Revazio - Instructions For Use, Tablets 20 Mg, Price, Reviews, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Revazio

Revazio: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Revatio

ATX code: C02KX

Active ingredient: sildenafil (sildenafilum)

Manufacturer: Fareva Amboise (France)

Description and photo update: 2018-27-11

Prices in pharmacies: from 12,299 rubles.

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Revazio is a drug for the treatment of pulmonary hypertension, a phosphodiesterase-5 (PDE-5) inhibitor.

Release form and composition

The drug is available in the form of film-coated tablets: almost white or white, round, biconvex, engraved on each side: on one side - RVT 20, on the other - Pfizer (15 pcs. In blisters, in a cardboard box 6 blisters and instructions for use Revazio).

1 tablet contains:

• active substance: sildenafil (in the form of sildenafil citrate) - 20 mg;
• auxiliary components: microcrystalline cellulose, calcium hydrogen phosphate, croscarmellose sodium, magnesium stearate;
• composition of the film shell: transparent opadry YS-2-19114-A (triacetin, hypromellose), white opadry II OY-LS-28914 (lactose monohydrate, hypromellose, triacetin, titanium dioxide).

Pharmacological properties

Pharmacodynamics

Revazio is a drug for the treatment of pulmonary hypertension, has a vasodilator effect. The active substance is sildenafil, which is a potent selective inhibitor of cGMP (cycloguanosine monophosphate) -specific PDE-5. Its mechanism of action is due to the ability to increase the content of cGMP in the smooth muscle cells of the lung vessels and cause their relaxation. Against the background of pulmonary hypertension, the effect of sildenafil on the expansion of the vessels of other organs is less pronounced.

Sildenafil exhibits selective selectivity for PDE-5 (in vitro). Its activity for this enzyme is higher than that for other isoenzymes of phosphodiesterase. So, in comparison with PDE-5, the activity of sildenafil in relation to PDE-6 is 10 times lower, PDE-1 - 80 times, PDE-2, PDE-4, PDE-7-11 - more than 700 times, the ratio of PDE-3, cAMP (cyclic adenosine monophosphate) -specific phosphodiesterase involved in the contraction of the heart - more than 4000 times.

A slight decrease in blood pressure (BP) while taking sildenafil is transient and, as a rule, is not accompanied by clinical symptoms. The maximum decrease in systolic blood pressure after ingestion of 100 mg of sildenafil in the supine position is 8.3 mm Hg, diastolic blood pressure - 5.3 mm Hg.

Taking Revazio at a dose of 80 mg 3 times a day in patients with systemic arterial hypertension causes a decrease in systolic and diastolic blood pressure by an average of 9.4 and 9.1 mm Hg, respectively. With the same dosage regimen in patients with pulmonary hypertension, there is a less pronounced (2 mm Hg) decrease in systolic and diastolic blood pressure and the absence of clinically significant changes in electrocardiography (ECG).

Compared with the baseline, a single dose of Revazio at a dose of 100 mg in patients with severe coronary atherosclerosis (stenosis of more than 70% of at least one coronary artery) causes a decrease in mean systolic blood pressure at rest by 7%, diastolic blood pressure - by 6%. In the pulmonary artery, systolic pressure decreased by an average of 9%. No effect of sildenafil on cardiac output or on impairment of blood flow in stenotic coronary arteries was noted.

In some cases, 1 hour after taking 100 mg of sildenafil, a slight impairment of the ability to perceive blue and green colors was revealed due to inhibition of PDE-6, which is involved in the process of light transmission in the retina of the eye. This condition is transient; within the next hour, these changes disappear. The active substance does not affect visual acuity, perception of contrast, intraocular pressure, pupil diameter or electroretinography data.

In patients with age-related macular degeneration, against the background of a single dose of 100 mg of sildenafil, a significant change in visual functions was noted (visual acuity, the ability to distinguish the colors of traffic lights, transient visual impairments).

Clinical studies of the efficacy of sildenafil were carried out with the participation of 278 patients, of whom 63% were with primary pulmonary hypertension, 30% with pulmonary hypertension associated with diffuse connective tissue diseases, and 7% with pulmonary hypertension that developed after surgical treatment of congenital heart defects. 107 patients (39%) had II functional class of pulmonary hypertension according to the WHO classification (World Health Organization), 160 patients (58%) - III class, 1 (0.4%) - I class, 9 people (3 %) - IV functional class. The study did not include patients with left ventricular ejection fraction less than 45%, left ventricular shortening fraction less than 0.2, and patients for whom bosentan therapy was ineffective. The study was carried out using sildenafil at a dose of 20 mg,40 mg and 80 mg in conjunction with standard therapy. 84 days after the start of treatment in all 3 groups of patients (while taking sildenafil in different doses), there was an increase in exercise tolerance without significant differences between the groups of patients. The average therapeutic effect persisted regardless of patient demographic and geographic populations or disease characteristics.

The most significant improvement in exercise tolerance in the 6-minute walk test was observed with sildenafil 20 mg. In patients with pulmonary hypertension of II and III functional classes, the improvement in the results of the six-minute walk test was 49 m and 45 m, respectively.

There was a significant decrease in the mean pressure in the pulmonary artery while taking sildenafil in all doses (compared with placebo). After adjusting for the placebo effect, when the drug was taken at a dose of 20 mg, it was 2.7 mm Hg. Art., 40 mg - 3 mm Hg. Art., 80 mg - 5.1 mm Hg. Art. In addition, improvements were found in indicators such as pulmonary vascular resistance, cardiac output and right atrial pressure. Heart rate (heart rate), systemic blood pressure changed insignificantly.

The decrease in pulmonary vascular resistance was superior to the decrease in total peripheral vascular resistance (OPSR). There was a tendency for an improvement in the clinical course of the disease, including a decrease in the frequency of hospitalizations for pulmonary hypertension, improvement in 28%, 36% and 42% of patients receiving sildenafil at doses of 20 mg, 40 mg and 80 mg, respectively, for 84 days, at least one functional class according to the WHO classification. However, compared with placebo, sildenafil treatment improved quality of life in terms of physical activity and Borg dyspnea. Against the background of the use of sildenafil, the number of patients who need additional prescription to the standard therapy of a drug of a different class decreases.

The results of the extended study of Revazio established an increased survival rate in patients with pulmonary hypertension.

The use of the drug in adult patients with a stable course of primary pulmonary hypertension and pulmonary hypertension associated with diffuse connective tissue diseases is effective when combined with intravenous (iv) administration of epoprostenol.

According to the results of the Kaplan-Meier procedure, which assessed the function of survival, the risk of worsening with sildenafil was three times lower than with placebo.

The profile of side effects with the simultaneous use of sildenafil and bosentan and bosentan monotherapy corresponds to the profile of adverse events with sildenafil.

Pharmacokinetics

After oral administration, absorption of sildenafil from the gastrointestinal tract occurs rapidly. Absolute bioavailability ranges from 25% to 63%. When taken on an empty stomach, its maximum concentration (C _max) in blood plasma is reached in 0.5–2 hours.

Against the background of the use of sildenafil in the dose range from 20 mg to 40 mg with a frequency of 3 times a day, an increase in AUC (total concentration) and C _max occurs in proportion to the dose, at a dose of 80 mg its concentration increases in blood plasma nonlinearly.

Simultaneous food intake reduces the rate of absorption of the active substance; when used in combination with fatty foods, it reduces C _{max by} an average of 29%, increasing the period for reaching C _max by 1 hour. At the same time, AUC decreases by only 11%, since the degree of absorption does not change significantly.

V _d (volume of distribution) in equilibrium - an average of 105 liters.

Plasma protein binding is about 96%.

Sildenafil metabolism occurs in the liver under the influence of cytochrome P ₄₅₀ microsomal isoenzymes: the main pathway is with the participation of CYP3A4, the secondary pathway is CYP2C9. As a result of N-demethylation of sildenafil, the main circulating metabolite is formed. The activity of its selective action on PDE is identical to that of sildenafil, and in relation to PDE-5 - in vitro is about 50% of the activity of sildenafil. The concentration of the active metabolite in blood plasma is up to 40% of the level of sildenafil. End T _1/2(half-life) of the N-demethyl metabolite after further conversion is about 4 hours. The ratio of the content of the N-demethyl metabolite to sildenafil is higher in patients with pulmonary hypertension. The concentration of the active metabolite in the blood plasma while taking 20 mg of Revazio 3 times a day is up to 72% of the level of sildenafil. The pharmacological activity of sildenafil is 36% due to the activity of the N-demethyl metabolite.

The total clearance of the active substance is 41 l / h, the final T _1/2 is 3-5 hours. It is excreted mainly in the form of metabolites: through the intestines - about 80% of the dose taken, through the kidneys - about 13%.

The clearance of sildenafil in patients aged 65 years and older is reduced, its concentration in blood plasma in unchanged form and in the form of an active N-demethyl metabolite is approximately 90% higher than in patients aged 18–45 years. In elderly patients, the concentration of free sildenafil in blood plasma is 40% higher than in younger patients.

In mild to moderate renal failure with creatinine clearance (CC) from 30 to 80 ml / min, the pharmacokinetics of sildenafil taken at a dose of 50 mg once is not disturbed. In severe renal failure (CC below 30 ml / min), there is a decrease in the clearance of sildenafil, an increase of 100% AUC and an increase of 88% C _max compared with the indicators of patients of the same age group with normal renal function. In severe renal failure, the AUC of the N-demethyl metabolite is 200% higher and C _max - by 79%, compared with patients with normal renal function.

With mild to moderate liver dysfunction (5-9 points on the Child-Pugh scale), the clearance of sildenafil decreases, causing an increase of 85% AUC and 47% C _max from the level of indicators of patients with normal liver function of the same age group. In severely impaired liver function (more than 9 points on the Child-Pugh scale), the pharmacokinetics of sildenafil has not been studied.

When studying the pharmacokinetics of Revazio in patients with pulmonary arterial hypertension, a population pharmacokinetic model included a wide range of demographic and laboratory parameters, including race, age, gender, renal and liver function indices. They did not have a statistically significant effect on the pharmacokinetics of sildenafil.

After taking sildenafil in doses from 20 to 80 mg 3 times a day in patients with pulmonary arterial hypertension, there is a decrease in clearance and / or an increase in the bioavailability of sildenafil compared to healthy volunteers.

Indications for use

The use of Revazio is indicated for the treatment of pulmonary hypertension.

Contraindications

• veno-occlusive lung disease;
• concomitant therapy with ketoconazole, itraconazole, ritonavir and other potent inhibitors of the CYP3A4 isoenzyme;
• the simultaneous use of donors of nitric oxide or nitrates in any form;
• loss of vision in one eye as a result of anterior non-arteritic ischemic neuropathy of the optic nerve;
• retinitis pigmentosa, an inherited degenerative disease of the retina of the eye;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome;
• severe liver dysfunction (more than 9 points on the Child-Pugh scale);
• severe arterial hypotension (systolic blood pressure is less than 90 mm Hg, diastolic - less than 50 mm Hg);
• a history of myocardial infarction or stroke;
• breast-feeding;
• age up to 18 years;
• hypersensitivity to the components of the drug.

With caution, Revazio tablets should be prescribed for pulmonary arterial hypertension of I or IV functional class, heart failure, life-threatening arrhythmias, unstable angina pectoris, arterial hypertension (blood pressure above 170/100 mm Hg), obstruction of the left ventricular outflow tract (hypertrophic obstructive cardiomyopathy, stenosis aorta), hypovolemia, multiple systemic atrophy syndrome (rare, manifested by severe impairment of blood pressure regulation by the autonomic nervous system), anatomical deformity of the penis (angulation, Peyronie's disease or cavernous fibrosis), diseases that predispose to the development of priapism (leukemia, multiple myeloma, sickle cell anemia), accompanied by bleeding diseases, exacerbation of gastric ulcer and duodenal ulcer,a history of anterior non-arteritis ischemic neuropathy of the optic nerve, in combination with alpha-blockers and moderate inhibitors of the CYP3A4 isoenzyme (including erythromycin, saquinavir, telithromycin, nefazodone, clarithromycin), concomitant use of CYPA4 inducers.

The use of Revacio during gestation is possible only in special cases when the expected therapeutic effect for the mother, in the opinion of the doctor, is much higher than the potential risk to the fetus.

Revazio, instructions for use: method and dosage

Revazio tablets are taken orally, regardless of the meal.

The dose of the drug should be determined by the doctor individually for each patient, this will avoid possible complications.

Recommended dosage of Revazio: 20 mg 3 times a day with an interval of 6-8 hours. The maximum daily dose is 60 mg.

Under the age of 65, with impaired renal function, impaired liver function of mild and moderate (5-9 points on the Child-Pugh scale), dose adjustment is not required. With poor tolerance, it is shown that the frequency of administration is reduced to 2 times a day at a dose of 20 mg.

Caution should be exercised if concomitant therapy with bosentan or iloprost is necessary; dose adjustment of sildenafil may be required.

There are no results of controlled studies regarding the need to increase the dose of sildenafil while using it with bosentan.

The safety and effectiveness of the combination of Revazio with other PDE-5 inhibitors for the treatment of pulmonary arterial hypertension has not been established.

Simultaneous use with such strong inhibitors of the CYP3A4 isoenzyme, such as ketoconazole, ritonavir, itraconazole, is not recommended. If it is necessary to prescribe sildenafil for the treatment of patients on therapy with inhibitors of the CYP3A4 isoenzyme in the form of erythromycin and saquinavir, its daily dose should be 40 mg (20 mg 2 times a day). If necessary, a combination with more powerful inducers of the CYP3A4 isoenzyme (including clarithromycin, telithromycin, nefazodone), Revazio should be taken at a dose of 20 mg once a day.

Side effects

• infections and invasions: often - unspecified sinusitis, inflammation of the subcutaneous tissue, influenza;
• from the side of metabolism: often - edema against the background of fluid retention;
• from the hematopoietic system: often - unspecified anemia;
• from the nervous system: very often - headache; often - a burning sensation of unspecified genesis, tremor, hypesthesia, paresthesia; frequency not established - migraine;
• mental disorders: often - anxiety, insomnia;
• on the part of the cardiovascular system: very often - redness of the facial skin (hyperemia); frequency not set - lowering blood pressure;
• on the part of the sense organs: often - vertigo, blurred vision, hemorrhage in the retina of the eye, visual impairment of unspecified origin, photophobia, cyanopsia, chromatopsia, inflammation and / or redness of the eyes; rarely - decreased visual acuity, impaired sensitivity of the eye, diplopia; very rarely - sudden deafness;
• from the digestive system: very often - dyspeptic symptoms, diarrhea; often - dry mouth, bloating, unspecified gastritis, gastroesophageal reflux disease, unspecified gastroenteritis, hemorrhoids;
• from the respiratory system: often - epistaxis, unspecified bronchitis, cough, nasal congestion, unspecified rhinitis;
• from the musculoskeletal system: very often - pain in the limbs; often - back pain, myalgia;
• from the reproductive system: often - hemospermia, gynecomastia; frequency not established - prolonged erection, priapism;
• dermatological reactions: often - increased night sweats, alopecia, erythema; frequency not established - skin rash;
• others: often - fever.

Overdose

Symptoms: dyspepsia, flushing of the face, nasal congestion, headache, dizziness, visual disturbance.

Treatment: the appointment of symptomatic therapy. Due to the active binding of sildenafil to blood plasma proteins, dialysis is ineffective.

special instructions

The effectiveness of using Revazio for the treatment of pulmonary hypertension of functional class IV has not been proven, therefore, in cases of deterioration of the patient's condition during therapy with the drug, consideration should be given to switching to therapy with epoprostenol.

When using sildenafil for the treatment of pulmonary hypertension of functional class I, it is necessary to assess the balance of benefits and risks from the proposed therapy. There are no data on the possibility of prescribing the drug for the treatment of secondary pulmonary hypertension, except for pulmonary hypertension caused by diseases of the connective tissue, and residual pulmonary hypertension.

It should be borne in mind that Revazio has a systemic vasodilating effect, which causes a slight transient decrease in blood pressure. When prescribing the drug to patients with arterial hypotension, hypovolemia, hypertrophic obstructive cardiomyopathy, aortic stenosis, multiple systemic atrophy syndrome, it is necessary to carefully assess the likelihood of an undesirable vasodilating effect. This is associated with the risk of developing symptomatic hypotension in sensitive patients when Revazio is combined with alpha-blockers. Patients should be informed of the action to be taken if symptoms of postural hypotension occur.

If, against the background of Revatio therapy, an erection persists for 4 hours or more, you should immediately consult a doctor, since without immediate medical intervention, the tissues of the penis may be damaged or a complete loss of potency may occur.

Cases of development of anterior non-arteritic ischemic neuropathy of the optic nerve more often occur in patients with such risk factors as age over 50 years, smoking, excavation (deepening) of the optic nerve head, diabetes mellitus, ischemic heart disease, arterial hypertension, hyperlipidemia.

In case of sudden loss of vision, deterioration or loss of hearing, immediate withdrawal of Revazio and immediate medical attention is required.

For the treatment of patients prone to bleeding, including exacerbation of gastric ulcer and duodenal ulcer, Revazio should be used with caution, especially in pulmonary hypertension associated with systemic diseases of the connective tissue, or in combination with a vitamin K antagonist.

The decision to prescribe the drug against the background of initial bosentan monotherapy in patients with primary pulmonary hypertension should be made by the physician relying on his experience in treating such diseases. In case of pulmonary hypertension associated with systemic connective tissue diseases, the combination therapy of Revazio and bosentan should not be prescribed.

The concomitant use of other PDE-5 inhibitors is not recommended.

Influence on the ability to drive vehicles and complex mechanisms

Revatio may have a negative effect on the patient's ability to drive vehicles or mechanisms, therefore it is recommended to carefully evaluate the individual effect of the drug, especially at the beginning of therapy and when changing the dose.

Application during pregnancy and lactation

The use of Revacio during gestation is possible only in special cases when the expected therapeutic effect for the mother, in the opinion of the doctor, is much higher than the potential risk to the fetus.

The use of sildenafil during lactation is contraindicated. Breastfeeding should be discontinued if it is necessary to take Revazio.

The negative effect of sildenafil on fertility has not been established.

Pediatric use

It is contraindicated to use Revazio for the treatment of patients under 18 years of age, since the safety and efficacy of sildenafil for this category of patients have not been established.

With impaired renal function

In case of impaired renal function, dose adjustment is not required, except in cases associated with poor tolerance to Revazio. In this case, a dosage regimen of 20 mg 2 times a day should be used.

For violations of liver function

The use of Revazio 20 mg tablets is contraindicated in case of severe liver dysfunction (more than 9 points on the Child-Pugh scale).

In mild and moderate (5-9 points on the Child-Pugh scale) liver dysfunction, dose adjustment is not required. In case of problems with the tolerance of Revazio, the daily dose can be reduced to 40 mg (20 mg 2 times a day).

Use in the elderly

No dose adjustment is required for the treatment of patients under the age of 65.

Drug interactions

Possible interactions while using Revazio:

• inhibitors of isoenzymes CYP3A4 and CYP2C9: in vitro reduce the clearance of sildenafil; in vivo weak / moderate inhibitors of the isoenzyme CYP3A4 cause a decrease in the clearance of sildenafil by about 30% in patients with pulmonary hypertension;
• inducers of isoenzymes CYP3A4 and CYP2C9: an increase in Revacio's clearance is possible;
• ritonavir: concomitant use is not recommended, there is an increased risk of a significant increase in the C _max and AUC of sildenafil (4 and 11 times, respectively), including in the treatment of pulmonary hypertension;
• ketoconazole, itraconazole, clarithromycin, telithromycin, nefazodone: it is not recommended to take these drugs simultaneously with sildenafil, since they can presumably have an effect similar to that of ritonavir;
• saquinavir is an inhibitor of HIV protease (human immunodeficiency virus) and isoenzyme CYP3A4: combination with saquinavir leads to an increase in C _max and AUC of sildenafil by 140% and 210%, respectively. AUC of saquinavir can increase by 7 times, so it is recommended to adjust its dose;
• bosentan: should be taken with caution, taking it in a daily dose of 250 mg may cause a decrease in the AUC and C _{max of} sildenafil. There were no clinically significant changes in blood pressure in the supine and standing positions. Sildenafil causes an increase in the AUC and C _{max of} bosentan;
• erythromycin (a moderate inhibitor of the isoenzyme CYP3A4): erythromycin taken in a daily dose of 1000 mg for 5 days causes an increase in the AUC of sildenafil by 182%, the AUC of erythromycin may increase by 7 times, therefore it is recommended to adjust its dose;
• azithromycin: taking azithromycin with a daily dose of 500 mg for 3 days does not affect the pharmacokinetic parameters of sildenafil and its active metabolite, including C _max, AUC, elimination rate constant, T _1/2;
• cimetidine (inhibitor of cytochrome P ₄₅₀ and nonspecific inhibitor of the isoenzyme CYP3A4): while taking cimetidine, the concentration of sildenafil in the blood plasma increases;
• magnesium hydroxide, aluminum hydroxide (antacids): a single dose of antacids does not interfere with the bioavailability of sildenafil;
• oral contraceptives (ethinyl estradiol or levonorgestrel): the pharmacokinetics of sildenafil do not change against the background of oral contraception. There was no clinically significant violation of the concentration of oral contraceptives in the blood plasma;
• beta-blockers: in patients with pulmonary hypertension against the background of concomitant therapy with beta-blockers, the clearance of sildenafil decreases by approximately 34%, the risk of developing clinically significant arterial hypotension in patients with sharp fluctuations in blood pressure increases;
• nitrates (nitric oxide donors): sildenafil causes an increase in the hypotensive effect of nitrates; joint use is contraindicated;
• doxazosin: there is a risk of developing orthostatic hypotension, including accompanied by dizziness;
• amlodipine: in patients with arterial hypertension, taking sildenafil at a dose of 100 mg causes an additional decrease in blood pressure in the supine position;
• tolbutamide, warfarin: these agents do not cause clinically significant interactions;
• acetylsalicylic acid: taking acetylsalicylic acid (150 mg) as an antiplatelet agent while using sildenafil at a dose of 50 mg is not accompanied by an additional increase in bleeding time;
• ethanol: sildenafil 50 mg does not enhance the hypotensive effect of ethanol at a maximum concentration of 80 mg / dl.

Analogs

Revazio's analogues are: Vizarsin, Alti-Met, Vekta, Viagra, Viasil, Vigrande, Novagra, Sildenafil, Sildenafil-C3.

Terms and conditions of storage

Keep out of the reach of children.

Store at temperatures up to 30 ° C, protected from moisture.

The shelf life is 5 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Revazio

The few reviews about Revazio are positive. Patients indicate the effectiveness of the drug in the treatment of pulmonary hypertension, noting a significant improvement in the general condition, a decrease in sweating and shortness of breath, and relief of breathing.

The disadvantages of the drug include the high cost, given the regular nature of the drug use.

Price for Revazio in pharmacies

The price of Revazio 20 mg per pack containing 90 tablets can range from 5862 rubles.

Revazio: prices in online pharmacies

Drug name Price Pharmacy

Revazio 20 mg film-coated tablets 90 pcs. RUB 12,299 Buy

Revacio tablets p.p. 20mg 90pcs RUB 16628 Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!