Visual impairment

In rare cases, during post-approval use of all of the inhibitors of PDE5, including Sildenafil Tablets Vegah Extra Cobra, 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 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 Cobra 120 Vega 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 120, in such patients should be used with caution and only in situations where the expected benefit outweighs the risk. In patients with episodes of development PINZN with loss of vision in one eye receiving Sildenafil Vega Extra 130 is contraindicated (see "Contraindications").

A small number of patients with hereditary retinitis pigmentosa have genetically determined disorders of the PDE of the retina. Information about the safety of the drug Vega Pills in patients with retinitis pigmentosa absent, so these patients should not be used Cobra Vega Extra Strong 120mg (see "Contraindications").

Influence of Sildenafil Vega Extra 130 on other drugs

Sildenafil Vega Extra 130 is a weak inhibitor of cytochrome P450 — 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 ISOENZYMES (IC50 >150 µmol). When taking Vegah Extra 120 Indication in recommended doses, its Cmax is about 1 µmol, so it is unlikely that Sildenafil Vega Extra 130 can affect the clearance of the substrates of these isoenzymes.

Sildenafil Vega Extra 130 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 Sildenafil Vega Extra 130 in combination with nitrates or nitric oxide donators is contraindicated. While taking α-adrenoblocker doxazosin (4 and 8 mg) and Vega Extra Cobra 130 Mg (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 Sildenafil Vega Extra 130 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.

Extra Vega (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 Extra Vega 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 (50 mg) does not cause an additional increase in bleeding time when taking acetylsalicylic acid (150 mg).

Vega 120 Mg (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 Sildenafil Vega Extra 130 (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 Sildenafil Vega Extra 130 in combination with antihypertensive agents does not lead to additional side effects.

Cardiovascular complications

During the post-marketing use of Sildenafil Vega Extra 130 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 Vega Coin. 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 Sildenafil Vega Extra 130 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 Vega Pills, 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 Cobra 120 Vega 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 Sildenafil Vega Extra 130, in such patients should be used with caution and only in situations where the expected benefit outweighs the risk.

When using the drug Vega 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 Sildenafil Vega Extra 130

The metabolism of Vega Visa occurs mainly under the action of CYP3A4 isoenzyme (main pathway), so inhibitors of this isoenzyme can reduce the clearance of Signature Cobra Vega, and inducers, respectively, increase the clearance of Sildenafil Vega Extra 130. A decrease in the clearance of Cobra Vega Extra Strong 120 Mg 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 Vega Cobra 120 in plasma by 56%.

A single dose of 100 mg of Sildenafil Vega Extra 130 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 Sildenafil Vega Extra 130 by 182%.

When co-administered Vega Extra Cobra 130 Mg (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 Cobra 120 Vega 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 Sildenafil Vega Extra 130.

The simultaneous use of Cobra Vega 120 Mg (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 Vega Cobra 120 by 300% (4 times), a AUC by 1000% (11-fold). After 24 h, the concentration of Sildenafil Vega Extra 130 in blood plasma is about 200 ng/ml (after a single application of one Sildenafil Tablets Vega Extra Cobra — 5 ng/ml). This is consistent with the ritonavir effect on a wide range of cytochrome P450 substrates. Sildenafil Vega Extra 130 does not affect the pharmacokinetics of ritonavir. Given these data, the simultaneous reception of ritonavir and Vega Extra 120 Mg is not recommended. In any case, the maximum dose of Cobra Vega 120 under any circumstances should not exceed 25 mg for 48 hours. If Sildenafil Vega Extra 130 is taken in the recommended doses, patients receiving strong inhibitors of CYP3A4 isoenzyme at the same time, then Cmax free Cobra Vega Extra Strong 120mg 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 Sildenafil Vega Extra 130.

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 Sildenafil Vega Extra 130 in Css (80 mg 3 times a day) showed a decrease in AUC and Cmax Sildenafil Vega Extra 130 by 62.6 and 52.4%, respectively. Vegah Cobra increased the AUC and Cmax of bosentan by 49.8 and 42%, respectively.

It is assumed that the simultaneous use of Sildenafil Vega Extra 130 with powerful inducers of CYP3A4 isoenzyme, such as rifampicin, can lead to a greater decrease in the concentration of Vegal Extra 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 Sildenafil Vega Extra 130.

Azithromycin (500 mg/day for 3 days) has no effect on AUC, Cmax, Tmax, excretion rate constant and T1/2 Vega 120 Mg or its main circulating metabolite.

The pharmacokinetics of Signature Cobra Vega in the recommended dose range is linear.

Suction. After intake of Sildenafil Vega Extra 130 is rapidly absorbed. Absolute bioavailability averages about 40% (25 to 63%). In vitro Sildenafil Vega Extra 130 at a concentration of about 1.7 ng/ml (3.5 nm) inhibits the activity of PDE-5 50%. After a single dose of Vega Coin 100 mg average Cmax free Vega Cobra in plasma men is about 18 ng/ml (38 nm). Cmax when taking Sildenafil Vega Extra 130 inside fasting is achieved for an average of 60 minutes (from 30 to 120 minutes). When taken in combination with fatty foods, the rate of absorption decreases: Cmax decreases by an average of 29%, and Tmax increases by 60 minutes, but the degree of absorption does not change significantly (AUC decreases by 11%).

Distribution. The average Vss of Vega Coin is 105 l. the Association of Sildenafil Vega Extra 130 and its main circulating N-demethyl metabolite with plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the dose of Vegah Extra 130 (an average of 188 ng) was found in sperm 90 minutes after taking the drug.

Metabolism. Sildenafil Vega Extra 130 is metabolized mainly in the liver by the action of CYP3A4 isoenzyme (main pathway) and CYP2C9 isoenzyme (minor pathway). The main circulating active metabolite, formed as a result of N-demethylation of Sildenafil Vega Extra 130, undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of Sildenafil Vega Extra 130, and its activity against PDE-5 in vitro is about 50% of the activity of Sildenafil Tablets Vega Extra Cobra. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of Sildenafil Vega Extra 130. N-demethyl metabolite undergoes further metabolism; its T1/2 is about 4 no.

Breeding. The total clearance of Sildenafil Vega Extra 130 is 41 l/h, and the final T1/2 — 3-5 h. After oral administration, as well as after I/V, Sildenafil Vega Extra 130 is excreted as metabolites, mainly by the intestine (about 80% oral dose) and to a lesser extent by the kidneys (about 13% oral dose).

Vegal Extra