Revazio

Revatio has a vasodilating effect on the body.

Indications Revazio

It is used to treat pulmonary hypertension, a group of pathologies in which there is a progressive increase in vascular resistance within the lungs, resulting in right ventricular failure.

Release form

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

Pharmacodynamics

Sildenafil is a selective substance with a powerful inhibitory effect on the cGMP element of the 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. Due to the increase in the level of cGMP inside the smooth muscle cells of the pulmonary vessels, the process of their relaxation is carried out. During the treatment of pulmonary hypertension, sildenafil dilates the pulmonary vessels and other vessels (but to a lesser extent).

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

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Pharmacokinetics

Absorption.

Sildenafil is absorbed fairly quickly. Absolute bioavailability rates are approximately 41%. It takes about 1 hour for the drug to reach peak plasma levels (this requires that the drug be taken on an empty stomach).

After taking 60-120 mg of the drug (three times a day), there is an increase in the Cmax values, as well as AUC, which is proportional to the dose size. When taking 240 mg of the drug per day, there is a non-linear increase in the drug indicators. Taking it with fatty dishes that have a high calorie content leads to a prolongation of the time to reach peak indicators by another 1 hour. In this case, the maximum plasma values of the drug decrease by approximately 29%, and the degree of absorption decreases by 11% (on average).

Distribution.

The distribution volume of sildenafil is 105 l. When taking 60 mg of the drug per day, the peak equilibrium values of the substance are about 113 ng / ml. The component sildenafil, together with its main circulating N-demethyl product of metabolism, is synthesized in the blood with plasma protein - approximately 96%. Excretion of the substance with sperm also occurs: after 1.5 hours, healthy men have about 0.0002% of the consumed portion.

Metabolic processes.

Metabolic processes are mainly carried out inside the liver, with the help of isoenzymes of the microsomes of the hemoprotein P450 system: such as the CYP3A4 element (the main metabolic pathway), as well as the CYP2C9 element (ancillary pathway). The main circulating product of metabolism - N-demethylated sildenafil also acts selectively with respect to PDE, the activity indicator with respect to the PDE-5 component in vitro tests is 50% of the total effect of sildenafil.

The plasma metabolite level is approximately 40% of that of sildenafil itself. These values differ in people with elevated pulmonary arterial pressure – they are approximately 72%. The N-demethyl metabolite is converted and its terminal half-life is approximately 4 hours.

Approximately 36% of the total medicinal activity of a drug comes from the breakdown product of the main substance.

Excretion.

The total clearance rate is 41 l/hour, and the terminal half-life of the drug is 3-5 hours. Excretion occurs in the form of metabolic products - about 80% of the dose taken is excreted through the intestines, and another 13% through the kidneys.

Pharmacokinetic characteristics for special patient categories.

Elderly people.

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

Presence of problems with kidney function.

If severe renal failure is observed, sildenafil clearance rates are significantly reduced, causing an increase in the active component values: AUC (by 100%) and Cmax (by 88%). The same indicators for the substance's metabolic product are: AUC - +200%, and Cmax - +79% (compared to the indicators of healthy people).

Presence of functional liver disorders.

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

The presence of PAH in the patient.

The Css level of the substance increases by 20–50%, and the Cmin values double. There is a tendency for clearance values to decrease or for the bioavailability of the active element to increase in individuals with PAH, compared to similar values in healthy individuals.

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Dosing and administration

The medicine is taken orally, and the standard daily dose is 60 mg, which is taken in 3 doses, with intervals between them of 6-8 hours, regardless of the diet. You cannot take more than the prescribed 60 mg per day.

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

If the patient requires combination therapy with saquinavir or erythromycin, the daily dosage of Revatio should be reduced to 40 mg – in this case it should be divided into 2 separate portions. When combined with telithromycin, clarithromycin, and nefazodone, the daily dosage is reduced to 20 mg.

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Use Revazio during pregnancy

Taking the drug is permitted only in situations where the probable benefit to the mother is greater than the occurrence of complications and negative reactions in the fetus.

Contraindications

Among the contraindications:

• the presence of hypersensitivity to all elements of the drug;
• veno-occlusive pathology in the lung area;
• the use of NO donors, any forms of nitrates, and in addition, powerful inhibitors of the CYP3 A4 isoenzyme (including ritonavir with itraconazole and ketoconazole);
• loss of vision in one eye as a result of the development of a non-arteritic inflammatory process of the ischemic type in the anterior part of the optic nerve;
• people with hereditary degenerative diseases in the area of the retina (including retinitis);
• severe stages of liver dysfunction (more than 9 points according to Child-Pugh);
• a history of myocardial infarction or stroke;
• severely reduced blood pressure – systemic indicators are up to 90 mm Hg, and diastolic indicators are up to 50 mm Hg;
• hypolactasia, lactase enzyme deficiency, and malabsorption syndrome;
• breastfeeding period;
• category of patients under 18 years of age.

Caution is required when prescribing in the following cases:

• elevated pulmonary arterial pressure (1st or 4th functional class);
• anatomical deformation of the penis (including cavernous fibrosis, angulation, and curvature of the penis);
• various pathologies that contribute to the development of priapism (these include sickle cell anemia, plasmacytoma, and leukemia);
• diseases that cause bleeding, as well as exacerbations of ulcerative processes in the gastrointestinal tract;
• cardiac insufficiency;
• unstable angina;
• types of arrhythmia that can be life-threatening;
• elevated blood pressure values – more than 170/100 mm Hg;
• obstruction in the area of the left ventricular outflow tract (including aortic stenosis, and also the obstructive form of cardiomyopathy, which has a hypertrophic nature);
• Shy syndrome or hypovolemia;
• non-arteritic ischemic neuropathy in the anterior region of the optic nerve or the presence of this pathology in the anamnesis;
• the use of moderately active drugs that inhibit the CYP3 A4 isoenzyme (these include saquinavir, telithromycin with erythromycin and clarithromycin, as well as nefazodone), and in addition, α-blockers;
• use in treatment with drugs that induce the CYP3 A4 isoenzyme.

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Side effects Revazio

The use of the drug may cause the following side effects:

• inflammatory process within the subcutaneous tissue, anemia, sinusitis in unspecified forms, as well as a decrease in blood pressure and flu;
• fluid retention in the body, which manifests itself in the form of swelling;
• the appearance of headaches, paresthesia, burning, feelings of anxiety, as well as insomnia, hypoesthesia and tremor;
• hemorrhage in the retinal area, visual disturbances (including diplopia, blurred vision, photophobia, cyanopsia, and chromatopsia), problems with eye sensitivity, redness or inflammation in the eye area. Deterioration in visual acuity may also be observed;
• sudden development of deafness, and in addition to this vertigo;
• the occurrence of nosebleeds, cough or runny nose, as well as the development of bronchitis and nasal congestion;
• the appearance of bloating, hemorrhoids, dyspepsia symptoms, as well as the development of gastritis, GERD, gastroenteritis and diarrhea. Dryness of the oral mucosa may also occur;
• development of erythema, skin rashes and alopecia, as well as nocturnal hyperhidrosis;
• myalgia and pain in the back and limbs;
• prolonged erection, hematospermia, gynecomastia, and priapism;
• a state of fever and the development of hyperemia.

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Overdose

The main signs of intoxication are hot flashes, headaches, nasal congestion, dizziness, as well as visual disturbances and indigestion.

To eliminate the resulting disorders, symptomatic treatment procedures are necessary, because hemodialysis does not produce results.

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Interactions with other drugs

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

Combination with ritonavir (at a dose of 1 g/day), drugs that inhibit HIV protease, and also drugs with a strong inhibitory effect on the CYP3A4 isoenzyme, leads to an increase in the Cmax level of sildenafil (by more than 300%), as well as AUC values (by approximately 1000%).

Combination with saquinavir, as well as CYP3A4 isoenzymes and drugs that inhibit HIV protease activity, increases peak sildenafil levels by approximately 140%, and AUC levels by 210%.

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

Combination with erythromycin or saquinavir increases the AUC values of Revatio sevenfold. Therefore, the dose sizes of the drug should be adjusted.

When taken simultaneously with cimetidine (0.8 g), drugs that inhibit the activity of hemoprotein P450, as well as drugs that non-specifically inhibit the action of the isoenzyme CYP3A4, there is an increase in plasma values of sildenafil (dosage 50 mg) in a healthy person (by 56%).

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

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Storage conditions

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

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Shelf life

Revatio can be used for 5 years from the date of manufacture of the drug.

Reviews

Revatio has very few reviews. Most patients note that the drug is quite expensive, but at the same time it is very effective in eliminating the symptoms of PAH - it facilitates the breathing process, and in addition reduces the severity of sweating and shortness of breath.