Sildenafil Vertex
To diagnose erectile dysfunction, determine its possible causes and select adequate treatment, it is necessary to obtain a complete medical history and conduct a thorough physical examination. Treatments for erectile dysfunction should be used with caution in patients with anatomical deformation of the penis (angulation, cavernous fibrosis, Peyronie's disease) or in patients with risk factors for the development of priapism (sickle cell anemia, multiple myeloma, leukemia) (see section "With caution") .
During post-marketing studies, cases of prolonged erection and priapism have been reported. If an erection persists for more than 4 hours, you should immediately seek medical help. If treatment for priapism is not carried out immediately, it can lead to damage to the tissue of the penis and irreversible loss of potency.
Medicines intended to treat erectile dysfunction should not be used by men for whom sexual activity is undesirable.
Sexual activity poses a certain risk in the presence of cardiovascular disease, so before starting any therapy for erectile dysfunction, the doctor should refer the patient for an examination of the state of the cardiovascular system. Sexual activity is not advisable in patients with heart failure, unstable angina, myocardial infarction or stroke in the past six months, life-threatening arrhythmias, hypertension (BP > 170/100 mm Hg) or hypotension (BP < 90/50 mm Hg. Art.) (see section “Contraindications”). Clinical studies have shown no difference in the incidence of myocardial infarction (1.1 per 100 people per year) or the incidence of cardiovascular mortality (0.3 per 100 people per year) in patients taking sildenafil compared with patients taking sildenafil. those receiving placebo.
Cardiovascular complications
During post-marketing use of sildenafil 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) have been reported. which had a temporary association with the use of sildenafil. Most of these patients, but not all of them, had risk factors for cardiovascular complications. Many of these adverse events occurred shortly after sexual activity, and some of them occurred after taking sildenafil without subsequent sexual activity. It is not possible to establish a direct connection between the observed adverse events and these or other factors.
Hypotension
Sildenafil has a systemic vasodilating effect, leading to a transient decrease in blood pressure, which is not a clinically significant phenomenon and does not lead to any consequences in most patients. However, before using sildenafil, the physician should carefully assess the risk of possible adverse effects of vasodilating effects in patients with relevant diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with the rare syndrome of multiple system atrophy, manifested by severe dysregulation of blood pressure from the autonomic nervous system.
Since the combined use of sildenafil and alpha-blockers may lead to symptomatic hypotension in selected sensitive patients, sildenafil should be used with caution in patients taking alpha-blockers (see sections "Precautions" and "Interactions with other drugs"). To minimize the risk of postural hypotension in patients taking alpha-blockers, sildenafil should be started only after hemodynamic stability has been achieved in these patients. You should also consider the advisability of reducing the initial dose of sildenafil (see section "Dosage and Administration"). The physician should inform the patient what actions to take if symptoms of postural hypotension occur.
Visual impairment
In rare cases, non-arteritic anterior ischemic optic neuropathy (NAIAON), a rare disease and cause of vision loss or reduction, has been reported during post-marketing use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors, including decreased papilledema/disc ratio (“congestive disc”), age over 50 years, diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and smoking. An observational study assessed whether recent use of the PDE5 inhibitor class of drugs was associated with acute onset of NPINSID. Results indicate an approximately two-fold increase in the risk of NPINSID within 5 half-lives of PDE5 inhibitor use. According to the published literature, the annual incidence of NPINSID is 2.2-11.8 cases per 100,000 men over the age of 50 years in the general population. In case of sudden loss of vision, patients should be advised to stop sildenafil therapy and consult a doctor immediately. Individuals who have already had a case of NPIND have an increased risk of recurrent NPIND. Therefore, the physician should discuss this risk with such patients, as well as discuss with them the potential for adverse effects from PDE5 inhibitors. PDE5 inhibitors, including sildenafil, should be used with caution in such patients and only in situations where the expected benefit outweighs the potential risk. In patients with episodes of NPINS with loss of vision in one eye, sildenafil is contraindicated (see section "Contraindications").
A small number of patients with hereditary retinitis pigmentosa have genetically determined dysfunction of retinal phosphodiesterases. There is no information on the safety of sildenafil in patients with retinitis pigmentosa, therefore the use of sildenafil in such patients is contraindicated (see section "Contraindications").
Hearing impairment
Some post-marketing and clinical studies have reported cases of sudden deterioration or loss of hearing associated with the use of all PDE5 inhibitors, including sildenafil. Most of these patients had risk factors for developing sudden deterioration or loss of hearing. A cause-and-effect relationship between the use of PDE5 inhibitors and sudden hearing loss or deterioration has not been established. The patient should be warned that in the event of sudden deterioration or sudden loss of hearing, discontinue sildenafil therapy and consult a physician immediately.
Bleeding
Sildenafil enhances the antiplatelet effect of sodium nitroprusside (nitric oxide donor) on human platelets in vitro. There are no data on the safety of sildenafil in patients with a tendency to bleeding or exacerbation of gastric and duodenal ulcers, so sildenafil should be used with caution in these patients (see section "With caution"). The incidence of epistaxis in patients with PH associated with diffuse connective tissue diseases was higher (sildenafil - 12.9%, placebo - 0%) than in patients with primary pulmonary arterial hypertension (sildenafil - 3.0%, placebo - 2%). ,4 %). Patients receiving sildenafil in combination with a vitamin K antagonist had a higher incidence of epistaxis (8.8%) than patients not taking a vitamin K antagonist (1.7%).
Use in conjunction with other means of treating erectile dysfunction
The safety and effectiveness of using sildenafil in combination with other drugs for the treatment of erectile dysfunction have not been studied, therefore the use of such combinations is not recommended (see section “Contraindications”).
Losartan-Vertex 12.5 mg 30 pcs. film-coated tablets Vertex JSC
pharmachologic effect
Diuretic, hypotensive.
Composition and release form Losartan-vertex 12.5 mg 30 pcs. film-coated tablets Vertex JSC
Tablet - 1 tablet:
- Active substance: losartan potassium 12.5 mg;
- Excipients: lactose monohydrate - 58.6 mg, microcrystalline cellulose - 20 mg, croscarmellose sodium - 4 mg, povidone (low molecular weight polyvinylpyrrolidone) - 3.2 mg, colloidal silicon dioxide - 0.7 mg, magnesium stearate - 1 mg;
- composition of the film shell: (hypromellose - 1.8 mg, talc - 0.6 mg, titanium dioxide - 0.33 mg, macrogol 4000 (polyethylene glycol 4000) - 0.27 mg) or (dry mixture for film coating containing hypromellose 60%, talc 20%, titanium dioxide 11%, macrogol 4000 (polyethylene glycol 4000) 9%) - 3 mg.
Tablets, 12.5 mg, in blisters, 30 pieces per pack.
Description of the dosage form
Yellow film-coated tablets, round, biconvex; On a cross section, the core is white or almost white.
Directions for use and doses
Arterial hypertension.
The standard initial and maintenance dose for most patients is 50 mg once daily. The maximum antihypertensive effect is achieved 3-6 weeks from the start of therapy.
In some patients, to achieve greater effect, the dose may be increased to a maximum daily dose of 100 mg once a day.
In patients with a reduced circulating blood volume (for example, when taking diuretics in large doses), the initial dose of the drug should be reduced to 25 mg 1 time per day.
There is no need to select the initial dose in elderly patients and in patients with renal failure, including patients on dialysis.
Patients with liver failure (less than 9 points on the Child-Pugh scale) during hemodialysis, as well as patients over 75 years of age, are recommended to prescribe the drug at a lower initial dose of 25 mg 1 time per day.
Reducing the risk of associated cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy.
The standard initial dose of the drug is 50 mg 1 time per day. In the future, it is recommended to add hydrochlorothiazide or increase the dose of Losartan to 100 mg (taking into account the degree of reduction in blood pressure (BP)) in one or two doses.
Kidney protection in patients with type 2 diabetes mellitus and proteinuria.
The standard initial dose of the drug is 50 mg 1 time per day. In the future, it is recommended to increase the dose of Losartan to 100 mg 1 time per day, taking into account the degree of blood pressure reduction. Losartan can be prescribed together with other antihypertensive drugs (diuretics, slow calcium channel blockers, alpha and beta blockers, centrally acting antihypertensive drugs), insulin and other hypoglycemic drugs (sulfonylurea derivatives, glitazones and glucosidase inhibitors).
Chronic heart failure.
The initial dose of the drug is 12.5 mg 1 time per day. Typically, the dose is titrated at weekly intervals (i.e., 12.5 mg once daily, 25 mg once daily, 50 mg once daily) to the usual maintenance dose of 50 mg once daily, depending on individual portability.
Pharmacodynamics
Antihypertensive agent. It is a non-peptide angiotensin II receptor blocker. It has high selectivity and affinity for AT1 type receptors (with the participation of which the main effects of angiotensin II are realized). By blocking these receptors, losartan prevents and eliminates the vasoconstrictor effect of angiotensin II, its stimulating effect on the secretion of aldosterone by the adrenal glands and some other effects of angiotensin II. It is characterized by a long-term effect (24 hours or more), which is due to the formation of its active metabolite.
Pharmacokinetics
After oral administration, losartan is rapidly absorbed from the gastrointestinal tract. Bioavailability is about 33%. Metabolized during the “first pass” through the liver to form a carboxyl metabolite, which has more pronounced pharmacological activity than losartan, and a number of inactive metabolites. Cmax in blood plasma of losartan and the active metabolite is achieved after 1 hour and 3-4 hours, respectively. Plasma protein binding of losartan and the active metabolite is high - more than 98%.
T1/2 of losartan and the active metabolite in the final phase is about 1.5-2.5 hours and 3-9 hours, respectively. Losartan is excreted in the urine and feces (with bile) unchanged and in the form of metabolites. About 35% is excreted in urine and about 60% in feces.
Indications for use Losartan-Vertex 12.5 mg 30 pcs. film-coated tablets Vertex JSC
Arterial hypertension.
Chronic heart failure with ineffective treatment with ACE inhibitors.
Kidney failure.
Left ventricular hypertrophy.
Contraindications
Use with caution in case of arterial hypotension, decreased blood volume, water-electrolyte imbalance, bilateral renal artery stenosis or stenosis of the artery of a single kidney, and renal/liver failure.
Application Losartan-vertex 12.5 mg 30 pcs. Vertex AO film-coated tablets during pregnancy and breastfeeding
Contraindicated.
special instructions
For patients who have fluid and/or sodium deficiency, fluid and electrolyte disturbances should be corrected or a lower initial dose should be used before starting treatment.
In patients with dehydration (for example, those receiving high-dose diuretics), symptomatic hypotension may occur when losartan treatment is initiated.
If renal function is impaired, a dose reduction of losartan may be required.
In patients with a history of liver disease, losartan should be used in low doses. In liver cirrhosis, the concentration of losartan in the blood plasma increases significantly.
During treatment, potassium levels in the blood should be regularly monitored, especially in elderly patients with impaired renal function.
The simultaneous use of losartan with potassium-sparing diuretics should be avoided.
Overdose
Marked decrease in blood pressure, change in heart rate (HR) (tachycardia or bradycardia due to parasympathetic (vagal) stimulation).
Side effects Losartan-Vertex 12.5 mg 30 pcs. film-coated tablets Vertex JSC
From the cardiovascular system: dizziness, orthostatic hypotension.
Metabolism: hyperkalemia.
Allergic reactions: angioedema (including swelling of the face, lips, pharynx and/or tongue), urticaria.
From the digestive system: diarrhea, increased ALT activity.
From the side of the central nervous system: headache.
Dermatological reactions: itching.
Other: renal dysfunction, myalgia.
Drug interactions
When used simultaneously with diuretics in high doses, arterial hypotension is possible.
When used simultaneously with potassium preparations and potassium-sparing diuretics, the risk of developing hyperkalemia increases.
When used simultaneously with indomethacin, the effectiveness of losartan may be reduced.
There is a report of the development of lithium intoxication when used simultaneously with lithium carbonate.
When used simultaneously with orlistat, the antihypertensive effect of losartan decreases, which can lead to a significant increase in blood pressure and the development of a hypertensive crisis.
When used simultaneously with rifampicin, the clearance of losartan increases and its effectiveness decreases.
