Olmax Strong - instructions for use, dose, side effects, contraindications

active substance: sildenafil citrate - 35.12 mg in terms of 25 mg of sildenafil; Excipients: lactose monohydrate - 62.38 mg, cellulose microcrystalline - 19.50 mg, povidone-K29-32 - 6.50 mg, croscarmellose sodium - 5.20 mg, magnesium stearate - 1.30 mg;

film coating: Opadry 03F20404 Blue (hypromellose-bsR - 1.65 mg, titanium dioxide 0.53 mg, macrogol-6000 - 0.30 mg, indigocarmine (dye indigo carmine aluminum varnish) - 0,12 mg) ~ 2,6 mg.

1 tablet, film-coated, 50 mg contains:

active substance: sildenafil citrate - 70.24 mg in terms of 50 mg of sildenafil; Excipients: lactose monohydrate - 124.76 mg, microcrystalline cellulose - 39.00 mg, povidone-K29-32 - 13.00 mg, croscarmellose sodium - 10.40 mg, magnesium stearate - 2.60 mg;

film coating: Opadry 03F20404 Blue (hypromellose-bsR - 3.30 mg, titanium dioxide - 1.06 mg, macrogol-6000 - 0.59 mg, indigo carmine (dye indigo carmine aluminum varnish) - 0.25 mg) ~ 5.2 mg.

1 tablet, film-coated, 100 mg contains:

active substance: sildenafil citrate - 140.48 mg in terms of 100 mg of sildenafil; Excipients: lactose monohydrate - 249.52 mg, microcrystalline cellulose - 78.00 mg, povidone-K29-32 - 26.00 mg, croscarmellose sodium - 20.80 mg, magnesium stearate - 5.20 mg;

film coating: Opadry 03F20404 Blue (hypromellose-bsR - 6.60 mg, titanium dioxide - 2.11 mg, macrogol-6000 - 1.19 mg, indigocarmine (indigo carmine aluminum lacquer dye) - 0.50 mg) ~ 10.4 mg

Description:

Tablets 25 mg

Oval, biconvex tablets, film-coated, blue with engraving "SL25" on one side of the tablet.

50 mg tablets

Oval, biconvex tablets, film-coated, blue with engraving "SL50" on one side of the tablet.

Tablets 100 mg

Oval, biconvex tablets, film-coated, blue with engraving "SL100 "on one side of the tablet.

Pharmacotherapeutic group:Erectile dysfunction remedy - PDE5-inhibitor

ATX: & nbsp

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

G.04.B.E.03 Sildenafil

Pharmacodynamics:

Sildenafil is a potent selective inhibitor of cyclic guanosine monophosphate (cGMP) - specific phosphodiesterase type 5 (PDE5). The implementation of the physiological mechanism of erection is associated with the release of nitric oxide (N0) in a 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 It has no direct relaxing effect on isolated human corpus cavernosum in, but enhances the effect of N0 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 significantly superior activity against other known PDE isoenzymes.

Pharmacokinetics:

The pharmacokinetics of sildenafil in the recommended dose range is linear.

Suction

After taking the drug inside sildenafil quickly 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 dose of sildenafil in a dose of 100 mg, the mean maximum concentration (C_max) free sildenafil in blood plasma is 18 ng / ml (38nM) and is achieved with fasting on average during 60 min (30-120 min). When taken in combination with fatty foods, the rate of absorption decreases: C_max decreases by an average of 29%, and the time to reach the maximum concentration (T_max) is increased by 60 min, but the degree of absorption does not change significantly (the area under the "concentration-time" curve, (AUC) decreases by 11%).

Distribution

The volume of distribution of sildenafil in the equilibrium state averages 105 liters. Sildenafil and its main circulating Na desmethyl metabolite approximately 96% bind to plasma proteins. Binding to proteins does not depend on the total concentration of sildenafil. Less than 0.0002% of the dose (an average of 188 ng) is detected in the sperm 90 minutes after taking sildenafil.

Metabolism

Sildenafil is metabolized mainly in the liver under the action of isoenzymes CYP3A4 (main path) and CYP2C9 (a secondary path). The main circulating metabolite, which is formed as a result of N-detylation 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. Na desmethyl metabolite undergoes further metabolism. The half-life period (T1/2) is about 4 hours.

Excretion

The total clearance of sildenafil is 41 liters / hour, and the final T_1/2- 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, by the kidneys (about 13% of the oral dose).

Pharmacokinetics in specific patient groups

Elderly patients

In healthy elderly patients (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.

Renal impairment

In mild (creatinine clearance (CK) is 50-80 ml / min) and moderate (QA is 30-49 ml / min), the degree of renal failure pharmacokinetics of sildenafil after a single oral intake at a dose of 50 mg does not change. With severe degree of renal failure (QC ≤ 30 ml / min), the clearance of sildenafil decreases, which leads to approximately a twofold increase in the value AUC (100%) and C_max (88%) in comparison with those for normal kidney function in patients of the same age group.

Dysfunction of the liver

In patients with cirrhosis of the liver (stages A and B according to the Child-Pugh classification), the clearance of sildenafil decreases, which leads to an increase in the value AUC (84%) and C_max (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 (Stage C according to the Child-Pugh classification) has not been studied.

Indications:

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

The drug is effective only with sexual stimulation.

Contraindications:

hypersensitivity to the active substance or any other component of the drug;
application 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);
age under 18 years (effectiveness and safety not established);
severe liver dysfunction (Child-Pugh Stage C);
co-administration with HIV-1 and HIV-2 inhibitor of proteas with ritonavir;
use in women;
patients with rare hereditary diseases of galactose intolerance, insufficiency of lactase or glucose-galactose malabsorption (contains lactose monohydrate).

Carefully:

with anatomical deformation of the penis (angulation, cavernous fibrosis or Peyronie's disease);
with diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocytopenia);
with diseases accompanied by bleeding;
with exacerbation of peptic ulcer of the stomach and duodenum;
with severe cardiovascular disorders (life-threatening arrhythmias, unstable angina or severe heart failure, stroke or myocardial infarction), transferred during the last 6 months;
with arterial hypotension (blood pressure less than 90/50 mm Hg) or hypertension (blood pressure more than 170/100 mm Hg);
in patients with impaired liver function;
with hereditary degenerative diseases of the retina, including hereditary retinitis pigmentosa.
in patients with impaired liver function (Child-Pugh Childhood A and B stages);
severe degree of renal failure (CK <30 ml / min);
patients with episodes of development of predecessors of non-arterial 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.

Dosing and Administration:

The drug is taken orally.

Recommended dose for most patients - 50 mg orally about 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.Maximum recommended multiplicity of application - 1 once a day.

Elderly patients

Correction of the dose is not required.

Impaired renal function

With renal insufficiency of mild and moderate severity (CK 30-80 ml / min) dose correction is not required, with expressed renal failure (CK <30 ml / min) the recommended dose is 25 mg.

Impaired liver function

In patients with impaired liver function, the dose should be reduced to 25 mg.

Use with other medicines

When combined with ritonavir the maximum single dose of the drug is 25 mg not more than, 1 time per 48 hours (see section

Interaction with other medicinal products).

When combined with cytochrome P450 inhibitors, ZA4 (such as erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose is 25 mg (see section Interaction with other medicinal products).

To minimize the risk of postural hypotension in patients taking alpha-blockers, it is necessary to start taking Olmax Strong only after the stabilization of hemodynamics in these patients has been achieved.In addition, one should consider the desirability of reducing the initial dose of sildenafil to 25 mg (see sections special instructions and Interaction with other medicinal products).

Side effects:

Frequency of adverse reactions (CPD): very often (≥10%); often (≥1% and <10%); infrequently (≥0,1% and < 1%); rarely (≥0,01% and <0,1%); very rarely (<0,01 %).

The frequency of NDP, reported in the post-registration period, is indicated as "unknown".

Disorders from the cardiovascular system: often - vasodilation

("tides"); infrequent - a feeling of palpitations, tachycardia; rarely - myocardial infarction, atrial fibrillation, increase or decrease in blood pressure (BP); unknown - ventricular arrhythmias, unstable angina, sudden cardiac arrest.

Impaired nervous system: very often - headache; often - dizziness; infrequently - drowsiness, hypoesthesia; rarely - a stroke, a faint; unknown - transient ischemic attack, convulsions, incl. recurrent.

Disorders 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 conjunctiva,violation of lacrimation; unknown - anterior non-artery ischemic neuropathy of the optic nerve, occlusion of the retinal vessels, narrowing of the visual fields.

Hearing disorders and labyrinthine disturbances: infrequently - vertigo, noise in the ears; rarely - deafness (sudden decrease or loss of hearing).

Disturbances from the respiratory system, chest and mediastinal organs: often - nasal congestion; rarely - epistaxis.

Disorders from the gastrointestinal tract: often - indigestion; infrequently - vomiting, nausea, dryness of the oral mucosa.

Disturbances from the skin and subcutaneous tissues: infrequently - a skin rash.

Disturbances from the osteomuscular and connective tissue: infrequently - myalgia. General disorders: infrequently - chest pain, fatigue.

Immune system disorders: rarely - hypersensitivity.

Violations of the genitals: infrequently - hematospermia and hemorrhage from the penis; it is not known - priapism, prolonged erection.

Overdose:

With a single dose of the drug in a dose of up to 800 mg, the adverse reactions were the same as in the case of lower doses, but were more common.

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.

Interaction:

The metabolism of sildenafil occurs mainly in the liver under the action of cytochrome isoenzymes CYP3A4 (main path) 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 isoenzyme CYP3A4 (such as ketoconazole, erythromycin, cimetidine) there was a decrease in the clearance of sildenafil. Cimetidine (800 mg), which is a nonspecific inhibitor of the isoenzyme CYP3A4, with simultaneous admission with sildenafil (50 mg) causes an increase in the concentration of sildenafil in plasma by 56%. A single dose of sildenafil in a dose 100 mg simultaneously with erythromycin, a specific isoenzyme inhibitor CYP3A4 (when taking erythromycin 2 times a day for 500 mg for 5 days), against the background of achieving a constant concentration of erythromycin in the blood, leads to an increase AUC 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 (when taking saquinavir 3 times a day in a dose 1200 mg), against the background of achieving a constant level of saquinavir in the blood, Cmax sildenafil in the blood increased by 140%, a AUC increased by 210%. Sildenafil did not influence the pharmacokinetic parameters of saquinavir. More potent inhibitors of isoenzyme CYP3A4, such as ketoconazole or itraconazole, can cause more pronounced changes in the pharmacokinetics of sildenafil.

With the simultaneous use of sildenafil (once in a dose of 100 mg) and ritonavir, which is an inhibitor of HIV protease and a strong inhibitor of cytochrome P450 isoenzymes (when ritonavir is taken 500 mg twice a day), against the background of achieving a constant level of ritonavir in the blood, C_max sildenafil increased by 300% (4 times), a AUC on 1000% (in 11 times). After 24 hours, the concentration of sildenafil in the blood plasma was approximately 200 ng / ml (with a single application of one sildenafil - 5 ng / ml).

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

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

Inhibitor inhibitors CYP2C9 (such as tolbutamide, warfarin), isoenzyme CYP2D6 (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazides and thiazide-like diuretics, angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists have no effect on the pharmacokinetic parameters of sildenafil.

Simultaneous administration of azithromycin (500 mg per day for 3 days) does not affect AUC, C_max, T_max, the rate constant of excretion and T_1/2 sildenafil or its main circulating metabolite.

Sildenafil is a weak inhibitor of cytochrome P450 - 1A2, 2C9, 2C19, 2D6, 2E1 and 4A (IR₅₀ > 150 μmol). It is unlikely that sildenafil can affect the clearance of the 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 donators of nitric oxide is contraindicated.

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

Signs of significant interaction of sildenafil with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the isoenzyme CYP2C9, not found. Sildenafil in a dose of 100 mg does not affect the pharmacokinetic parameters of HIV protease inhibitors at their constant concentration in the blood, such as saquinavir and ritonavir, which are simultaneously the substrates of the isoenzyme CYP3A4. Sildenafil (50 mg) does not cause an additional increase in bleeding time when taking acetylsalicylic acid (150 mg).

Sildenafil (50 mg) does not increase the hypotensive effect of ethanol in healthy volunteers with a maximum level of ethanol in the blood, on average 80 mg / dl.

In patients with hypertension, there was no evidence of interaction between sildenafil (100 mg) and amlodipine. The use of sildenafil in combination with antihypertensive drugs does not lead to additional side effects.

Special instructions:

Before beginning 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 leading to

minor transient decreases in blood pressure. However, increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (for example, aortic stenosis, hypertrophic obstructive cardiomyopathy), or in patients with a rare syndrome of multiple systemic atrophy, manifesting a severe violation of regulation of blood pressure from the autonomic nervous system.

During the post-marketing period, serious cardiovascular events were reported that included myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmias, cerebrovascular bleeding, transient ischemic attack, increased or decreased BP, which were in temporary communication with sildenafil. Most of these patients had cardiovascular risk factors. It has been reported that many 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 caution should be given to patients taking alpha-blockers. To minimize the risk of postural hypotension in patients taking alpha-adrenoblockers,how will stabilization of hemodynamics be achieved in these patients. 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 antiaggregant effect of sodium nitroprusside (a donator 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, reported a sudden decrease or loss of hearing in patients. However, in most cases, these patients had risk factors for this pathology, and there was no correlation between the use of PDE5 inhibitors and sudden decline 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.

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

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 at 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

Form release / dosage:

Film coated tablets, 25 mg, 50 mg and 100 mg.

Packaging:1 or 4 tablets per blister PVC / PVDC / Aluminum foil. For 1 or 2 blisters for 1 tablet, 1, 2 or 3 blisters for 4 tablets with instructions for use in a cardboard pack

Storage conditions:

At a temperature of no higher than 25 ° C. Keep out of the reach of children!

Shelf life:3 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002629

Date of registration:22.09.2014 / 03.04.2017

Expiration Date:22.09.2019

The owner of the registration certificate:AKTAVIS GROUP, AO AKTAVIS GROUP, AO Iceland

Manufacturer: & nbsp

ACTAVIS, Ltd. Iceland

Representation: & nbspACTAVIS GROUP AO ACTAVIS GROUP AO Iceland

Information update date: & nbsp06.06.2017

Illustrated instructions

Instructions

Olmax Strong (Allmax strong)