50 mg) does not cause an additional increase in bleeding time at the reception of acetylsalicylic acid (150 mg).
Sildenafil (50 mg), does not potentiate the hypotensive effect of ethanol was in healthy volunteers at the maximum level in the blood ethanol in average 80 mg / dl.
Patients with signs of hypertension interaction sildenafil (100 mg) with amlodipine was not revealed. The use of sildenafil in combination with antihypertensive agents does not cause any additional side effects.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 3 years.
