Vega Extra is a potent selective inhibitor of cGMP-specific PDE-5.
Mechanism of action
The implementation of the physiological mechanism of erection is associated with the release of nitric oxide (NO) in the cavernous body during sexual stimulation. This, in turn, leads to an increase in the level of cGMP, the subsequent relaxation of smooth muscle tissue of the cavernous body and an increase in blood flow.
Vegal Extra does not have a direct relaxing effect on the isolated cavernous human body, but enhances the effect of nitric oxide by inhibiting PDE-5, which is responsible for the disintegration of cGMP.
Selective Sildenafil Vega Extra 130 Mg Cobra against PDE5 in vitro, its activity against PDE5 superior activity against other known PDE isoenzymes: PDE-6 — 10 times; PDE-1 more than 80 times; PDE-2, PDE-4, PDE-7 PDE–11 more than 700 times. Vegal Extra is 4000 times more selective for PDE-5 than PDE-3, which is crucial because PDE-3 is one of the key enzymes in the regulation of myocardial contractility.
A prerequisite for the effectiveness of Cobra Vega Extra is sexual stimulation.
Vegal Extra restores impaired erectile function in conditions of sexual stimulation by increasing blood flow to the cavernous bodies of the penis.
Side effect
The most common side effects were headache and tides.
Usually the side effects of Cobra Vega Extra are mild or moderate and are transient.
Studies using a fixed dose have shown that the frequency of some adverse events increases with increasing dose.
The frequency of adverse reactions is presented in the following classification: very often — ≥10%; often — ≥1% and <10%; infrequently — ≥0.1% and <1%; rarely — ≥0.01% and <0.1%; very rarely — <0.01%; frequency unknown — cannot be determined based on available data.
Co side of the immune system: infrequently — hypersensitivity reactions (including skin rash), allergic reactions.
On the part of the organ of vision: often — blurred vision, blurred vision, cyanopsia; rarely, eye pain, photophobia, photopsia, chromatopsia, eye redness/injection of the sclera, changing the brightness of cvetovete, mydriasis, conjunctivitis, hemorrhage in the tissue of the eye, cataract, a disorder of the lacrimal apparatus; rarely — swelling of the eyelids and adjacent tissues, a feeling of dryness in the eyes, the presence of iridescent circles in the field of view around the light source, increased fatigue of the eyes, vision of objects in yellow (xanthopsia), vision of objects in red (erythropsia), conjunctival hyperemia, irritation of the mucous membrane of the eyes, unpleasant sensations in the eyes; the frequency is unknown — NPINZN, occlusion of retinal veins, visual field defect, diplopia*, temporary vision loss or decreased visual acuity, increased IHD, edema retina, retinal vascular disease, vitreous detachment/vitreal traction.
On the part of the organ of hearing: infrequent — a sudden decrease or loss of hearing, tinnitus, pain in the ears.
From the CCC: often — tides; infrequently — tachycardia, palpitations, decreased blood PRESSURE, increased heart rate, unstable angina, AV-blockade, myocardial infarction, cerebral thrombosis, cardiac arrest, heart failure, deviations in ECG readings, cardiomyopathy; rarely — atrial fibrillation, sudden cardiac death*, ventricular arrhythmia*.
The blood and lymphatic system: rarely — anemia, leukopenia.
On the part of metabolism and nutrition: infrequently — a feeling of thirst, swelling, gout, uncompensated diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemia, hypernatremia.
From the respiratory system: often — nasal congestion; infrequent — nosebleeds, rhinitis, asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, increased volume of sputum, increased cough; rarely — a feeling of tightness in the throat, dryness of the nasal mucosa, swelling of the nasal mucosa.
From the digestive tract: often — nausea, dyspepsia; uncommon — GERD, vomiting, pain in the abdomen, dryness of the mucous membrane of the mouth, glossitis, gingivitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, rejection of liver function tests from normal, rectal bleeding; rarely, hypesthesia of the mucous membrane of the oral cavity.
On the part of the musculoskeletal system: often — back pain; infrequently — myalgia, pain in the limbs, arthritis, arthrosis, tendon rupture, tenosynovitis, bone pain, myasthenia gravis, synovitis.
From the genitourinary system: infrequently — cystitis, nicturia, breast enlargement, urinary incontinence, hematuria, ejaculation disorders, genital edema, anorgasmia, hematospermia, damage to the tissues of the penis; rarely — prolonged erection and/or priapism.
From the Central and peripheral nervous system: very often — headache; often — dizziness; infrequently — drowsiness, migraine, ataxia, hypertension, neuralgia, neuropathy, paresthesia, tremor, vertigo, symptoms of depression, insomnia, unusual dreams, increased reflexes, hypesthesia; rarely — convulsions*, repeated convulsions*, fainting.
On the part of the skin and subcutaneous tissues: infrequently — skin rash, urticaria, herpes simplex, itching, sweating, skin ulceration, contact dermatitis, exfoliative dermatitis; the frequency is unknown — Stevens-Johnson syndrome, toxic epidermal necrolysis.
Other: infrequently — a feeling of heat, swelling of the face, photosensitivity reaction, shock, asthenia, fatigue, pain of various localization, chills, accidental falls, chest pain, accidental injuries; rarely — irritability.
Cardiovascular complications
During the post-marketing use of Vega Visa for the treatment of erectile dysfunction, adverse events such as severe cardiovascular complications (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension) were reported, which had a temporary connection with the use of Vegal Extra. Most of these patients, but not all of them, had risk factors for cardiovascular complications. Many of these adverse events were observed shortly after sexual activity, and some were observed after taking Vegal Extra without subsequent sexual activity. It is not possible to establish a direct link between the reported adverse events and those or other factors.
Visual impairment
In rare cases, during post-approval use of all of the inhibitors of PDE5, including Vegah Extra 120 Indication, reported NESN is a rare disease and the cause of the decrease or loss of vision. Most of these patients had risk factors, such as decreased ratios of excavation diameter to optic disc (stagnant disc), age over 50, diabetes, hypertension, CHD, hyperlipidemia, and Smoking. In an observational study evaluated whether recent use of drugs class of inhibitors PDE-5 with an acute onset NESN. The results indicate approximately a 2-fold increase in risk of developing NESN within 5T1/2 after application of the PDE-5 inhibitor. According to published literature, the annual incidence of npins IS 2.5–11.8 cases per 100,000 men aged ≥50 years in the General population. Patients should be advised to stop Vegal Extra therapy in case of sudden loss of vision and consult a doctor immediately. Persons who have already had a case NESN have an increased risk of relapse NESN. Therefore, the doctor should discuss this risk with such patients, as well as the potential chance of adverse effects of PDE-5 inhibitors. PDE-5 inhibitors, including Vega Extra Cobra, in such patients should be used with caution and only in situations where the expected benefit outweighs the risk.
When using the drug Vegal Extra in doses exceeding the recommended, adverse events were similar to those noted above, but usually more common.
*Side effects identified during post-marketing studies.
Interaction
Effect of other drugs on the pharmacokinetics of Vegal Extra
The metabolism of Sildenafil Vega Extra 130 occurs mainly under the action of CYP3A4 isoenzyme (main pathway), so inhibitors of this isoenzyme can reduce the clearance of Vega Extra Strong 120, and inducers, respectively, increase the clearance of Vegal Extra. A decrease in the clearance of Vega Extra with simultaneous use of inhibitors of CYP3A4 isoenzyme (ketoconazole, erythromycin, cimetidine).
Cimetidine (800 mg), a nonspecific inhibitor of CYP3A4 isoenzyme, when taken together with Vegal Extra (50 mg) causes an increase in the concentration of Vegal Extra in plasma by 56%.
A single dose of 100 mg of Vegal Extra together with erythromycin (500 mg/day 2 times a day for 5 days), a moderate inhibitor of CYP3A4 isoenzyme, while achieving a constant concentration of erythromycin in the blood, leads to an increase in the AUC of Vega Cobra 120 Mg by 182%.
When co-administered Vegal Extra (once 100 mg) and saquinavir (1200 mg/day 3 times daily), an inhibitor of HIV protease and of CYP3A4, on the background to achieve a constant concentration of saquinavir in the blood, Cmax of Vegal Extra was increased by 140% and the AUC increased by 210%.
Stronger inhibitors of CYP3A4 isoenzyme, such as ketoconazole and Itraconazole, can cause more pronounced changes in the pharmacokinetics of Extra Vega.
The simultaneous use of Vegal Extra (100 mg once) and ritonavir (500 mg 2 times a day), an inhibitor of HIV protease and a strong inhibitor of cytochrome P450, on the background to achieve a constant concentration of ritonavir in the blood leads to an increase in Cmax of Vegal Extra by 300% (4 times), a AUC by 1000% (11-fold). After 24 h, the concentration of Cobra Vega Extra Strong 120 Mg in blood plasma is about 200 ng/ml (after a single application of one Sildenafil Vega Extra 120 — 5 ng/ml). This is consistent with the ritonavir effect on a wide range of cytochrome P450 substrates. Vegah Extra 130 does not affect the pharmacokinetics of ritonavir. Given these data, the simultaneous reception of ritonavir and Vegal Extra is not recommended. In any case, the maximum dose of Vegal Extra under any circumstances should not exceed 25 mg for 48 hours. If Vegal Extra is taken in the recommended doses, patients receiving strong inhibitors of CYP3A4 isoenzyme at the same time, then Cmax free Cobra Vega 120 does not exceed 200 nm, and the drug is well tolerated.
Single administration of antacid (magnesium hydroxide/aluminum hydroxide) does not affect the bioavailability of Vegal Extra.
Studies involving healthy volunteers with simultaneous use of endothelin receptor antagonist, bosentan (CYP3A4 isoenzyme inducer (moderate), CYP2C9, and possibly CYP2C19) in Css (125 mg 2 times a day) and Vegal Extra in Css (80 mg 3 times a day) showed a decrease in AUC and Cmax Vegal Extra by 62.6 and 52.4%, respectively. Vegal Extra increased the AUC and Cmax of bosentan by 49.8 and 42%, respectively.
It is assumed that the simultaneous use of Cobra Vega Extra Strong 120 Mg with powerful inducers of CYP3A4 isoenzyme, such as rifampicin, can lead to a greater decrease in the concentration of Sildenafil Vega Extra 130 Mg Cobra in blood plasma.
CYP2D6 isoenzyme inhibitors (SSRIs, tricyclic antidepressants), thiazide and thiazide-like diuretics, ACE inhibitors and calcium antagonists have no effect on the pharmacokinetics of Vegal Extra.
Azithromycin (500 mg/day for 3 days) has no effect on AUC, Cmax, Tmax, excretion rate constant and T1/2 Vega Extra 120 or its main circulating metabolite.
Vega Extra Cobra 120 is a weak inhibitor of cytochrome P450 — 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 ISOENZYMES (IC50 >150 µmol). When taking Vegal Extra in recommended doses, its Cmax is about 1 µmol, so it is unlikely that Vegal Extra can affect the clearance of the substrates of these isoenzymes.
Vegal Extra increases the hypotensive effect of nitrates both with long-term use of the latter, and with their appointment for urgent indications. In this regard, the use of Vegal Extra in combination with nitrates or nitric oxide donators is contraindicated. While taking α-adrenoblocker doxazosin (4 and 8 mg) and Vegal Extra (25, 50 and 100 mg) in patients with benign prostate hyperplasia with stable hemodynamics, the average additional decrease in sad/dad in the supine position was 7/7, 9/5 and 8/4 mm Hg.article, respectively, while in the standing position — 6/6, 11/4 mmHg, and 4/5.art. respectively. Reported rare cases of symptomatic postural hypotension in such patients, manifested in the form of dizziness (without fainting). In some sensitive patients receiving α-blockers, simultaneous use of Vega Cobra 120 Mg can lead to symptomatic hypotension.
There were no signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by CYP2C9 isoenzyme.
Sildenafil Vega Extra 130 (100 mg) has no effect on the pharmacokinetics of the HIV protease inhibitor, saquinavir, which is a substrate of CYP3A4 isoenzyme, at its constant level in the blood.
The simultaneous use of Sildenafil Vega Extra 130 Mg at equilibrium (80 mg 3 times a day) leads to an increase in the AUC and Cmax of bosentan (125 mg 2 times a day) by 49.8 and 42%, respectively.
Cobra Vega 120 Mg (50 mg) does not cause an additional increase in bleeding time when taking acetylsalicylic acid (150 mg).
Vegal Extra (50 mg) does not increase the hypotensive effect of alcohol in healthy volunteers with Cmax of alcohol in the blood on average 0.08‰ (80 mg/DL).
In patients with hypertension, no signs of interaction of Vega Coin (100 mg) with amlodipine were found. The average additional reduction in blood PRESSURE in the supine position is 8 mm Hg.V. (systolic) and 7 mm Hg.V. (diastolic).
The use of Vegal Extra in combination with antihypertensive agents does not lead to additional side effects.
Cobra Vega Extra Strong 120mg
