Taxiere - instructions for use, dose, side effects, contraindications

film sheath: sepiphilm 3048 yellow (hypromellose 40-45%, microcrystalline cellulose 30-40%, macro goal 40 stearate 4-12 %, titanium dioxide 10-15%, dye quinoline yellow 0.15-0.5%) 12.00 mg, macrogol 6000 0.12 mg.

Tablets 100 mg active substance:

sildenafil citrate 140.48 mg (in terms of sildenafil - 100 mg), Excipients:

core: calcium hydrophosphate 251.52 mg, microcrystalline cellulose 140.00 mg, croscarmellose sodium 16.80 mg, magnesium stearate 11.20 mg,

film sheath: sepiphilm 3048 yellow (hypromellose 40-45%, microcrystalline cellulose 30-40%, macropoda 40 stearate 4-12%, titanium dioxide 10-15 %, dye quinoline yellow 0.15-0.5%) 20.00 mg, macrogol 6000 0.24 mg.

Description:

Tablets 50 mg: round biconvex tablets, covered with a film coating of yellow color, marked "50" on one side.

Tablets 100 mg: round biconvex tablets, covered with a film coating of yellow color, marked "100" on one side.

Pharmacotherapeutic group:Erectile dysfunction medication is a 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 realization of the physiological mechanism of erection is associated with the release of nitric oxide (NO) in the cavernous body during sexual stimulation. The ego, in turn, leads to an increase in the level of cGMP, the 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 decay 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 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 intake of sildenafil in a dose of 100 mg orally, the average maximum concentration of (free) sildenafil in the blood plasma is 18 ng / ml (38 and M) and is achieved with fasting on average during 60 minutes (30-120 min). When taken in conjunction with a fatty syringe, the rate of absorption decreases: Cum, decreases by an average of 29%, and the time

reaching the maximum concentration (Tmax) increases 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 N-desmethyl metabolite is approximately 96% bound 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 found in the semen 90 minutes after taking sildenafil Metabolism

Sildenafil is metabolized mainly in the liver under the action of isoenzymes CYP3A4 (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 sildenafil concentration. The N-desmethyl metabolite undergoes further metabolism. Its half-life (T1 / 2) is about 4 hours.

Excretion

The total clearance of sildenafil is 41 l / h, and the final T1 / 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 special patient groups

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 renal disease

(<30 ml / min), the clearance of sildenafil is reduced, which leads to approximately a two-fold increase in AUC (100%) and St1k (88%) compared 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 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 (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 sildenafil or to any component of the drug;
Simultaneous reception of donators of nitric oxide or organic nitrates or nitrites in any dosage forms;
Simultaneous reception of other drugs that stimulate erection, ritonavir;
Patients for whom sexual activity is undesirable (including those with severe cardiovascular diseases, such as unstable angina, severe heart failure);
Arterial hypotension (blood pressure less than 90/50 mm Hg);
Recently suffered impairment of cerebral circulation or myocardial infarction;
Hereditary degenerative diseases of the retina, including retinitis pigmentosa (a smaller chale of such patients has a genetic disorder of the retina PDE);
Severe hepatic impairment;
Age to 18 years;
Female.

Carefully:

With anatomical deformation of the penis (angulation.cavernous fibrosis or Peyronie's disease);

In diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia, thrombocytopenia);

In diseases accompanied by bleeding;

With exacerbation of peptic ulcer of the stomach and duodenum;

In patients taking alpha-adrenoblockers (the risk of developing orthostatic hypotension).

Pregnancy and lactation:

According to the registered indication, the drug Taxiere is not intended for use in women.

Dosing and Administration:

Tablets are taken orally for one hour before sexual activity. Upon admission TAXIER® at mealtime start action of the drug may be delayed by compared with taking on an empty stomach.

The recommended dose is 50 mg. FROM taking into account the effectiveness and tolerability of this the dose can be increased to 100 mg.

The maximum recommended dose and frequency of admission is 100 mg once a day.

Dose adjustments in elderly patients are not it takes.

Use in patients with impaired kidney function

Patients with mild to moderate degree Renal insufficiency (CK = 30-80 ml / min) dose adjustment is not required.

Use in patients with impaired function of the liver.

In patients with impaired liver function (stages A and B according to the Child-Pugh classification), the appointment of the drug should be coordinated with the attending physician.

Use in patients taking other medicines

Patients receiving concomitant treatment with other isoenzyme inhibitors cytochrome CYP3A4 (erythromycin, saquinavir, ketoconazole, itraconazole), before starting the use of the drug should consult a doctor.

To reduce the risk of developing Orthostatic hypotension in patients taking alpha-adrenoblockers, the use of sildenafil should be started only after stabilizing their condition against the background of therapy with alpha-blockers.

Side effects:

Classification of the incidence of adverse events (WHO): very often> 1/10, often> 1/100 to <1/10, infrequently from> 1/1000 to <1/100, rarely> 1/10000 to <1 / 1000, very rarely from <1/10000, including individual messages.

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

From the cardiovascular system: often - "hot flashes"; infrequent - a feeling of palpitations, tachycardia; rarely - increase or decrease in blood pressure, myocardial infarction, atrial fibrillation; frequency unknown - ventricular arrhythmia, unstable angina, sudden death.

From the side of the organ of vision: often - impaired vision, violation of color perception; infrequently - defeat of conjunctiva, violation of lacrimation; frequency unknown - anterior ischemic optic neuropathy, retinal vascular occlusion, visual field defects.

From the side of the organ of hearing: infrequently - vertigo, noise in the ears; rarely - deafness.

On the part of the respiratory system: often - nasal congestion; rarely - epistaxis. From the gastrointestinal tract: often - dyspepsia; infrequently - vomiting, nausea, dryness of the oral mucosa

Allergic reactions: infrequent - skin rash; frequency is unknown - Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

On the part of the genitals: the frequency is unknown - priapism, prolonged erection. Other: rarely - chest pain, fatigue.

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. Doses of 200 mg did not lead to increased efficacy, but the incidence of adverse reactions (headache, hot flashes, dizziness, dyspepsia, nasal congestion, impaired vision) increased.

In case of an overdose, if necessary, standard measures should be taken to maintain the vital functions of the body. Treatment is symptomatic. Dialysis does not accelerate clearance, because sildenafil is largely associated with plasma proteins and is not excreted in the urine.

Interaction:

Metabolism of sildenafil occurs mainly in the liver under the action of cytochrome isoenzymes CYP3A4 (the main pathway) and CYP2C9, therefore inhibitors of these isoenzymes can reduce the clearance of sildenafil, and inductors, respectively, increase the clearance of sildenafil With simultaneous application of inhibitors of the 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, 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 simultaneously with erythromycin, a specific inhibitor of isozyme CYP3A4 (when receiving erythromycin 2 times daily at 500 mg for 5 days), during achieved continuous erythromycin concentration in the blood leads to an increase in AUC of sildenafil in 182%.

With simultaneous use of sildenafil (single dose 100 mg) and saquinavir, which is both an inhibitor of HIV protease, and inhibitor of isozyme CYP3A4 (when taking saquinavir 3 times a day in a dose of 1200 mg) on a background until a constant level of saquinavir in blood, Cmax sildenafil in the blood increased by 140%, and the AUC increased by 210%. Sildenafil did not influence the pharmacokinetic parameters of saquinavir. More potent inhibitors of the CYP3A4 isoenzyme, such as ketoconazole or itraconazole, can cause more pronounced changes in the pharmacokinetics of sildenafil.

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 (when receiving ritonavir 500 mg 2 times a day) during achieved a constant level of ritonavir in blood, Cmax sildenafil increased by 300% (4 times), and AUC by 1000% (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 patients receiving simultaneously strong inhibitors of the isoenzyme CYP3A4, Cmax 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.

Inhibitors of the isoenzyme 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 reception of azithromycin (500 mg per day for 3 days) does not affect AUC, Cmax, Tmax, rate of elimination rate and sildenafil or its main circulating metabolite.

Sildenafil is a weak inhibitor of cytochrome P450 - 1A2, 2C9, 2C19, 2D6, 2E1 and 3C4 isoenzymes (IC50> 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, have not been identified.

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 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 pharmacological treatment for diagnosis of erectile dysfunction is necessary withdraw a full medical history and conduct a physical examination.

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 given to men for whom sexual activity is undesirable (see "Contraindications"),

TAXIER® has vasodilating properties, resulting in insignificant transient decreases in blood pressure. However, increased susceptibility to

vasodilators are 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, manifested a severe violation of regulation of blood pressure from the autonomic nervous system.

In the post-registration period, serious cardiovascular events were reported, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmias, cerebrovascular bleeding, transient ischemic attack, increase or decrease in blood pressure, which,They were in a temporary connection with the use of 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 should be administered with caution to patients taking alpha-blockers. To minimize the risk of orthostatic hypotension in patients taking alpha-adrenoblockers, the initiation of sildenafil should be started only after the stabilization of hemodynamics in these patients has been achieved. Consider the desirability of reducing the initial dose of sildenafil. In addition, the doctor should inform patients about what to do in case of symptoms of orthostatic hypotension.

Sildenafil increases antiaggregant effect of sodium nitroprusside (donor nitric oxide) on human platelets in vitro.

Information about the safety of the use of TAXIER® in patients with internal bleeding or active peptic ulcer of the stomach is absent, therefore in such cases the drug should be used only after a thorough assessment of the relationship between the benefits and risks of therapy. The drug TAXIER® is not intended for use in women (see "Contraindications").

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

Against the background of taking the drug TAXIER®,no adverse effect on the ability to drive a car or other technical means was observed.

However, since a decrease in blood pressure is possible, 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 be careful when driving vehicles and engage in potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 50 mg, 100 mg.

For 1 or 4 tablets in PVC / PVDC / A1 blister.For 1 blister for 1 or 4 tablets or 2 blisters for 4 tablets are placed in a cardboard box together with instructions for use.

Packaging:For 1 or 4 tablets in PVC / PVDC / A1 blister. For 1 blister for 1 or 4 tablets or 2 blisters for 4 tablets are placed in a cardboard box together with instructions for use.

Terms of leave from pharmacies:On prescription

Registration number:LP-001716

Date of registration:02,07.2012

The owner of the registration certificate:Zentiva as.Zentiva as. Czech Republic

Manufacturer: & nbsp

ZENTIVA, a.s. Czech Republic

Information update date: & nbsp27.05.2015

Illustrated instructions

Instructions

Taxiere® (Taxier® )