Erectile disfunction. Efficacy and safety of the drug Maxigra

Contraindications

• 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 interfere with the nitric oxide/cyclic guanosine monophosphate (cGMP) metabolic pathway and potentiate the hypotensive effect of nitrates.
• Concomitant use of PDE5 inhibitors (including sildenafil) with guanylate cyclase stimulants such as riociguat is contraindicated as it may lead to symptomatic hypotension.
• Conditions for which sexual activity is not recommended (for example, severe cardiovascular disorders such as unstable angina or severe heart failure).
• Loss of vision in one eye due to non-arterial anterior ischemic optic neuropathy, regardless of whether this pathology is associated with previous use of PDE-5 inhibitors or not.
• The presence of such diseases: severe liver dysfunction, arterial hypotension (blood pressure below 90/50 mm Hg).
• Recent stroke or myocardial infarction and known hereditary retinal degenerative diseases such as retinitis pigmentosa (a small number of these patients have genetic retinal PDE disorders), since the safety of sildenafil has not been studied in such diseases.

Maxigra tablets p/o 100 mg No. 4x1

Name

Maxigra tab. p/o 100 mg per bl. in pack №4x1

Description

Blue film-coated tablets, round, biconvex.

Main active ingredient

sildenafil citrate

Release form

Pills

Dosage

100mg

special instructions

Before prescribing the drug, it is necessary to collect a medical history and conduct a physical examination in order to diagnose erectile dysfunction and determine the possible causes of its development. Drugs for the treatment of erectile dysfunction should be used with caution in patients with anatomical deformation of the penis (angulation, cavernous fibrosis, Peyronie's disease) or in patients with risk factors for the development of priapism (sickle cell anemia, multiple myeloma, leukemia). If an erection persists for more than 4 hours, the patient should immediately seek medical help. If priapism therapy is not carried out in a timely manner, this can lead to damage to the tissue of the penis and irreversible loss of potency. Medicines intended to treat erectile dysfunction should not be prescribed to men for whom sexual activity is not desirable. Since sexual activity poses a certain risk in patients with heart disease, before starting any therapy for erectile dysfunction, the doctor should examine the patient's cardiovascular system. Sexual activity is not advisable in patients with heart failure, unstable angina, myocardial infarction or stroke in the last 6 months, life-threatening arrhythmias, arterial hypertension (BP >170/100 mm Hg) or hypotension (BP

pharmachologic effect

A drug for the treatment of erectile dysfunction. Sildenafil is a potent selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5). With sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis. Sildenafil does not have a direct relaxing effect on the isolated corpus cavernosum, but actively enhances the relaxing effect of nitric oxide (NO) by inhibiting PDE5, which is responsible for the breakdown of cGMP in the corpus cavernosum. When the NO/cGMP pathway is activated, PDE5 inhibition by sildenafil leads to an increase in cGMP levels in the corpus cavernosum, resulting in relaxation of smooth muscle tissue and increased blood flow in the corpus cavernosum. The activity of sildenafil against PDE5 is 10-10,000 times higher than the activity against other PDE isoenzymes (1-11). The pharmacological effect is achieved only in the presence of sexual stimulation. In clinical studies, it was shown that the average time to achieve a 60% stable erection (sufficient for sexual intercourse) was 25 minutes (range from 12 to 37 minutes). In some patients, 1 hour after taking the drug at a dose of 100 mg, a mild and transient impairment of the ability to distinguish colors (blue/green) was detected using the Farnsworth-Munsell 100 test; 2 hours after taking the drug, these changes were absent. Color vision impairment is thought to be caused by inhibition of PDE6, which is involved in light transmission in the retina. Sildenafil has no effect on visual acuity, contrast perception, electroretinogram, intraocular pressure or pupil diameter. In healthy volunteers, no effects on sperm motility or morphology were observed after a single dose of sildenafil 100 mg.

Pharmacokinetics

Absorption After oral administration, sildenafil is rapidly absorbed. Absolute bioavailability averages 41% (25-63%). After a single dose of the drug orally on an empty stomach at a dose of 100 mg, Cmax in plasma is 18 ng/ml (38 nM) and is achieved within 30-120 minutes (average 60 minutes). When taking sildenafil in combination with fatty foods, Cmax is reduced by 20-40% and is achieved after 1.5-3 hours. The distribution of Vd of sildenafil at steady state averages 105 liters. The binding of sildenafil and its main circulating N-desmethyl metabolite to plasma proteins is approximately 96% and is independent of the total concentration of sildenafil. In healthy volunteers receiving sildenafil (single dose of 100 mg), less than 0.0002% (on average 188 ng) of the administered dose was detected in semen 90 minutes after oral administration. Metabolism Sildenafil is metabolized primarily in the liver under the influence of microsomal isoenzymes CYP3A4 (major pathway) and CYP2C9 (minor pathway). The main circulating metabolite is formed from sildenafil by N-desmethylation. In terms of selectivity of action on PDE, the metabolite is comparable to sildenafil; its activity against PDE5 in vitro is approximately 50% of the activity of sildenafil. The concentration of the main metabolite in plasma is approximately 40% of the concentration of sildenafil. The N-demethyl metabolite undergoes further metabolism, and its T1/2 is about 4 hours. Elimination The total clearance of sildenafil is 41 l/h, and the final T1/2 is 3-5 hours. After oral administration, sildenafil is excreted in the form of metabolites mainly through intestines (approximately 80% of the dose) and to a lesser extent by the kidneys (approximately 13% of the dose). Pharmacokinetics in special groups of patients In elderly patients (over 65 years), the clearance of sildenafil is reduced, and the concentration of the free active substance in plasma is approximately 40% higher than its concentration in young (18-45 years) patients. In case of mild (creatinine clearance 50-80 ml/min) and moderate (creatinine clearance 30-49 ml/min) renal failure, the pharmacokinetic parameters of sildenafil do not change after a single oral dose of 50 mg. In severe renal failure (creatinine clearance ≤30 ml/min), the clearance of sildenafil is reduced, which leads to an approximately twofold increase in AUC (100%) and Cmax (88%) compared to those with normal renal function in patients of the same age group. In patients with mild to moderate liver cirrhosis (Child-Pugh class A and B), the clearance of sildenafil is reduced, resulting in an increase in AUC (84%) and Cmax (47%) compared to those with normal liver function. patients of the same age group. The pharmacokinetic parameters of sildenafil in patients with severe hepatic impairment have not been studied.

Indications for use

treatment of erectile dysfunction, characterized by the inability to achieve or maintain a penile erection sufficient for satisfactory sexual intercourse. Sildenafil is only effective during sexual stimulation.

Directions for use and doses

The drug is taken orally, approximately 1 hour before planned sexual activity. When taken simultaneously with fatty foods, the onset of action of the drug may be delayed compared to administration on an empty stomach. The recommended dose is 50 mg 1 time/day. Taking into account effectiveness and tolerability, the dose can be increased to 100 mg or reduced to 25 mg. The maximum single dose is 100 mg. The maximum recommended frequency of use is 1 time/day. In elderly patients, no dose adjustment is required. For mild to moderate renal failure (creatinine clearance 30-80 ml/min), no dose adjustment is required. In patients with severe renal failure (SC

Use during pregnancy and lactation

According to its registered indication, sildenafil is not intended for use in women.

Interaction with other drugs

The influence of other drugs on the metabolism of sildenafil The metabolism of sildenafil occurs mainly in the liver under the influence of the isoenzymes CYP3A4 (the main route) and CYP2C9, therefore inhibitors of these isoenzymes may reduce the clearance of sildenafil. When used simultaneously with CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine), a decrease in the clearance of sildenafil was observed. A single dose of sildenafil in a dose of 100 mg together with erythromycin, a specific inhibitor of CYP3A4 (when taking erythromycin 500 mg 2 times a day for 5 days), when the equilibrium concentration of erythromycin in the blood is achieved, leads to an increase in the AUC of sildenafil by 182%. Cimetidine (at a dose of 800 mg), which is a nonspecific inhibitor of CYP3A4, when combined with sildenafil (at a dose of 50 mg) in healthy volunteers caused an increase in plasma concentrations of sildenafil by 56%. The simultaneous use of sildenafil (single dose of 100 mg) and the HIV protease inhibitor ritonavir (500 mg 2 times / day), which is a powerful inhibitor of cytochrome P450 isoenzymes, against the background of achieving an equilibrium concentration of ritonavir in the blood led to an increase in Cmax of sildenafil by 300% (4 times), and the AUC of sildenafil is 1000% (11 times). After 24 hours, the concentration of sildenafil in the blood plasma was approximately 200 ng/ml (with sildenafil alone - approximately 5 ng/ml). The simultaneous use of sildenafil (single dose of 100 mg) and the HIV protease inhibitor saquinavir (at a dose of 1200 mg 3 times / day), which is a CYP3A4 inhibitor, while achieving the equilibrium concentration of saquinavir in the blood led to an increase in Cmax of sildenafil by 140%, and AUC sildenafil - by 210%. Sildenafil had no effect on the pharmacokinetics of saquinavir. Stronger CYP3A4 inhibitors, such as ketoconazole and itraconazole, may cause more pronounced changes in the pharmacokinetics of sildenafil. CYP2C9 inhibitors (such as tolbutamide, warfarin, phenytoin), CYP2D inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazides and thiazide-like diuretics, loop and potassium-sparing diuretics, ACE inhibitors, beta-blockers, calcium antagonists do not have any effect influence on the pharmacokinetics of sildenafil. In studies involving healthy volunteers, with simultaneous use of the endothelin receptor antagonist bosentan (inducer of the isoenzyme CYP3A4 (moderate), CYP2C9 and possibly CYP2C19) at equilibrium concentration (125 mg 2 times / day) and sildenafil at equilibrium concentration (80 mg 3 times / day). day) there was a decrease in AUC and Cmax of sildenafil by 62.6% and 52.4%, respectively. Sildenafil increased the AUC and Cmax of bosentan by 49/8% and 42%, respectively. It is assumed that the simultaneous use of sildenafil with powerful inducers of the CYP3A4 isoenzyme, such as rifampicin, may lead to a greater decrease in the concentration of sildenafil in the blood plasma. A single dose of an antacid (magnesium hydroxide/aluminum hydroxide) does not affect the bioavailability of sildenafil. In healthy male volunteers, simultaneous administration of azithromycin (500 mg/day for 3 days) has no effect on the AUC, Cmax, Tmax, elimination rate constant and T1/2 of sildenafil or its main circulating metabolite. Grapefruit juice is a weak inhibitor of CYP3A4 and may cause a moderate increase in plasma sildenafil levels. Effect of sildenafil on other drugs Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 >150 µmol). It is unlikely that sildenafil could affect the clearance of substrates of these isoenzymes. Sildenafil enhances the hypotensive effect of nitrates, so its combined use with nitric oxide donors or nitrates in any form is contraindicated. Preclinical studies have demonstrated an additional (additive) reduction in blood pressure with the combined use of PDE5 inhibitors and riociguat. Clinical trials have shown an enhanced antihypertensive effect of PDE5 inhibitors when administered in combination with riociguat. No positive clinical effect was observed when using a combination of these drugs in the study population. The simultaneous use of riociguat and PDE5 inhibitors, including sildenafil, is contraindicated. In selected sensitive patients receiving alpha-blockers, concomitant use of sildenafil may lead to symptomatic hypotension. With simultaneous administration of the alpha-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) in patients with benign prostatic hyperplasia with stable hemodynamics, the average additional reduction in systolic/diastolic blood pressure in the supine position was 7/7 mmHg, 9/5 mmHg. and 8/4 mm Hg. respectively, and in a standing position - 6/6 mm Hg, 11/4 mm Hg. and 4/5 mm Hg. respectively. Rare cases of symptomatic orthostatic hypotension, manifested in the form of dizziness (without fainting), have been reported in such patients. There were no signs of significant interactions between sildenafil (50 mg) and tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by CYP2C9. Sildenafil at a dose of 100 mg does not affect the pharmacokinetic parameters of HIV protease inhibitors at constant concentrations in the blood, such as saquinavir and ritonavir, which are also CYP3A4 substrates. Sildenafil at a dose of 50 mg does not cause an additional increase in bleeding time caused by taking acetylsalicylic acid at a dose of 150 mg. Sildenafil at a dose of 50 mg does not enhance the hypotensive effect of ethanol in healthy volunteers with a maximum ethanol concentration in the blood of an average of 80 mg/dl. In patients with arterial hypertension, there were no signs of interaction between sildenafil (at a dose of 100 mg) and amlodipine. The average additional reduction in blood pressure in the supine position is 8 mm Hg. (systolic) and 7 mm Hg. (diastolic). The use of sildenafil in combination with antihypertensive drugs does not lead to additional side effects.

Contraindications

simultaneous use of nitric oxide donors or organic nitrates or nitrites in any form; concomitant use of PDE5 inhibitors, including sildenafil, with guanylate cyclase stimulators, such as riociguat; combined use with other means of treating erectile dysfunction; simultaneous use of ritonavir; severe liver failure (class C according to the Child-Pugh classification); severe cardiovascular diseases (severe heart failure, unstable angina, stroke or myocardial infarction within the last 6 months, life-threatening arrhythmias, hypertension (BP >170/100 mm Hg) or arterial hypotension (BP

Compound

sildenafil citrate 70.24 mg, which corresponds to the content of sildenafil 50 mg Excipients: mannitol - 70.76 mg, crospovidone - 6 mg, povidone - 6 mg, corn starch - 10 mg, colloidal silicon dioxide - 2 mg, sodium lauryl sulfate - 2 mg, magnesium stearate - 3 mg. Shell composition: hypromellose - 4.13 mg, macrogol 6000 - 1.3 mg, titanium dioxide - 0.9 mg, talc - 0.43 mg, indigo carmine (E132) - 0.24 mg.

Overdose

Symptoms: with a single dose of the drug up to 800 mg in studies in healthy volunteers, adverse events were comparable to those when taking sildenafil at lower doses, but their frequency and severity increased. The use of the drug at a dose of 200 mg did not lead to increased effectiveness, but the frequency of adverse events increased (headache, flushing, dizziness, dyspepsia, nasal congestion, blurred vision). Treatment: symptomatic therapy. Sildenafil is not excreted during hemodialysis.

Side effect

The frequency of side effects is determined as follows: very often (≥1/10); common (≥1/100, 50 years in the general population. Patients who experience sudden vision loss should be advised to stop sildenafil therapy and consult a physician immediately. Persons who have had a previous episode of NPINSID have an increased risk of recurrence of NPINSID. Therefore, the physician should discuss this risk with such patients, and also discuss with them the potential for adverse effects of PDE5 inhibitors. PDE5 inhibitors, including sildenafil, should be used with caution in such patients and only in situations where the expected benefit outweighs the risk. When using sildenafil in doses , exceeding the recommended, adverse events were similar to those noted above, but usually occurred more often.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C.

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Instructions for use for Maxigra tablets p/o 100 mg No. 4x1

Mode of application

The drug is administered orally. Chew the tablet before swallowing.

For the drug to be effective, sexual arousal is required.

Adults. The recommended dose is 50 mg and is used, if necessary, about an hour before sexual intercourse. Depending on the effectiveness and tolerability of the drug, 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 use of the drug is 1 time per day. When using the drug during a meal, the effect of the drug may occur later than when used on an empty stomach.

Efficiency mark.

It was carried out by calculating reference values ​​for the tests:

1. Erection quality assessment by domain - the number of points is calculated for each domain: erectile function (maximum 25 points), satisfaction with the act (maximum 15 points), orgasm (maximum 10 points), libido (maximum 10 points), overall satisfaction (maximum 10 points) (Table 2).
2. Assessing the dynamics of changes in the total IIEF score is the summation of scores for all domains (maximum 70 points) (Table 2).
3. Pharmacopenile duplex ultrasonography – peak systolic velocity (PSV), end-diastolic velocity (EDV), mean blood flow velocity (TAV), resistance index (RI), pulsatility index (PI) (Table 3).

Table 2.

Dynamics of erectile function indicators on the IIEF scale before and after treatment

Table 3.

Dynamics of pharmacopenile duplex ultrasonography indicators before and after treatment

Overdose

In studies involving volunteers using single doses of sildenafil up to 800 mg, adverse reactions were similar to those observed with lower doses of sildenafil, but were more frequent and more severe. The use of sildenafil at a dose of 200 mg did not lead to an increase in effectiveness, but caused an increase in the number of cases of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, visual disturbances).

In case of overdose, if necessary, resort to the usual supportive measures. Acceleration of the clearance of sildenafil 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.

Note!

Description of the drug Maxigra table. p/o 50 mg No. 4 on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.