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

Active ingredient

Composition

1 film-coated tablet contains:

the active ingredient:

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

auxiliary substances (core):

Cellulose microcrystalline – 50.0 mg;

croscarmellose sodium (primellose) – 7.5 mg,

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

Lactose monohydrate (milk sugar) – 58.4 mg;

Magnesium stearate – 1.5 mg;

accompanied substances (coating):

Hypromellose – 2.39988 mg;

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

Talc – 0.99995 mg;

Titanium dioxide E 171 – 0.49998 mg;

Carmoisine (azorubin) dye – 0.00025 mg.

Interaction

Directions for use

Special Instructions

To avoid complications, use strictly as directed by your physician! The efficacy 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, consider switching to the therapy used for treatment of this stage of pulmonary hypertension (e.g., epoprostenol) (see section “Dosage and administration”). If Sildenafil Cardio is coadministered with bosentan or other CYP3A4 isoenzyme inducers, a dose adjustment may be required.

The benefit/risk ratio of Sildenafil Cardio in patients with functional class I pulmonary hypertension has not been established. There have been no studies on the use of Sildenafil Cardio in the treatment of secondary pulmonary hypertension, except for pulmonary hypertension associated with connective tissue disease and residual pulmonary hypertension.

Arterial hypotension

Sildenafil Cardio has a systemic vasodilatory effect resulting in a slight transient decrease in BP. Before prescribing the drug, the risk of possible adverse effects of vasodilatation in patients with arterial hypotension (BP < 90/50 mmHg at rest), hypovolemia, severe left ventricular outflow tract obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), and the rare multiple systemic atrophy syndrome manifested by severe autonomic nervous system BP dysregulation. Since co-administration of Sildenafil Cardio and α-adrenoblockers may cause symptomatic arterial hypotension in sensitive patients, Sildenafil Cardio should be prescribed with caution in patients taking α-adrenoblockers. To minimize the risk of postural hypotension in patients taking a-adrenoblockers, Sildenafil Cardio should be started only after hemodynamic stabilization has been achieved in these patients. Patients should be informed by their physician as to what action to take if symptoms of postural hypotension occur.

Cardiovascular complications

In the postmarketing 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 arrhythmias, hemorrhagic stroke, transient ischemic attack, arterial hypertension, and arterial hypotension) that were temporarily associated with sildenafil use. Most, but not all, of these patients had risk factors for cardiovascular complications. Many of these adverse events were observed shortly after sexual activity, and some were noted after administration of sildenafil cardio without subsequent sexual activity. It is not possible to establish a direct relationship between the reported adverse events and these factors or other causes.

Visual impairment

Rare cases of anterior nonarteritic ischemic optic neuropathy have been reported as a cause of visual impairment or loss with all FDE5 inhibitors, including Sildenafil Cardio. Most of these patients had risk factors such as optic disc excavation (deepening), age over 50 years, diabetes mellitus, arterial hypertension, coronary heart disease, hyperlipidemia, and smoking. If there is sudden loss of vision, patients should immediately stop taking Sildenafil Cardio and seek medical attention.

Patients with a history of anterior nonarteritic ischemic optic neuropathy have an increased risk of developing this condition. Therefore, the physician should discuss possible risks with the patient when using FDE5 inhibitors. In such patients, Sildenafil Cardio should be used with caution and after careful assessment of the benefit-risk ratio.

Hearing impairment

Some postmarketing and clinical studies have reported cases of sudden hearing impairment or loss associated with use of all FDE5 inhibitors, including Sildenafil Cardio. Most of these patients had risk factors for sudden deterioration or hearing loss. No causal relationship was established between the use of FDE5 inhibitors and sudden hearing impairment or hearing loss. Consult a physician immediately if you experience sudden hearing loss or hearing loss while taking Sildenafil Cardio.

Bleeding

Sildenafil enhances the antiplatelet effect of sodium nitroprusside, a nitric oxide donor, on human platelets in vitro. There are no data on safety of Sildenafil Cardio in patients with a tendency to bleeding or exacerbation of peptic ulcer disease, so Sildenafil Cardio should be used with caution in these patients. The incidence of nasal bleeding in patients with LAS associated with systemic connective tissue diseases was higher than in patients with primary LAS. Patients who received Sildenafil Cardio in combination with a vitamin K antagonist had a higher incidence of nasal bleeding than patients who did not take a vitamin K antagonist.

Priapism

If an erection lasts longer than 4 hours, immediate medical attention should be sought. If immediate medical intervention is not performed, penile tissue damage and complete loss of potency may occur.

Simultaneous use with bosentan

When using Sildenafil Cardio with initial therapy with bosentan, no improvement was noted in patients (assessed by the 6-minute walk test) compared to use of bosentan monotherapy. The results of the 6-minute walk test differed in patients with primary LAS and LAS associated with systemic connective tissue diseases. Patients with LAH associated with systemic connective tissue disease had worse results with the concomitant use of Sildenafil Cardio and bosentan than with bosentan monotherapy, but better than patients with primary LAH who received bosentan monotherapy. Thus, the physician should evaluate the outcome of therapy with concomitant use of Sildenafil Cardio and bosentan in patients with primary LAH based on his or her experience with LAH therapy. Simultaneous use of Sildenafil Cardio and bosentan in patients with LAS associated with systemic connective tissue disease is not recommended.

Simultaneous use with other FDE5 inhibitors

The efficacy and safety of simultaneous use of Sildenafil Cardio with other FDE5 inhibitors, including Viagra®, in patients with LAS has not been studied, so this combination is not recommended.

Sildenafil Cardio has negligible effect on ability to operate vehicles or other machinery.

But because taking Sildenafil Cardio may cause marked decrease in blood pressure, dizziness, development of chromatopsia, blurred vision and other side effects, careful consideration should be given to the individual action of the drug in the above situations, especially at the beginning of treatment and when changing the dosing regimen.

Synopsis

Features

Introduction

Sildenafil is rapidly absorbed in the gastrointestinal tract after oral administration. Absolute bioavailability is about 41% (25% to 63%). Maximal concentration of sildenafil in plasma (Cmax) is reached after 30-120 min (on average – 60 min) after oral intake 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 pharmacokinetic curve “concentration-time” (AUC) and Cmax increase in proportion to the dose. When taking sildenafil at a dose of 80 mg 3 times a day, its plasma concentration increases nonlinearly. If sildenafil is taken simultaneously with food, sildenafil absorption rate is reduced. When concomitant use with fatty food: time to maximum concentration (ТСmах) is increased by 60 min, and Сmах is decreased by 29 % on average, but absorption degree does not change significantly (AUC is decreased by 11 %).

Distribution

The volume of distribution of sildenafil in the equilibrium state averages 105 liters. After oral sildenafil at a dose of 20 mg 3 times daily, the maximum sildenafil plasma concentration in equilibrium is about 113 ng/ml. Binding of sildenafil and its main circulating N-demethyl metabolite with plasma proteins is about 96% and does not depend on the total concentration of sildenafil. Less than 0.0002% of the sildenafil dose (188 ng on average) was detected in the semen of healthy volunteers 90 min after taking the drug.

Metabolism

Sildenafil is metabolized primarily in the liver by microsomal cytochrome P450 isoenzymes: CYP3A4 isoenzyme (main route) and CYP2C9 isoenzyme (minor route). The main circulating active metabolite is formed as a result of N-demethylation of sildenafil. Selectivity of this metabolite on FDE is comparable with that of sildenafil, and its activity against FDE5 in vitro is about 50% of sildenafil activity. Concentration of this metabolite in blood plasma is about 40% of sildenafil concentration. The N-demethyl metabolite is further converted; its terminal elimination half-life (T1/2) is about 4 hours. In patients with pulmonary arterial hypertension (PAH), the ratio of concentrations of the N-demethyl metabolite to sildenafil is higher. The plasma concentration of the N-demethyl metabolite is about 72% of that of sildenafil (20 mg 3 times daily). The contribution of the metabolite to the pharmacological activity of sildenafil is 36%; its contribution to the clinical effect of the drug is unknown.

Contraindications

Side effects

Overdose

Symptoms: headache, blood rushes to the face, dizziness, dyspepsia, nasal congestion, visual disturbances.

Treatment: symptomatic.

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

Similarities