Revacio

Revacio has a vasodilating effect on the body.

Indications of the revacio

It is used for the treatment of pulmonary type hypertension - it is a group of pathologies in which there is a progressive increase in vascular resistance within the lungs, as a result of which the right ventricle of the heart develops.

Release form

The release occurs in tablets, in an amount of 15 pieces packed in blister plates. In a pack - 90 tablets or 6 blister packs.

Pharmacodynamics

Sildenafil is a selective substance with a powerful retarding effect on the cGMP element of a specific component of PDE-5. The latter promotes the process of decay of the cGMP element, and is present inside the cavernous bodies of the penis, as well as inside the pulmonary vessels. By increasing the level of cGMP inside the cells of the smooth muscles of the pulmonary vessels, the process of their relaxation is carried out. During the treatment of pulmonary hypertension, sildenafil expands pulmonary vessels and other vessels (but to a lesser extent).

Sildenafil is selective for the PDE-5 component - it acts on it much more actively than other known isoenzymes, such as PDE-11 (700 times stronger), and PDE-1 (80 times stronger).

[1], [2], [3], [4], [5], [6]

Pharmacokinetics

Absorption.

Sildenafil is absorbed rather quickly. The absolute bioavailability is about 41%. To reach the peak level inside the blood plasma, the drug needs about 1 hour (this requires that the drug was used on an empty stomach).

After consuming 60-120 mg of the drug (three times a day), there is an increase in Cmax, as well as AUC, which proportionally corresponds to the size of the dose. When you use 240 mg of LS per day, there is a nonlinear increase in the indices of the medicine. Consumption with fat dishes, which have a high caloric content, leads to a prolongation of the time to reach peak values for another hour. In this case, the maximum plasma values of LS decrease by approximately 29%, and the degree of absorption decreases by 11% (on average).

Distribution.

The distribution volume of sildenafil is 105 liters. At reception for a day of 60 mg of the drug the peak equilibrium values of the substance are about 113 ng / ml. The sildenafil component, together with its main circulating N-demethyl metabolic product, is synthesized inside the blood with a plasma protein - approximately 96%. There is also excretion of the substance with sperm: after 1.5 hours in healthy men, about 0.0002% of the portion consumed.

Metabolic processes.

The metabolic processes are mainly carried out inside the liver, using isoenzymes microsomes of the hemoprotein P450 system: such as the CYP3A4 element (the main metabolic pathway), and the element CYP2C9 (ancillary pathway). The main circulating metabolite, N-demethylated sildenafil, also acts selectively on PDE, the activity of the PDE-5 component in in vitro tests is 50% of the total effect of sildenafil.

The level of the metabolite inside the plasma is approximately 40% of the indices of sildenafil itself. These values differ in people with elevated pulmonary arterial pressure - they are approximately 72%. The N-demethyl product of metabolism is converted, and its final half-life is about 4 hours.

Approximately 36% of the total drug activity of drugs is accounted for by the decay product of the basic substance.

Excretion.

The total clearance is 41 l / h, and the final half-life of the drug is 3-5 hours. Excretion takes place in the form of metabolic products - about 80% of the taken portion is excreted by the intestine, and about 13% by the kidneys.

Pharmacokinetic characteristics for specific categories of patients.

Aged people.

Since the clearance rates are lowered, the level of free sildenafil with its metabolic product will be higher by 90%. Because the protein synthesis of sildenafil inside the plasma is determined by age, the parameters of the freely moving sildenafil will be higher by approximately 40%.

Having problems with kidney function.

If there is a severe kidney failure, the sildenafil clearance is significantly reduced, causing an increase in the active component values: AUC (100%) and Cmax (88%). The same indicators for the product of metabolism of the substance are: AUC - + 200%, and Cmax - + 79% (in comparison with the indicators of healthy people).

Presence of functional hepatic disorders.

In mild to moderate forms of disorders (with Child-Pugh score 5-9), the clearance level decreases, causing an increase in AUC (+ 85%) and Cmax (+ 47%).

The patient has PAH.

The Css level of the substance is increased by 20-50%, and the Cmin values are doubled. There is a tendency to decrease the clearance values or increase the level of bioavailability of the active element in persons with PAH, in comparison with similar markers in healthy people.

[7], [8]

Dosing and administration

The medication is taken orally, and the standard portion per day is 60 mg, which is consumed in 3 doses, with intervals between them of 6-8 hours, regardless of the diet. During the day you can not take more than 60 mg.

Correction of the dosage size in case the patient has disorders in renal activity. If there is a poor tolerance of sildenafil substance, it is required to reduce the dosage - take 20 mg of the drug twice a day.

If a patient needs a combination treatment with saquinavir or erythromycin, the daily dosage of Revacio should be reduced to 40 mg, while dividing it into 2 separate portions. When combined with telithromycin, clarithromycin, as well as nefazodone, the daily dosage is reduced to 20 mg.

[13]

Use of the revacio during pregnancy

Taking the drug is only allowed in situations where the probable benefit to the mother is higher than the occurrence of complications and adverse reactions in the fetus.

Contraindications

Among the contraindications:

• the presence of hypersensitivity to all elements of the drug;
• venokklyuzionnaya pathology in the lungs;
• use donators NO, any form of nitrate, and in addition to this potent inhibitors of isoenzyme CYP3 A4 (among them ritonavir with itraconazole and ketoconazole);
• loss of vision with one eye as a result of the development of a non-artery inflammatory process of the ischemic type in the anterior part of the optic nerve;
• people with degenerative diseases of a hereditary nature in the eye retina (among such retinitis);
• severe stages of a disorder of hepatic activity (more than 9 points on Child-Pugh);
• a previous myocardial infarction or stroke;
• decreased blood pressure in severe form - system indicators are up to 90 mm Hg, and diastolic - up to 50 mm Hg. P.
• hypolactasia, insufficiency of lactase enzyme, as well as malabsorption syndrome;
• the period of breastfeeding;
• category of patients under the age of 18 years.

Caution is required when appointing in such cases:

• increased values of pulmonary arterial pressure (1st or 4th functional class);
• the anatomical deformation of the penis (among them cavernous fibrosis, angulation, and also the curvature of the penis);
• different pathologies that contribute to the emergence of priapism (this includes anemia sickle-cell type, plasmacytoma, as well as anemia);
• diseases against which bleeding occurs, as well as exacerbations of ulcerative processes in the gastrointestinal tract;
• insufficiency of cardiac activity;
• an unstable form of angina pectoris;
• types of arrhythmia that can be life threatening;
• elevated values of blood pressure - more than 170/100 mm Hg. P.
• obstruction in the left ventricular outflow tract (among them aortic stenosis, and at the same time obstructive form of cardiomyopathy, which is hypertrophic in nature);
• Shia syndrome or hypovolemia;
• neuropathy of a non-arterial ischemic character in the anterior part of the optic nerve or the presence of this pathology in the anamnesis;
• use of moderately acting drugs slowing the isoenzyme CYP3 A4 (this includes saquinavir, telithromycin with erythromycin and clarithromycin, as well as nefazodone), and in addition to this, α-blockers;
• use in the treatment of drugs that induce isoenzyme CYP3 A4.

[9], [10], [11]

Side effects of the revacio

The use of medication can cause the appearance of such side effects:

• inflammation in the subcutaneous tissue, anemia, sinusitis in unspecified forms, as well as a decrease in blood pressure and influenza;
• fluid retention within the body, which manifests itself in the form of swelling;
• the appearance of headaches, paresthesias, burning, a sense of anxiety, and besides insomnia, hypesthesia and tremor;
• hemorrhage in the eye retina, visual disturbances (among them diplopia, blurred vision, photophobia, cyanopsy, and chromatopsy), problems with eye sensitivity, redness or inflammation in the eye area. There may be a deterioration in visual acuity;
• sudden development of deafness, and in addition to this vertigo;
• the occurrence of bleeding from the nose, cough or runny nose, and in addition the development of bronchitis and nasal congestion;
• the appearance of swelling, hemorrhoids, symptoms of dyspepsia, and in addition the development of gastritis, GERD, gastroenteritis and diarrhea. Also, dry mouth mucous membranes may occur;
• the development of erythema, rashes on the skin and alopecia, and in addition to this night hyperhidrosis;
• Myalgia and pain in the back and limbs;
• prolonged erection, hematospermia, gynecomastia, as well as priapism;
• a condition of a fever and development of a hyperemia.

[12]

Overdose

The main signs of intoxication: the occurrence of tides, headaches, nasal congestion, dizziness, as well as visual disorders and indigestion.

To remove the violations, symptomatic treatment procedures are needed, because hemodialysis does not work.

[14], [15],

Interactions with other drugs

When combined with drugs that slow the activity of isoenzymes of the hemoprotein system P450 (elements such as CYP3A4 and CYP2C9), a decrease in the level of drug clearance is observed. When combined with inductor drugs, these values increase on the contrary.

Combination with ritonavir (1 g / day), drugs slowing down the HIV protease, and in addition with agents with a powerful retardation effect against isoenzyme CYP3A4, leads to an increase in the Cmax level of the sildenafil substance (by more than 300%), and AUC values (approximately 1000%).

The combination with saquinavir, as well as isoenzymes CYP3A4 and drugs that slow down the activity of HIV protease, increases the peak values of sildenafil by about 140%, and 210% - the AUC level.

When the drug interacts with telithromycin, clarithromycin, or nefazodone, symptoms may appear that are similar in properties to those of ritonavir.

Combination with substances erythromycin or saquinavir increases the AUC Revacio sevenfold. In this regard, the size of portions of the drug should be adjusted.

With simultaneous admission with cimetidine (in the amount of 0.8 g), means inhibiting the activity of hemoprotein P450, as well as drugs that non-specifically slow the action of isoenzyme CYP3A4, there is an increase in the plasma values of sildenafil (50 mg dose) in a healthy person (56%) .

When combined with drugs that slightly induce isoenzyme CYP3A4, the level of clearance of the active component of drugs is tripled. The use of sildenafil even at a dosage of 60 mg during therapy with PAH, together with bosentan, reduces the values of AUC sildenafil.

[16],

Storage conditions

Revacio must be kept in a dry place. The temperature should be a maximum of + 30 ° C.

[17], [18]

Shelf life

Revacio is allowed to be used for 5 years from the date of manufacture of the medicament.

Reviews

Revacio has quite a few reviews. Most patients note that the drug is quite expensive, but it is very effective in eliminating the symptoms of PAH - it facilitates the respiratory process, and in addition reduces the intensity of sweating and shortness of breath.