Sildenafil Cardio, 20 mg 90 pcs

Sildenafil is a powerful selective inhibitor of cycloguanosine monophosphate (cGMP)-specific phosphodiesterase-5 (PDE5). Since FDE5, responsible for cGMF breakdown, is contained not only in the corpora cavernosa of the penis but also in the pulmonary vessels, sildenafil, being an inhibitor of this enzyme, increases cGMF content in the smooth muscle cells of pulmonary vessels and causes their relaxation. In patients with pulmonary hypertension (PH), taking sildenafil leads to dilation of pulmonary vessels and, to a lesser extent, of other vessels.

Indications

Pulmonary hypertension.

Pharmacological effect

Sildenafil is a powerful selective inhibitor of cycloguanosine monophosphate (cGMP) – a specific phosphodiesterase-5 (PDE5). Since PDE5, which is responsible for the breakdown of cGMP, is found not only in the corpus cavernosum of the penis, but also in the vessels of the lungs, sildenafil, being an inhibitor of this enzyme, increases the content of cGMP in the smooth muscle cells of the pulmonary vessels and causes their relaxation. In patients with pulmonary hypertension (PH), taking sildenafil leads to vasodilation of the lungs and, to a lesser extent, other vessels.

Special instructions

To avoid complications, use strictly as prescribed by your doctor! The effectiveness and safety of Sildenafil Cardio in patients with severe pulmonary hypertension (functional class IV) has not been proven. If the patient’s condition worsens during therapy with Sildenafil Cardio, the possibility of switching to therapy used to treat this stage of pulmonary hypertension (for example, epoprostenol) should be considered (see section “Dosage and Administration”). When using Sildenafil Cardio together with bosentan or other inducers of the CYP3A4 isoenzyme, dose adjustment may be required.

The benefit/risk ratio of Sildenafil Cardio in patients with functional class I pulmonary hypertension has not been established. Studies on the use of Sildenafil Cardio in the treatment of secondary pulmonary hypertension, with the exception of pulmonary hypertension associated with connective tissue diseases and residual pulmonary hypertension, have not been conducted.

Arterial hypotension

The drug Sildenafil Cardio has a systemic vasodilating effect, leading to a slight transient decrease in blood pressure. Before prescribing the drug, it is necessary to carefully assess the risk of possible undesirable manifestations of the vasodilating effect in patients with arterial hypotension (BP < 90/50 mm Hg at rest), hypovolemia, severe obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with the rare syndrome of multiple system atrophy, manifested by severe dysregulation of blood pressure from the autonomic nervous system. Since the combined use of Sildenafil Cardio and α-blockers may lead to the development of symptomatic arterial hypotension in sensitive patients, Sildenafil Cardio should be administered with caution to patients taking α-blockers. To minimize the risk of developing postural hypotension in patients taking alpha-blockers, Sildenafil Cardio should be started only after stabilization of hemodynamic parameters in these patients has been achieved. The physician should inform patients about what actions to take if symptoms of postural hypotension occur.

Cardiovascular complications

During post-marketing use of Sildenafil Cardio for the treatment of erectile dysfunction, adverse events such as serious cardiovascular complications (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, arterial hypertension and arterial hypotension) were reported, which were temporarily associated with the use of sildenafil. Most of these patients, but not all of them, had risk factors for cardiovascular complications. Many of these adverse events occurred shortly after sexual activity, and some of them occurred after taking Sildenafil Cardio without subsequent sexual activity. It is not possible to establish a direct connection between the observed adverse events and the specified factors or other reasons.

Visual impairment

Rare cases of anterior non-arteritic ischemic optic neuropathy as a cause of deterioration or loss of vision have been reported with the use of all PDE5 inhibitors, including Sildenafil Cardio. Most of these patients had risk factors such as optic disc excavation, age over 50 years, diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and smoking. In case of sudden loss of vision, patients should immediately stop taking Sildenafil Cardio and seek medical help.

Patients who have previously had cases of anterior non-arteritic ischemic optic neuropathy have an increased risk of developing this disease. In this regard, the doctor should discuss with the patient the possible risks of using PDE5 inhibitors. In such patients, Sildenafil Cardio should be used with caution and after a careful assessment of the benefit-risk ratio.

Hearing impairment

Some post-marketing and clinical studies have reported cases of sudden deterioration or loss of hearing associated with the use of all PDE5 inhibitors, including Sildenafil Cardio. Most of these patients had risk factors for sudden deterioration or loss of hearing. A cause-and-effect relationship between the use of PDE5 inhibitors and sudden hearing loss or deterioration has not been established. If there is a sudden deterioration in hearing or hearing loss while taking Sildenafil Cardio, you should immediately consult your doctor.

Bleeding

Sildenafil enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide donor, on human platelets in vitro. There are no data on the safety of using Sildenafil Cardio in patients with a tendency to bleeding or exacerbation of gastric and duodenal ulcers, so Sildenafil Cardio should be used with caution in these patients. The incidence of epistaxis in patients with PAH associated with systemic connective tissue diseases was higher than in patients with primary PAH. Patients receiving Sildenafil Cardio in combination with a vitamin K antagonist had a higher incidence of epistaxis than patients not receiving a vitamin K antagonist.

Priapism

If an erection lasts more than 4 hours, you should immediately seek medical help. If immediate medical intervention is not carried out, damage to the tissues of the penis and complete loss of potency are possible.

Concomitant use with bosentan

When using Sildenafil Cardio during initial therapy with bosentan, there was no improvement in patient condition (assessed using the 6-minute walk test) compared with bosentan monotherapy. The results of the 6-minute walk test differed between patients with primary PAH and PAH associated with systemic connective tissue diseases. In patients with PAH associated with systemic connective tissue diseases, the outcome of concomitant use of Sildenafil Cardio and bosentan was worse than with bosentan monotherapy, but better than in patients with primary PAH receiving bosentan monotherapy. Thus, the physician should evaluate the outcome of therapy when using the drug Sildenafil Cardio and bosentan simultaneously in patients with primary PAH, based on their experience in treating PAH. The simultaneous use of Sildenafil Cardio and bosentan in patients with PAH associated with systemic connective tissue diseases is not recommended.

Concomitant use with other PDE5 inhibitors

The effectiveness and safety of simultaneous use of Sildenafil Cardio with other PDE5 inhibitors, including Viagra®, have not been studied in patients with PAH, so the use of this combination is not recommended.

Impact on the ability to drive vehicles. Wed and fur.:

The drug Sildenafil Cardio does not significantly affect the ability to drive vehicles or operate other machinery.

However, since when taking the drug Sildenafil Cardio, a pronounced decrease in blood pressure, dizziness, the development of chromatopsia, blurred vision and other side effects are possible, you should be careful about the individual effect of the drug in these situations, especially at the beginning of treatment and when changing the dosage regimen.

Active ingredient

Sildenafil

Composition

1 film-coated tablet contains:

active ingredient:

sildenafil citrate – 28.1 mg (in terms of sildenafil – 20 mg)

excipients (core):

microcrystalline cellulose – 50.0 mg;

croscarmellose sodium (primellose) – 7.5 mg,

povidone K-30 (medium molecular weight polyvinylpyrrolidone) – 4.5 mg,

lactose monohydrate (milk sugar) – 58.4 mg;

magnesium stearate – 1.5 mg;

excipients (shell):

hypromellose – 2.39988 mg;

polysorbate-80 (tween-80) – 1.09994 mg;

talc – 0.99995 mg;

titanium dioxide E 171 – 0.49998 mg;

dye carmoisine (azorubine) – 0.00025 mg.

Contraindications

Hypersensitivity to any component of the drug.

Veno-occlusive pulmonary disease.

Combined use with nitric oxide donors or nitrates in any form.

Combined use with potent inhibitors of the CYP3A4 isoenzyme (including ketoconazole, itraconazole and ritonavir) (see section “Interaction with other drugs”).

Concomitant use of PDE5 inhibitors, including sildenafil, with antihypertensive drugs that stimulate guanylate cyclase, such as riociguat, as this may lead to symptomatic arterial hypotension.

Loss of vision in one eye due to anterior non-arteritic ischemic optic neuropathy, hereditary degenerative diseases of the retina (retinitis pigmentosa).

Severe liver dysfunction (more than 9 points on the Child-Pugh scale).

History of stroke or myocardial infarction.

Severe arterial hypotension (systolic blood pressure less than 90 mm Hg, diastolic blood pressure less than 50 mm Hg).

Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Age under 18 years (efficacy and safety studies have not been conducted).

With caution:

I or IV (efficacy and safety have not been established) functional classes of PAH.
Anatomical deformation of the penis (angulation, cavernous fibrosis or Peyronie’s disease) and diseases predisposing to the development of priapism (sickle cell anemia, multiple myeloma, leukemia).

Diseases accompanied by bleeding, or exacerbation of peptic ulcer of the stomach and duodenum.

Heart failure, unstable angina, life-threatening arrhythmias, arterial hypertension (BP > 170/100 mm Hg), left ventricular outflow tract obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), rare multiple system atrophy syndrome, manifested by severe dysregulation of blood pressure from the autonomic nervous system, hypovolemia.

History of anterior non-arteritic ischemic optic neuropathy.

Combined use with moderate inhibitors of the CYP3A4 isoenzyme (including erythromycin, saquinavir, clarithromycin, telithromycin and nefazodone) and α-blockers.

Combined use with inducers of the CYP3A4 isoenzyme.

Side Effects

Adverse events are classified according to the MedDRA classification system by organ system and frequency: very common (> 1/10), common (> 1/100, 1/1000. < 1/100), very rare (< 1/1000), frequency unknown (frequency cannot be determined based on available data).

Interaction

Interaction studies of sildenafil with other drugs were conducted in healthy volunteers, except where otherwise noted. These results are valid for other patient groups and administration methods.

Overdose

Symptoms: headache, flushes of blood to the skin of the face, dizziness, dyspepsia, nasal congestion, visual impairment.

Treatment: symptomatic.

Hemodialysis is ineffective (sildenafil actively binds to blood plasma proteins).

Recommendations for use

Inside. The recommended dose of Sildenafil Cardio is 20 mg 3 times a day with an interval of about 6-8 hours, regardless of meals. The maximum recommended dose is 60 mg.

Functional features

Suction

Sildenafil is rapidly absorbed from the gastrointestinal tract after oral administration. Absolute bioavailability is about 41% (from 25% to 63%). The maximum concentration of sildenafil in blood plasma (Cmax) is achieved 30-120 minutes (on average 60 minutes) after ingestion on an empty stomach. After taking sildenafil 3 times a day in a dose range from 20 mg to 40 mg, the area under the concentration-time pharmacokinetic curve (AUC) and Cmax increase proportionally to the dose. When taking sildenafil at a dose of 80 mg 3 times a day, its concentration in the blood plasma increases nonlinearly. When taken simultaneously with food, the rate of absorption of sildenafil is reduced. When taken simultaneously with fatty foods: the time to reach maximum concentration (TCmax) increases by 60 minutes, and Cmax decreases by an average of 29%, but the degree of absorption does not change significantly (AUC decreases by 11%).

Distribution

The volume of distribution of sildenafil at steady state averages 105 liters. After oral administration of sildenafil at a dose of 20 mg 3 times a day, the maximum concentration of sildenafil in blood plasma at steady state is about 113 ng/ml. The binding of sildenafil and its main circulating N-demethyl metabolite to plasma proteins is about 96% and does not depend on the total concentration of sildenafil. 90 minutes after taking the drug, less than 0.0002% of the dose of sildenafil (average 188 ng) was found in the sperm of healthy volunteers.

Metabolism

Sildenafil is metabolized mainly in the liver under the influence of microsomal cytochrome P450 isoenzymes: the CYP3A4 isoenzyme (major pathway) and the CYP2C9 isoenzyme (minor pathway). The main circulating active metabolite is formed as a result of N-demethylation of sildenafil. The selectivity of this metabolite for PDE is comparable to that of sildenafil, and its activity against PDE5 in vitro is about 50% of the activity of sildenafil. The concentration of the metabolite in the blood plasma is about 40% of the concentration of sildenafil. The N-demethyl metabolite undergoes further conversion; its final half-life (T1/2) is about 4 hours. In patients with pulmonary arterial hypertension (PAH), the concentration ratio of the N-demethyl metabolite to sildenafil is higher. The concentration of N-demethyl metabolite in blood plasma is about 72% of that of sildenafil (20 mg 3 times a day). The contribution of the metabolite to the pharmacological activity of sildenafil is 36%; its contribution to the clinical effect of the drug is unknown.

Removal

The total clearance of sildenafil is 41 l/h, and the terminal half-life is 3-5 hours. After oral administration, sildenafil is excreted in the form of metabolites, mainly through the intestines (about 80% of the dose) and, to a lesser extent, by the kidneys (about 13% of the dose).

Elderly patients

In elderly patients (65 years and older), the clearance of sildenafil is reduced, and the concentration of free sildenafil and its active N-demethyl metabolite in the blood plasma is approximately 90% higher than in younger patients (18-45 years). Since the binding of sildenafil to plasma proteins depends on the age of the patient, the concentration of free sildenafil in the blood plasma in elderly patients is approximately 40% higher.

Renal dysfunction

In mild to moderate renal failure (creatinine clearance (CC) 30-80 ml/min), the pharmacokinetics of sildenafil after a single oral dose of 50 mg does not change. In severe renal failure (creatinine clearance less than 30 ml/min), the clearance of sildenafil is reduced, leading to an increase in AUC by 100% and Cmax by 88% compared to values ​​with normal renal function in patients of the same age group. In patients with severe renal failure, the AUC and Cmax of the N-demethyl metabolite are 200% and 79% higher. respectively, than in patients with normal renal function.

Liver dysfunction

In volunteers with mild or moderate hepatic impairment (Child-Pugh score 5-9), the clearance of sildenafil is reduced, resulting in an increase in AUC (85%) and Cmax (47%) compared to values ​​with normal liver function in patients of the same age group. The pharmacokinetics of sildenafil in patients with severe liver dysfunction (more than 9 points on the Child-Pugh scale) has not been studied.

Population pharmacokinetics

When studying the pharmacokinetics of sildenafil in patients with PAH, the population pharmacokinetic model included age, gender, race, and indicators of renal and liver function. The data used for the population-based analysis included a wide range of demographic and laboratory parameters associated with liver and kidney function. Demographic indicators, as well as parameters of liver or kidney function, did not have a statistically significant effect on the pharmacokinetics of sildenafil in patients with PAH.

In patients with PAH, after taking sildenafil in doses from 20 mg to 80 mg 3 times a day, its average steady-state concentrations were 20% – 50% higher than in healthy volunteers. The minimum concentration of sildenafil in blood plasma (Cmin) was 2 times higher than in healthy volunteers. The data obtained indicate a decrease in clearance and/or increase in bioavailability of sildenafil after oral administration in patients with PAH compared to healthy volunteers.

Storage conditions

In a place protected from light, at a temperature not exceeding 25 ° C.

Shelf life

3 years.
Do not use after the expiration date stated on the package.

Manufacturer

North Star NAO, Russia